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Fedorchenko SV, Klimenko Z, Martynovich T, Solianyk I, Suprunenko T. Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing second-generation NS5A inhibitors with sofosbuvir + glecaprevir/pibrentasvir and ribavirin for 16-24 weeks. J Virol 2025; 99:e0184324. [PMID: 39840947 PMCID: PMC11852967 DOI: 10.1128/jvi.01843-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025] Open
Abstract
The outcomes of retreatment patients infected with hepatitis C virus genotype 3, cirrhosis, with velpatasvir may be affected by treatment failure with velpatasvir. The efficacy of SOF+GLE/PIB+RIB 16-24 weeks of treatment has been shown. The presence of NS5A resistance-associated substitution mutations, including Y93H, and the number and regimens of the past failed therapy do not influence the likelihood of achieving sustained virological response. When velpatasvir treatment fails, pibrentasvir should be used as the first choice for retreatment.
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Affiliation(s)
- Sergii V. Fedorchenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Zhanna Klimenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Tatiana Martynovich
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Iryna Solianyk
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Tatiana Suprunenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
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Koga M, Fukuda A, Nojima M, Ishizaka A, Itoh T, Eguchi S, Endo T, Kakinuma A, Kinai E, Goto T, Takahashi S, Takeda H, Tanaka T, Teruya K, Hanai J, Fujii T, Fujitani J, Hosaka T, Mita E, Minami R, Moro H, Yokomaku Y, Watanabe D, Watanabe T, Yotsuyanagi H. Non-acquired immunodeficiency syndrome defining malignancies in people living with haemophilia and human immunodeficiency virus after direct-acting antiviral era. Glob Health Med 2024; 6:316-323. [PMID: 39483444 PMCID: PMC11514628 DOI: 10.35772/ghm.2024.01036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 07/03/2024] [Accepted: 07/24/2024] [Indexed: 11/03/2024]
Abstract
Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.
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Affiliation(s)
- Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Akari Fukuda
- Division of Infectious Diseases, Advanced Clinical Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Masanori Nojima
- Centre for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan
| | - Aya Ishizaka
- Division of Infectious Diseases, Advanced Clinical Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Toshihiro Itoh
- Department of Infectious Diseases, NHO Sendai Medical Centre, Miyagi, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomoyuki Endo
- Department of Hematology, Hokkaido University Hospital, Hokkaido, Japan
| | - Akiko Kakinuma
- Social Welfare Corporation Habataki Welfare Project, Tokyo, Japan
| | - Ei Kinai
- Department of Laboratory Medicine, Tokyo Medical University, Tokyo, Japan
| | - Tomomi Goto
- Social Welfare Corporation Habataki Welfare Project, Tokyo, Japan
| | - Shunji Takahashi
- Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroki Takeda
- Social Welfare Corporation Habataki Welfare Project, Tokyo, Japan
| | - Takahiro Tanaka
- Division of Infectious Diseases, Advanced Clinical Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Katsuji Teruya
- AIDS Clinical Centre, The National Centre for Global Health and Medicine, Tokyo, Japan
| | - Jugo Hanai
- Medical Care and Human Rights Network, Osaka, Japan
| | - Teruhisa Fujii
- Division of Transfusion Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Junko Fujitani
- Department of Rehabilitation, National Centre for Global Health and Medicine, Tokyo, Japan
| | - Takashi Hosaka
- Division of Infectious Diseases, Advanced Clinical Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Eiji Mita
- Department of Gastroenterology and Hepatology, NHO Osaka National Hospital, Osaka, Japan
| | - Rumi Minami
- Department of Internal Medicine, Immunology and Infectious Diseases, Clinical Research Centre, NHO Kyushu Medical Centre, Fukuoka, Japan
| | - Hiroshi Moro
- Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | | | - Dai Watanabe
- AIDS Medical Centre, NHO Osaka National Hospital, Osaka, Japan
| | - Tamayo Watanabe
- Department of Immunology and Infectious Disease, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Sistayanarain A, Kunthalert D. Molecular characterization of the nonstructural 5A (NS5A) region of hepatitis C virus in Thai blood donors. Arch Microbiol 2024; 206:215. [PMID: 38619622 DOI: 10.1007/s00203-024-03950-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/27/2024] [Accepted: 04/01/2024] [Indexed: 04/16/2024]
Abstract
Direct acting antivirals (DAAs) have been developed for hepatitis C virus (HCV) therapy, and they are usually effective, however resistance to DAA regimens has also been reported to have a significant impact. Resistance associated substitutions (RASs) in the NS5A region are known to be correlated with failure of DAA therapy. HCV genotypes 3a and 1 are the most prevalent genotypes in Thailand. This study analyzed the type and frequency of RASs associated with DAA failure, focusing on the NS5A region. Serum samples of HCV genotype 3a, 1a, and 1b infection from Thai blood donors were selected. The NS5A region was amplified using reverse transcription-polymerase chain reaction (RT-PCR). A phylogenetic tree was constructed to identify the genotypes of HCV. Nucleotide sequencing and amino acid sequencing were conducted to determine the prevalence of RASs. Construction of the phylogenetic tree indicated that 29 samples were genotype 3a, 11 samples were genotype 1a, and 9 were genotype 1b. Both HCV genotypes 1a and 3a can be categorized into two subclades. Results showed that the NS5A substitutions A30V/K, A62T/V/I/M/P/S/L, and S98G were present in HCV genotype 3a. In HCV genotype 1a, only NS5A RASs H54Y was detected. NS5A amino acid substitutions Q54H and P58L were found in HCV genotype 1b. In conclusion, NS5A RASs at amino acid positions 30, 62, 54, 58, and 98 are present within HCV genotypes 3a and 1. While keeping in mind that additional information was not available on the anonymous blood donors tested in this study, these findings can contribute to understand the NS5A mutation. Further study with known patients under drug treatment is recommended.
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Affiliation(s)
- Anchalee Sistayanarain
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
| | - Duangkamol Kunthalert
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
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Farooq HZ, James M, Abbott J, Oyibo P, Divall P, Choudhry N, Foster GR. Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review. World J Gastrointest Oncol 2024; 16:1596-1612. [PMID: 38660636 PMCID: PMC11037048 DOI: 10.4251/wjgo.v16.i4.1596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/21/2023] [Accepted: 01/23/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
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Affiliation(s)
- Hamzah Z Farooq
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Michael James
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Jane Abbott
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Patrick Oyibo
- School of Health and Psychological Sciences, University of London, London EC1V 0HB, United Kingdom
| | - Pip Divall
- University Hospitals of Leicester Library, University Hospitals of Leicester NHS Trust, Leicester LE3 9QP, United Kingdom
| | - Naheed Choudhry
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Graham R Foster
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
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Meyers NL, Ashuach T, Lyons DE, Khalid MM, Simoneau CR, Erickson AL, Bouhaddou M, Nguyen TT, Kumar GR, Taha TY, Natarajan V, Baron JL, Neff N, Zanini F, Mahmoudi T, Quake SR, Krogan NJ, Cooper S, McDevitt TC, Yosef N, Ott M. Hepatitis C virus infects and perturbs liver stem cells. mBio 2023; 14:e0131823. [PMID: 37938000 PMCID: PMC10746249 DOI: 10.1128/mbio.01318-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 06/20/2023] [Indexed: 11/09/2023] Open
Abstract
IMPORTANCE The hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.
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Affiliation(s)
| | - Tal Ashuach
- Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, California, USA
| | | | - Mir M. Khalid
- Gladstone Institute of Virology, San Francisco, California, USA
| | | | - Ann L. Erickson
- California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Mehdi Bouhaddou
- Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
- Gladstone Institute of Data Science and Biotechnology, San Francisco, California, USA
- Quantitative Biosciences Institute, University of California, San Francisco, California, USA
| | - Thong T. Nguyen
- Gladstone Institute of Virology, San Francisco, California, USA
| | - G. Renuka Kumar
- Gladstone Institute of Virology, San Francisco, California, USA
| | - Taha Y. Taha
- Gladstone Institute of Virology, San Francisco, California, USA
| | - Vaishaali Natarajan
- Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA
| | - Jody L. Baron
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Norma Neff
- Chan Zuckerburg Biohub, San Francisco, California, USA
| | - Fabio Zanini
- Department of Bioengineering, Stanford University, Stanford, California, USA
| | - Tokameh Mahmoudi
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Stephen R. Quake
- Chan Zuckerburg Biohub, San Francisco, California, USA
- Department of Bioengineering, Stanford University, Stanford, California, USA
| | - Nevan J. Krogan
- Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
- Gladstone Institute of Data Science and Biotechnology, San Francisco, California, USA
- Quantitative Biosciences Institute, University of California, San Francisco, California, USA
| | - Stewart Cooper
- California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Todd C. McDevitt
- Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA
- Bioengineering & Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA
| | - Nir Yosef
- Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, California, USA
- Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Cambridge, Massachusetts, USA
| | - Melanie Ott
- Gladstone Institute of Virology, San Francisco, California, USA
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
- Chan Zuckerburg Biohub, San Francisco, California, USA
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6
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Han CL, Tian BW, Yang CC, Yang YF, Ma YL, Ding ZN, Yan LJ, Liu H, Dong ZR, Chen ZQ, Hong JG, Wang DX, Li T. The association of fatty liver and risk of hepatocellular carcinoma in HBV or HCV infected individuals: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:189-198. [PMID: 36625022 DOI: 10.1080/17474124.2023.2166930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. RESEARCH DESIGN AND METHODS Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. RESULTS Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69-5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83-14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93-2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02-3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44-1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45-1.08). CONCLUSIONS Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC.
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Affiliation(s)
- Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Chun-Cheng Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ya-Fei Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yun-Long Ma
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.,Department of Hepatobiliary Surgery, the Second Hospital of Shandong University, Jinan, P.R. China
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Shiha G, Soliman R, Mikhail NNH, Carrat F, Azzi J, Nathalie GC, Toyoda H, Uojima H, Nozaki A, Takaguchi K, Hiraoka A, Atsukawa M, Abe H, Matsuura K, Mikami S, Watanabe T, Tsuji K, Ishikawa T, Suri V, Osinusi A, Ni L, Zou J, Sarin SK, Kumar M, Jalal PK, Hashim MA, Hassan M, Lopez SA, Bañares R, Ahumada AM, Mousa NH, Eslam M, Waked I. International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients. J Viral Hepat 2022; 29:807-816. [PMID: 35657138 DOI: 10.1111/jvh.13717] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 03/15/2022] [Accepted: 04/03/2022] [Indexed: 12/28/2022]
Abstract
We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs.
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Affiliation(s)
- Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), El Mansoura, Egypt
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), El Mansoura, Egypt
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Fuad, Egypt
| | - Nabiel N H Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), El Mansoura, Egypt
- Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Asyut, Egypt
| | - Fabrice Carrat
- Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France
- AP-HP, Sorbonne Université, Hôpital Saint-Antoine, Santé Publique, Paris, France
| | - Jessica Azzi
- Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France
| | - Ganne-Carrié Nathalie
- APHP, Liver Unit, AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Bobigny, France
- Université Sorbonne Paris Nord, Bobigny, France
- Inserm, UMR-1138 « Functional Genomics of solid tumors », Centre de Recherche des Cordeliers, Université de Paris, Paris, France
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akito Nozaki
- Gastroenterology Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Kentaro Matsuura
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Vithika Suri
- Gilead Sciences, Inc, Foster City, California, USA
| | - Anu Osinusi
- Gilead Sciences, Inc, Foster City, California, USA
| | - Liyun Ni
- Gilead Sciences, Inc, Foster City, California, USA
| | - Jun Zou
- Gilead Sciences, Inc, Foster City, California, USA
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Prasun Kumar Jalal
- Division of Abdominal Transplantation, Baylor College of Medicine, Houston, Texas, USA
| | - Mahmoud A Hashim
- Division of Abdominal Transplantation, Baylor College of Medicine, Houston, Texas, USA
| | - Manal Hassan
- Division of Abdominal Transplantation, Baylor College of Medicine, Houston, Texas, USA
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, MD Anderson, Houston, Texas, USA
| | - Sonia Alonso Lopez
- Liver Unit, Hospital General Universitario Gregorio Marañon, Madrid, Spain
- Instituto De Investigación SanitariaGregorio Marañón (IiSGM), Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Rafael Bañares
- Liver Unit, Hospital General Universitario Gregorio Marañon, Madrid, Spain
- Instituto De Investigación SanitariaGregorio Marañón (IiSGM), Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Adriana M Ahumada
- Liver Unit, Hospital General Universitario Gregorio Marañon, Madrid, Spain
| | - Nasser Hamed Mousa
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia
| | - Imam Waked
- Hepatology Department, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
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Loo JH, Xu WXF, Low JT, Tay WX, Ang LS, Tam YC, Thurairajah PH, Kumar R, Wong YJ. Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis: A meta-analysis. World J Hepatol 2022; 14:1248-1257. [PMID: 35978662 PMCID: PMC9258247 DOI: 10.4254/wjh.v14.i6.1248] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 11/18/2021] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear. AIM To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients. METHODS We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (I 2) were estimated using Review Manager version 5.3. RESULTS From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I 2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I 2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I 2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients. CONCLUSION Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.
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Affiliation(s)
- Jing Hong Loo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Wen Xin Flora Xu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Jun Teck Low
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Wei Xuan Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Le Shaun Ang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Yew Chong Tam
- Education Resource Center, Medical Board, Singapore General Hospital, Singapore 100059, Singapore
| | - Prem Harichander Thurairajah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore 119077, Singapore
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
- Duke-NUS Medicine Academic Clinical Program, Singapore 100059, Singapore
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
- Duke-NUS Medicine Academic Clinical Program, Singapore 100059, Singapore.
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9
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Stella L, Santopaolo F, Gasbarrini A, Pompili M, Ponziani FR. Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment. World J Gastroenterol 2022; 28:2251-2281. [PMID: 35800182 PMCID: PMC9185215 DOI: 10.3748/wjg.v28.i21.2251] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/08/2021] [Accepted: 04/26/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.
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Affiliation(s)
- Leonardo Stella
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
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10
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Liu X, Chen Z, Tang Q, Hu P. Phylogenetic signature and prevalence of natural resistance-associated substitutions for hepatitis C virus genotypes 3a and 3b in southwestern China. J Virus Erad 2022; 8:100071. [PMID: 35757658 PMCID: PMC9218835 DOI: 10.1016/j.jve.2022.100071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 03/01/2022] [Accepted: 06/08/2022] [Indexed: 11/19/2022] Open
Abstract
Background Patients infected with hepatitis C (HCV) genotype (GT) 3, especially GT3b, are still difficult to cure. GT3b is more common than GT3a in southwestern China. Here we aimed to investigate the prevalence of naturally occurring RASs in HCV GT3 in southwestern China and performed phylogenetic analysis. Methods Serum samples were collected from patients with HCV GT3 infection. Sanger sequencing was used to validate resistance-associated substitutions (RASs). Phylogenetic analysis was performed using MEGA X and the observed-minus-expected-squared algorithm was used to analyze amino acid covariance. Results A total of 136 patients were enrolled, including 41 HCV GT3a and 95 GT3b infected patients. In the NS5A region, the proportion of RASs found in GT3b (99%) was notably higher than in GT3a (9%). In the NS3 region, RASs prevalence in GT3b (5%) was lower than in GT3a (24%). NS5B-specific RASs were rare. Both the NS5A30k and L31 M substitutions occurred in 96% of GT3b sequences. The A30K + L31M combination was found in 94% of GT3b isolates, however, there were no A30K or L31M mutations observed in the GT3a sequence. Conclusions Significant differences were observed between HCV GT3a and GT3b in terms of RAS prevalence. The origin of GT3a appears to be more diverse compared with GT3b in southern China. Studies specifically aimed at HCV GT3b infection should be initiated to gain more insight into this subtype.
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Affiliation(s)
| | | | | | - Peng Hu
- Corresponding author. Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400010, China.,
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11
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Azzi J, Dorival C, Cagnot C, Fontaine H, Lusivika-Nzinga C, Leroy V, De Ledinghen V, Tran A, Zoulim F, Alric L, Gournay J, Bronowicki JP, Decaens T, Riachi G, Mikhail N, Soliman R, Shiha G, Pol S, Carrat F, Ganne-Carrié N. Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response. Clin Res Hepatol Gastroenterol 2022; 46:101923. [PMID: 35405354 DOI: 10.1016/j.clinre.2022.101923] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/07/2022] [Accepted: 04/05/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND & AIMS Prediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging. METHODS Among HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival. RESULTS During follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score <12) and low risk of HCC (score < 7/22) with 3-yrs HCC incidence of 18.96%, 5.50% and 1.65%, respectively. The integrated time-dependent area under the ROC curve (i-AUC) was 0.76 in our patients and 0.61 in the validation cohort. CONCLUSION The externally validated HEPATHER HCC score has good short-term predictive performance in HCV- patients who achieved SVR12 after DAAs allowing to identify high-risk patients in whom HCC screening may be cost-effective and low-risk patients in whom HCC screening may be superfluous in the first 3 years after SVR.
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Affiliation(s)
- Jessica Azzi
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Céline Dorival
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Carole Cagnot
- ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), Unit for Basic and Clinical Research on Viral Hepatitis, Paris, France
| | | | - Clovis Lusivika-Nzinga
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Vincent Leroy
- Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - Victor De Ledinghen
- Hepatology Unit Hôpital Haut-Lévêque, Pessac, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
| | - Albert Tran
- Université Côte d'Azur, Nice, France; CHU de Nice, Digestive Center, Nice, France; INSERM, U1065, C3M, Team 8 « Chronic liver diseases associated with obesity and alcohol », Nice, France
| | - Fabien Zoulim
- Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152 Pharma Dev, IRD Toulouse 3 University, France
| | - Jérôme Gournay
- Gastroenterology and Hepatology Department, Institut des Maladies de l'Appareil Digestif, University Hospital of Nantes, Nantes, France
| | - Jean-Pierre Bronowicki
- Inserm U1254 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Thomas Decaens
- Department of Hepatology and Gastroenterology, CHU Grenoble-Alpes, Université Grenoble-Alpes, Institute for Advanced Biosciences INSERM U1209, Grenoble, France
| | - Ghassan Riachi
- Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France
| | - Nabiel Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt; Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assuit, Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt; Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
| | - Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt; Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Stanislas Pol
- AP-HP, Hôpital Cochin, Unité d'Hépatologie, Paris, France; Université de Paris, INSERM U1223 and USM-20, Institut Pasteur, Paris, France
| | - Fabrice Carrat
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; AP-HP, Sorbonne Université, Hôpital Saint-Antoine, Santé Publique, Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, APHP, Liver Unit, Bobigny, France; Université Sorbonne Paris Nord, Bobigny, France; Inserm, UMR-1138 « Functional Genomics of solid tumors », Centre de Recherche des Cordeliers, Université de Paris, France.
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12
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Yang J, Liu HX, Su YY, Liang ZS, Rao HY. Distribution and changes in hepatitis C virus genotype in China from 2010 to 2020. World J Clin Cases 2022; 10:4480-4493. [PMID: 35663077 PMCID: PMC9125278 DOI: 10.12998/wjcc.v10.i14.4480] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 02/28/2022] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) causes a large number of infections worldwide. New infections seem to be increasing according to a report of the World Health Organization in 2015. Although direct-acting antivirals are quite effective for most genotypes of the HCV, some genotypes fail to respond. Therefore, the trend of genotype distribution is vital to better control the development of this infection.
AIM To analyze the distribution and trends of the HCV genotype before and after the emergence of direct-acting antivirals in China.
METHODS We searched all literature published in five electronic databases-China National Knowledge Infrastructure, Wan Fang Data, VIP Chinese Journal Database, Chinese Biomedical Literature Service System, and PubMed-from January 1, 2010 to December 31, 2020. The search strategy combined medical subject headings and free-text terms, including “hepatitis C virus” or “HCV” and “genotype” or “subtype” and ”China” or “Chinese”. Additional relevant articles were searched by manual selection. Data were extracted to build a database. All of the data were totaled according to regions, periods, routes of transmission, and sexes. The percentages in various stratifications were calculated.
RESULTS There were 76110 samples from 30 provinces included in the study. Genotype 1 (G1) accounted for 58.2% of cases nationwide, followed by G2, G6, G3b, G3a, unclassified and mixed infections (17.5%, 7.8%, 6.4%, 4.9%, 1.8%, and 1.2%, respectively). The constitution of genotype varied among different regions, with G6 and G3b being more common in the south and southwest, respectively (28.1%, 15.4%). The past ten years have witnessed a decrease in G1 and G2 and an increase in G3 and G6 in almost all regions. The drug-use population had the most abundant genotypes, with G6 ranking first (33.3%), followed by G1 and G3b (23.4%, 18.5%).
CONCLUSION G3 and G6 pose a new challenge for HCV infection. This study revealed the distribution of HCV genotypes in China over the past 10 years, providing information for HCV management strategies.
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Affiliation(s)
- Jia Yang
- Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Hui-Xin Liu
- Department of Clinical Epidemiology and Biostatistics, Peking University People’s Hospital, Beijing 100044, China
| | - Ying-Ying Su
- National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361000, Fujian Province, China
| | - Zhi-Sheng Liang
- Department of Global Health, School of Public Health, Peking University, Beijing 100044, China
| | - Hui-Ying Rao
- Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People’s Hospital, Beijing 100044, China
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13
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Cherepnin MA, Tsukanov VV, Savchenko AA, Vasyutin AV, Kasparov EV, Tonkikh JL, Borisov AG. Comparison of clinical and laboratory characteristics and frequency of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2022:98-103. [DOI: 10.21518/2079-701x-2022-16-7-98-103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/12/2024]
Abstract
Introduction. There is a discussion about which genotype of viral hepatitis C (HCV) is the most aggressive. Some authors consider that the 1st genotype is the most aggressive, others define the 3rd HCV genotype as a factor that determines the high activity of the pathological process. The solution of this issue is important for optimizing the tactics of patient management.Aim. To compare the clinical and laboratory characteristics and the incidence of liver fibrosis in patients with chronic viral hepatitis C of the first and third genotypes.Materials and methods. 297 patients with genotype 1 of HCV and 231 patients with genotype 3 of HCV were examined. The diagnosis of chronic viral hepatitis C was established according to the recommendations of the European Association for the Study of the Liver (2016, 2018). Liver fibrosis was studied by shear wave transient elastometry with METAVIR score.Results and discussion. The frequency of elevated ALT in the blood prevailed in patients with HCV genotype 3 compared with persons with HCV genotype 1 (90.5% vs. 82.8%, p = 0.02). ALT levels above 3 norms were registered in 29.0% of patients with genotype 3 and in 16.8% patients with HCV genotype 1 (p = 0.001). The frequency of liver fibrosis F2 according to METAVIR was 11.8% in patients with genotype 1 and 21.2% in patients with genotype 3 of HCV (p = 0.005); the frequency of liver fibrosis F3–F4 according to METAVIR was 20.5% in patients with genotype 1 and 32.5% in patients with genotype 3 of HCV (p = 0.003). The combination of high viral load and high inflammatory activity, which was associated with liver fibrosis F3–F4 according to METAVIR in both compared groups, was determined in 16.9% of patients with genotype 3 and only in 10.4% of patients with genotype 1 of HCV (p = 0.04).Conclusion. The obtained data allow us to consider that in the surveyed population the course of chronic viral hepatitis C with genotype 3 is clearly more aggressive than in persons with genotype 1 of HCV.
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Affiliation(s)
- M. A. Cherepnin
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
| | - V. V. Tsukanov
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
| | - A. A. Savchenko
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
| | - A. V. Vasyutin
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
| | - E. V. Kasparov
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
| | - J. L. Tonkikh
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
| | - A. G. Borisov
- Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Separate Subdivision “Scientific Research Institute of medical problems of the North”
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14
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Mushtaq S, Hashmi AH, Khan A, Asad Raza Kazmi SM, Manzoor S. Emergence and Persistence of Resistance-Associated Substitutions in HCV GT3 Patients Failing Direct-Acting Antivirals. Front Pharmacol 2022; 13:894460. [PMID: 35571102 PMCID: PMC9091354 DOI: 10.3389/fphar.2022.894460] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 03/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The hepatitis C virus has a high mutation rate, which results in the emergence of resistance-associated substitutions (RASs). Despite direct-acting antivirals (DAAs) efforts to treat chronically infected HCV genotype 3 (GT3) patients, there are concerns about the emergence and persistence of RASs in DAA failures. The objective of this study was to determine the prevalence of clinically relevant RASs in HCV NS5A and NS5B regions before and after treatment to better understand the role of RASs in treatment failures. Methods: Viral RNA was extracted before and after treatment from serum samples. NS5A and NS5B regions of HCV were amplified by nested PCR, followed by Sanger sequencing. The nucleotide sequences were aligned against HCV GT3 reference sequences, and amino acid substitutions were analyzed using the geno2pheno [hcv] webserver. Results: A total of 76 patients failing DAA therapy were stratified from the cohort of 1388. RASs were detected at the baseline in 15/76 patients and at relapse in 20/76 patients with cirrhosis and previously treated with interferons. The most prevalent NS5A RAS was Y93H found in all treatment-failing patients (14/54 in DCV vs. 6/22 in VEL), followed by A62S/T and A30K. No RASs were identified in NS5B. RASs that were present at the baseline persisted through the 24-week follow-up period and were enriched with emerging RASs during the treatment. The presence of RASs may be one of the causes of treatment failures in 26.3% of patients. Amino acid substitutions were present at the baseline in most of the patients with RASs against NS5A inhibitors. Patients with the baseline Y93H and/or A30K relapse more frequently than patients harboring A62S/T. Conclusion: Treatment-failing patients harbored NS5A RASs, and the most frequent were A30K (5/20), A62S/T (20/20), and Y93H (20/20). Direct resistance testing is recommended for optimizing re-treatment strategies in treatment-failing patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | | | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | | | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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15
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Elsheikh MEA, McClure CP, Tarr AW, Irving WL. Sero-reactivity to three distinct regions within the hepatitis C virus alternative reading frame protein (ARFP/core+1) in patients with chronic HCV genotype-3 infection. J Gen Virol 2022; 103:001727. [PMID: 35230930 PMCID: PMC9176264 DOI: 10.1099/jgv.0.001727] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Hepatitis C virus (HCV) infection affects more than 71 million people worldwide. The disease slowly progresses to chronic, long-term liver injury which leads to hepatocellular carcinoma (HCC) in 5 % of infections. The alternative reading frame protein (ARFP/core+1) is encoded by a sequence overlapping the HCV core gene in the +1 reading frame. Its role in hepatitis C pathogenesis and the viral life cycle is unclear, although some observers have related its production to disease progression and the development of HCC. The aim of this study was to determine whether ARFP is immunogenic in patients with chronic HCV genotype 3 infection and to assess whether sero-reactivity is associated with disease progression, particularly to HCC. Immunogenic epitopes within the protein were predicted by a bioinformatics tool, and three -20 aa length-peptides (ARFP-P1, ARFP-P2 and ARFP-P3) were synthesized and used in an avidin-biotin ARFP/core+1 peptide ELISA. Serum samples from 50 patients with chronic HCV genotype 3 infection, 50 genotype-1 patients, 50 HBV patients and 110 healthy controls were tested. Sero-reactivity to the ARFP peptides was also tested and compared in 114 chronic HCV genotype-3 patients subdivided on the basis of disease severity into non-cirrhotic, cirrhotic and HCC groups. Chronic HCV genotype-3 patients showed noticeable rates of reactivity to ARFP and core peptides. Seropositivity rates were 58% for ARFP-P1, 47 % for ARFP-P2, 5.9 % for ARFP-P3 and 100 % for C22 peptides. There was no significant difference between these seroreactivities between HCV genotype-3 patients with HCC, and HCV genotype-3 patients with and without liver cirrhosis. Patients with chronic HCV genotype-3 infection frequently produce antibodies against ARFP/core+1 protein. ARFP peptide reactivity was not associated with disease severity in patients with HCV genotype-3. These results support the conclusion that ARFP/core+1 is produced during HCV infection, but they do not confirm that antibodies to ARFP can indicate HCV disease progression.
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Affiliation(s)
- Mosaab E A Elsheikh
- School of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, UK
| | - C Patrick McClure
- School of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, UK.,Wolfson Centre for Global Virus Infections, The University of Nottingham, Nottingham, UK
| | - Alexander W Tarr
- School of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, UK.,Wolfson Centre for Global Virus Infections, The University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - William L Irving
- School of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham, UK.,Wolfson Centre for Global Virus Infections, The University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
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16
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Chen M, Xu Y, Li N, Yin P, Zhou Q, Feng S, Wu T, Wei L, Wang H, Fu Y, Li YP. Development of full-length cell-culture infectious clone and subgenomic replicon for a genotype 3a isolate of hepatitis C virus. J Gen Virol 2021; 102. [PMID: 34949310 DOI: 10.1099/jgv.0.001704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
Hepatitis C virus (HCV) genotype 3 is widely distributed, and genotype 3-infected patients achieve a lower cure rate in direct-acting antiviral (DAA) therapy and are associated with a higher risk of hepatic steatosis than patients with other genotypes. Thus, the study of the virology and pathogenesis of genotype 3 HCV is increasingly relevant. Here, we developed a full-length infectious clone and a subgenomic replicon for the genotype 3a isolate, CH3a. From an infected serum, we constructed a full-length CH3a clone, however, it was nonviable in Huh7.5.1 cells. Next, we systematically adapted several intergenotypic recombinants containing Core-NS2 and 5'UTR-NS5A from CH3a, and other sequences from a replication-competent genotype 2 a clone JFH1. Adaptive mutations were identified, of which several combinations facilitated the replication of CH3a-JFH1 recombinants; however, they failed to adapt to the full-length CH3a and the recombinants containing CH3a NS5B. Thus, we attempted to separately adapt CH3a NS5B-3'UTR by constructing an intragenotypic recombinant using 5'UTR-NS5A from an infectious genotype 3a clone, DBN3acc, from which L3004P/M in NS5B and a deletion of 11 nucleotides (Δ11nt) downstream of the polyU/UC tract of the 3'UTR were identified and demonstrated to efficiently improve virus production. Finally, we combined functional 5'UTR-NS5A and NS5B-3'UTR sequences that carried the selected mutations to generate full-length CH3a with 26 or 27 substitutions (CH3acc), and both revealed efficient replication and virus spread in transfected and infected cells, releasing HCV of 104.2 f.f.u. ml-1. CH3acc was inhibited by DAAs targeting NS3/4A, NS5A and NS5B in a dose-dependent manner. The selected mutations permitted the development of subgenomic replicon CH3a-SGRep, by which L3004P, L3004M and Δ11nt were proven, together with a single-cycle virus production assay, to facilitate virus assembly, release, and RNA replication. CH3acc clones and CH3a-SGRep replicon provide new tools for the study of HCV genotype 3.
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Affiliation(s)
- Mingxiao Chen
- Joint Program in Pathology, Department of Internal Medicine, Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510623, PR China
| | - Yi Xu
- Joint Program in Pathology, Department of Internal Medicine, Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510623, PR China
| | - Ni Li
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Ping Yin
- Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China
| | - Qing Zhou
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Shengjun Feng
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Tiantian Wu
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, PR China
| | - Haihe Wang
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Yongshui Fu
- Guangzhou Blood Center, Guangzhou 510095, PR China
| | - Yi-Ping Li
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, PR China
- Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, PR China
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17
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Broquetas T, Herruzo-Pino P, Mariño Z, Naranjo D, Vergara M, Morillas RM, Forns X, Carrión JA. Elastography is unable to exclude cirrhosis after sustained virological response in HCV-infected patients with advanced chronic liver disease. Liver Int 2021; 41:2733-2746. [PMID: 34525253 DOI: 10.1111/liv.15058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 08/23/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)-infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown. AIMS To evaluate TE accuracy at identifying cirrhosis 3 years after HCV-eradication. METHODS Prospective, multi-centric study including HCV-cACLD patients before direct-acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated. RESULTS Among 746 HCV-infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non-invasive tests (APRI and FIB-4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV-genotype 3 (20.81 (2.12-201.47), .009), and TE before treatment (1.21 (1.09-1.34), <.001) were the only variables associated with cirrhosis after SVR. However, the accuracy of TE after SVR was poor (AUROC = 0.75) and 6 (27.3%) out of 22 patients with a TE <8 kPa had cirrhosis. Similar results were found with APRI and FIB-4 scores. CONCLUSIONS Cirrhosis is present, 3 years after SVR, in more than half of HCV-cACLD patients even with the normalisation of liver function parameters, serological non-invasive tests and TE values. The low diagnostic accuracy of non-invasive methods after SVR reinforces the need for long-term surveillance.
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Affiliation(s)
- Teresa Broquetas
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain.,Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
| | - Paula Herruzo-Pino
- Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Dolores Naranjo
- Gastrointestinal and Hepatobiliary Pathology Section, Department of Pathology, Hospital del Mar, Barcelona, Spain
| | - Mercedes Vergara
- Liver Unit, Digestive Disease Department, Parc Taulí Sabadell Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rosa Mª Morillas
- Hepatology Department, Hospital Germans Trias i Pujol, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - José A Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain.,Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
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Siphepho PY, Liu YT, Shabangu CS, Huang JF, Huang CF, Yeh ML, Yu ML, Wang SC. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines 2021; 9:1491. [PMID: 34680608 PMCID: PMC8533513 DOI: 10.3390/biomedicines9101491] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic derangement is characteristic in patients with hepatitis C virus (HCV) infection. Aside from established liver injury, various extrahepatic metabolic disorders impact the natural history of the disease, clinical outcomes, and the efficacy of antiviral therapy. The presence of steatosis, recently redefined as metabolic-associated fatty liver disease (MAFLD), is a common feature in HCV-infected patients, induced by host and/or viral factors. Most chronic HCV-infected (CHC) patients have mild steatosis within the periportal region of the liver with an estimated prevalence of 40% to 86%. Indeed, this is higher than the 19% to 50% prevalence observed in patients with other chronic liver diseases such as chronic hepatitis B (CHB). The histological manifestations of HCV infection are frequently observed in genotype 3 (G-3), where relative to other genotypes, the prevalence and severity of steatosis is also increased. Steatosis may independently influence the treatment efficacy of either interferon-based or interferon-free antiviral regimens. This review aimed to provide updated evidence of the prevalence and risk factors behind HCV-associated steatosis, as well as explore the impact of steatosis on HCV-related outcomes.
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Affiliation(s)
- Phumelele Yvonne Siphepho
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
| | - Yi-Ting Liu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ciniso Sylvester Shabangu
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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19
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Chouikha A, Ghrabi A, Ghodbane A, Hammemi W, Khedhiri M, Sadraoui A, Touzi H, Hassine HB, Maatoug S, Bensaoud C, Abdelhak S, Bouarrouj S, Gdoura M, Chaouachi H, Triki H. Distribution of HCV Genotypes Among People Who Inject Drugs in Tunisia: New Evidence for Scaling Up Prevention and Treatment Toward National Elimination Goal. Front Microbiol 2021; 12:697859. [PMID: 34385988 PMCID: PMC8353188 DOI: 10.3389/fmicb.2021.697859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/24/2021] [Indexed: 11/13/2022] Open
Abstract
Little is known about the distribution of hepatitis C virus (HCV) genotypes among people who inject drugs (PWID) in North African countries, including Tunisia. This study aims to describe HCV genotypes circulating among Tunisian PWID. A cross-sectional study was conducted, and 128 HCV-positive PWID were recruited between 2018 and 2019 from community-based harm reduction centers. After informed consent, sociodemographic characteristics and risk behavior data were obtained using an interviewer-administrated questionnaire. Blood samples were collected for further serological and molecular testing. Overall, five women and 123 men were included. The median age was 39.5 years. The majority of PWID (56.3%) had less than a secondary level of education, were single (57%), were unemployed (65.6%), were incarcerated at least once (93.0%), and had a history of residency in at least one foreign country (50.8%). During the previous 12 months, 82.0% reported having reused syringes at least once, 43.8% shared syringes at least once, while 56.2% had at least one unprotected sexual relation, and 28.1% had more than two different sexual partners. Tattooing was reported among 60.2%. All positive results for HCV-infection by rapid testing were confirmed by enzyme-linked immunosorbent assay (ELISA). HCV-RNA was detectable in 79.7%. Genotyping showed a predominance of genotype 1 (52%) followed by genotype 3 (34%) and genotype 4 (10%). Four patients (4%) had an intergenotype mixed infection. Subtyping showed the presence of six different HCV subtypes as follows: 1a (53.2%), 1b (6.4%), 3a (33.0%), 4a (3.2%), and 4d (4.3%). This is the first study describing circulating HCV genotypes among PWID in Tunisia. The distribution of HCV genotypes is distinct from the general population with a predominance of subtypes 1a and 3a. These findings can be used to guide national efforts aiming to optimize the access of PWID to relevant HCV prevention and treatment measures including pangenotypic regimens for patients infected with HCV genotype 3.
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Affiliation(s)
- Anissa Chouikha
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Amine Ghrabi
- Association Tunisienne d'Information et d'Orientation sur le SIDA et la Toxicomanie (Tunisian Association for Information and Orientation on HIV/AIDS and Toxicomania - ATIOST), Tunis, Tunisia
| | - Amira Ghodbane
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Walid Hammemi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Marwa Khedhiri
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Amel Sadraoui
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Henda Touzi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | | | - Sonia Maatoug
- Science Shop, Institut Pasteur de Tunis, Tunis, Tunisia
| | - Chaima Bensaoud
- Science Shop, Institut Pasteur de Tunis, Tunis, Tunisia.,Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czechia
| | | | - Samir Bouarrouj
- Association Tunisienne d'Information et d'Orientation sur le SIDA et la Toxicomanie (Tunisian Association for Information and Orientation on HIV/AIDS and Toxicomania - ATIOST), Tunis, Tunisia
| | - Mariem Gdoura
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
| | - Hedia Chaouachi
- Association Tunisienne d'Information et d'Orientation sur le SIDA et la Toxicomanie (Tunisian Association for Information and Orientation on HIV/AIDS and Toxicomania - ATIOST), Tunis, Tunisia
| | - Henda Triki
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, Tunis El Manar University, Tunis, Tunisia
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20
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Zarębska-Michaluk D, Jaroszewicz J, Parfieniuk-Kowerda A, Janczewska E, Dybowska D, Pawłowska M, Halota W, Mazur W, Lorenc B, Janocha-Litwin J, Simon K, Piekarska A, Berak H, Klapaczyński J, Stępień P, Sobala-Szczygieł B, Citko J, Socha Ł, Tudrujek-Zdunek M, Tomasiewicz K, Sitko M, Dobracka B, Krygier R, Białkowska-Warzecha J, Laurans Ł, Flisiak R. Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics. J Clin Med 2021; 10:jcm10153280. [PMID: 34362064 PMCID: PMC8347334 DOI: 10.3390/jcm10153280] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 07/20/2021] [Accepted: 07/22/2021] [Indexed: 12/14/2022] Open
Abstract
There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this difficult-to-treat population. A total of 236 patients with mean age 52.3 ± 11.3 years and male predominance (72%) selected from EpiTer-2 database were included in the analysis; 72% of them were treatment-naïve. The majority of patients (55%) received the combination of sofosbuvir/velpatasvir (SOF/VEL), 71 without and 58 with ribavirin (RBV), whereas the remaining 107 individuals were assigned to glecaprevir/pibrentasvir (GLE/PIB). The effectiveness of the treatment following GLE/PIB and SOF/VEL regimens (96% and 93%) was higher compared to SOF/VEL + RBV option (79%). The univariate analysis demonstrated the significantly lower sustained virologic response in males, in patients with baseline HCV RNA ≥ 1,000,000 IU/mL, and among those who failed previous DAA-based therapy. The multivariate logistic regression analysis recognized only the male gender and presence of ascites at baseline as the independent factors of non-response to treatment. It should be emphasized that despite the availability of pangenotypic, strong therapeutic options, GT3 infected patients with cirrhosis still remain difficult-to-treat, especially those with hepatic impairment and DAA-experienced.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, 25-317 Kielce, Poland;
- Correspondence: ; Tel.: +48-66-244-1465; Fax: +48-41-368-2262
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland; (J.J.); (B.S.-S.)
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland; (A.P.-K.); (R.F.)
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Health Sciences in Bytom, Medical University of Silesia, 41-902 Bytom, Poland;
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia in Katowice, 41-500 Chorzów, Poland;
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, 80-214 Gdańsk, Poland;
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland; (J.J.-L.); (K.S.)
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland; (J.J.-L.); (K.S.)
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland;
| | - Hanna Berak
- Hospital for Infectious Diseases in Warszawa, 02-091 Warsaw, Poland;
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 00-241 Warszawa, Poland;
| | - Piotr Stępień
- Department of Infectious Diseases, Jan Kochanowski University, 25-317 Kielce, Poland;
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland; (J.J.); (B.S.-S.)
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, 10-561 Olsztyn, Poland;
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; (Ł.S.); (Ł.L.)
| | - Magdalena Tudrujek-Zdunek
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland; (M.T.-Z.); (K.T.)
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland; (M.T.-Z.); (K.T.)
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, 31-088 Kraków, Poland;
| | | | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland;
| | | | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; (Ł.S.); (Ł.L.)
- Multidisciplinary Regional Hospital, 66-418 Gorzów Wielkopolski, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland; (A.P.-K.); (R.F.)
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21
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Lin SK, De Maio N, Pedergnana V, Wu CH, Thézé J, Wilson DJ, Barnes E, Ansari MA. Using host genetics to infer the global spread and evolutionary history of HCV subtype 3a. Virus Evol 2021; 7:veab065. [PMID: 34532064 PMCID: PMC8438900 DOI: 10.1093/ve/veab065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 06/16/2021] [Accepted: 07/08/2021] [Indexed: 11/17/2022] Open
Abstract
Studies have shown that hepatitis C virus subtype 3a (HCV-3a) is likely to have been circulating in South Asia before its global spread. However, the time and route of this dissemination remain unclear. For the first time, we generated host and virus genome-wide data for more than 500 patients infected with HCV-3a from the UK, North America, Australia, and New Zealand. We used the host genomic data to infer the ancestry of the patients and used this information to investigate the epidemic history of HCV-3a. We observed that viruses from hosts of South Asian ancestry clustered together near the root of the tree, irrespective of the sampling country, and that they were more diverse than viruses from other host ancestries. We hypothesized that South Asian hosts are more likely to have been infected in South Asia and used the inferred host ancestries to distinguish between the location where the infection was acquired and where the sample was taken. Next, we inferred that three independent transmission events resulted in the spread of the virus from South Asia to the UK, North America, and Oceania. This initial spread happened during or soon after the end of World War II. This was subsequently followed by many independent transmissions between the UK, North America, and Oceania. Using both host and virus genomic information can be highly informative in studying the virus epidemic history, especially in the context of chronic infections where migration histories need to be accounted for.
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Affiliation(s)
| | | | - Vincent Pedergnana
- MIVEGEC, Université de Montpellier, CNRS, 911 avenue Agropolis, Montpellier 34000, France
| | - Chieh-Hsi Wu
- Building 54, Mathematical Sciences University of Southampton, Highfield, Southampton SO17 1BJ, UK
| | - Julien Thézé
- Department of Zoology, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3PS, UK,Université Clermont Auvergne, INRAE, VetAgro Sup, UMR EPIA, Centre INRAE Clermont-Auvergne-Rhône-Alpes, Saint-Genès-Champanelle 63122, France
| | | | - Eleanor Barnes
- Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3SY, UK
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22
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Tang Q, Wei L, Liu X, Hu P. Sofosbuvir-Based Therapies Achieved Satisfactory Virological Response in Chinese Individuals with Genotypes 3 and 6 Infections: A Real-World Experience. Infect Drug Resist 2021; 14:2297-2307. [PMID: 34188496 PMCID: PMC8233542 DOI: 10.2147/idr.s312902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/28/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection. METHODS This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12). RESULTS Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred. CONCLUSION Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.
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Affiliation(s)
- Qiao Tang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Li Wei
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Xiaoqing Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
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Zarębska-Michaluk D. Genotype 3-hepatitis C virus’ last line of defense. World J Gastroenterol 2021; 27:1006-1021. [PMID: 33776369 PMCID: PMC7985731 DOI: 10.3748/wjg.v27.i11.1006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-369, Świętokrzyskie, Poland
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Dar GA, Yattoo GN, Gulzar GM, Sodhi JS, Gorka S, Laway MA. Treatment of Chronic Hepatitis C Genotype 3 With Ledipasvir and Sofosbuvir: An Observational Study. J Clin Exp Hepatol 2021; 11:227-231. [PMID: 33746448 PMCID: PMC7953013 DOI: 10.1016/j.jceh.2020.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 06/14/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Sofosbuvir/ledipasvir (SOF/LED) is recommended for treatment of genotypes 1, 4, 5 and 6. Despite some preliminary data from the ELECTRON-2 trial regarding use of SOF/LED combination in chronic hepatitis C genotype 3, there are no guidelines recommending this combination in such patients. We conducted this study to evaluate the efficacy of the overall sustained virologic response at 12 weeks (SVR 12) and safety of SOF/LED in chronic hepatitis C genotype 3 infection in our population. METHODS It was a prospective, hospital-based observational study. All patients with chronic hepatitis C genotype 3 treated with SOF/LED were divided into two groups: patients with cirrhosis and without cirrhosis. Patients without cirrhosis received SOF/LED (90/400 mg) for 12 weeks; however, patients with cirrhosis received treatment for 24 weeks. RESULTS We enrolled 104 patients with chronic hepatitis C over a period of 24 months. Of the total, 66 were women (63.5%) and 38 were men (36.5%). The average age was 40 years (range: 18-76 years). Of 104 patients, 86 (82.7%) were of genotype 3, 15 (14.9%) were of genotype 1 and 3 (2.9%) were of genotype 4. Ninety-two (88%) were noncirrhotic and 12 (11.5%) were cirrhotic. Ninety-five (95.2%) were treatment naïve. Among genotype 1 and 4, all patients achieved rapid virologic response and SVR 12. Of 86 genotype 3 patients, 78 (90.6%) were noncirrhotic and 8 (9.3%) were cirrhotic. Among genotype 3 patients without cirrhosis, 75 (96%) achieved SVR 12 while 6 (75%) with cirrhosis achieved SVR 12. All patients tolerated the combination well; however, some patients experienced nausea (26%), headache (25%) and fatigue (21%). No patient had to discontinue therapy due to adverse drug reactions. CONCLUSIONS Single tablet LED and SOF combination is safe and effective in genotype 3 patients without cirrhosis even without ribavirin. Being effective in genotype 3, the combination can be used as a pangenotypic drug in patients without cirrhosis.
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Affiliation(s)
- Gulzar A. Dar
- Department of Gastroenterology, SKIMS, Srinagar, India
| | | | | | | | - Suresh Gorka
- Department of Gastroenterology, SKIMS, Srinagar, India
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25
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Sacco R, Messina V, Gentilucci UV, Adinolfi LE, Ascione A, Barbarini G, Barlattani A, Cariti G, Cozzolongo R, Fimiani B, Francavilla R, Furlan C, Garrucciu G, Iovinella V, Rinaldi L, Marignani M, Begini P, Palitti VP, Pellicelli AM, Scifo G, Facciorusso A, Giacomelli L, Shah A, Bertino G, Perazzo S, Bresci G, Izzi A. Sustained virological response in patients with HCV treated with daclatasvir plus sofosbuvir, with or without ribavirin: a large, field-practice study. Drugs Context 2020; 9:2020-4-11. [PMID: 33408749 PMCID: PMC7747789 DOI: 10.7573/dic.2020-4-11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 11/03/2020] [Accepted: 11/14/2020] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND The once-daily oral combination of daclatasvir (DCV) and sofosbuvir (SOF), with or without ribavirin (RBV), is effective and well tolerated in patients with hepatitis C virus (HCV). However, further field-practice studies are necessary to investigate the effectiveness and safety of the DCV+SOF combination in diverse subpopulations of patients with HCV, including those who are more challenging to treat such as patients with a genotype 3 (G3) infection. The aim of this retrospective, multicenter, field-practice study was to investigate the therapeutic efficacy and safety of the oral combination of DCV and SOF, with or without RBV (DCV+SOF±RBV), in a large unselected cohort of patients with chronic HCV infection (CHC). PATIENTS AND METHODS Consecutive patients received DCV+SOF±RBV for 12 or 24 weeks. The efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12). Safety factors were also considered. RESULTS A total of 620 patients were included in this study; the predominant genotype was G3 (55.3%). Of the total sample, 248 (40%) patients were treated with DCV+SOF+RBV and 372 (60%) did not receive RBV. The majority of patients assessed at week 12 (98%, 596/608) achieved SVR12. Among G3 patients, 98.8% (335/339) achieved SVR12. The most common adverse event was elevated bilirubin (30.6%), recorded in 4.9% of cases as a grade 3-4 adverse event. CONCLUSION This study shows the high pan-genotypic effectiveness and safety of the DCV+SOF±RBV combination in a large, unselected sample of CHC patients with G1-4, including a wide proportion of G3 CHC patients.
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Affiliation(s)
- Rodolfo Sacco
- Gastroenterology and Metabolic Diseases Unit – Pisa University Hospital, Pisa, Italy
| | - Vincenzo Messina
- Infectious Disease Unit Sant’Anna e San Sebastiano Hospital Caserta, Italy
| | | | | | - Antonio Ascione
- Center for Liver Diseases “Buon Consiglio-Fatebenefratelli” Hospital, Naples, Italy
| | | | | | - Giuseppe Cariti
- Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy
| | - Raffaele Cozzolongo
- Division of Gastroenterology, IRCCS “S De Bellis Hospital”, Castellana Grotte, Italy
| | - Basilio Fimiani
- Internal Medicine Unit, “Umberto I” Hospital, Nocera Inferiore, Italy
| | | | - Caterina Furlan
- Infectious and Tropical Diseases Policlinico “Umberto I”, Rome, Italy
| | | | | | - Luca Rinaldi
- Internal Medicine Unit “L Vanvitelli” University, Naples, Italy
| | | | - Paola Begini
- Digestive and Liver Diseases “S. Andrea” Hospital Rome, Italy
| | | | - Adriano M Pellicelli
- Liver Disease unit Department of Liver Transplantation “San Camillo” Hospital Rome, Italy
| | - Gaetano Scifo
- Infectious Disease Unit “Umberto I” Hospital, Siracusa, Italy
| | | | - Luca Giacomelli
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | | | | | - Serena Perazzo
- Department of Infectious Diseases and Emergency Infectious Diseases “D. Cotugno” Hospital Naples, Italy
| | - Giampaolo Bresci
- Gastroenterology and Metabolic Diseases Unit – Pisa University Hospital, Pisa, Italy
| | - Antonio Izzi
- Department of Infectious Diseases and Emergency Infectious Diseases “D. Cotugno” Hospital Naples, Italy
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26
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Lionetti R, Piccolo P, Lenci I, Siciliano M, Visco-Comandini U, De Santis A, Pompili M, Milana M, Taibi C, Dell'Isola S, Montalbano M, Mastroianni C, Begini P, Garbuglia AR, Angelico M, D'Offizi G. Daclatasvir, sofosbuvir with or without ribavirin for 24 weeks in hepatitis C genotype 3 cirrhosis: A real-life study. Ann Hepatol 2020; 18:434-438. [PMID: 31023614 DOI: 10.1016/j.aohep.2018.09.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 09/02/2018] [Accepted: 09/05/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Cirrhotic patients with hepatitis C virus genotype 3 infection show unsatisfactory outcomes after 12 weeks' treatment with direct antiviral agents. The National Italian Drug Agency allows 24 weeks of therapy in difficult-to-treat patients, including genotype 3 cirrhotics. Aim of this study was to evaluate efficacy and safety of a 24-week course of sofosbuvir plus daclatasvir±ribavirin in this population. MATERIALS AND METHODS 106 consecutive cirrhotics (70.8% males, mean age 55.3±7.6 years) in 8 tertiary hepatology centers received sofosbuvir plus daclatasvir for 24 weeks. Ribavirin was administered in 85 (80.2%) based expected tolerability, at a mean dose of 964±202mg/day. Baseline Child-Pugh class was A 91.5%, B 6.6%, C 1.9%; mean baseline MELD was 8.5±2.7. RESULTS All patients completed 12-week follow-up post-treatment, and 104 (98.1%) obtained sustained virological response (100% in ribavirin -treated patients vs. 90.4% without ribavirin; p=0.04). No worsening in renal and liver function was observed, no serious adverse events occurred. Two virological failures showed resistance associated variants (Y93H and S282T). CONCLUSION An extended 24-week treatment with sofosbuvir plus daclatasvir+ribavirin obtained 100% efficacy in genotype 3 hepatitis C cirrhosis, with very limited side effects. The role of ribavirin seems crucial in this setting and should be administered if clinically feasible.
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Affiliation(s)
- Raffaella Lionetti
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy.
| | - Paola Piccolo
- Internal Medicine Unit, Fatebenefratelli Hospital Isola Tiberina, Rome, Italy; Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Ilaria Lenci
- Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Massimo Siciliano
- Gastroenterology and Liver Unit, Policlinico Gemelli, Catholic University, Rome, Italy
| | - Ubaldo Visco-Comandini
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Adriano De Santis
- Gastroenterology and Liver Unit, Policlinico Umberto I, Sapienza University, Rome, Italy
| | - Maurizio Pompili
- Gastroenterology and Liver Unit, Policlinico Gemelli, Catholic University, Rome, Italy
| | - Martina Milana
- Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Chiara Taibi
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Serena Dell'Isola
- Medicina Protetta-Infectious Diseases, Belcolle Hospital, Viterbo, Italy
| | - Marzia Montalbano
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Claudio Mastroianni
- Infectious Diseases, Policlinico Umberto I, Sapienza University, Rome, Italy
| | - Paola Begini
- Liver Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Anna Rosa Garbuglia
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Mario Angelico
- Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Gianpiero D'Offizi
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
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Japan Society of Hepatology guidelines for the management of hepatitis C virus infection: 2019 update. Hepatol Res 2020; 50:791-816. [PMID: 32343477 DOI: 10.1111/hepr.13503] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/03/2020] [Accepted: 03/22/2020] [Indexed: 12/12/2022]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the Committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the Committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.
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Afzal M, Ali A, Sheikh N, Rafique S, Idrees M. Peripheral Expression of CXCL10 Gene in Chronic Hepatitis C Patients Treated with Sofosbuvir, Daclatasvir, and Ribavirin. J Interferon Cytokine Res 2020; 40:301-309. [PMID: 32486887 DOI: 10.1089/jir.2019.0185] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) causes persistent infection and invades host's innate and adaptive immune systems. During the eradication of this pathogen, the components of immune system may cause bystander damage to host, which might be even worse than the viral pathogenesis. Thus, the therapy should not only eliminate primary virus infection but also improve the inflammatory immune responses. The breakthrough of interferon free direct acting antiviral (DAA) drugs has provided the opportunity to unravel the association of HCV with immune response. This study aimed to examine the expression level of C-X-C motif chemokine ligand 10 (CXCL10) in the Peripheral blood mononuclear cells (PBMCs) of HCV infected patients treated with DAAs + Ribavirin. In this study we analyzed the expression levels of CXCL10 mRNA in the 90 chronic HCV patients using quantitative PCR (qPCR) prior, after, and during therapy with sofosbuvir/ribavirin (SOF+RBV) and sofosbuvir/daclatasvir/ribavirin (SOF+DCV+RBV), and further, the results were analyzed relative to treatment response. Significantly elevated CXCL10 mRNA was seen in naive patients having higher viral load (P = 0.005) and those suffering from hepatocellular carcinoma (P = 0.006). HCV patients had remarkable decline in CXCL10 level after 4, 12, and 24 weeks of therapy with DAAs. An approximate one-fold decrease was observed in patients who attained sustained virological response compared to untreated patients (P < 0.0001). Comparing the 2 regimens, the reduction in peripheral CXCL10 expression was more pronounced in patients undergoing SOF+DCV+RBV therapy. The current study implicitly shows the role of CXCL10 as an indicator of disruption of host-virus equilibrium and consequent pathogenesis of HCV during successful antiviral therapy. Furthermore, the drop in CXCL10 level after HCV viral clearance might reflect the DAA-induced alleviation in the extrahepatic manifestation of this infection.
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Affiliation(s)
- Maira Afzal
- Molecular Virology Laboratory, Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Department of Genetics, Hazara University Mansehra, Khyber Pakhtunkhwa, Pakistan
| | - Nadeem Sheikh
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Shazia Rafique
- Divison of Molecular Virology, Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Divison of Molecular Virology, Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan
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Poordad F, Shiffman ML, Ghesquiere W, Wong A, Huhn GD, Wong F, Ramji A, Shafran SD, McPhee F, Yang R, Noviello S, Linaberry M. Daclatasvir and sofosbuvir with ribavirin for 24 weeks in chronic hepatitis C genotype-3-infected patients with cirrhosis: a Phase III study (ALLY-3C). Antivir Ther 2020; 24:35-44. [PMID: 30382942 DOI: 10.3851/imp3278] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2018] [Indexed: 01/13/2023]
Abstract
BACKGROUND Optimal treatment for patients with HCV genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks. METHODS This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary end point was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks' daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% CI lower bound >79.0%). RESULTS A total of 78 patients were treated (54 treatment-naive, 24 treatment-experienced including 8 with prior sofosbuvir exposure). SVR12 was achieved by 87% (68/78; 95% CI 77.7, 93.7%) of patients in the primary analysis of central laboratory data. One additional patient achieved SVR12 by local testing resulting in an overall SVR12 rate of 88% (95% CI 79.2, 94.6%) and the lower bound of the 95% CI above the historical threshold. SVR12 rates were 93% (50/54) for treatment-naive and 79% (19/24) for treatment-experienced patients. Of the nine non-SVR12 patients, four were lost to follow-up, two relapsed (both sofosbuvir-experienced), two had end-of-treatment virological failure and one discontinued early. There were no unexpected safety signals; only one patient discontinued for an adverse event. CONCLUSIONS Daclatasvir+sofosbuvir+ribavirin for 24 weeks was well tolerated and efficacious in HCV genotype-3-infected patients with compensated cirrhosis, with SVR12 outcomes comparable to previously reported outcomes in patients treated with this regimen for 12-16 weeks. ClinicalTrials.gov ID NCT02673489.
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Affiliation(s)
- Fred Poordad
- The Texas Liver Institute, University of Texas Health, San Antonio, TX, USA
| | - Mitchell L Shiffman
- Bon Secours Liver Institute of Richmond, Bon Secours Health System of Virginia, Richmond, VA, USA
| | | | - Alexander Wong
- Regina General Hospital, University of Saskatchewan, Regina, SK, Canada
| | | | - Florence Wong
- Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Alnoor Ramji
- Gastroenterology Division, St Paul's Hospital, Vancouver, BC, Canada
| | | | - Fiona McPhee
- Bristol-Myers Squibb Research and Development, Wallingford, CT, USA
| | - Rong Yang
- Bristol-Myers Squibb Research and Development, Wallingford, CT, USA
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Gorka S, Gulzar GM, Yattoo GN, Sodhi JS, Dar GA, Laway MA, Kaushik S, Dhar N, Mushfiq S, Aziz RA. Genotype 1 and 3 Response to Velpatasvir and Sofosbuvir in Chronic Hepatitis C in the Kashmiri Population: An Observational Study. J Clin Exp Hepatol 2020; 10:155-162. [PMID: 32189931 PMCID: PMC7068023 DOI: 10.1016/j.jceh.2019.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 07/05/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Our data is one of the earliest study from the Indian subcontinent on Velpatasvir/Sofosbuvir (VEL/SOF) combination in chronic hepatitis C (CHC). The primary end point was to evaluate sustained virologic response (SVR) 12 in CHC-infected patients and to determine its effect in patients with hepatitis C virus-related cirrhosis. The secondary end point was to observe any adverse events related to treatment. METHODS All patients with CHC were randomized into two groups: noncirrhotic and cirrhotic. The combination of VEL/SOF was given as recommended. RESULTS One hundred patients with CHC infection treated with the VEL/SOF regimen were evaluated. A total of 79 (79%) of 100 patients were noncirrhotic, and 21 (21%) were cirrhotic. We achieved SVR12 in 99 (99%) of 100 patients. Among cirrhotics, the mean serum bilirubin (mg/dl), albumin (g/dl), and platelet count (×10³/μL) improved from baseline 1.82 ± 0.87, 3.22 ± 0.69, and 80.19 ± 46.03 to 1.74 ± 0.87, 3.48 ± 0.72, and 85.05 ± 42.50, respectively, at SVR12 (P-value > 0.05). Mean serum alanine aminotransferase (ALT) (U/L) improved from baseline 71.28 ± 59.17 to 35.38 ± 17.39 at SVR12 (P-value < 0.024). Baseline mean liver stiffness measurement (LSM) in cirrhotic patients was 28.24 ± 10.87 kPa, which decreased to 24.04 ± 9.33 kPa at SVR12 (P-value, 0.02). The baseline Model for End-Stage Liver Disease (MELD) score was 13.47 ± 3.66, which decreased to 12.33 ± 5.46 at SVR12 (P-value, 0.28). The Child-Turcotte-Pugh score improved by 1 point in 33.33% (7/21) patients and 2 points in 9.52% (2/21) patients, and in the majority, that is, 38.09% (8/21), the score remained as it is. CONCLUSION A single daily dose of the tablet SOF/VEL combination is safe and effective in all types of CHC. There was a significant improvement in the mean transaminase level and LSM at SVR12. And the MELD score improved by 1 point at SVR12 among cirrhotics.
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Affiliation(s)
- Suresh Gorka
- Department of Gastroenterology, SKIMS, Srinagar 190011, India
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Margusino-Framiñán L, Cid-Silva P, Rotea-Salvo S, Mena-de-Cea Á, Suárez-López F, Vázquez-Rodríguez P, Delgado-Blanco M, Sanclaudio-Luhia AI, Martín-Herranz I, Castro-Iglesias Á. Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients. Eur J Hosp Pharm 2020; 27:e41-e47. [PMID: 32296504 DOI: 10.1136/ejhpharm-2019-002060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 01/14/2020] [Accepted: 01/16/2020] [Indexed: 12/15/2022] Open
Abstract
Objectives Sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are the drug combinations of choice for treating individuals with genotype 3 hepatitis C virus (G3-HCV) infection. The objective of this study was to evaluate the effectiveness and safety of SOF/VEL±RBV compared with GLE/PIB for treating G3-HCV infection under routine clinical practice conditions. Methods We conducted a prospective observational cohort study of individuals with G3-HCV infection who initiated treatment with SOF/VEL +/-RBV or GLE/PIB between April 2017 and July 2018. Prisoners and children were excluded. The outcome variable of effectiveness was sustained virological response 12 weeks after completing treatment (SVR12). The safety variable was withdrawal secondary to severe adverse events (SAEs). Covariates included sex, age, HIV co-infection, previous liver transplant, cirrhosis, hepatic fibrosis and previous antiviral treatment. Statistical significance was calculated using Fisher's exact test or the Mann-Whitney U-test. Results A total of 76 patients were included in the analysis, of whom 46 were treated with SOF/VEL±RBV and 30 were treated with GLE/PIB. No baseline differences were observed between treatment groups with respect to age, sex, HIV co-infection, fibrosis stage, cirrhosis and previous antiviral treatment. Of the patients treated with SOF/VEL±RBV and GLE/PIB, 95.7% and 96.7% reached SVR12, respectively (P=0.7). Of patients with and without cirrhosis, 83.3% and 98.4% reached SVR12, respectively (P=0.09). Of the patients with low-grade hepatic fibrosis (F0-2) and advanced fibrosis (F3-4), 100% and 85.7% reached SVR12, respectively (P=0.03). In treatment-naïve and treatment-experienced patients, 95.7% and 100% reached SVR12, respectively (P=0.57), without significant differences independent of the treatment group (P=0.28 for SOF/VEL±RBV; P=0.18 for GLE/PIB). The incidence of AEs was 21.1% (95% CI 11.3% to 30.9%). None of the patients developed an SAE or required antiviral treatment withdrawal. Conclusions SOF/VEL±RBV or GLE/PIB are safe and effective for treating G3-HCV-infections, with a lower effectiveness in patients with advanced fibrosis F3-4.
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Affiliation(s)
- Luis Margusino-Framiñán
- Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain
| | - Purificación Cid-Silva
- Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain
| | | | - Álvaro Mena-de-Cea
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Francisco Suárez-López
- Hepatology Unit, Digestive System Service, University Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Pilar Vázquez-Rodríguez
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Manuel Delgado-Blanco
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Hepatology Unit, Digestive System Service, University Hospital of A Coruña (CHUAC), A Coruña, Spain
| | | | | | - Ángeles Castro-Iglesias
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
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Örmeci N, Gülşen MT, Sezgin O, Aghayeva S, Demir M, Köksal I, Güner R, Erarslan E, Asiller ÖÖ, Balkan A, Yaraş S, Kartal AÇ. Treatment of HCV infection with direct-acting antiviral agents. Real life experiences from the Euro-Asian region. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2020; 31:148-155. [PMID: 32141824 PMCID: PMC7062133 DOI: 10.5152/tjg.2020.19440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 10/22/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND/AIMS Hepatitis C virus (HCV) infection is a common disease that causes liver cirrhosis, hepatocellular carcinoma, and extra hepatic manifestations with high mortality and morbidity rates. This study aimed to present real-life experiences and results of treatment of HCV infection with direct-acting antiviral agents (DAAs) from the Euro-Asian region, including Turkey and Azerbaijan. MATERIALS AND METHODS A total of 1224 patients with chronic HCV infection were treated with DAAs in accordance with the international guidelines for the management of HCV infection. The mean age was 58.74±14.75 years, with 713 (58.25%) females. The genotypes of the patients were as follows: genotype 1b, 83.36% (n=1024); genotype 1a, 8.08% (n=99); genotype 2, 2.85% (n=35); genotype 3, 3.34% (n=41); genotype 4, 1.71% (n=21); and combined genotypes, 0.32% (n=4). Approximately 808 patients were treated with sofosbuvir-based DAAs with or without Ribavirin for 12 or 24 weeks, whereas 416 patients were treated with the Paritaprevir, Ombitasvir, Ritonavir.Dasabuvir (PROD) regimen with or without Ribavirin for 12 weeks or 24 weeks. RESULTS At the end of follow-up examinations, 1183 patients (97.93%) had sustained virological response (SVR), 17 (1.40%) died of reasons unrelated to the treatment regimen, 12 had recurrence after treatment, and 129 (10.67%) had adverse events like anemia, itching, and weakness. CONCLUSION In this large cohort of HCV-infected patients, treatment with DAAs yielded a high overall SVR rate of 97.93%. DAAs were safe and well-tolerated. Thus, the elimination of HCV infection is no longer a dream worldwide.
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Affiliation(s)
- Necati Örmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Murat Taner Gülşen
- Department of Gastroenterology, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Orhan Sezgin
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Sevda Aghayeva
- Department of Gastroenterology, Azerbaijan Medical University School of Medicine, Baku, Azerbaijan
| | - Mehmet Demir
- Department of Gastroenterology, Hatay Mustafa Kemal University School of Medicine, Hatay, Turkey
| | - Iftihar Köksal
- Department of Gastroenterology, Karadeniz Technical University School of Medicine, Trabzon, Turkey
| | - Rahmet Güner
- Department of Infectious Diseases and Clinical Microbiology, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | - Elife Erarslan
- Department of Gastroenterology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Özgün Ömer Asiller
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ayhan Balkan
- Department of Gastroenterology, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Serkan Yaraş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Aysun Çalışkan Kartal
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
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Torres AD, Sparvoli JMH, Sparvoli AC, Gonçalves CV. SUSTAINED VIROLOGIC RESPONSE RATE IN CHRONIC HEPATITIS C PATIENTS THROUGH DIRECT-ACTING ANTIVIRALS THERAPY. ARQUIVOS DE GASTROENTEROLOGIA 2020; 56:394-398. [PMID: 31800735 DOI: 10.1590/s0004-2803.201900000-79] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/14/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND In recent years the management of hepatitis C virus infection and the possibility of its eradication have been researched due to the importance that they represent in the health of the world population. Obtaining data that help to cope with this pathology improves the quality of life of those affected by it. The present study evaluated the effectiveness of direct-acting antiviral therapies provided by the Brazilian Ministry of Health in accordance to the Clinical Protocol and Therapeutic Guidelines of 2015. OBJECTIVE To evaluate the epidemiological profile of patients with chronic hepatitis C and the rate of sustained virologic response using direct-acting antivirals of all individuals that attended the referral service for the treatment of chronic hepatitis C at the Hospital of the Federal University of Rio Grande. METHODS This was an observational, retrospective/prospective study with all patients with chronic hepatitis C who had their treatments available from December 2015 to August 2017 according to the criteria of the Clinical Protocol and Therapeutic Guidelines of 2015. In the first phase, the clinical and demographic variables of all individuals enrolled in a treatment for hepatitis C were selected and collected from the Reference Service database. In the second phase, treatment data were collected. The outcome variable, sustained virologic response, was defined as an undetectable viral load on the blood test three months after the end of treatment. The descriptive and bivariate analyzes were performed with Pearson's chi-square and Fisher's Exact test, adopting a P value ≤0.05 in the SPSS 20 software. RESULTS Of the 252 participants in the study, 228 (90.5%) had a sustained virologic response, 55.2% were male with an average age of 58.6 years (SD±9.1). Genotype 1 was the most prevalent, observed in 54.4% of the participants, and 87.4% of the patients had moderate/advanced hepatic fibrosis. After the statistical analysis, it was observed that the individuals with genotype 3 and moderate/advanced hepatic fibrosis had lower sustained virologic response rate (P=0.05 and P=0.04, respectively). CONCLUSION It was observed that the use of direct-acting antivirals, in comparison to previous therapeutic regimens, increases the sustained virologic response, reaching all patients with mild fibrosis. This study provides information that helps in the hepatitis C treatment by showing that prescribing early treatment for patients without hepatic fibrosis and/or genotype 3 virus could increase therapeutic effectiveness.
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Affiliation(s)
- Andréa Delfino Torres
- Universidade Federal do Rio Grande (FURG), Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde. Rio Grande, RS, Brasil
| | - Jucéli Maria Hendges Sparvoli
- Universidade Federal do Rio Grande (FURG), Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde. Rio Grande, RS, Brasil
| | - Antonio Cardoso Sparvoli
- Universidade Federal do Rio Grande (FURG), Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde. Rio Grande, RS, Brasil
| | - Carla Vitola Gonçalves
- Universidade Federal do Rio Grande (FURG), Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde. Rio Grande, RS, Brasil
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HCV genotype profile in Brazil of mono-infected and HIV co-infected individuals: A survey representative of an entire country. PLoS One 2020; 15:e0227082. [PMID: 31905224 PMCID: PMC6944355 DOI: 10.1371/journal.pone.0227082] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 12/10/2019] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION To be eligible for government-provided treatment in Brazil, all HCV-infected individuals are required to be genotyped shortly after diagnosis. We describe the HCV genotype (G) profiles by geographic region, gender, age and HIV co-infection. METHODS We assessed 29,071 genotypes collected from HCV-infected individuals from March 2016 to March 2018 (Abbott Real-Time HCV Genotype). We randomly selected 12,336 samples for HIV co-infection testing using an EIA rapid test kit (TR DPP HIV 1/2 Bio-Manguinhos). Descriptive statistical analyses were performed using R. RESULTS Overall, HCV genotype distribution was 40.9% G1A, 30.2% G1B, 23.8% G3, 3.8% G2, 0.7% G4, 0.1% G5 and 0.6% with multiples genotypes. G1A prevalence was 44.4% among males and 35.8% among females. G1B and G2 were more prevalent in older individuals than G1A and G3. G3 was more prevalent in the South region. Of samples tested for HIV co-infection, 15% were HIV+. Median age among HCV/HIV co-infected individuals was 50 years old compared to 57 years old among mono-infected individuals. Distinct HCV genotype prevalence between HCV/HIV co-infected and HCV mono-infected individuals were respectively: G1A 60.6% versus 37.8%, G1B 15.2% versus 32.9%, and G3 18.9% versus 24.7%. G4 was detected among co-infected young men (3.5% versus 0.2% among mono-infected). CONCLUSION The increasing prevalence of G3, as inferred by the younger ages of the HCV-infected individuals, poses an extra challenge with regards to disease progression. Distinct genotypical profiles between HCV mono-infection and HCV/HIV co-infection warrant future research in order to better understand and help mitigate HCV chains of transmission.
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Abstract
Introduction: Unlike other hepatitis C virus (HCV) genotypes (GTs), patients infected with GT3 are associated with an increased risk of accelerated liver disease progression. Although early immuno-modulator therapies yielded moderate sustained virologic response (SVR) rates, treatment of GT3 patients has proven more challenging in the era of direct-acting antivirals (DAAs). Areas covered: The review provides an overview of the evolution of therapies against GT3 since the approval of the first immunomodulatory agent nearly 30 years ago. Expert opinion: A greater choice of treatment options is now available for HCV GT3-infected patients. In treatment-naïve patients with or without compensated cirrhosis, SVR rates are comparably high approaching 100% irrespective of treatment option. For treatment-experienced patients, choosing the right therapy is important, especially for those with advanced liver disease. For the few patients who fail with multiple persistent highly resistant DAA substitutions, retreatment options are limited. Additional real-world treatment comparisons are required to confirm differences in SVR in these more difficult-to-treat patients. This also includes patients infected with GT3 subtypes such as GT3b where multiple DAA-resistant substitutions occur naturally. In the absence of new drugs with non-overlapping drug-resistant profiles, an interferon-based therapy may still be beneficial in select patient populations with high-level multiple DAA-resistant substitutions.
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Affiliation(s)
- Fiona McPhee
- Translational Medicine, Bristol-Myers Squibb Company , Cambridge , MA , USA
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Construction and characterization of Genotype-3 hepatitis C virus replicon revealed critical genotype-3-specific polymorphism for drug resistance and viral fitness. Antiviral Res 2019; 171:104612. [PMID: 31542377 DOI: 10.1016/j.antiviral.2019.104612] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/17/2019] [Accepted: 09/18/2019] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus (HCV), a major causative agent of chronic hepatitis, is a positive-stranded RNA virus and has a high degree of genetic diversity due to its error-prone RNA-dependent RNA polymerase. Development of direct-acting antiviral agents (DAAs) has greatly improved the therapeutic outcome of chronic hepatitis C patients. However, naturally existing resistance-associated variants (RAVs) or occurrence of resistance-associated substitutions (RASs) in the HCV genome may impose a challenge to the long-term success of the DAA-based therapies. Genotype-3 HCV is the most difficult genotype to treat by DAAs, but the underlying molecular mechanisms remain to be explored. Here we developed a novel genotype-3a subgenomic replicon PR87A7 by screening a HCV cDNA pool amplified from a patient serum RNA. PR87A7 replicon displayed strong resistance to anti-NS3 DAAs, mainly owing to a genotype-3-specific polymorphism 168Q in NS3. Introduction of NS3 168Q into a genotype-2a JFH1 strain rendered resistance to anti-NS3 DAAs while greatly diminished the viral replication, and yet this fitness defect can be rescued by additional genotype-3-specific polymorphism. In conclusion, we developed a novel genotype-3a subgenomic replicon by a functional screening approach, and revealed genotype-3-specfic amino acid residues that confer resistance to anti-NS3 DAAs while retaining viral fitness.
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Senkerikova R, Frankova S, Jirsa M, Kreidlova M, Merta D, Neroldova M, Chmelova K, Spicak J, Sperl J. PNPLA3 rs738409 G allele carriers with genotype 1b HCV cirrhosis have lower viral load but develop liver failure at younger age. PLoS One 2019; 14:e0222609. [PMID: 31527889 PMCID: PMC6748417 DOI: 10.1371/journal.pone.0222609] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 09/03/2019] [Indexed: 12/19/2022] Open
Abstract
Background PNPLA3 rs738409 minor allele c.444G represents a risk factor for liver steatosis and fibrosis progression also in chronic hepatitis C (HCV). We investigated its impact on the timing of liver transplantation (LT) in patients with genotype 1b HCV cirrhosis. Methods We genotyped and evaluated 172 LT candidates with liver cirrhosis owing to chronic HCV infection, genotype 1b. One hundred patients needed LT for chronic liver failure (CLF) and 72 for a small hepatocellular carcinoma (HCC) in the cirrhotic liver without CLF. Population controls (n = 647) were selected from the Czech cross-sectional study MONICA. Results The CLF patients were younger (53.5 ± 7.2 vs. 59.6 ± 6.6, P < 0.001) with more advanced liver disease than HCC patients (Child-Pugh’s score 9.1 ± 1.8 vs. 7.1 ± 1.9, P < 0.001, MELD 14.1 ± 3.9 vs. 11.1 ± 3.7, P < 0.001). PNPLA3 G allele increased the risk of LT for CLF in both allelic and recessive models (CG + GG vs. CC: OR, 1.90; 95% CI, 1.017–3.472, P = 0.045 and GG vs. CC + CG: OR, 2.94; 95% CI, 1.032–7.513, P = 0.042). Multivariate analysis identified younger age (P < 0.001) and the G allele (P < 0.05) as risk factors for CLF. The genotype frequencies between the CLF group and MONICA study significantly differed in both, allelic and recessive model (P = 0.004, OR 1.87, 95% CI 1.222–2.875; P < 0.001, OR 3.33, 95% CI 1.824–6.084, respectively). The OR values almost doubled in the recessive model compared with the allelic model suggesting the additive effect of allele G. In contrast, genotype frequencies in the HCC group were similar to the MONICA study in both models. Pretransplant viral load was significantly lower in GG than in CC + CG genotypes (median, IQR; 162,500 (61,550–319,000) IU/ml vs. 570,000 (172,000–1,595,000) IU/ml, P < 0.0009). Conclusions Our results suggest that PNPLA3 rs738409 G allele carriage may be associated with a faster progression of HCV cirrhosis to chronic liver failure.
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Affiliation(s)
- Renata Senkerikova
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Charles University, First Faculty of Medicine, Prague, Czech Republic
| | - Sona Frankova
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Milan Jirsa
- Charles University, First Faculty of Medicine, Prague, Czech Republic
- Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Miluse Kreidlova
- Institute of Medical Biochemistry and Laboratory Diagnostics First Faculty of Medicine Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Dusan Merta
- Anesthesiology, Resuscitation and Intensive Care Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Magdalena Neroldova
- Charles University, First Faculty of Medicine, Prague, Czech Republic
- Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Klara Chmelova
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Charles University, First Faculty of Medicine, Prague, Czech Republic
| | - Julius Spicak
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jan Sperl
- Department of Hepatogastroenterology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Charles University, First Faculty of Medicine, Prague, Czech Republic
- * E-mail:
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A 2-year retrospective study of viral and host-associated risk factors in Pakistani hepatocellular carcinoma patients. Eur J Gastroenterol Hepatol 2019; 31:1103-1109. [PMID: 30829691 DOI: 10.1097/meg.0000000000001384] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Persistent chronic hepatitis C (CHC) infection is associated strongly with serious complications such as hepatitis C virus-associated liver cirrhosis (HCV-LC) and hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC). The aim of this study was to assess the distribution of hepatitis C virus (HCV) genotypes among HCV-positive patients and examine the potential associations between viral and host-associated factors with the risk of developing HCV-HCC. PATIENTS AND METHODS HCV-positive patients (n = 300) were enrolled and divided into three groups: CHC (n = 171), HCV-LC (n = 51), and HCV-HCC (n = 78). RESULTS HCV genotype 3a showed the highest prevalence among HCV-positive individuals (66% of patients), followed by genotype 1a (15% of patients). The proportion of individuals infected with mixed HCV genotypes was higher among HCV-HCC patients. Interestingly, there were a significantly higher proportion of women (54/78; 69.2%) among HCV-HCC patients compared with CHC patients (89/171 or 52%; χ = 6.47; P=1 × 10). Women with HCV had two-fold higher odds of developing HCV-HCC (odds ratio = 2.07, 95% confidence interval: 1.18-3.71). In comparison with CHC patients, significantly more HCV-HCC patients were 50 years of age or older (59/78 or 75.6% of HCV-HCC patients and 61/171 or 35.7% of CHC patients; χ = 34.27; P < 0.0001), suggesting that HCV-positive patients aged 50 years or older had an ~five-fold higher risk of developing HCV-HCC (odds ratio = 5.6, 95% confidence interval: 3.02-10.01). CONCLUSION In summary, HCV genotype 3a had the highest prevalence in the studied HCV-positive population, and women and older patients were at a higher risk of developing HCV-LC and HCV-HCC following CHC infections.
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Park HK, Lee SS, Im CB, Im C, Cha RR, Kim WS, Cho HC, Lee JM, Kim HJ, Kim TH, Jung WT, Lee OJ. Hepatitis C virus genotype affects survival in patients with hepatocellular carcinoma. BMC Cancer 2019; 19:822. [PMID: 31429755 PMCID: PMC6700836 DOI: 10.1186/s12885-019-6040-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 08/14/2019] [Indexed: 12/23/2022] Open
Abstract
Background There is currently no evidence that hepatitis C virus (HCV) genotype affects survival in patients with hepatocellular carcinoma (HCC). This study aimed to investigate whether the HCV genotype affected the survival rate of patients with HCV-related HCC. Methods We performed a retrospective cohort study using the data of patients with HCV-related HCC evaluated at two centers in Korea between January 2005 and December 2016. Propensity score matching between genotype 2 patients and non-genotype 2 patients was performed to reduce bias. Results A total of 180 patients were enrolled. Of these, 86, 78, and 16 had genotype 1, genotype 2, and genotype 3 HCV-related HCC, respectively. The median age was 66.0 years, and the median overall survival was 28.6 months. In the entire cohort, patients with genotype 2 had a longer median overall survival (31.7 months) than patients with genotype 1 (28.7 months; P = 0.004) or genotype 3 (15.0 months; P = 0.003). In the propensity score–matched cohort, genotype 2 patients also showed a better survival rate than non-genotype 2 patients (P = 0.007). Genotype 2 patients also had a longer median decompensation-free survival than non-genotype 2 patients (P = 0.001). However, there was no significant difference in recurrence-free survival between genotype 2 and non-genotype 2 patients who underwent curative treatment (P = 0.077). In multivariate Cox regression analysis, non-genotype 2 (hazard ratio, 2.19; 95% confidence interval, 1.29–3.71) remained an independent risk factor for death. Conclusion Among patients with HCV-related HCC, those with genotype 2 have better survival. Electronic supplementary material The online version of this article (10.1186/s12885-019-6040-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hye Kyong Park
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea. .,Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea. .,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
| | - Chang Bin Im
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Changjo Im
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Ra Ri Cha
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Wan Soo Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Hyun Chin Cho
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.,Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.,Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Tae Hyo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Woon Tae Jung
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Ok-Jae Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, 15, Jinju-daero 816, Jinju, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
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Han Q, Fan X, Wang X, Wang Y, Deng H, Zhang X, Zhang K, Li N, Liu Z. High sustained virologic response rates of sofosbuvir-based regimens in Chinese patients with HCV genotype 3a infection in a real-world setting. Virol J 2019; 16:74. [PMID: 31159813 PMCID: PMC6547524 DOI: 10.1186/s12985-019-1184-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 05/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with hepatitis C virus (HCV) genotype 3 infection remain a difficult-to-cure population. This study evaluated the efficacy and safety of sofosbuvir-based regimen in genotype 3 patients in a real-world setting. METHODS HCV genotype 3a-infected adults with compensated liver disease were treated with sofosbuvir (SOF)/velpatasvir (VEL) or SOF/daclatasvir (DCV) with or without ribavirin (RBV) for 12 or 24 weeks, respectively. Efficacy was measured by sustained virologic response at post-treatment week 12 (SVR12). Adverse events were evaluated throughout the treatment and follow-up course. RESULTS A total of 41 genotype 3a-infected patients were included. Of them, 10 patients (24%) had cirrhosis, 3 (7%) had renal impairment, and 2 (5%) failed previous treatment. Nine patients (22%) were treated with SOF/VEL and 32 (78%) with SOF/DCV with or without RBV. SVR 12 was achieved in 100% (9/9) of patients treated with SOF/VEL for 12 weeks and in 97% (31/32) of those treated with SOF/DCV for 12 or 24 weeks. RBV addition and extension of treatment duration did not improve the SVR of SOF/DCV (RR: 1.04; P = 0.99 and RR: 1.09; P = 0.375, respectively). Ten patients with cirrhosis, 1 on hemodialysis and 2 with treatment-experience achieved SVR12. One treatment-naïve non-cirrhotic patient on hemodialysis treated with SOF/DCV for 24 weeks relapsed at week 8 post-treatment. No serious adverse events and relevant laboratory abnormalities were observed. CONCLUSION SOF/VEL and SOF/DCV are highly efficacious and well tolerated in genotype 3a-infected patients with or without cirrhosis. RBV coadministration and extension of SOF/DCV treatment appear to add no improvement for efficacy.
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Affiliation(s)
- Qunying Han
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Xiude Fan
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Xiaoyun Wang
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Ye Wang
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Huan Deng
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Xiaoge Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Kun Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Na Li
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
| | - Zhengwen Liu
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061 Shaanxi Province People’s Republic of China
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Smith D, Magri A, Bonsall D, Ip CL, Trebes A, Brown A, Piazza P, Bowden R, Nguyen D, Ansari MA, Simmonds P, Barnes E, STOP‐HCV Consortium. Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors. Hepatology 2019; 69:1861-1872. [PMID: 29425396 PMCID: PMC6492296 DOI: 10.1002/hep.29837] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 02/03/2018] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus (HCV) genotype (gt) 3 is highly prevalent globally, with non-gt3a subtypes common in Southeast Asia. Resistance-associated substitutions (RASs) have been shown to play a role in treatment failure. However, the role of RASs in gt3 is not well understood. We report the prevalence of RASs in a cohort of direct-acting antiviral treatment-naive, gt3-infected patients, including those with rarer subtypes, and evaluate the effect of these RASs on direct-acting antivirals in vitro. Baseline samples from 496 gt3 patients enrolled in the BOSON clinical trial were analyzed by next-generation sequencing after probe-based enrichment for HCV. Whole viral genomes were analyzed for the presence of RASs to approved direct-acting antivirals. The resistance phenotype of RASs in combination with daclatasvir, velpatasvir, pibrentasvir, elbasvir, and sofosbuvir was measured using the S52 ΔN gt3a replicon model. The nonstructural protein 5A A30K and Y93H substitutions were the most common at 8.9% (n = 44) and 12.3% (n = 61), respectively, and showed a 10-fold and 11-fold increase in 50% effect concentration for daclatasvir compared to the unmodified replicon. Paired RASs (A30K + L31M and A30K + Y93H) were identified in 18 patients (9 of each pair); these combinations were shown to be highly resistant to daclatasvir, velpatasvir, elbasvir, and pibrentasvir. The A30K + L31M combination was found in all gt3b and gt3g samples. Conclusion: Our study reveals high frequencies of RASs to nonstructural protein 5A inhibitors in gt3 HCV; the paired A30K + L31M substitutions occur in all patients with gt3b and gt3g virus, and in vitro analysis suggests that these subtypes may be inherently resistant to all approved nonstructural protein 5A inhibitors for gt3 HCV. (Hepatology 2018).
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Affiliation(s)
- David Smith
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
| | - Andrea Magri
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
- Oxford Martin SchoolUniversity of OxfordOxfordUK
| | - David Bonsall
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
- Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
| | - Camilla L.C. Ip
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
- Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
| | - Amy Trebes
- Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
| | - Anthony Brown
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
| | - Palo Piazza
- Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
| | - Rory Bowden
- Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
| | - Dung Nguyen
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
| | - M. Azim Ansari
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
- Oxford Martin SchoolUniversity of OxfordOxfordUK
| | - Peter Simmonds
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
| | - Eleanor Barnes
- Nuffield Department of Medicine and the Oxford NIHR BRCUniversity of OxfordOxfordUK
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Yan J, Fu XB, Zhou PP, He X, Liu J, Huang XH, Yu GL, Yan XG, Li JR, Li Y, Lin P. Complicated HCV subtype expansion among drug users in Guangdong province, China. INFECTION GENETICS AND EVOLUTION 2019; 73:139-145. [PMID: 31048077 DOI: 10.1016/j.meegid.2019.04.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/24/2019] [Accepted: 04/27/2019] [Indexed: 12/14/2022]
Abstract
Guangdong Province is one of the most developed and populous provinces in southern China. The subtype situation of hepatitis C virus (HCV) in Guangdong remains unknown. The aim of this study was to investigate and estimate the HCV subtypes in drug users (DU) using a city-based sampling strategy to better understand the characteristics of HCV transmission in Guangdong. Archived plasma samples (n = 1074) from DU who were anti-HCV positive in 2014 were selected randomly from 20 cities in Guangdong Province. Subtypes were determined based on core and/or E1 sequences using phylogenetic analysis. The distributions of HCV subtypes in DU and different regions were analyzed. A total of 8 genotypes were identified. The three main HCV subtypes in DU in Guangdong were 6a (63.0%), 3a (15.2%), and 3b (11.8%). Significant differences were discovered among different registered residency and regions but not among genders, marital status, education level, or drug use patterns. HCV subtype 3b was significantly higher in Guangdong residents than in non-Guangdong residents. In contrast, HCV subtype 6a was significantly lower in Guangdong residents than in non-Guangdong residents. Subtype 1b in eastern Guangdong (eastern) was significantly lower, while 6a was significantly higher when compared with other regions. Subtype 3a in the Pearl River Delta (PRD) region was significantly higher, while 3b was significantly lower when compared with other regions. In western Guangdong, HCV subtype 3a was significantly lower when compared with other regions. Additionally, in northern Guangdong subtypes 1b and 3b were significantly higher, while 6a was significantly lower when compared with other regions. Our study revealed the diversity and distribution of HCV subtypes in DU in nearly all the cities in Guangdong. The results provide essential information that will allow the establishment of specific intervention strategies that may help prevent HCV transmission.
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Affiliation(s)
- Jin Yan
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China.
| | - Xiao-Bing Fu
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Ping-Ping Zhou
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Xiang He
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Jun Liu
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Xu-He Huang
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Guo-Long Yu
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Xin-Ge Yan
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Jian-Rong Li
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Yan Li
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
| | - Peng Lin
- Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Panyu District, Guangzhou 511430, Guangdong, China
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Lee SS, Kim CY, Kim BR, Cha RR, Kim WS, Kim JJ, Lee JM, Kim HJ, Ha CY, Kim HJ, Kim TH, Jung WT, Lee OJ. Hepatitis C virus genotype 3 was associated with the development of hepatocellular carcinoma in Korea. J Viral Hepat 2019; 26:459-465. [PMID: 30516858 DOI: 10.1111/jvh.13047] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/03/2018] [Accepted: 11/14/2018] [Indexed: 12/22/2022]
Abstract
Although hepatitis C virus (HCV) genotype 3 infection is thought to be an important risk factor for hepatocellular carcinoma (HCC), current evidence is limited because only a few Western studies have evaluated the occurrence of HCC in patients with HCV genotype 3 infection. We evaluated the impact of genotype 3 and non-3 on HCC incidence and on disease progression in chronic HCV patients; this is the first study reporting such findings in an Asian population. We performed a retrospective cohort study using the data of 1448 consecutive chronic HCV patients evaluated at three centres in Korea between January 2005 and December 2016. Of these, 604, 675 and 169 had genotype 1, genotype 2 and genotype 3 HCV infections, respectively. Over a mean follow-up period of 53.2 months, 75 and 143 patients of all the patients developed HCC and experienced disease progression, respectively. The incidences of HCC were 1.10, 0.92 and 2.50 per 100 person-years, and those of disease progression were 1.95, 1.62 and 6.72 per 100 person-years for HCV genotypes 1, 2 and 3, respectively. In multivariate Cox regression analysis, genotype 3 was associated with an increased risk of HCC (hazard ratio [HR] = 4.26, 95% confidence interval [CI] = 2.02-8.97) and an increased risk of disease progression (HR = 4.88, 95%; CI = 2.94-8.08). Our study proposes that HCV genotype 3 is an independent risk factor for HCC and disease progression in chronic HCV patients.
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Affiliation(s)
- Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.,Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Cha Young Kim
- Department of Internal Medicine, Chinju Jeil Hospital, Jinju, Korea
| | - Bo Ra Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Ra Ri Cha
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Wan Soo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Jin Joo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.,Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Hong Jun Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Chang Yoon Ha
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.,Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Tae Hyo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Woon Tae Jung
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
| | - Ok-Jae Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju, Korea
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Flamm S, Mutimer D, Asatryan A, Wang S, Rockstroh J, Horsmans Y, Kwo PY, Weiland O, Villa E, Heo J, Gane E, Ryder SD, Welzel TM, Ruane PJ, Agarwal K, Ng TI, Xue Z, Lovell SS, Krishnan P, Kopecky‐Bromberg S, Trinh R, Mensa FJ, Wyles DL. Glecaprevir/Pibrentasvir in patients with chronic HCV genotype 3 infection: An integrated phase 2/3 analysis. J Viral Hepat 2019; 26:337-349. [PMID: 30421537 PMCID: PMC7379735 DOI: 10.1111/jvh.13038] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 10/22/2018] [Indexed: 02/06/2023]
Abstract
Glecaprevir coformulated with pibrentasvir (G/P) is approved to treat hepatitis C virus (HCV) infection and was highly efficacious in phase 2 and 3 studies. Treating HCV genotype (GT) 3 infection remains a priority, as these patients are harder to cure and at a greater risk for liver steatosis, fibrosis progression and hepatocellular carcinoma. Data were pooled from five phase 2 or 3 trials that evaluated 8-, 12- and 16-week G/P in patients with chronic HCV GT3 infection. Patients without cirrhosis or with compensated cirrhosis were either treatment-naïve or experienced with interferon- or sofosbuvir-based regimens. Safety and sustained virologic response 12 weeks post-treatment (SVR12) were assessed. The analysis included 693 patients with GT3 infection. SVR12 was achieved by 95% of treatment-naïve patients without cirrhosis receiving 8-week (198/208) and 12-week (280/294) G/P. Treatment-naïve patients with cirrhosis had a 97% (67/69) SVR12 rate with 12-week G/P. Treatment-experienced, noncirrhotic patients had SVR12 rates of 90% (44/49) and 95% (21/22) with 12- and 16-week G/P, respectively; 94% (48/51) of treatment-experienced patients with cirrhosis treated for 16 weeks achieved SVR12. No serious adverse events (AEs) were attributed to G/P; AEs leading to study drug discontinuation were rare (<1%). G/P was well-tolerated and efficacious for patients with chronic HCV GT3 infection, regardless of cirrhosis status or prior treatment experience. Eight- and 12-week durations were efficacious for treatment-naïve patients without cirrhosis and with compensated cirrhosis, respectively; 16-week G/P was efficacious in patients with prior treatment experience irrespective of cirrhosis status.
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Affiliation(s)
- Steven Flamm
- Northwestern Feinberg School of MedicineChicagoIllinois
| | - David Mutimer
- Queen Elizabeth Hospital and NIHR Liver Biomedical Research UnitBirminghamUK
| | | | | | | | - Yves Horsmans
- Cliniques Universitaires Saint‐LucUCLBrusselsBelgium
| | - Paul Y. Kwo
- Division of Gastroenterology and HepatologyStanford UniversityPalo AltoCalifornia
| | - Ola Weiland
- Karolinska University Hospital Huddinge at Karolinska InstituteStockholmSweden
| | - Erica Villa
- University of Modena and Reggio EmiliaModenaItaly
| | - Jeong Heo
- Department of Internal MedicineCollege of MedicinePusan National University and Medical Research InstitutePusan National University HospitalBusanRepublic of Korea
| | - Edward Gane
- Liver UnitAuckland City HospitalAucklandNew Zealand
| | - Stephen D. Ryder
- NIHR Nottingham Biomedical Research Centre and Nottingham University Hospitals NHS TrustNottinghamUK
| | | | - Peter J. Ruane
- Ruane Medical & Liver Health InstituteLos AngelesCalifornia
| | - Kosh Agarwal
- Institute of Liver StudiesKings College HospitalLondonUK
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Aziz B, Nazar T, Akhlaq S. The frequency of occurrence of Hepatocellular Carcinoma after direct antiviral therapy in Hepatitis C virus patients. Pak J Med Sci 2019; 35:101-105. [PMID: 30881405 PMCID: PMC6408676 DOI: 10.12669/pjms.35.1.109] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective To study the frequency of occurrence of hepatocellular carcinoma (HCC) in hepatitis C virus patients treated with direct acting antiviral (DAA) agents. Methods This hospital based cross-sectional study was conducted in Mayo Hospital, Lahore from June, 2016 to January, 2018. Total 300 patients with HCV genotype 3, selected via Non-Probability Purposive Sampling technique, without prior or concurrent history of HCC, were given DAA agents and were followed up for 6 months after completion of therapy. Results were based on Quantitative PCR to assess Sustained Virological Response (SVR) and Ultrasound Abdomen to look for the appearance of any new lesion. Data was presented as mean ±SD, frequency and percentages and was analyzed using SPSS Version 24.0. Results Out of 300 patients, 179 (59.7%) were males and 121(40.3%) were females. Mean age of the patients was 55.08 ± 5.602 years. 214(71.3%) patients had compensated cirrhosis at the start of treatment and 86(28.7%) had decompensated cirrhosis. SVR was achieved in 200(93.4%) out of 214 patients with compensated cirrhosis and in 76(88.3%) out of 86 patients with decompensated cirrhosis. At six months post- treatment, 10(3.33%) patients developed HCC,2(0.7%) in the compensated group and 8(2.7%) in the decompensated group, out of which 5(6.6%) patients had achieved SVR. Conclusion The frequency of HCC following DAA agents is significant (3.3%) even after achieving SVR. Caution must be exercised in prescribing DAA agents to HCV patients keeping this complication of HCC in mind.
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Affiliation(s)
- Bilal Aziz
- Dr. Bilal Aziz, MBBS, MD(GI), FCPS(Med). Assistant Professor of Medicine, Mayo Hospital, Lahore, Pakistan
| | - Tazeen Nazar
- Dr. Tazeen Nazar, MBBS, FCPS(Med). Assistant Professor of Medicine, Mayo Hospital, Lahore, Pakistan
| | - Suhair Akhlaq
- Suhair Akhlaq, MSc Statistics. Biostatistician, Ministry of Health and Prevention, Dubai, UAE
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Huang JF, Huang CF, Yeh ML, Dai CY, Yu ML, Chuang WL. Updates in the management and treatment of HCV genotype 3, what are the remaining challenges? Expert Rev Anti Infect Ther 2018; 16:907-912. [PMID: 30396303 DOI: 10.1080/14787210.2018.1544492] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Accepted: 11/01/2018] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis C (CHC) genotype-3 (G-3) infection is the next most prevalent genotype with 54.3 million patients globally. It is associated with an increasing risk of fibrosis, liver-related events, hepatocellular carcinoma, and overall mortality. G-3 infection may have a negative impact on histological and clinical outcomes in CHC patients. In addition, its characteristic features of steatosis and metabolic abnormalities may add more difficulty in the disease management. Area covered: Fortunately, the landscape of management has been drastically changed in the past decade with the blooming of all oral direct antiviral agents (DAAs). The extremely high efficacy, high safety, short treatment duration, low adverse effects, and easy dosing of DAAs provide an excellent exploration of medical therapeutics in human history. The review consisted of the updated management of CHC G-3, and also touched upon what are the remaining challenges currently. Some challenges and unmet needs were also raised in a clinical setting, including treatment barriers, clinical outcomes, and metabolic abnormalities. Expert commentary: There is a pressing need for management of G-3 infection because of its large patient burden and poor clinical outcomes than other genotypes. Further investigation is warranted in terms of its treatment barriers and clinical outcomes.
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Affiliation(s)
- Jee-Fu Huang
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
- b Graduate Institute of Clinical Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- c Faculty of Internal Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Chung-Feng Huang
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
- c Faculty of Internal Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Ming-Lun Yeh
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
- c Faculty of Internal Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Chia-Yen Dai
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
- b Graduate Institute of Clinical Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- c Faculty of Internal Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Ming-Lung Yu
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
- b Graduate Institute of Clinical Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- c Faculty of Internal Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Wan-Long Chuang
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
- b Graduate Institute of Clinical Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- c Faculty of Internal Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
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47
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Du G, Li X, Musa TH, Ji Y, Wu B, He Y, Ni Q, Su L, Li W, Ge Y. The nationwide distribution and trends of hepatitis C virus genotypes in mainland China. J Med Virol 2018; 91:401-410. [PMID: 30192393 DOI: 10.1002/jmv.25311] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 09/03/2018] [Indexed: 12/15/2022]
Abstract
Comprehensive data on hepatitis C virus (HCV) genotypes distribution is critical for treatment regimen selection, vaccine design, and drug development. This study aimed to understand the dynamic distribution of HCV genotypes in Mainland China. Three hundred sixty-two studies published from January 1993 to December 2017 involving 64 891 samples (5133 injecting drug users, 2748 volunteer blood donors, 1509 former paid plasma donors, 160 sexually encounters, and 1992 human immunodeficiency virus (HIV)/HCV coinfection patients) were eligible for the quantitative synthesis estimation. Pooled proportion of HCV genotypes (and 95% confidence intervals [CIs]) was estimated through the Freeman-Tukey double arcsine transformation by period, region, and risk group. A sharp decline of the subtype 1b was observed in all regions except in northwestern and central regions. The genotypes 3 and 6 showed an obvious increase in southern and southwestern regions and have already spread nationwide. After 2010, subtype 1b was the most dominant variant in all regions and risk groups, accounting for 54.0% (95% CI, 51.9-56.1) of all national infections. Subtype 2a was the second most prevalent strain in all regions except in the south and southwest, with 15.4% (95% CI, 13.1-17.8) national infections. The subtype 6a in southern region and 3b and 3a in southwestern region had a higher proportion of infections than that in other regions. In addition, the genotypes 3 and 6 are already prevalent in almost all risk groups. The distribution of HCV genotypes were sharply shifting in China in the past three decades. The HCV subtype 1b posed a sharp decline, whereas genotypes 3 and 6 played an increasing role in the regional and populational HCV pandemic.
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Affiliation(s)
- Guoping Du
- Hospital Office, Southeast University Hospital, Nanjing, China
| | - Xiaoshan Li
- Department of Lung Transplants Center, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Taha Hussein Musa
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
| | - Yu Ji
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
| | - Bo Wu
- Department of Lung Transplants Center, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Yan He
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
| | - Qian Ni
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
| | - Ling Su
- Sichuan Provincial Center for Disease Control and Prevention, Center for AIDS/STD Control and Prevention, Chengdu, China
| | - Wei Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
| | - You Ge
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Department Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
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Jacobson IM. Does Ribavirin Still Have a Role in Sofosbuvir and Velpatasvir Therapy for Patients With HCV Genotype 3 Infection and Cirrhosis? Gastroenterology 2018; 155:969-971. [PMID: 30201359 DOI: 10.1053/j.gastro.2018.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Ira M Jacobson
- Division of Gastroenterology and Hepatology, NYU School of Medicine, New York, New York.
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49
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Shahnazarian V, Ramai D, Reddy M, Mohanty S. Hepatitis C virus genotype 3: clinical features, current and emerging viral inhibitors, future challenges. Ann Gastroenterol 2018; 31:541-551. [PMID: 30174390 PMCID: PMC6102453 DOI: 10.20524/aog.2018.0281] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/18/2018] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) represents a global burden on healthcare that affects over 150 million people worldwide. In the past, HCV genotype 3 was considered difficult to treat relative to other genotypes. Genotype 3 has been associated with a higher rate of complications, including fatty liver disease, fibrosis, hepatocellular carcinoma and mortality. However, with the advent of first- and second-generation direct-acting antivirals, genotype 3 can be treated effectively. Additionally, these new drugs are well tolerated by patients and have significantly fewer side effects compared to ribavirin and interferon-based regimens. However, while great strides have been made in overcoming biological barriers, our next challenge lies in overcoming economic and financial obstacles if we are to eradicate HCV genotype 3. Herein, we review the clinical features associated with HCV genotype 3, current and emerging treatment regimens, and challenges associated with treatment.
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Affiliation(s)
- Vahe Shahnazarian
- Division of Gastroenterology, Hepatology, and Advanced Endoscopy, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY (Vahe Shahnazarian, Daryl Ramai, Madhavi Reddy), USA
| | - Daryl Ramai
- Division of Gastroenterology, Hepatology, and Advanced Endoscopy, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY (Vahe Shahnazarian, Daryl Ramai, Madhavi Reddy), USA
- School of Medicine, St George’s University, True Blue, Grenada, WI (Daryl Ramai), USA
| | - Madhavi Reddy
- Division of Gastroenterology, Hepatology, and Advanced Endoscopy, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY (Vahe Shahnazarian, Daryl Ramai, Madhavi Reddy), USA
| | - Smruti Mohanty
- Division of Gastroenterology and Hepatology, New York Presbyterian Brooklyn Methodist Hospital, Clinical Affiliate of Weill Cornell Medicine, Brooklyn, NY (Smruti Mohanty), USA
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50
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Wei B, Ji F, Yeo YH, Ogawa E, Stave CD, Dang S, Li Z, Furusyo N, Cheung RC, Nguyen MH. Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia. BMJ Open Gastroenterol 2018; 5:e000209. [PMID: 30147941 PMCID: PMC6104766 DOI: 10.1136/bmjgast-2018-000209] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/10/2018] [Accepted: 05/19/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Genotype 3 (GT3) is a common chronic hepatitis C (CHC) genotype in Asia. Direct-acting antiviral (DAA) regimens have high cure rates, but real-world results are limited for Asia. AIM To determine the real-world effectiveness of DAAs for patients with CHC GT3 in Asia. METHODS A systematic search was performed in PubMed (including MEDLINE), Embase, and selected international meeting abstract repositories. Eligible studies were postmarketing observational studies from Asia with the primary outcome of sustained virological response 12 weeks after completion of treatment (SVR12). RESULTS A total of 15 studies with 4230 patients yielded a pooled SVR12 of 92.7%. High heterogeneity (I2=93.2%, P<0.0001) was noted. In subgroup analyses, patients with cirrhosis had 10.9% lower SVR12 than non-cirrhotic patients (88.6% vs 98.9%; P<0.0001) and contributed 69.5% of the heterogeneity. Prior treatment failure did not reduce the pooled SVR12 (treatment-naïve: 94.6%, 95% CI 91.3% to 96.7% vs treatment-experienced: 94.0%, 95% CI 77.5% to 98.6%; P=0.89). Twenty-four weeks of sofosbuvir+ribavirin dual therapy was the most commonly used regimen which led to similar SVR12 (OR=1.1, P=0.73) but lower adverse event rate than 12 weeks of sofosbuvir+ribavirin+pegylated interferon triple therapy. CONCLUSION Sofosbuvir+ribavirin for 24 weeks is the most widely used and generally well-tolerated DAA therapy in Asia. However, its effectiveness is not optimal in GT3 patients with cirrhosis.
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Affiliation(s)
- Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Fanpu Ji
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Christopher D Stave
- Lane Library, School of Medicine, Stanford University, Stanford, California, USA
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Zongfang Li
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
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