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Billi M, Soloperto S, Bonora S, D’Avolio A, De Nicolò A. Clinical Pharmacology of Bulevirtide: Focus on Known and Potential Drug-Drug Interactions. Pharmaceutics 2025; 17:250. [PMID: 40006617 PMCID: PMC11859527 DOI: 10.3390/pharmaceutics17020250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/07/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Hepatitis D virus (HDV) is a defective virus requiring co-infection with hepatitis B virus (HBV) to replicate, occurring in 5% of HBV+ patients. Bulevirtide (BLV) is now the first-in-class specific anti-HDV agent, inhibiting HDV binding to NTCP, with good tolerability and good virological and biochemical response rates. Currently, little is known about its pharmacokinetic/pharmacodynamic (PK/PD), as well as potential drug-drug interaction (DDI) profile. In this work we provide a systematic review of the current knowledge on these aspects. Methods: A literature review of PK, PD and DDI profiles of BLV was conducted from Pubmed and EMA websites. Experimentally tested interactions and hypothetical mechanisms of interaction were evaluated, mostly focusing on usually co-administered anti-infective agents and other drugs interacting on NTCP. Results: BLV shows non-linear PK, due to target-mediated drug disposition, so its PK as well as PD is expected to be influenced by interactions of other drugs with NTCP, while it is not substrate of CYPs and ABC transporters. In-vivo investigated DDIs showed no clinically relevant interactions, but a weak inhibitory effect was suggested on CYP3A4 in a work when used at high doses (10 mg instead of 2 mg). In vitro, a weak inhibitory effect on OATP transporters was observed, but at much higher concentrations than the ones expected in vivo. Conclusions: The drug-drug interaction potential of BLV can be considered generally very low, particularly at the currently approved dose of 2 mg/day. Some attention should be paid to the coadministration of drugs with known binding and/or inhibition of NTCP.
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Joseph A, Kumar D, Sukumar MBA, Kaur H, Peter RM. Exploring Perceptions and Treatment-Seeking Behaviors for Viral Hepatitis Among the Ethnic Irula Tribe in Tamil Nadu, India: A Qualitative Study on Health Disparities. J Racial Ethn Health Disparities 2025:10.1007/s40615-025-02287-y. [PMID: 39815130 DOI: 10.1007/s40615-025-02287-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 12/27/2024] [Accepted: 01/02/2025] [Indexed: 01/18/2025]
Abstract
OBJECTIVES Qualitative research was undertaken to determine the perceptions and treatment-seeking behaviors of the Irula tribal populations in Tamil Nadu, India, and to explore the depth, diversity, and complexity of viral hepatitis. METHODS An in-depth interview (IDI) was conducted among the eligible respondents. A purposive sampling technique was used to obtain the study subjects. The IDI was conducted among the community leader, male and female participants, and other representatives, e.g., ward members (Panchayat). We gathered data regarding the perceptions of viral hepatitis and behavioral intentions. Thematic analysis was used to generate the results of the qualitative research. RESULTS Four themes emerged from the codes of the current qualitative study: (1) the general perception, transmission, and treatment of viral hepatitis; (2) stigma and discrimination; (3) health-seeking behavior towards viral hepatitis; and (4) morbidity patterns were significant themes. Most of the nomadic tribes hold incorrect perceptions regarding viral hepatitis and liver cancer risk, and women were reported to have a higher perceived risk than men. CONCLUSION The participants displayed high hope and confidence, which motivated them to participate actively in viral hepatitis prevention activities. Programs and policies geared towards enhancing viral hepatitis prevention in this sub-population may consider sociocultural factors observed to influence prevention behaviors.
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Affiliation(s)
- Alex Joseph
- Division of Epidemiology, SRM School of Public Health, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Dhasarathi Kumar
- Division of Epidemiology, SRM School of Public Health, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Margret Beaula Alocious Sukumar
- Division of Epidemiology, SRM School of Public Health, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Harpreet Kaur
- Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research, Department of Health Research, New Delhi, India
| | - Roshni Mary Peter
- Department of Community Medicine, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.
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Curici A, Ilie OM, Mindru DE. Prevalence of HDV, HCV, and HIV Infection in the Population of Patients Infected with HBV in a Romanian Cohort. Microorganisms 2025; 13:118. [PMID: 39858886 PMCID: PMC11768068 DOI: 10.3390/microorganisms13010118] [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: 12/26/2024] [Revised: 01/02/2025] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
Hepatitis B virus (HBV) infections remain a significant global health challenge, especially in low- and middle-income countries where access to healthcare services is often limited. This study aimed to assess the prevalence of hepatitis B virus (HBV), hepatitis delta virus (HDV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) co-infections in a cohort of 426,528 patients tested for HBsAg in Romania between 2018 and 2023. Of the 17,082 HBsAg-positive individuals (4.0% prevalence), the highest HBV positivity rates were observed in the 30-39 and over 60 age groups. Chronic HBV infection was identified in 13.2% of the cohort, with 3.6% testing positive for HBeAg, indicating active viral replication. Co-infection rates were 11.3% for HDV, 1.4% for HCV, and 0.45% for HIV. The incidence of HDV co-infection increased significantly from 2018 to 2023, particularly in older populations. HCV co-infection was more prevalent in individuals aged 50-59 and over 60, with a declining trend from 2020 onward. The study also revealed a weak correlation between liver enzyme levels (ALT and AST) and HBV viral load, suggesting that liver function tests may not fully reflect the severity of HBV infection. HIV co-infection was notably rare compared to other regions, likely due to regional healthcare interventions. The findings from our study highlight the need for targeted interventions, particularly for high-risk groups such as older adults and middle-aged individuals, to reduce the burden of chronic HBV and its complications.
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Affiliation(s)
- Antoanela Curici
- Department of Cellular and Molecular Biology and Histology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Synevo Romania, 021408 Bucharest, Romania
| | | | - Dana Elena Mindru
- Department of Pediatrics, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
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Badshah Y, Shabbir M, Khan K, Zafar S, Afsar T, Husain FM, Amor H, Razak S. HCV and HBV genotypes: vital in the progression of HCV/ HBV co-infection. BMC Gastroenterol 2025; 25:6. [PMID: 39780058 PMCID: PMC11708002 DOI: 10.1186/s12876-025-03587-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 01/01/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Viral hepatitis is the major contributor to liver cirrhosis and hepatocellular carcinoma (HCC). Studies indicated that the co-infection of hepatitis C and hepatitis B virus also prompts liver damage progression. Therefore, in the present study, the prevalence of HCV-HBV co-infection and the impact of HCV-HBV co-infection on the progression of liver damage was evaluated amongst the HCV-infected patients in Pakistan. METHODS In this study 2500 HCV-positive patients were recruited from Pakistan. The presence and prevalence of HCV and HBV was confirmed through ELISA and nested PCR. To determine the liver damage due to viral infection levels of ALT, ALP, and total bilirubin were also determined. Diagnostic history of patients was thoroughly documented through serological tests and liver biopsy reports. Viral genotypes and viral loads were determined through multiplex polymerase chain reaction (PCR) and time PCR, respectively. RESULTS The study outcomes showed that 12.5% of the HCV-infected patients were co-infected with HBV. Co-infection development was more common in females than in males, and females were at a higher risk of developing the infection (p-value = < 0.0001, OR = 2.437). Despite the variation among different age groups, there was no significant difference in co-infection prevalence. HCV genotype 3a was found to be most prevalent while in HBV genotype D was found to be prevalent among the patients. The HCV patients frequently developed co-infection with HBV genotype D. It was also determined that viral load for HBV genotype D was higher compared to non-D genotypes while for HCV viral load was higher in non-3a genotypes. CONCLUSIONS This study evaluated the prevalence of HCV and HBV co-infection among HCV-positive patients, revealing that 12.5% patients were co-infected with HBV. Co-infection was more common in females, who had a higher risk of developing it. The study also revealed that HBV genotype D was the most prevalent in co-infected patients, with no significant age-related differences in co-infection rates.
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Affiliation(s)
- Yasmin Badshah
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan.
| | - Maria Shabbir
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Khushbukhat Khan
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Sameen Zafar
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Fohad Mabood Husain
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Houda Amor
- Department of Obstetrics, Gynecology and Reproductive Medicine, Saarland University Clinic, Homburg, Germany
| | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia.
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Smirne C, Crobu MG, Landi I, Vercellino N, Apostolo D, Pinato DJ, Vincenzi F, Minisini R, Tonello S, D’Onghia D, Ottobrelli A, Martini S, Bracco C, Fenoglio LM, Campanini M, Berton AM, Ciancio A, Pirisi M. Chronic Hepatitis C Infection Treated with Direct-Acting Antiviral Agents and Occurrence/Recurrence of Hepatocellular Carcinoma: Does It Still Matter? Viruses 2024; 16:1899. [PMID: 39772206 PMCID: PMC11680226 DOI: 10.3390/v16121899] [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] [Received: 10/09/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs.
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Affiliation(s)
- Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy;
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Irene Landi
- Emergency Medicine Department, Michele e Pietro Ferrero Hospital, 12060 Verduno, Italy;
| | - Nicole Vercellino
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Daria Apostolo
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - David James Pinato
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London SW7 2AZ, UK
| | - Federica Vincenzi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Stelvio Tonello
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Davide D’Onghia
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Antonio Ottobrelli
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
| | - Silvia Martini
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
| | - Christian Bracco
- Department of Internal Medicine, Santa Croce e Carle Hospital, 12100 Cuneo, Italy; (C.B.); (L.M.F.)
| | - Luigi Maria Fenoglio
- Department of Internal Medicine, Santa Croce e Carle Hospital, 12100 Cuneo, Italy; (C.B.); (L.M.F.)
| | - Mauro Campanini
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Alessandro Maria Berton
- Division of Endocrinology, Diabetes and Metabolism, City of Health and Science University Hospital, 10126 Turin, Italy;
| | - Alessia Ciancio
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
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Treviño-Nakoura A, Sepúlveda-Crespo D, Bellon JM, Codina H, Quero-Delgado M, Ryan P, Martínez I, Resino S. Diagnostic performance of hepatitis C virus core antigen testing for detecting hepatitis C in people living with hepatitis B: a systematic review and meta-analysis. Infect Dis Poverty 2024; 13:89. [PMID: 39617947 PMCID: PMC11610273 DOI: 10.1186/s40249-024-01264-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/21/2024] [Indexed: 12/10/2024] Open
Abstract
BACKGROUND The current diagnostic strategy for hepatitis C virus (HCV) infection involves a two-step approach: antibody HCV screening followed by confirmatory nucleic acid testing. This study aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay in serum/plasma samples as a potential one-step alternative for diagnosing active HCV infection in people living with hepatitis B virus (PLWHB) through a systematic review and meta-analysis. METHODS A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. This protocol was registered on PROSPERO (CRD42023402093). A comprehensive search of electronic databases identified studies published up to 1 November 2024, comparing the ARCHITECT HCV Ag assay to an HCV-RNA reference standard. Sensitivity, specificity, and likelihood ratios were pooled using a random-effects model within the MIDAS module of Stata software. Study quality was assessed using QUADAS-2. Heterogeneity was evaluated using the Q statistic, quantified using the I², and further explored through meta-regression. RESULTS Ten studies (n = 494 participants) met inclusion criteria. The Abbott ARCHITECT HCV Ag assay demonstrated high sensitivity [91%, 95% confidence interval (CI): 76-97%] and specificity (99%, 95% CI: 99-100%). The positive likelihood ratio (PLR) was 81.20 (95% CI: 12.34-534.36), and the negative likelihood ratio (NLR) was 0.09 (95% CI: 0.03-0.27). The area under the summary receiver operating characteristic curve (AUC-SROC) was 99% (95% CI 98-100%). In regions with high HCV prevalence (≥ 10%), the test accurately confirmed active HCV infection in over 90% of cases. However, confirmatory testing remains necessary in low-prevalence settings (≤ 5%). The assay demonstrated an excellent ability to identify individuals without HCV infection, with a low false-negative rate (≤ 2%) regardless of HCV prevalence. Heterogeneity analysis revealed moderate to substantial variation in test performance (I² = 72.09% for sensitivity, 35.47% for PLR, and 78.33% for NLR). QUADAS-2 applicability concerns predicted heterogeneity, but differences were likely insignificant due to minimal variations and limited studies. CONCLUSIONS The Abbott ARCHITECT HCV Ag assay exhibited promising accuracy in detecting active HCV infection among PLWHB. This test might help diagnose active HCV infection in high-prevalence scenarios (≥ 10%) but needs further confirmation in low-prevalence settings (≤ 5%).
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Affiliation(s)
- Ana Treviño-Nakoura
- Servicio de Medicina Preventiva y Salud Pública, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain
- Instituto Mixto de Investigación Escuela Nacional de Sanidad-Universidad Nacional de Educación a Distancia (IMIENS-UNED), Madrid, Spain
| | - Daniel Sepúlveda-Crespo
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain.
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
| | - José M Bellon
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Helena Codina
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain
| | - Marta Quero-Delgado
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain
| | - Pablo Ryan
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Km 2.2, 28220, Majadahonda (Madrid), Spain.
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
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Li S, Gulisija D, Carja O. The evolutionary cost of homophily: Social stratification facilitates stable variant coexistence and increased rates of evolution in host-associated pathogens. PLoS Comput Biol 2024; 20:e1012619. [PMID: 39576842 PMCID: PMC11623455 DOI: 10.1371/journal.pcbi.1012619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 12/06/2024] [Accepted: 11/07/2024] [Indexed: 11/24/2024] Open
Abstract
Coexistence of multiple strains of a pathogen in a host population can present significant challenges to vaccine development or treatment efficacy. Here we discuss a novel mechanism that can increase rates of long-lived strain polymorphism, rooted in the presence of social structure in a host population. We show that social preference of interaction, in conjunction with differences in immunity between host subgroups, can exert varying selection pressure on pathogen strains, creating a balancing mechanism that supports stable viral coexistence, independent of other known mechanisms. We use population genetic models to study rates of pathogen heterozygosity as a function of population size, host population composition, mutant strain fitness differences and host social preferences of interaction. We also show that even small periodic epochs of host population stratification can lead to elevated strain coexistence. These results are robust to varying social preferences of interaction, overall differences in strain fitnesses, and spatial heterogeneity in host population composition. Our results highlight the role of host population social stratification in increasing rates of pathogen strain diversity, with effects that should be considered when designing policies or treatments with a long-term view of curbing pathogen evolution.
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Affiliation(s)
- Shuanger Li
- Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
| | - Davorka Gulisija
- Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America
| | - Oana Carja
- Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
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8
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Li Z, Huang L, Yu C. Advanced Prediction of Hepatic Oncogenic Transformation in HBV Patients via RNA-Seq Data Analysis and Deep Learning Techniques. Int J Mol Sci 2024; 25:9827. [PMID: 39337315 PMCID: PMC11432201 DOI: 10.3390/ijms25189827] [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] [Received: 07/29/2024] [Revised: 09/09/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Liver cancer, recognized as a significant global health issue, is increasingly correlated with Hepatitis B virus (HBV) infection, as evidenced by numerous scientific studies. This study aims to examine the correlation between HBV infection and the development of liver cancer, focusing on using RNA sequencing (RNA-seq) to detect HBV sequences and applying deep learning techniques to estimate the likelihood of oncogenic transformation in individuals with HBV. Our study utilized RNA-seq data and employed Pathseq software and sophisticated deep learning models, including a convolutional neural network (CNN), to analyze the prevalence of HBV sequences in the samples of patients with liver cancer. Our research successfully identified the prevalence of HBV sequences and demonstrated that the CNN model achieved an exceptional Area Under the Curve (AUC) of 0.998 in predicting cancerous transformations. We observed no viral synergism that enhanced the pathogenicity of HBV. A detailed analysis of sequences misclassified by the CNN model revealed that longer sequences were more conducive to accurate recognition. The findings from this study provide critical insights into the management and prognosis of patients infected with HBV, highlighting the potential of advanced analytical techniques in understanding the complex interactions between viral infections and cancer development.
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Affiliation(s)
| | | | - Changyuan Yu
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China; (Z.L.)
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Demirchyan A, Mozalevskis A, Sahakyan S, Musheghyan L, Aslanyan L, Muradyan D, Sargsyants N, Ghukasyan G, Petrosyan V. Seroprevalence of Hepatitis C Virus and Factors Associated with It in Armenia, 2021. Viruses 2024; 16:1446. [PMID: 39339922 PMCID: PMC11437486 DOI: 10.3390/v16091446] [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: 07/24/2024] [Accepted: 08/27/2024] [Indexed: 09/30/2024] Open
Abstract
Hepatitis C virus (HCV) infection is among the leading causes of cirrhosis and hepatocellular carcinoma. Knowledge of its prevalence and risk factors can help to effectively fight the virus. This study was the first to investigate the seroprevalence of HCV, its genotypes, and factors associated with it among the general adult population of Armenia selected countrywide via cluster sampling. Anti-HCV antibodies were detected using third-generation immunoassay. Polymerase chain reaction and genotyping was performed among anti-HCV-positive individuals. Shortly after testing, the participants underwent a telephone survey. Logistic regression models were fitted to identify factors associated with anti-HCV antibody positivity and chronic HCV infection. The prevalence of anti-HCV antibodies among 3831 tested individuals was 2% (99% CI 1.4, 2.5), and chronic HCV infection was 0.7% (99% CI 0.4, 1.0), with genotypes 3 and 2 being the most common. The risk factors for chronic HCV infection included self-reported chronic liver disease (95% CI 1.47, 15.28), having tattoos (95% CI 1.34, 10.94), ever smoking (95% CI 1.16, 9.18), and testing positive for hepatitis B virus core antibody (95% CI 1.02, 7.17). These risk factors demonstrate that there could be room for strengthening infection control measures to prevent the transmission of HCV in Armenia.
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Affiliation(s)
- Anahit Demirchyan
- Turpanjian College of Health Sciences, American University of Armenia, 40 Marshal Baghramyan Ave., Yerevan 0019, Armenia; (S.S.); (L.M.); (L.A.); (D.M.); (V.P.)
| | - Antons Mozalevskis
- Global HIV, Hepatitis and Sexually Transmitted Infections Programmes, World Health Organization, 1211 Geneva, Switzerland;
| | - Serine Sahakyan
- Turpanjian College of Health Sciences, American University of Armenia, 40 Marshal Baghramyan Ave., Yerevan 0019, Armenia; (S.S.); (L.M.); (L.A.); (D.M.); (V.P.)
| | - Lusine Musheghyan
- Turpanjian College of Health Sciences, American University of Armenia, 40 Marshal Baghramyan Ave., Yerevan 0019, Armenia; (S.S.); (L.M.); (L.A.); (D.M.); (V.P.)
| | - Lusine Aslanyan
- Turpanjian College of Health Sciences, American University of Armenia, 40 Marshal Baghramyan Ave., Yerevan 0019, Armenia; (S.S.); (L.M.); (L.A.); (D.M.); (V.P.)
| | - Diana Muradyan
- Turpanjian College of Health Sciences, American University of Armenia, 40 Marshal Baghramyan Ave., Yerevan 0019, Armenia; (S.S.); (L.M.); (L.A.); (D.M.); (V.P.)
| | - Narina Sargsyants
- National Institute of Health, Ministry of Health, Republic of Armenia, Yerevan 0051, Armenia;
| | - Gayane Ghukasyan
- World Health Organization Country Office in Armenia, Yerevan 0015, Armenia;
| | - Varduhi Petrosyan
- Turpanjian College of Health Sciences, American University of Armenia, 40 Marshal Baghramyan Ave., Yerevan 0019, Armenia; (S.S.); (L.M.); (L.A.); (D.M.); (V.P.)
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10
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Chang YP, Huang CB, Kao JH, Su TH, Huang SC, Tseng TC, Chen PJ, Liu CJ, Liu CH. Factors associated with pre-treatment hyperferritinemia in patients with chronic hepatitis C virus infection. Sci Rep 2024; 14:19219. [PMID: 39160295 PMCID: PMC11333767 DOI: 10.1038/s41598-024-70233-9] [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: 05/19/2024] [Accepted: 08/14/2024] [Indexed: 08/21/2024] Open
Abstract
Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09-1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04-1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11-1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21-1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20-3.75), p < 0.001) were associated hyperferritinemia. The log10 value of HBV or HCV viral load was not associated with the log10 value of ferritin level (Spearman's rank correlation coefficient: - 0.025, p = 0.81 and 0.002, p = 0.92). In conclusion, host factors, rather than viral factors, are associated with hyperferritinemia in patients with HCV.
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Affiliation(s)
- Yu-Ping Chang
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Chiuan-Bo Huang
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Chin Huang
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan.
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11
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Sadraeian M, Maleki R, Moraghebi M, Bahrami A. Phage Display Technology in Biomarker Identification with Emphasis on Non-Cancerous Diseases. Molecules 2024; 29:3002. [PMID: 38998954 PMCID: PMC11243120 DOI: 10.3390/molecules29133002] [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] [Received: 03/12/2024] [Revised: 04/17/2024] [Accepted: 04/29/2024] [Indexed: 07/14/2024] Open
Abstract
In recent years, phage display technology has become vital in clinical research. It helps create antibodies that can specifically bind to complex antigens, which is crucial for identifying biomarkers and improving diagnostics and treatments. However, existing reviews often overlook its importance in areas outside cancer research. This review aims to fill that gap by explaining the basics of phage display and its applications in detecting and treating various non-cancerous diseases. We focus especially on its role in degenerative diseases, inflammatory and autoimmune diseases, and chronic non-communicable diseases, showing how it is changing the way we diagnose and treat illnesses. By highlighting important discoveries and future possibilities, we hope to emphasize the significance of phage display in modern healthcare.
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Affiliation(s)
- Mohammad Sadraeian
- Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia
| | - Reza Maleki
- Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
| | - Mahta Moraghebi
- Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia
| | - Abasalt Bahrami
- Department of Chemistry and Biochemistry, Bioengineering, and Materials Science and Engineering, University of California, Los Angeles, CA 90095, USA
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12
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Asandem DA, Segbefia SP, Kusi KA, Bonney JHK. Hepatitis B Virus Infection: A Mini Review. Viruses 2024; 16:724. [PMID: 38793606 PMCID: PMC11125943 DOI: 10.3390/v16050724] [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] [Received: 01/27/2024] [Revised: 03/27/2024] [Accepted: 03/28/2024] [Indexed: 05/26/2024] Open
Abstract
Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections are recorded annually, especially in poorly resourced places which have lax vaccination policies. Again, as HBV has no cure and chronic infection is lifelong, vaccines cannot help those already infected. Studies to thoroughly understand the HBV biology and pathogenesis are limited, leaving much yet to be understood about the genomic features and their role in establishing and maintaining infection. The current knowledge of the impact on disease progression and response to treatment, especially in hyperendemic regions, is inadequate. This calls for in-depth studies on viral biology, mainly for the purposes of coming up with better management strategies for infected people and more effective preventative measures for others. This information could also point us in the direction of a cure. Here, we discuss the progress made in understanding the genomic basis of viral activities leading to the complex interplay of the virus and the host, which determines the outcome of HBV infection as well as the impact of coinfections.
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Affiliation(s)
- Diana Asema Asandem
- West African Center for Cell Biology of Infectious Pathogens, University of Ghana, Accra P.O. Box LG 52, Ghana;
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra P.O. Box LG 581, Ghana
| | - Selorm Philip Segbefia
- Department of Immunology, Noguchi Memorial Noguchi Memorial Institute for Medical Research, University of Ghana, Accra P.O. Box LG 581, Ghana; (S.P.S.); (K.A.K.)
| | - Kwadwo Asamoah Kusi
- Department of Immunology, Noguchi Memorial Noguchi Memorial Institute for Medical Research, University of Ghana, Accra P.O. Box LG 581, Ghana; (S.P.S.); (K.A.K.)
| | - Joseph Humphrey Kofi Bonney
- Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra P.O. Box LG 581, Ghana
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13
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Ciupe SM, Conway JM. Incorporating Intracellular Processes in Virus Dynamics Models. Microorganisms 2024; 12:900. [PMID: 38792730 PMCID: PMC11124127 DOI: 10.3390/microorganisms12050900] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 04/25/2024] [Accepted: 04/26/2024] [Indexed: 05/26/2024] Open
Abstract
In-host models have been essential for understanding the dynamics of virus infection inside an infected individual. When used together with biological data, they provide insight into viral life cycle, intracellular and cellular virus-host interactions, and the role, efficacy, and mode of action of therapeutics. In this review, we present the standard model of virus dynamics and highlight situations where added model complexity accounting for intracellular processes is needed. We present several examples from acute and chronic viral infections where such inclusion in explicit and implicit manner has led to improvement in parameter estimates, unification of conclusions, guidance for targeted therapeutics, and crossover among model systems. We also discuss trade-offs between model realism and predictive power and highlight the need of increased data collection at finer scale of resolution to better validate complex models.
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Affiliation(s)
- Stanca M. Ciupe
- Department of Mathematics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA
| | - Jessica M. Conway
- Department of Mathematics and Center for Infectious Disease Dynamics, Penn State University, State College, PA 16802, USA
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14
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Perera DJ, Koger-Pease C, Paulini K, Daoudi M, Ndao M. Beyond schistosomiasis: unraveling co-infections and altered immunity. Clin Microbiol Rev 2024; 37:e0009823. [PMID: 38319102 PMCID: PMC10938899 DOI: 10.1128/cmr.00098-23] [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] [Indexed: 02/07/2024] Open
Abstract
Schistosomiasis is a neglected tropical disease caused by the helminth Schistosoma spp. and has the second highest global impact of all parasites. Schistosoma are transmitted through contact with contaminated fresh water predominantly in Africa, Asia, the Middle East, and South America. Due to the widespread prevalence of Schistosoma, co-infection with other infectious agents is common but often poorly described. Herein, we review recent literature describing the impact of Schistosoma co-infection between species and Schistosoma co-infection with blood-borne protozoa, soil-transmitted helminths, various intestinal protozoa, Mycobacterium, Salmonella, various urinary tract infection-causing agents, and viral pathogens. In each case, disease severity and, of particular interest, the immune landscape, are altered as a consequence of co-infection. Understanding the impact of schistosomiasis co-infections will be important when considering treatment strategies and vaccine development moving forward.
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Affiliation(s)
- Dilhan J. Perera
- Division of Experimental Medicine, McGill University, Montreal, Canada
- Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Canada
| | - Cal Koger-Pease
- Division of Experimental Medicine, McGill University, Montreal, Canada
- Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Canada
| | - Kayla Paulini
- Department of Microbiology and Immunology, McGill University, Montreal, Canada
| | - Mohamed Daoudi
- Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Canada
- Department of Microbiology and Immunology, McGill University, Montreal, Canada
| | - Momar Ndao
- Division of Experimental Medicine, McGill University, Montreal, Canada
- Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Canada
- Department of Microbiology and Immunology, McGill University, Montreal, Canada
- National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, Canada
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15
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Al-Shuaili HH, Al-Busafi SA, Al-Naamani K, Al-Naamani Z. Predictors of survival among patients with chronic hepatitis C at a tertiary care center in Oman. Saudi J Gastroenterol 2024; 30:45-52. [PMID: 38190454 PMCID: PMC10852148 DOI: 10.4103/sjg.sjg_201_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/09/2023] [Accepted: 08/26/2023] [Indexed: 01/10/2024] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. This study aimed to determine rates and predictors of survival among Omani patients with CHC at a tertiary hospital in Muscat, Oman. METHODS This ambidirectional cohort study included all CHC patients who presented to the Sultan Qaboos University Hospital between January 2009 and December 2017. Baseline demographic, clinical, laboratory, and radiological data were analyzed. Patients were followed-up until death or the endpoint of the study (April 2022) to determine survival and associations with other parameters. RESULTS A total of 702 CHC patients were included, of which 398 (56.7%) were under 50 years of age and 477 (67.9%) were male. Overall, 180 patients (25.6%) died by the study endpoint. The mean duration of follow-up was 93.3 ± 48.0 months. The 5-year survival rate was estimated to be 80.5%, while the 10-year survival was 73%. Sustained virological response and the absence of diabetes mellitus, chronic kidney disease, HCC, or other malignancies were associated with significantly better overall survival. The 3- and 5-year survival rate of patients with hepatitis C virus (HCV)-related HCC was 46.5% and 27.6%, respectively, with a median survival of 29.5 months. Co-infection with hepatitis B was associated with poor survival among this subgroup; conversely, early HCV screening and the presence of a single HCC lesion were associated with better overall survival. CONCLUSIONS National policies for early CHC screening and rapid treatment are needed to improve survival rates in this population.
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Affiliation(s)
| | - Said A. Al-Busafi
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
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16
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Medina C, García AH, Crespo FI, Toro FI, Mayora SJ, De Sanctis JB. A Synopsis of Hepatitis C Virus Treatments and Future Perspectives. Curr Issues Mol Biol 2023; 45:8255-8276. [PMID: 37886964 PMCID: PMC10605161 DOI: 10.3390/cimb45100521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/10/2023] [Accepted: 10/10/2023] [Indexed: 10/28/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN-RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV-HCV and HCV-HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.
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Affiliation(s)
- Christian Medina
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Alexis Hipólito García
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Francis Isamarg Crespo
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Félix Isidro Toro
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Soriuska José Mayora
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Juan Bautista De Sanctis
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, 779 00 Olomouc, Czech Republic
- The Czech Advanced Technology and Research Institute (Catrin), Palacky University, 779 00 Olomouc, Czech Republic
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17
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Maqsood Q, Sumrin A, Iqbal M, Younas S, Hussain N, Mahnoor M, Wajid A. Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives. Antivir Ther 2023; 28:13596535231189643. [PMID: 37489502 DOI: 10.1177/13596535231189643] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/26/2023]
Abstract
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
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Affiliation(s)
- Quratulain Maqsood
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Aleena Sumrin
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Maryam Iqbal
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Saima Younas
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Nazim Hussain
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Muhammada Mahnoor
- Department of Rehabilitation Science, The University of Lahore, Lahore, Pakistan
| | - Abdul Wajid
- Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Science, Quetta, Pakistan
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18
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Prevalence of overt and occult hepatitis B virus infection among an incarcerated population of Central-Western Brazil. Acta Trop 2023; 241:106886. [PMID: 36871619 DOI: 10.1016/j.actatropica.2023.106886] [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: 12/10/2022] [Revised: 02/03/2023] [Accepted: 03/01/2023] [Indexed: 03/07/2023]
Abstract
Brazilian prison complexes are characterized by overcrowded cells and precarious conditions, leading to chronically low vacancy. Brazilian studies involving overt and occult infection (OBI) in this population are still scarce despite the vulnerability of people deprived of liberty to hepatitis B. Therefore, this study estimated the prevalence of HBV infection (overall and OBI) in individuals deprived of liberty in prisons in Central-Western Brazil. In addition, factors associated with HBV infection were evaluated. This cross-sectional study was conducted with a total of 1083 prisoners who were tested for serological hepatitis B markers and HBV DNA from 2017 to 2020. Factors associated with lifetime HBV infection were investigated using logistic regression. An overall prevalence of HBV infection of 10.1% (95% CI: 8.42-12.11) was detected. Only 32.8% (95% CI: 30.08-35.76) had isolated anti-HBs positivity (serological evidence of HBV vaccination). Indeed, more than half of the population was susceptible to HBV infection (57.1%; 95% CI: 54.15-60.13). HBV DNA was detected in one HBsAg-positive sample (n=1/9; 11%). Also, HBV DNA was detected in five HBsAg-negative samples (n=5/1074), resulting in a prevalence of 0.5% (95% CI: 0.15-1.08) for occult infection. After the multivariate analysis, sexual intercourse with a partner living with HIV was a predictor independently associated with HBV exposure (OR: 4.3; 95% CI: 1.26-14.55; p<0.020). These data demonstrate the need for preventive measures, mainly aimed at health education and better strategies for hepatitis B screening to control this infection in prisons more effectively.
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Zou X, Xu Q, You R, Yin G. Efficacy and Safety of TACE Combined with Regorafenib Plus PD-1 Inhibitor in the Treatment of Hepatocellular Carcinoma After Sorafenib Resistance. J Hepatocell Carcinoma 2023; 10:267-279. [PMID: 36815093 PMCID: PMC9940502 DOI: 10.2147/jhc.s399874] [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: 12/01/2022] [Accepted: 02/07/2023] [Indexed: 02/17/2023] Open
Abstract
Purpose To evaluate the efficacy and safety of TACE combined with regorafenib plus PD-1 inhibitor as a second-line therapy for hepatocellular carcinoma after sorafenib resistance. Materials and Methods The clinical data of 76 patients with hepatocellular carcinoma who were drug-resistant to sorafenib from September 2018 to May 2022 in the tumor intervention department were collected. Among them, 35 patients used TACE combined with regorafenib plus PD-1 inhibitor (TACE-R-P) as second-line treatment, and the remaining 41 patients used TACE combined with regorafenib (TACE-R) as second-line treatment. The mRECIST (modified Response Evaluation Criteria in Solid Tumors) standard was used to evaluate the therapeutic effect. The progression-free survival (PFS) and overall survival (OS) of the two groups were compared. Blood samples were collected before and after treatment to detect the changes in biochemical indicators, and the adverse events (AEs) related to treatment were recorded. Results A total of 76 patients were included in the study, including 35 patients receiving TACE-R-P treatment and 41 patients receiving TACE-R treatment. Patients in the TACE-R-P group had longer median OS (19.7months vs 15.2months, HR:0.7716, 95% CI:0.4767-1.2490, P=0.03), longer median PFS (6.3months vs 3.8months, HR:0.6032, 95% CI:0.3727-0.9763, P=0.0029), higher objective response rate (37.14% vs 19.51%, P=0.001) and higher disease control rate (71.43% vs 48.78%, P=0.001) than those in the TACE-R group. Multivariate analysis showed that Child-Pugh grade (B/A; HR=1.283, 95% CI: 0.623-1.707, P=0.014), PVTT (Yes/No, HR=1.455, 95% CI: 0.977-2.038, P=0.018), extrahepatic metastasis (Yes/No, HR=1.766, 95% CI: 1.135-2.302, P=0.022) and treatment option (TACE-R/TACE-R-P, HR=1.930, 95% CI: 1.461-2.850, P=0.017) were independent prognostic factors for OS. There was no significant difference in the incidence and severity of AEs between the two groups. Conclusion TACE-R-P treatment can be more effective than TACE-R treatment for HCC after sorafenib resistance and can be given priority as a second-line treatment for HCC.
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Affiliation(s)
- Xinhua Zou
- Department of Tumor Interventional Therapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing City, People’s Republic of China
| | - Qingyu Xu
- Department of Tumor Interventional Therapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing City, People’s Republic of China
| | - Ran You
- Department of Tumor Interventional Therapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing City, People’s Republic of China
| | - Guowen Yin
- Department of Tumor Interventional Therapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing City, People’s Republic of China,Correspondence: Guowen Yin, Tel +86-19868589105, Email
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20
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Lasagna A, Albi G, Maserati R, Zuccarini A, Quaccini M, Baldanti F, Sacchi P, Bruno R, Pedrazzoli P. Occult hepatitis B in patients with cancer during immunotherapy with or without chemotherapy: A real-life retrospective single-center cohort study. Front Oncol 2023; 13:1044098. [PMID: 36761977 PMCID: PMC9902935 DOI: 10.3389/fonc.2023.1044098] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 01/11/2023] [Indexed: 01/26/2023] Open
Abstract
Introduction Few data about the safety of immune checkpoint inhibitors (ICIs) in the patients with solid tumor with Occult Hepatitis B Virus (OBI) are available. According to the Taormina Workshop on Occult HBV Infection Faculty Members we defined as potential-OBI (pOBI) the HBV DNA negativity with anti-hepatitis B core antibody (anti-HBc) positivity (pOBI seropositive), and the patients with HBsAg-negative and anti-HBc-negative and Hepatitis B surface antibody (anti-HBs)-negative are defined pOBI seronegative. The aim of this study is to investigate the prevalence of OBI in patients with solid tumors undergoing ICIs with or without chemotherapy and the incidence of reactivation (HBVr). Methods We retrospectively enrolled all HBsAg negative subjects who had received ICIs for at least three months. HBsAg and HBV DNA levels were repeated every 3 months until the end of the study and/or in case of ALT alterations. A univariate analysis was conducted in order to study for each variable available its ability to distinguish a potential OBI seropositive patient from a seronegative one. Results 150 patients in our Oncology Unit were eligible. One hundred and seventeen patients (78%) received ICI as monotherapy, whereas 33 patients (22%) were treated with chemo-immunotherapy. The mainly used drugs for the ICI monotherapy were Pembrolizumab (47%), Nivolumab (33%) and Atezolizumab (11%). The prevalence of pOBI seropositive patients was 25.3%. We did not observe alterations of liver biochemistry nor HBVr. Discussion This study highlights that about a quarter of our population had a potential occult hepatitis B. Immunotherapy might be considered as low risk of reactivation, regardless of the potential presence of episomal covalently closed circular DNA (cccDNA) in the liver, but the correct management still represents a challenge for oncologists and hepatologists.
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Affiliation(s)
- Angioletta Lasagna
- Medical Oncology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy,*Correspondence: Angioletta Lasagna,
| | - Giuseppe Albi
- Division of Infectious Diseases I, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
| | - Renato Maserati
- Division of Infectious Diseases I, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
| | - Andrea Zuccarini
- Medical Oncology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
| | - Mattia Quaccini
- Medical Oncology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
| | - Fausto Baldanti
- Microbiology and Virology Department, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy,Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Paolo Sacchi
- Division of Infectious Diseases I, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
| | - Raffaele Bruno
- Division of Infectious Diseases I, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy,Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Paolo Pedrazzoli
- Medical Oncology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy,Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
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Neto BV, Tavares V, Santos JMO, Cerqueira F, Pereira D, Medeiros R. Map of thrombogenesis in viral infections and viral-driven tumours. Discov Oncol 2023; 14:3. [PMID: 36617364 PMCID: PMC9826626 DOI: 10.1007/s12672-022-00610-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 12/28/2022] [Indexed: 01/09/2023] Open
Abstract
Viruses are pathogenic agents responsible for approximately 10% of all human cancers and significantly contribute to the global cancer burden. Until now, eight viruses have been associated with the development of a broad range of malignancies, including solid and haematological tumours. Besides triggering and promoting oncogenesis, viral infections often go hand-in-hand with haemostatic changes, representing a potential risk factor for venous thromboembolism (VTE). Conversely, VTE is a cardiovascular condition that is particularly common among oncological patients, with a detrimental impact on patient prognosis. Despite an association between viral infections and coagulopathies, it is unclear whether viral-driven tumours have a different incidence and prognosis pattern of thromboembolism compared to non-viral-induced tumours. Thus, this review aims to analyse the existing evidence concerning the association of viruses and viral tumours with the occurrence of VTE. Except for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, which are associated with a high risk of VTE, little evidence exists concerning the thrombogenic potential associated with oncoviruses. As for tumours that can be induced by oncoviruses, four levels of VTE risk are observed, with hepatocellular carcinoma (HCC) and gastric carcinoma (GC) associated with the highest risk and nasopharyngeal carcinoma (NPC) associated with the lowest risk. Unfortunately, the incidence of cancer-related VTE according to tumour aetiology is unknown. Given the negative impact of VTE in oncological patients, research is required to better understand the mechanisms underlying blood hypercoagulability in viral-driven tumours to improve VTE management and prognosis assessment in patients diagnosed with these tumours.
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Affiliation(s)
- Beatriz Vieira Neto
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/ Pathology and Laboratory Medicine Dep., Clinical Pathology SV/ RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072, Porto, Portugal
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal
| | - Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/ Pathology and Laboratory Medicine Dep., Clinical Pathology SV/ RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072, Porto, Portugal
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal
| | - Joana M O Santos
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/ Pathology and Laboratory Medicine Dep., Clinical Pathology SV/ RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072, Porto, Portugal
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal
| | - Fátima Cerqueira
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/ Pathology and Laboratory Medicine Dep., Clinical Pathology SV/ RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072, Porto, Portugal
- FP-I3ID, FP-ENAS, FP-BHS, University Fernando Pessoa, Praça 9 de Abril, 349, 4249-004, Porto, Portugal
- Faculty of Health Sciences, University Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150, Porto, Portugal
| | - Deolinda Pereira
- Oncology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072, Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/ Pathology and Laboratory Medicine Dep., Clinical Pathology SV/ RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072, Porto, Portugal.
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal.
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
- FP-I3ID, FP-ENAS, FP-BHS, University Fernando Pessoa, Praça 9 de Abril, 349, 4249-004, Porto, Portugal.
- Faculty of Health Sciences, University Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150, Porto, Portugal.
- Research Department, Portuguese League Against Cancer (NRNorte), 4200-172, Porto, Portugal.
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Qian J, Yue M, Huang P, Ai L, Zhu C, Wang C, Luo Y, Yue N, Wu Y, Zhang Y, Wang C, Tan W. Spatiotemporal heterogeneity and impact factors of hepatitis B and C in China from 2010 to 2018: Bayesian space-time hierarchy model. Front Cell Infect Microbiol 2023; 13:1115087. [PMID: 36923590 PMCID: PMC10008934 DOI: 10.3389/fcimb.2023.1115087] [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] [Received: 12/03/2022] [Accepted: 02/13/2023] [Indexed: 03/03/2023] Open
Abstract
Introduction Viral hepatitis is a global public health problem, and China still faces great challenges to achieve the WHO goal of eliminating hepatitis. Methods This study focused on hepatitis B and C, aiming to explore the long-term spatiotemporal heterogeneity of hepatitis B and C incidence in China from 2010 to 2018 and quantify the impact of socioeconomic factors on their risk through Bayesian spatiotemporal hierarchical model. Results The results showed that the risk of hepatitis B and C had significant spatial and temporal heterogeneity. The risk of hepatitis B showed a slow downward trend, and the high-risk provinces were mainly distributed in the southeast and northwest regions, while the risk of hepatitis C had a clear growth trend, and the high-risk provinces were mainly distributed in the northern region. In addition, for hepatitis B, illiteracy and hepatitis C prevalence were the main contributing factors, while GDP per capita, illiteracy rate and hepatitis B prevalence were the main contributing factors to hepatitis C. Disussion This study analyzed the spatial and temporal heterogeneity of hepatitis B and C and their contributing factors, which can serve as a basis for monitoring efforts. Meanwhile, the data provided by this study will contribute to the effective allocation of resources to eliminate viral hepatitis and the design of interventions at the provincial level.
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Affiliation(s)
- Jiaojiao Qian
- Department of Epidemiology, School of Public Health, Nanjing Medical University., Nanjing, China
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Ming Yue
- Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Peng Huang
- Department of Epidemiology, School of Public Health, Nanjing Medical University., Nanjing, China
| | - Lele Ai
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Changqiang Zhu
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Chongcai Wang
- Department of infectious diseases prevention, Hainan International Travel Healthcare Center, Haikou, China
| | - Yizhe Luo
- Department of Epidemiology, School of Public Health, Nanjing Medical University., Nanjing, China
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Na Yue
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Yifan Wu
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Yun Zhang
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
| | - Chunhui Wang
- Department of Epidemiology, School of Public Health, Nanjing Medical University., Nanjing, China
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
- *Correspondence: Chunhui Wang, ; Weilong Tan,
| | - Weilong Tan
- Department of Epidemiology, School of Public Health, Nanjing Medical University., Nanjing, China
- Department of infectious diseases prevention, Nanjing Bioengineering (Gene) Technology Center for Medicines, Nanjing, China
- *Correspondence: Chunhui Wang, ; Weilong Tan,
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The role of HIV/hepatitis B virus/hepatitis C virus RNA+ triple infection in end-stage liver disease and all-cause mortality in Europe. AIDS 2023; 37:91-103. [PMID: 36476454 DOI: 10.1097/qad.0000000000003406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND There are limited data on end-stage liver disease (ESLD) and mortality in people with HIV (PWH) coinfected with both hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS All PWH aged greater than 18 under follow-up in EuroSIDA positive for HBsAg (HBV), and/or HCVRNA+, were followed from baseline (latest of 1 January 2001, EuroSIDA recruitment, known HBV/HCV status) to ESLD, death, last visit, or 31 December 2020. Follow-up while HCVRNA- was excluded. In two separate models, Poisson regression compared three groups updated over time; HIV/HBV, HIV/HCV, and HIV/HBV/HCV. RESULTS Among 5733 included individuals, 4476 (78.1%) had HIV/HCV, 953 (16.6%) had HIV/HBV and 304 (5.3%) had HIV/HBV/HCV. In total, 289 (5%) developed ESLD during 34 178 person-years of follow-up (PYFU), incidence 8.5/1000 PYFU [95% confidence interval (CI) 7.5-9.4] and 707 deaths occurred during 34671 PYFU (incidence 20.4/1000 PYFU; 95% CI 18.9-21.9). After adjustment, compared with those with HIV/HCV, persons with HIV/HBV had significantly lower rates of ESLD [adjusted incidence rate ratio (aIRR) 0.53; 95% CI 0.34-0.81]. Those with HIV/HBV/HCV had marginally significantly higher rates of ESLD (aIRR 1.49; 95% CI 0.98-2.26). Those under follow-up in 2014 or later had significantly lower rates of ESLD compared with 2007-2013 (aIRR 0.65; 95% CI 0.47-0.89). Differences in ESLD between the three groups were most pronounced in those aged at least 40. After adjustment, there were no significant differences in all-cause mortality across the three groups. CONCLUSION HIV/HBV-coinfected individuals had lower rates of ESLD and HIV/HBV/HCV had higher rates of ESLD compared with those with HIV/HCV, especially in those aged more than 40. ESLD decreased over time across all groups. CLINICALTRIALSGOV IDENTIFIER NCT02699736.
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Gedefie A, Seid A, Molla Fenta G, Tilahun M, Shibabaw A, Ali A. Hepatitis B and C virus infections and associated factors among HIV-positive and HIV-negative tuberculosis patients in public health facilities, Northeast Ethiopia: A comparative cross-sectional study. SAGE Open Med 2023; 11:20503121231166642. [PMID: 37123386 PMCID: PMC10134168 DOI: 10.1177/20503121231166642] [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: 07/22/2022] [Accepted: 03/13/2023] [Indexed: 05/02/2023] Open
Abstract
Objective Viral hepatitis, particularly hepatitis B virus and hepatitis C virus, is the leading cause of global liver-related morbidity and mortality. Concomitant infections of hepatitis B virus, hepatitis C virus, and tuberculosis are risks of hepatotoxicity and death due to antituberculosis therapy. Hepatitis and human immunodeficiency virus coinfection poses challenges in treating hepatotoxic patients and leads to mortality during antituberculosis treatment. Thus, this study aimed to determine the prevalence of hepatitis B virus and hepatitis C virus infections, and associated factors among human immunodeficiency virus-positive and human immunodeficiency virus-negative tuberculosis patients attending public health facilities, Northeast Ethiopia. Methods A comparative cross-sectional study was conducted among 229 tuberculosis patients from January 1 to April 30, 2021 in public health facilities' tuberculosis treatment centers. Study participants were selected using a consecutive sampling technique. Data on sociodemographic and other risk factors were collected using an interviewer-based pretested questionnaire by trained data collectors. Anti-hepatitis C virus and hepatitis B surface antigen were determined in serum using enzyme-linked immunosorbent assay. Data were entered and analyzed using SPSS version 22. Logistic regression analysis was computed, and then variables with a p value <0.05 were considered as statistically significant. Result The overall hepatitis virus infection among human immunodeficiency virus-positive and human immunodeficiency virus-negative tuberculosis patients was 14.03% and 8.14%, respectively. The prevalence of hepatitis B virus infection in human immunodeficiency virus positives and human immunodeficiency virus negatives was 10.5% and 6.4% and hepatitis C virus infection in human immunodeficiency virus positives and human immunodeficiency virus negatives was 3.5% and 1.75%, respectively. Hepatitis B virus and hepatitis C virus coinfections were not observed. Older age, history of problematic alcohol use, history of blood transfusion, ear-noise piercing, and history of multiple heterosexual partners were predictors for the hepatitis virus infection. Conclusion Hepatitis virus infection increases morbidity and mortality of tuberculosis patients. Therefore, screening tuberculosis patients for hepatitis virus infection is necessary to reduce the risk of antituberculosis complications.
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Affiliation(s)
- Alemu Gedefie
- Alemu Gedefie, Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie 1145, Ethiopia.
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Zou G, Park JI. Wnt signaling in liver regeneration, disease, and cancer. Clin Mol Hepatol 2023; 29:33-50. [PMID: 35785913 PMCID: PMC9845677 DOI: 10.3350/cmh.2022.0058] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 06/30/2022] [Indexed: 02/02/2023] Open
Abstract
The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. In this review, we discussed the role of Wnt signaling in liver regeneration, precancerous lesion, and liver cancer. Furthermore, we summarized the basic and clinical approaches of Wnt signaling blockade and proposed the therapeutic prospects of cancer-specific Wnt signaling blockade for liver cancer treatment.
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Affiliation(s)
- Gengyi Zou
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,Corresponding author : Gengyi Zou Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd Unit 1054, Houston, TX 77030, USA Tel: +1-713-792-3659, Fax: +1-713-794-5369, E-mail:
| | - Jae-Il Park
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,Genetics and Epigenetics Program, The University of Texas MD Anderson Cancer Center Graduate School of Biomedical Sciences, Houston, TX, USA,Jae-Il Park Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd. Unit 1052, Houston, TX 77030, USA Tel: +1-713-792-3659, Fax: +1-713-794-5369, E-mail:
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Domovitz T, Ayoub S, Werbner M, Alter J, Izhaki Tavor L, Yahalom-Ronen Y, Tikhonov E, Meirson T, Maman Y, Paran N, Israely T, Dessau M, Gal-Tanamy M. HCV Infection Increases the Expression of ACE2 Receptor, Leading to Enhanced Entry of Both HCV and SARS-CoV-2 into Hepatocytes and a Coinfection State. Microbiol Spectr 2022; 10:e0115022. [PMID: 36314945 PMCID: PMC9769977 DOI: 10.1128/spectrum.01150-22] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 09/28/2022] [Indexed: 11/09/2022] Open
Abstract
Recent studies suggest the enhancement of liver injury in COVID-19 patients infected with Hepatitis C virus (HCV). Hepatocytes express low levels of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor, raising the possibility of HCV-SARS-CoV-2 coinfection in the liver. This work aimed to explore whether HCV and SARS-CoV-2 coinfect hepatocytes and the interplay between these viruses. We demonstrate that SARS-CoV-2 coinfects HCV-infected Huh7.5 (Huh7.5HCV) cells. Both viruses replicated efficiently in the coinfected cells, with HCV replication enhanced in coinfected compared to HCV-mono-infected cells. Strikingly, Huh7.5HCV cells were eight fold more susceptible to SARS-CoV-2 pseudoviruses than naive Huh7.5 cells, suggesting enhanced SARS-CoV-2 entry into HCV-preinfected hepatocytes. In addition, we observed increased binding of spike receptor-binding domain (RBD) protein to Huh7.5HCV cells, as well as enhanced cell-to-cell fusion of Huh7.5HCV cells with spike-expressing Huh7.5 cells. We explored the mechanism of enhanced SARS-CoV-2 entry and identified an increased ACE2 mRNA and protein levels in Huh7.5HCV cells, primary hepatocytes, and in data from infected liver biopsies obtained from database. Importantly, higher expression of ACE2 increased HCV infection by enhancing its binding to the host cell, underscoring its role in the HCV life cycle as well. Transcriptome analysis revealed that shared host signaling pathways were induced in HCV-SARS-CoV-2 coinfection. This study revealed complex interactions between HCV and SARS-CoV-2 infections in hepatocytes, which may lead to the increased liver damage recently reported in HCV-positive COVID-19 patients. IMPORTANCE Here, we provide the first experimental evidence for the coexistence of SARS-CoV-2 infection with HCV, and the interplay between them. The study revealed a complex relationship of enhancement between the two viruses, where HCV infection increased the expression of the SARS-CoV-2 entry receptor ACE2, thus facilitating SARS-CoV-2 entry, and potentially, also HCV entry. Thereafter, SARS-CoV-2 infection enhanced HCV replication in hepatocytes. This study may explain the aggravation of liver damage that was recently reported in COVID-19 patients with HCV coinfection and suggests preinfection with HCV as a risk factor for severe COVID-19. Moreover, it highlights the possible importance of HCV treatment for coinfected patients. In a broader view, these findings emphasize the importance of identifying coinfecting pathogens that increase the risk of SARS-CoV-2 infection and that may accelerate COVID-19-related co-morbidities.
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Affiliation(s)
- Tom Domovitz
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Samer Ayoub
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Michal Werbner
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Joel Alter
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lee Izhaki Tavor
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Yfat Yahalom-Ronen
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Evgeny Tikhonov
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Tomer Meirson
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Yaakov Maman
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Nir Paran
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Tomer Israely
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Moshe Dessau
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Meital Gal-Tanamy
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
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Abstract
In nature, viral coinfection is as widespread as viral infection alone. Viral coinfections often cause altered viral pathogenicity, disrupted host defense, and mixed-up clinical symptoms, all of which result in more difficult diagnosis and treatment of a disease. There are three major virus-virus interactions in coinfection cases: viral interference, viral synergy, and viral noninterference. We analyzed virus-virus interactions in both aspects of viruses and hosts and elucidated their possible mechanisms. Finally, we summarized the protocol of viral coinfection studies and key points in the process of virus separation and purification.
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Vekariya V, Passi K, Jain CK. Predicting liver cancer on epigenomics data using machine learning. FRONTIERS IN BIOINFORMATICS 2022; 2:954529. [PMID: 36304318 PMCID: PMC9580905 DOI: 10.3389/fbinf.2022.954529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/05/2022] [Indexed: 11/20/2022] Open
Abstract
Epigenomics is the branch of biology concerned with the phenotype modifications that do not induce any change in the cell DNA sequence. Epigenetic modifications apply changes to the properties of DNA, which ultimately prevents such DNA actions from being executed. These alterations arise in the cancer cells, which is the only cause of cancer. The liver is the metabolic cleansing center of the human body and the only organ, which can regenerate itself, but liver cancer can stop the cleansing of the body. Machine learning techniques are used in this research to predict the gene expression of the liver cells for the liver hepatocellular carcinoma (LIHC), which is the third biggest reason of death by cancer and affects five hundred thousand people per year. The data for LIHC include four different types, namely, methylation, histone, the human genome, and RNA sequences. The data were accessed through open-source technologies in R programming languages for The Cancer Genome Atlas (TCGA). The proposed method considers 1,000 features across the four types of data. Nine different feature selection methods were used and eight different classification methods were compared to select the best model over 5-fold cross-validation and different training-to-test ratios. The best model was obtained for 140 features for ReliefF feature selection and XGBoost classification method with an AUC of 1.0 and an accuracy of 99.67% to predict the liver cancer.
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Affiliation(s)
- Vishalkumar Vekariya
- School of Engineering and Computer Science, Laurentian University, Sudbury, ON, Canada
| | - Kalpdrum Passi
- School of Engineering and Computer Science, Laurentian University, Sudbury, ON, Canada
| | - Chakresh Kumar Jain
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
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Su YT, Chang ML, Chien RN, Liaw YF. Hepatitis C Virus Reactivation in Anti-HCV Antibody-Positive Patients with Chronic Hepatitis B Following Anti-HBV Therapies. Viruses 2022; 14:v14091858. [PMID: 36146665 PMCID: PMC9502903 DOI: 10.3390/v14091858] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/17/2022] [Accepted: 08/22/2022] [Indexed: 12/02/2022] Open
Abstract
Background and Aims: Whether hepatitis C virus (HCV) reactivation occurs and how the viral load evolves in anti-HCV antibody-positive chronic hepatitis B (CHB) patients who underwent nucleos(t)ide analogue (Nuc) therapies remain unsolved. Methods: A cohort of 66 such patients was studied. Results: At the start of Nuc treatment (baseline), all patients had detectable hepatitis B virus (HBV) DNA levels (6.05 ± 1.88 log IU/mL), while HCV RNA levels (3.79 ± 1.43 log IU/mL) were detected (i.e., chronic hepatitis C (CHC)) in only 13 patients (19.7%). Following Nuc therapies, HBV DNA levels reached the nadirs at end of therapy (EOT) (6.05 ± 1.88 vs. 0.25 ± 0.99 log IU/mL, p < 0.0001) and relapsed at 6 months after EOT (6mEOT) at a level of 3.45 ± 2.64 log IU/mL compared with EOT (p < 0.0001). Among the 13 CHC patients, a non-significant decrease in HCV RNA was noted at EOT (3.52 ± 1.71 vs. 2.77 ± 2.63 log IU/mL, p = 0.166) but tended to decrease further at 6mEOT (2.77 ± 2.63 vs. 1.89 ± 2.06 log IU/mL, p = 0.063). Two of the thirteen CHC patients showed an increase in HCV-RNA ≥ 1 log10 IU/mL at EOT, and one of the fifty-three patients with undetectable HCV RNA at baseline (i.e., resolved past HCV infection) showed detectable HCV RNA at year 1 (3200 IU/mL) and year 2 (1240 IU/mL) following entecavir therapy. Conclusions: HCV reactivation did occur during HBV suppression, and the rate was 4.5% (3/66), 15.4% (2/13), and 1.9% (1/53), for all patients, CHC patients, and patients with resolved past HCV infection, respectively. The reverse HBV and HCV viral evolutions at 6mEOT indicate that HBV relapse may suppress HCV replication again.
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Affiliation(s)
- Yi-Tse Su
- Division of Hepatology, Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Ming-Ling Chang
- Division of Hepatology, Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Correspondence: (M.-L.C.); (Y.-F.L.); Tel.: +886-3-3281200-8107 (M.-L.C.); Fax: +886-3-3272-236 (M.-L.C.); +886-3-3282-824 (Y.-F.L.)
| | - Rong-Nan Chien
- Division of Hepatology, Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Yun-Fan Liaw
- Division of Hepatology, Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Correspondence: (M.-L.C.); (Y.-F.L.); Tel.: +886-3-3281200-8107 (M.-L.C.); Fax: +886-3-3272-236 (M.-L.C.); +886-3-3282-824 (Y.-F.L.)
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The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients. Viruses 2022; 14:v14081812. [PMID: 36016434 PMCID: PMC9414824 DOI: 10.3390/v14081812] [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: 05/14/2022] [Revised: 07/19/2022] [Accepted: 08/11/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086−4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was <8 IU/mL. Serum HBcrAg and HBV pgRNA levels had no role in predicting HBVr. In conclusion, HBV/HCV coinfected patients are at risk of HBVr after DAA treatment. The baseline HBsAg level was the predictive factor associated with HBVr. Patients with a baseline HBsAg titer < 8 IU/mL can be considered as not having HBVr.
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Determining the Prevalence of Hepatitis Delta Virus, Hepatitis C Virus, and HIV Among Mothers and Infants with Hepatitis B Virus Chronic Infection. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm-127879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Infection with hepatitis B, C, and delta viruses (HBV/HCV/HDV) caused by mother-to-child transmission (MTCT) is still a serious health problem worldwide. Coinfection with HBV/HDV or HCV has been shown to accelerate the progression of chronic HBV infection, resulting in higher mortality. Objectives: The aim of this study was to evaluate the prevalence of anti-HCV, anti-HDV, and anti-HIV antibodies in mothers with chronic HBV infection and their infants. Methods: This cross-sectional study was performed on 100 mothers with chronic HBV (hepatitis B surface antigen-positive [HBsAg+]/hepatitis B core antibody-positive [HBcAb+]) and their infants between 2020 and 2021 in northeastern Iran. The presence of serological markers of HBV, anti-HCV, anti-HDV, and HIV antibodies, as well as the liver function tests, were evaluated in all mothers. The obtained data were analyzed using SPSS version 20, and the level of the statistical significance was set at a P-value < 0.05. Results: The mean age in all individuals was 37.45 ± 17.95 years. In mothers with chronic HBV and their infants, 3%, 11%, and 15% were serologically positive for anti-HCV, HCV/HDV, and anti-HDV, respectively. Also, all participants were serologically negative for anti-HIV. A statistical analysis showed a significant correlation of anti-HDV (95% CI, 0.113 - 0.332) with education, place of residence, and anti-HCV (95% CI, 0.313 - 0.416) in mothers with chronic HBV. The percentages of mothers and infants with simultaneous infection HBV were reported to be 1%, 2%, and 1% when anti-HCV, anti-HDV, and anti-HCV/HDV antibodies were measured, respectively. Conclusions: Intellectual strategies in the diagnosis of HCV, HIV, and HDV in patients with chronic HBV have challenged public and global health, and preventing viral infections in newly born infants is the most effective way to control the HBV/HCV or HDV epidemic.
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Said ZNA, El-Sayed MH. Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings. World J Hepatol 2022; 14:1333-1343. [PMID: 36158908 PMCID: PMC9376770 DOI: 10.4254/wjh.v14.i7.1333] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 01/30/2022] [Accepted: 06/13/2022] [Indexed: 02/06/2023] Open
Abstract
The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.
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Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Microbiology & Immunology, Faculty of Medicine for Girls Al-Azhar University, Cairo, Egypt.
| | - Manal Hamdy El-Sayed
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Ahmed Z, Shetty A, Victor DW, Kodali S. Viral hepatitis: A narrative review of hepatitis A–E. World J Meta-Anal 2022; 10:99-121. [DOI: 10.13105/wjma.v10.i3.99] [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: 02/16/2022] [Revised: 04/27/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis continues to be a major health concern leading to hepatic decompensation ranging from acute hepatitis to cirrhosis and hepatocellular carcinoma. The hepatic and extrahepatic manifestations are not only debilitating but also associated with a significant economic burden. Over the last two decades, the field of virology has made significant breakthroughs leading to a better understanding of the pathophysiology of viral hepatitis, which in turn has led to new therapeutic options. The advent of direct-acting antiviral agents changed the landscape of hepatitis C virus (HCV) therapy, and new drugs are in the pipeline for chronic hepatitis B virus (HBV) treatment. There has also been a significant emphasis on screening and surveillance programs, widespread availability of vaccines, and linkage of care. Despite these efforts, significant gaps persist in care, and there is a pressing need for increased collaboration and teamwork across the globe to achieve a reduction of disease burden and elimination of HBV and HCV.
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Affiliation(s)
- Zunirah Ahmed
- Division of Gastroenterology and Hepatology, Underwood Center for Digestive Disorders, Houston Methodist Hospital, Houston, TX 77030, United States
| | - Akshay Shetty
- Department of Gastroenterology and Hepatology, University of California, Los Angeles, CA 90095, United States
| | - David W Victor
- Department of Hepatology, J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston, TX 77030, United States
| | - Sudha Kodali
- Department of Hepatology, J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston, TX 77030, United States
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Enhanced host immune responses in presence of HCV facilitate HBV clearance in coinfection. Virol Sin 2022; 37:408-417. [PMID: 35523417 PMCID: PMC9243674 DOI: 10.1016/j.virs.2022.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 03/21/2022] [Indexed: 01/21/2023] Open
Abstract
Hepatitis B virus (HBV)/Hepatitis C virus (HCV) coinfection is frequently observed because of the common infection routine. Despite the reciprocal inhibition exerted by HBV and HCV genomes, the coinfection of HBV and HCV is associated with more severe forms of liver diseases. However, the complexity of viral interference and underlying pathological mechanism is still unclarified. With the demonstration of absence of direct viral interplay, some in vitro studies suggest the indirect effects of viral-host interaction on viral dominance outcome. Here, we comprehensively investigated the viral replication and host immune responses which might mediate the interference between viruses in HBV/HCV coinfected Huh7-NTCP cells and immunocompetent HCV human receptors transgenic ICR mice. We found that presence of HCV significantly inhibited HBV replication in vitro and in vivo irrespective of the coinfection order, while HBV did not affect HCV replication. Pathological alteration was coincidently reproduced in coinfected mice. In addition to the participation of innate immune response, an involvement of HCV in up-regulating HBV-specific immune responses was described to facilitate HBV clearance. Our systems partially recapitulate HBV/HCV coinfection and unveil the uncharacterized adaptive anti-viral immune responses during coinfection, which renews the knowledge on the nature of indirect viral interaction during HBV/HCV coinfection.
HCV inhibited HBV replication in Huh7-NTCP cells. HCV suppressed HBV in immunocompetent mice. Induced innate immune response by HCV limited HBV replication. Presence of HCV enhanced HBV specific immune response. Moderate and acute live injure was caused by HBV/HCV coinfection.
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Hanif FM, Majid Z, Luck NH, Tasneem AA, Laeeq SM, Mubarak M. Revolution in the diagnosis and management of hepatitis C virus infection in current era. World J Hepatol 2022; 14:647-669. [PMID: 35646260 PMCID: PMC9099099 DOI: 10.4254/wjh.v14.i4.647] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 02/05/2022] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is a major global public health problem, particularly in developing part of the world. Significant advances have been made in the early diagnosis and treatment of the disease. Its management has been particularly revolutionized during the past two decades. In this review, we summarize the major advances in the diagnostic and management armamentarium for chronic HCV infection. The focus of the present review is on the newer directly acting anti-viral agents, which have revolutionized the management of chronic HCV infection. Management of uncomplicated chronic HCV infection and of specific complications and special at-risk populations of patients will be covered in detail. Despite the advent and approval of highly effective and well tolerable oral agents, still many challenges remain, particularly the affordability, the equitable distribution and access to later drugs. The World Health Organization aims to eliminate viral hepatitis including HCV by 2030 since its poses a major public health threat. There is an urgent need to ensure uniform and early access to diagnostic and therapeutic facilities throughout the world if the later goal has to be realized.
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Affiliation(s)
- Farina M Hanif
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Zain Majid
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Nasir Hassan Luck
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Abbas Ali Tasneem
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Syed Muddasir Laeeq
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
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Sampaio RMA, Dantas PEF, da Silva MIC, da Silva JR, Nunes PF, Gomes AC, Martins LC. Comparison of Patients Monoinfected with Hepatitis C Virus and Coinfected with Hepatitis B/C in the Amazon Region of Brazil. Viruses 2022; 14:v14050856. [PMID: 35632598 PMCID: PMC9147603 DOI: 10.3390/v14050856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/07/2022] [Accepted: 04/16/2022] [Indexed: 11/28/2022] Open
Abstract
Hepatitis B and C are the most common causes of liver disease worldwide. The two infections share many similarities such as a global distribution, the same routes of transmission, hepatotropism, and the ability to cause chronic infection. The consequences of HBV/HCV coinfection are still being studied. The aim of this study is to describe and compare the epidemiological and laboratory profile and the degree of hepatic fibrosis between HCV-monoinfected and HBV/HCV-coinfected patients in the Brazilian Amazon region. ELISA tests were used for the investigation of HBV and HCV serological markers, and molecular tests were used for the detection and genotyping of these viruses. Additionally, transaminases were measured, and a FibroScan was performed for the analysis of liver function. A total of 328 patients with HCV participated in the study. The serological prevalence of HCV/HBV coinfection was 10.77%. A comparison of risk factors between the monoinfected and coinfected groups showed that illicit drug use, sharing sharp instruments, and tattooing/piercing are significantly associated with coinfection. The monoinfected patients had a higher HCV load than the coinfected patients. A viral interaction was observed in this study in which the presence of a coinfection with HBV appears to influence HCV replication. Further studies are necessary to better understand this interaction.
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Affiliation(s)
- Regiane M. A. Sampaio
- Laboratory of Clinical Pathology of Tropical Diseases, Federal University of Pará (UFPA), Tropical Medicine Center (NMT), Umarizal, Belém-Pará 66055-240, Brazil; (R.M.A.S.); (P.E.F.D.); (M.I.C.d.S.); (J.R.d.S.); (P.F.N.)
| | - Paola Eduarda F. Dantas
- Laboratory of Clinical Pathology of Tropical Diseases, Federal University of Pará (UFPA), Tropical Medicine Center (NMT), Umarizal, Belém-Pará 66055-240, Brazil; (R.M.A.S.); (P.E.F.D.); (M.I.C.d.S.); (J.R.d.S.); (P.F.N.)
- Institute of Health Sciences, School of Pharmacy, Federal University of Pará (UFPA), Belém-Pará 66075-110, Brazil
| | - Maria Inês C. da Silva
- Laboratory of Clinical Pathology of Tropical Diseases, Federal University of Pará (UFPA), Tropical Medicine Center (NMT), Umarizal, Belém-Pará 66055-240, Brazil; (R.M.A.S.); (P.E.F.D.); (M.I.C.d.S.); (J.R.d.S.); (P.F.N.)
| | - Joseane R. da Silva
- Laboratory of Clinical Pathology of Tropical Diseases, Federal University of Pará (UFPA), Tropical Medicine Center (NMT), Umarizal, Belém-Pará 66055-240, Brazil; (R.M.A.S.); (P.E.F.D.); (M.I.C.d.S.); (J.R.d.S.); (P.F.N.)
| | - Patrícia F. Nunes
- Laboratory of Clinical Pathology of Tropical Diseases, Federal University of Pará (UFPA), Tropical Medicine Center (NMT), Umarizal, Belém-Pará 66055-240, Brazil; (R.M.A.S.); (P.E.F.D.); (M.I.C.d.S.); (J.R.d.S.); (P.F.N.)
| | - Amanda C. Gomes
- Graduation in Medicine, University Center of the State of Pará (CESUPA), Belém-Pará 66613-903, Brazil;
| | - Luisa C. Martins
- Laboratory of Clinical Pathology of Tropical Diseases, Federal University of Pará (UFPA), Tropical Medicine Center (NMT), Umarizal, Belém-Pará 66055-240, Brazil; (R.M.A.S.); (P.E.F.D.); (M.I.C.d.S.); (J.R.d.S.); (P.F.N.)
- Correspondence: ; Tel.: +55-91-32010986
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Tseng CW, Liu WC, Chen CY, Chang TT, Tseng KC. Impact of HCV viremia on HBV biomarkers in patients coinfected with HBV and HCV. BMC Infect Dis 2022; 22:351. [PMID: 35397497 PMCID: PMC8994285 DOI: 10.1186/s12879-022-07326-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 03/29/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUNDS Hepatitis B virus (HBV) biomarkers reflect the status of HBV infection; however, their role in patients with chronic hepatitis B and C (HBV/HCV) coinfection remains unknown. This study evaluated the characteristics of HBV biomarkers in patients with chronic HBV/HCV coinfection. METHODS One hundred untreated HBV/HCV coinfected patients were enrolled. Active viral infection was defined as viral load above 2000 U/L and 15 U/L for HBV and HCV, respectively. Blood samples were analyzed for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), HBV DNA, and HBV pregenomic RNA (HBV pgRNA). The impact of HCV viremia was also studied. RESULTS A total of 15 patients were HBV-inactive/HCV-inactive, 63 patients were HBV-inactive/HCV-active, 14 patients were HBV-active/HCV-inactive and 8 patients were HBV-active/HCV-active. A total of 71 (71%) patients were active HCV and 22 (22%) were active HBV. HBsAg, HBcrAg, and HBV DNA correlated with each other (P < 0.001). HBV pgRNA displayed no correlations with HBV DNA, HBsAg, or HBcrAg. Patients with HCV viremia had significantly lower HBV DNA, HBsAg, and HBcrAg levels as well as higher HBV pgRNA levels and lower HBV DNA:pgRNA ratio than those without viremia (HBV DNA, P < 0.001; HBsAg, P = 0.015; HBcrAg, P = 0.006; HBV pgRNA, P = 0.073; and HBV DNA:pgRNA ratio, P < 0.001). CONCLUSIONS In patients coinfected with HBV and HCV, HBsAg, HBcrAg, and HBV DNA significantly correlated with each other. HBV and HCV coinfected patients with HCV viremia have lower HBV DNA, HBsAg, HBcrAg, and HBV DNA:pgRNA ratio as well as higher HBV pgRNA levels.
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Affiliation(s)
- Chih-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No 2, Ming-Shen Road, Dalin Town, Chia-Yi County, 622, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No 2, Ming-Shen Road, Dalin Town, Chia-Yi County, 622, Taiwan.
- School of Medicine, Tzuchi University, Hualien, Taiwan.
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Zaongo SD, Ouyang J, Chen Y, Jiao YM, Wu H, Chen Y. HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection. Front Immunol 2022; 13:853346. [PMID: 35432307 PMCID: PMC9010668 DOI: 10.3389/fimmu.2022.853346] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/14/2022] [Indexed: 11/25/2022] Open
Abstract
Human immunodeficiency virus (HIV) selectively targets and destroys the infection-fighting CD4+ T-lymphocytes of the human immune system, and has a life cycle that encompasses binding to certain cells, fusion to that cell, reverse transcription of its genome, integration of its genome into the host cell DNA, replication of the HIV genome, assembly of the HIV virion, and budding and subsequent release of free HIV virions. Once a host is infected with HIV, the host’s ability to competently orchestrate effective and efficient immune responses against various microorganisms, such as viral infections, is significantly disrupted. Without modern antiretroviral therapy (ART), HIV is likely to gradually destroy the cellular immune system, and thus the initial HIV infection will inexorably evolve into acquired immunodeficiency syndrome (AIDS). Generally, HIV infection in a patient has an acute phase, a chronic phase, and an AIDS phase. During these three clinical stages, patients are found with relatively specific levels of viral RNA, develop rather distinctive immune conditions, and display unique clinical manifestations. Convergent research evidence has shown that hepatitis B virus (HBV) co-infection, a common cause of chronic liver disease, is fairly common in HIV-infected individuals. HBV invasion of the liver can be facilitated by HIV infection at each clinical stage of the infection due to a number of contributing factors, including having identical transmission routes, immunological suppression, gut microbiota dysbiosis, poor vaccination immune response to hepatitis B immunization, and drug hepatotoxicity. However, there remains a paucity of research investigation which critically describes the influence of the different HIV clinical stages and their consequences which tend to favor HBV entrenchment in the liver. Herein, we review advances in the understanding of the mechanisms favoring HBV infection at each clinical stage of HIV infection, thus paving the way toward development of potential strategies to reduce the prevalence of HBV co-infection in the HIV-infected population.
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Affiliation(s)
- Silvere D. Zaongo
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Jing Ouyang
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Yaling Chen
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
| | - Yan-Mei Jiao
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hao Wu
- Department of Infectious Diseases, You’an Hospital, Capital Medical University, Beijing, China
| | - Yaokai Chen
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
- Clinical Research Center, Chongqing Public Health Medical Center, Chongqing, China
- *Correspondence: Yaokai Chen,
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Steckstor M, Katsounas A, Canbay A. [Chronic hepatitis B virus infection - silent companion with serious complications]. MMW Fortschr Med 2022; 164:42-50. [PMID: 35359292 DOI: 10.1007/s15006-022-0831-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Affiliation(s)
- Michael Steckstor
- Sektion Gastroenterologie, Hepatologie, interventionelle Endoskopie, Medizinische Universitätsklinik Knappschaftskrankenhaus Bochum GmbH, In der Schornau 23-25, 44892, Bochum, Germany.
| | - Antonios Katsounas
- Sektion Gastroenterologie, Hepatologie, interventionelle Endoskopie, Medizinische Universitätsklinik Knappschaftskrankenhaus Bochum GmbH, In der Schornau 23-25, 44892, Bochum, Germany
| | - Ali Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, In der Schornau 23-25, 44892, Bochum, Germany
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Silva RCMC, Ribeiro JS, da Silva GPD, da Costa LJ, Travassos LH. Autophagy Modulators in Coronavirus Diseases: A Double Strike in Viral Burden and Inflammation. Front Cell Infect Microbiol 2022; 12:845368. [PMID: 35433503 PMCID: PMC9010404 DOI: 10.3389/fcimb.2022.845368] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 03/02/2022] [Indexed: 12/12/2022] Open
Abstract
Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases.
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Affiliation(s)
- Rafael Cardoso Maciel Costa Silva
- Laboratório de Imunoreceptores e Sinalização Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Jhones Sousa Ribeiro
- Laboratório de Imunoreceptores e Sinalização Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gustavo Peixoto Duarte da Silva
- Laboratório de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luciana Jesus da Costa
- Laboratório de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leonardo Holanda Travassos
- Laboratório de Imunoreceptores e Sinalização Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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41
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Ko CC, Ho SY, Liu PH, Hsu CY, Hsia CY, Huang YH, Su CW, Lei HJ, Lee RC, Hou MC, Huo TI. Dual hepatitis B and C-associated hepatocellular carcinoma: clinical characteristics, outcome, and prognostic role of albumin-bilirubin grade. Int J Clin Oncol 2022; 27:739-748. [PMID: 35119581 DOI: 10.1007/s10147-022-02117-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 01/06/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND Albumin-bilirubin (ALBI) grade is used to evaluate the outcome of patients with hepatocellular carcinoma (HCC) which is often associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study aimed to investigate the clinical characteristics, outcome, and prognostic role of ALBI grade in dual HBV/HCV-related HCC. METHODS A total 3341 HCC patients with viral etiology were prospectively enrolled and retrospectively analyzed. Multivariate Cox proportional hazards model was used to identify independent prognostic predictors. RESULTS Of all patients, 2083 (62%), 1068 (32%), and 190 (6%) patients had HBV, HCV, and dual HBV/HCV infection, respectively. The mean age of HBV, HCV, and dual virus group was 60, 68, and 64 years (p < 0.001), respectively. There was no significant survival difference between HBV, HCV, and dual HBV/HCV-related HCC group (p = 0.712). Multivariate Cox analysis in dual HBV/HCV-related HCC showed that multiple tumors [hazard ratio (HR): 1.537, p = 0.044], tumor size >3 cm (HR 2.014, p = 0.044), total tumor volume (TTV) >50 cm3 (HR 3.050, p < 0.001), vascular invasion (HR 3.258, p < 0.001), performance status 2-4 (HR 2.232, p < 0.001), ALBI grade 2-3 (HR 2.177, p < 0.001), and BCLC stage B-D (HR 2.479, p < 0.001) were independent predictors of poor survival. CONCLUSIONS Dual viral infection does not accelerate the development of HCC in HBV carriers. Patient survival is similar between dual HBV/HCV-related HCC and single HBV- or HCV-related HCC group. The ALBI grade is a robust prognostic model in dual virus-related HCC to discriminate patient long-term survival.
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Affiliation(s)
- Chih-Chieh Ko
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shu-Yein Ho
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan, ROC
| | - Po-Hong Liu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Chia-Yang Hsu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,VA Sierra Nevada Health Care System, Reno, NV, USA
| | - Cheng-Yuan Hsia
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Hao-Jan Lei
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Rheun-Chuan Lee
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.,Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan, ROC. .,Institute of Pharmacology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC.
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42
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Toka B, Köksal AŞ, Dertli R, Şirin G, Fidan S, Ülger Y, Harmandar F, Yıldırım AE, Eminler AT, Asil M, Kayar Y, Bıyık M, Kuran S, Uslan MI, Hülagü S. Hepatitis B Reactivation in Patients Treated with Direct-Acting Antivirals for Hepatitis C. Dig Dis 2022; 40:635-643. [PMID: 35108715 DOI: 10.1159/000521298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 12/01/2021] [Indexed: 02/02/2023]
Abstract
INTRODUCTION There is limited research about HBV reactivation (HBVr) due to direct-acting antivirals (DAA) for HCV and most are limited by short duration of follow-up, small sample size, and absence of baseline HBV DNA. We aimed to determine the incidence and clinical course of HBVr in HBsAg and/or anti-HBcIgG positive patients treated with DAA for HCV. METHODS Seven centers retrospectively analyzed their database on HCV patients treated with DAA between 2015 and 2019. Patients with HBV coinfection or resolved HBV infection were enrolled. Serum transaminases, HBsAg, HBeAg, and HBV DNA were followed every 4 weeks during DAA treatment and every 12 weeks 1 year after treatment. Entecavir or tenofovir disoproxil fumarate was started in case of HBVr. The development of HBVr, HBV flare, liver failure, and mortality were determined. RESULTS 852 patients received DAA treatment for HCV. Among them, 35 (4.1%) had HBV coinfection and 246 (28.9%) had resolved HBV infection. 257 patients (53.3% male, mean age: 63 ± 9) constituted the study group (29 with coinfection and 228 with resolved infection). Three patients with coinfection were HBV DNA positive. HBVr developed in 10 (34.5%) HBsAg positive patients, either during (n = 3) or 12-48 weeks after finishing DAA treatment. HBV flare and acute liver failure developed in 1 patient (3.4%), each. Two patients with resolved infection developed HBVr (0.87%) and one (0.44%) had HBV flare. Overall, none of the patients died or underwent liver transplantation due to HBVr. CONCLUSION Patients with HBV/HCV coinfection have a high risk of HBVr after DAA treatment and should receive antiviral prophylaxis. Patients with resolved infection have a low risk of HBVr and can be monitored by serial ALT measurements.
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Affiliation(s)
- Bilal Toka
- Department of Gastroenterology, Health Sciences University Konya Training and Research Hospital, Konya, Turkey
| | - Aydın Şeref Köksal
- Department of Gastroenterology, Sakarya University Faculty of Medicine, Adapazarı, Turkey
| | - Ramazan Dertli
- Department of Gastroenterology, Malatya Education and Research Hospital, Malatya, Turkey
| | - Göktuğ Şirin
- Department of Gastroenterology, Kocaeli University School of Medicine, İzmit, Turkey
| | - Sami Fidan
- Department of Gastroenterology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Yakup Ülger
- Department of Gastroenterology, Cukurova University Faculty of Medicine, Adana, Turkey
| | - Ferda Harmandar
- Department of Gastroenterology, Health Sciences University Antalya Training and Research Hospital, Antalya, Turkey
| | - Abdullah Emre Yıldırım
- Department of Gastroenterology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
| | - Ahmet Tarik Eminler
- Department of Gastroenterology, Sakarya University Faculty of Medicine, Adapazarı, Turkey
| | - Mehmet Asil
- Department of Gastroenterology, Konya Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
| | - Yusuf Kayar
- Department of Gastroenterology, University of Health Sciences, Van Education and Research Hospital, Van, Turkey
| | - Murat Bıyık
- Department of Gastroenterology, Konya Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
| | - Sedef Kuran
- Department of Gastroenterology, Cukurova University Faculty of Medicine, Adana, Turkey
| | - Mustafa Ihsan Uslan
- Department of Gastroenterology, Sakarya University Faculty of Medicine, Adapazarı, Turkey
| | - Sadettin Hülagü
- Department of Gastroenterology, Kocaeli University School of Medicine, İzmit, Turkey
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Malik F, Chulanov V, Pimenov N, Fomicheva A, Lundin R, Levina N, Thorne C, Turkova A, Indolfi G. Treatment and monitoring of children and adolescents with hepatitis C in Russia: Results from a multi-centre survey on policy and practice. J Virus Erad 2022; 8:100063. [PMID: 35198235 PMCID: PMC8844707 DOI: 10.1016/j.jve.2022.100063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/10/2022] [Accepted: 02/01/2022] [Indexed: 11/17/2022] Open
Abstract
Background The Russian Federation has the largest paediatric hepatitis C virus (HCV) disease burden in the World Health Organization European region with an estimated 118,000 children living with HCV viraemia. Direct-acting antivirals (DAAs) have been available for adults in Russia since 2015 and approved for treatment of adolescents aged ≥12 years since 2019. We evaluated DAA availability and uptake for HCV treatment of children and adolescents and clinical practices on diagnosis and management of paediatric HCV in Russia. Methods A survey was distributed to regional ministries of health in 85 administrative regions during September 2020. The survey consisted of 22 items collecting data on: type of facility, aggregate patient characteristics, HCV testing practices for children and pregnant women and HCV management and treatment practices for children. Results Survey responses were received from 37 of the 85 regions in Russia (response rate 44%). 2159 children and adolescents with chronic HCV were in follow-up; 1089 (50%) were female. Of 2080 children with available data on age-groups, 134 (6%) were <3 years, 336 (16%) 3-<6 years, 718 (35%) 6-<12 years and 892 (43%) 12-<18 years. 134 (15%) of 892 adolescents ≥12 years received DAAs, 96 (72%) glecaprevir/pibrentasvir, 26 (19%) sofosbuvir, 8 (6%) daclatasvir and 4 (3%) sofosbuvir/ledipasvir. Conclusions This study provides a baseline of DAA uptake in early stages of rollout for children and adolescents. The use of DAAs for treatment of adolescents in Russia presents a unique opportunity for HCV micro-elimination in this population.
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Krag A, Roskams T, Pinzani M, Mueller S. Diagnostic challenges in patients with alcohol-related liver disease. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:45-57. [PMID: 35042253 DOI: 10.1055/a-1713-4372] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Alcohol is globally the leading risk factor for cirrhosis and is subsumed under the term alcohol-related liver disease (ALD). However, only ca. 10% of people with harmful alcohol consumption (>40 gram alcohol per day) develop cirrhosis, while 15% have normal liver histology. Unfortunately, laboratory parameters and ultrasound hold little value to neither rule-in nor rule out alcohol related liver fibrosis. While several indices with combinations of liver associated markers such as FIB4 seem to be promising, non-invasive test strategies are urgently needed with cut-off's that can be applied to guide clinical decision making. The aims of this review article are to highlight novel developments for the diagnosis of ALD and to identify topics of controversy and potential future directions. In the last 15 years, elastography to measure liver stiffness (LS) has significantly improved our screening strategies for cirrhosis. LS values below 6 kPa are considered as normal and exclude ALD. LS of 8 and 12.5 kPa represent generally accepted cut-off values for F3 and F4 fibrosis. Especially, transient elastography (TE) has been assessed in numerous studies, but similar performance can be obtained with point shear wave elastography, 2 SD shear wave elastography or MR elastography. Important confounders of elevated LS such as inflammation should also be considered and alcohol withdrawal not only improves liver inflammation but also LS. Liver stiffness measurement has signficiantly improved early diagnosis and follow-up of fibrosis in patients with ALD and patients with diagnosed manifest but clinically compensated cirrhosis should undergo further clinical examinations to rule out complications of portal hypertension. In addition, surveillance for the occurrence of hepatocellular carcinoma is recommended in all cirrhotic patients.
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Affiliation(s)
- Aleksander Krag
- Centre for Liver Research/Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Tania Roskams
- Department of Imaging and Pathology, University of Leuven, Leuven, Netherlands
| | - Massimo Pinzani
- University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom of Great Britain and Northern Ireland
| | - Sebastian Mueller
- Centre of Alcohol Research, University of Heidelberg, Heidelberg, Germany.,Department of Medicine, Salem KH, Heidelberg, Germany
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45
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Jacob R, Danta M. Pharmacotherapeutic strategies for hepatitis B and hepatitis C coinfection. Expert Opin Pharmacother 2021; 23:465-472. [PMID: 34937470 DOI: 10.1080/14656566.2021.2019708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Hepatitis B (HBV) and Hepatitis C (HCV) infection place a significant burden on the global health system, with chronic carriage leading to cirrhosis and hepatocellular carcinoma. HBV/HCV coinfection can be seen in highly endemic areas and present a heterogenous group given varying virologic profiles. Coinfected patients have a greater risk of advanced liver disease; hence, diagnosis and early antiviral therapy (AVT) should be a priority. Optimal treatment regimens for coinfected patients remain unknown with differing recommendations, particularly relating to the risk of HBV reactivation whilst on AVT for HCV. AREAS COVERED This article summarizes the available data on HBV/HCV coinfection with regards to epidemiology, virologic interactions, and risk of HBV reactivation. The authors also provide a framework for the assessment and treatment of coinfected patients. EXPERT OPINION There is a moderate risk of HBV reactivation in hepatitis B surface antigen (HBsAg) positive patients undergoing HCV direct-acting antiviral (DAA) treatment; however, clinically significant events are rare. The risk of HBV reactivation in HBsAg negative patients undergoing HCV DAA treatment is negligible. Thus, prophylactic HBV treatment in both groups is not required. The authors recommend close monitoring with HBV treatment if there is evidence of HBV reactivation or elevated alanine aminotransferase levels.
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Affiliation(s)
- Rachael Jacob
- Department of Gastroenterology, St Vincent's Hospital, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, Unsw Sydney, St Vincent's Hospital, Sydney, Australia
| | - Mark Danta
- Department of Gastroenterology, St Vincent's Hospital, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, Unsw Sydney, St Vincent's Hospital, Sydney, Australia
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Grattagliano I, Rossi A, Marconi E, Lapi F, Cricelli C. Determinants of HCV-related complications in Italian primary care patients. Liver Int 2021; 41:2857-2865. [PMID: 34268863 DOI: 10.1111/liv.15017] [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: 12/07/2020] [Revised: 06/01/2021] [Accepted: 07/05/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS This study aimed to assess the demographic and clinical determinants of liver complications in Hepatitis C virus (HCV)-positive patients in primary care setting. METHODS Using the Health Search database, we selected a cohort of patients aged ≥14 diagnosed with HCV between 2002 and 2017. Patients were followed up until the occurrence of cirrhosis and other disease progressions such as oesophageal varices, hepatocellular carcinoma and/or liver transplantation. The candidate determinants for the risk of HCV-related complications included sex, age, smoking status, liver fibrosis (measured by fibrosis 4 index [FIB-4]), infections by the human immunodeficiency virus (HIV), hepatitis B virus (HBV), other forms of hepatitis, abuse of alcohol or illicit substances or drugs, obesity, metabolic syndrome, diabetes mellitus and renal disease. Cox regression was used to test the association between candidate determinants and the outcome. RESULTS The cohort included 8299 HCV-positive patients (50.93% men) with an overall prevalence rate equal to 0.61%. At least one HCV-related complication was found in 12.2% of patients, with a mean time-to-event equal to 8.1 year. Along with male sex and advanced age, a FIB-4 greater than 3.25 and the presence of diabetes were associated with a greater risk of HCV-related complications. CONCLUSION Our study shows that patients with certain demographics and clinical characteristics are more prone to incur in HCV-related complications. The knowledge and early identification of these determinants by GPs may result in reducing disease progression and related healthcare costs through a closer monitoring.
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Affiliation(s)
| | - Alessandro Rossi
- Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Ettore Marconi
- Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Francesco Lapi
- Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Claudio Cricelli
- Italian College of General Practitioners and Primary Care, Florence, Italy
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Sudhindar PD, Wainwright D, Saha S, Howarth R, McCain M, Bury Y, Saha SS, McPherson S, Reeves H, Patel AH, Faulkner GJ, Lunec J, Shukla R. HCV Activates Somatic L1 Retrotransposition-A Potential Hepatocarcinogenesis Pathway. Cancers (Basel) 2021; 13:5079. [PMID: 34680227 PMCID: PMC8533982 DOI: 10.3390/cancers13205079] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/29/2021] [Accepted: 10/07/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance.
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Affiliation(s)
- Praveen D. Sudhindar
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Daniel Wainwright
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Santu Saha
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
| | - Rachel Howarth
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Misti McCain
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
| | - Yvonne Bury
- Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK;
| | - Sweta S. Saha
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
| | - Stuart McPherson
- The Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Heaton NE7 7DN, UK;
| | - Helen Reeves
- Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (S.S.); (M.M.); (S.S.S.); (H.R.)
- The Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Heaton NE7 7DN, UK;
| | - Arvind H. Patel
- MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UK;
| | - Geoffrey J. Faulkner
- Mater Research Institute, University of Queensland, Woolloongabba, QLD 4102, Australia;
- Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
| | - John Lunec
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
| | - Ruchi Shukla
- Newcastle University Centre for Cancer, Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; (P.D.S.); (D.W.); (R.H.); (J.L.)
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Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet 2021; 398:1359-1376. [PMID: 34543610 DOI: 10.1016/s0140-6736(21)01374-x] [Citation(s) in RCA: 710] [Impact Index Per Article: 177.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/02/2021] [Accepted: 06/10/2021] [Indexed: 02/06/2023]
Abstract
Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.
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Affiliation(s)
- Pere Ginès
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institute of Biomedical Investigation August Pi I Sunyer, Barcelona, Spain; Hepatic and Digestive Diseases Biomedical Investigation Center, Madrid, Spain.
| | - Aleksander Krag
- Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Elsa Solà
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Núria Fabrellas
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institute of Biomedical Investigation August Pi I Sunyer, Barcelona, Spain; Hepatic and Digestive Diseases Biomedical Investigation Center, Madrid, Spain
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Cheng Z, Lin P, Cheng N. HBV/HIV Coinfection: Impact on the Development and Clinical Treatment of Liver Diseases. Front Med (Lausanne) 2021; 8:713981. [PMID: 34676223 PMCID: PMC8524435 DOI: 10.3389/fmed.2021.713981] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/23/2021] [Indexed: 02/05/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a common contributor to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Approximately 10% of people with human immunodeficiency virus (HIV) also have chronic HBV co-infection, owing to shared transmission routes. HIV/HBV coinfection accelerates the progression of chronic HBV to cirrhosis, end-stage liver disease, or hepatocellular carcinoma compared to chronic HBV mono-infection. HBV/HIV coinfection alters the natural history of hepatitis B and renders the antiviral treatment more complex. In this report, we conducted a critical review on the epidemiology, natural history, and pathogenesis of liver diseases related to HBV/HIV coinfection. We summarized the novel therapeutic options for these coinfected patients.
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Affiliation(s)
- Zhimeng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Panpan Lin
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Nansheng Cheng
- Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, China
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Implementation of Microelimination Strategy in Eradication of Chronic Hepatitis C Infection in Patients with Hemophilia in the Northern region of Serbia: Is Eradication Possible? Mediterr J Hematol Infect Dis 2021; 13:e2021058. [PMID: 34527210 PMCID: PMC8425382 DOI: 10.4084/mjhid.2021.058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 08/08/2021] [Indexed: 11/17/2022] Open
Abstract
Background Treating HCV in people with hemophilia prevents the development of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) and greatly increases the quality of life for people living with hemophilia. There are many obstacles in reaching the WHO goal of globally eradicating HCV by 2030, mainly its scale, complexity, and implementation. That is why many countries have implemented a micro-elimination strategy: a pragmatic elimination approach in populations with the most efficacy. The aim of this publication is to present the morbidity and mortality rates, the clinical course and treatment outcomes of chronic HCV infection in people with hemophilia (PwH), as well as to show an example of a successfully conducted HCV micro-elimination strategy among people with hemophilia in the Province of Vojvodina. Methods A retrospective, single-center study, performed using medical documentation of all registered PwH in the Clinical Center of Vojvodina from 1994. until 2020. It included 74 hemophilia patients, out of which 32 were patients with hemophilia and chronic HCV infection. Results The mean age of HCV-positive positive people with hemophilia (PwH) was 42.3 years, with the duration of infection of 30–35 years. Co-infection with HIV was observed in 6.25% of cases. Furthermore, 18.75% of patients had spontaneous HCV elimination, and 75% were treated with antiviral protocols. Cirrhosis developed in 21.87% with an incidence rate of 0.6 per 100 patient-years. After treatment with Pegylated IFN and ribavirin (RBV), 58.3% achieved SVR. Side effects of IFN-based therapy regimens were recorded in 20.8% of treated (PwH). In 37.5% PWH, DAA protocols were administered, and these patients achieved SVR. HCV- PwH have a statistically higher mortality rate than non-infected people with hemophilia. Among the HCV-positive PwH, hemophilia-related deaths were 6.25%, and HCV-related deaths were 9.37%. Currently, in the Registry of PwH in Vojvodina, there are no patients with active HCV infection. Conclusion The micro-elimination strategy in the subpopulation of PwH was successfully implemented in Vojvodina by hematologists and infectious diseases specialists in close collaboration.
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