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Jiang FR, Ye XT, Huang HQ, Hu YT, Wang DH, Jiang SW, Wang JL, Hu AR. Effectiveness of sofosbuvir-based treatments for patients with hepatitis C virus genotype 6 infection: a real-world study from East China. Front Med (Lausanne) 2024; 11:1462706. [PMID: 39659627 PMCID: PMC11628284 DOI: 10.3389/fmed.2024.1462706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 11/08/2024] [Indexed: 12/12/2024] Open
Abstract
Background Over the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC). Methods A retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots. Results A total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p < 0.001). Significant improvements were observed in the levels of total bilirubin, ALT, AST, albumin, globulin, albumin/globulin ratio, gamma-glutamyl transferase, alkaline phosphatase, platelet, fibrosis-4 (FIB-4), and aspartate transaminase to platelet ratio index (APRI) between baseline and EOT (p < 0.05). Conclusion SOF-based treatments achieved high virological and biochemical response rates in patients with HCV GT 6 infection.
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Affiliation(s)
- Fan-Rong Jiang
- Department of Pharmacy, Ningbo No. 2 Hospital, Ningbo, China
| | - Xiao-Ting Ye
- Department of Infectious Diseases, Ruian People’s Hospital, Ruian, China
| | - He-Qing Huang
- Department of Infectious Diseases, Zhuji People’s Hospital, Zhuji, China
| | - Yu-Tao Hu
- Department of Infectious Diseases, Xiangshan Hospital Affiliated to Wenzhou Medical University, Ningbo, China
| | - Dong-Hui Wang
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo, China
| | - Su-Wen Jiang
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo, China
| | - Jia-Lan Wang
- Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, China
| | - Ai-Rong Hu
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo, China
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Maekawa S, Takano S, Enomoto N. Risk of hepatocellular carcinoma after viral clearance achieved by DAA treatment. J Formos Med Assoc 2024; 123:1124-1130. [PMID: 38245398 DOI: 10.1016/j.jfma.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/18/2023] [Accepted: 01/09/2024] [Indexed: 01/22/2024] Open
Abstract
The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in a short period. On the other hand, it is gradually being recognized that a significant proportion of patients are still at risk of developing de novo and recurrent hepatocellular carcinoma (HCC), even after HCV elimination, and therefore, elucidation of the risk of de novo and recurrent HCC, investigation of its molecular basis, and construction of accurate prediction models are emerging as new important clinical topics. In this review, we present recent advances regarding these issues.
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Affiliation(s)
- Shinya Maekawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
| | - Shinichi Takano
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuyuki Enomoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
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Bader El Din NG, Farouk S. Exploring the Impact of Different Inflammatory Cytokines on Hepatitis C Virus Infection. J Interferon Cytokine Res 2024; 44:233-243. [PMID: 38563804 DOI: 10.1089/jir.2024.0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024] Open
Abstract
Hepatitis C virus (HCV) infection is a global health concern affecting millions worldwide. Chronic HCV infection often leads to liver inflammation and can progress to cirrhosis and hepatocellular carcinoma. Inflammatory cytokines are crucial in modulating the immune response during HCV infection. This review aims to investigate the impact of different inflammatory cytokines on HCV infection and associated immune responses. This review was conducted to identify relevant studies on the interplay between inflammatory cytokines and HCV infection. The analysis focused on the effects of key inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), and interferon-gamma (IFN-γ), on HCV replication, immune cell activation, and liver inflammation. The findings reveal that these inflammatory cytokines can significantly influence HCV infection and the subsequent immune response. TNF-α, IL-6, and IL-1 have been shown to enhance HCV replication, while IFN-γ exerts antiviral effects by inhibiting viral replication and promoting immune cell-mediated clearance of infected hepatocytes. Moreover, these cytokines contribute to the recruitment and activation of immune cells, such as natural killer cells, T cells, and macrophages, which play critical roles in controlling HCV infection. Understanding the precise mechanisms by which inflammatory cytokines impact HCV infection is crucial for developing more targeted therapeutic strategies. Modulating the levels or activity of specific cytokines may provide opportunities to attenuate HCV replication, reduce liver inflammation, and improve treatment outcomes. In conclusion, this review highlights the significance of inflammatory cytokines in influencing HCV infection and associated immune responses.
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Affiliation(s)
- Noha G Bader El Din
- Microbial Biotechnology Department, Biotechnology Institute, National Research Center, Cairo, Egypt
| | - Sally Farouk
- Microbial Biotechnology Department, Biotechnology Institute, National Research Center, Cairo, Egypt
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Farooq HZ, James M, Abbott J, Oyibo P, Divall P, Choudhry N, Foster GR. Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review. World J Gastrointest Oncol 2024; 16:1596-1612. [PMID: 38660636 PMCID: PMC11037048 DOI: 10.4251/wjgo.v16.i4.1596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/21/2023] [Accepted: 01/23/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
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Affiliation(s)
- Hamzah Z Farooq
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Michael James
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Jane Abbott
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Patrick Oyibo
- School of Health and Psychological Sciences, University of London, London EC1V 0HB, United Kingdom
| | - Pip Divall
- University Hospitals of Leicester Library, University Hospitals of Leicester NHS Trust, Leicester LE3 9QP, United Kingdom
| | - Naheed Choudhry
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Graham R Foster
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
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Chow VYS, Cheung WI. Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong. BMC Gastroenterol 2024; 24:49. [PMID: 38273255 PMCID: PMC10811862 DOI: 10.1186/s12876-023-03099-2] [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: 09/14/2023] [Accepted: 12/14/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND & AIM To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.
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Tang Q, Chen Z, Li H, Zhang L, Peng M, Zeng Y, Liu X, Liu Z, Hu P. Molecular epidemiology of hepatitis C virus genotypes in different geographical regions of Chinese mainland and a phylogenetic analysis. Infect Dis Poverty 2023; 12:66. [PMID: 37430328 DOI: 10.1186/s40249-023-01106-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 05/16/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection remains a major public health problem in Chinese mainland. Investigation of the distribution of genotypes contributed to the prevention, diagnosis and treatment of HCV infection. Therefore, we conducted a study on the distribution of HCV genotypes and phylogenetic analysis to provide an up-to-date understanding of the molecular epidemiology of genotypes in Chinese mainland. METHODS Our retrospective multicenter study enrolled 11,008 samples collected between August 2018 and July 2019 from 29 provinces/municipalities (Beijing, Hebei, Inner Mongolia, Shanxi, Tianjin, Gansu, Ningxia, Shaanxi, Xinjiang, Heilongjiang, Jilin Liaoning, Henan, Hubei Hunan, Anhui, Fujian, Jiangsu, Jiangxi, Shandong, Shanghai Zhejiang, Guangdong, Guangxi, Hainan, Chongqing, Guizhou, Sichuan and Yunnan). Phylogenetic analysis of each subtype was performed to infer the evolutionary relationship of sequences from diverse regions. Two independent samples t tests were used for the comparison of continuous variables, and chi-square tests were used for the comparison of categorical variables. RESULTS Four genotypes (1, 2, 3 and 6) were found, including 14 subtypes. HCV genotype 1 was dominant, accounting for 49.2%, followed by genotypes 2, 3 and 6, accounting for 22.4%, 16.4%, and 11.9%, respectively. Additionally, the top five subtypes were 1b, 2a, 3b, 6a and 3a. Proportions of genotypes 1 and 2 decreased while genotypes 3 and 6 increased over past years (P < 0.001). Genotypes 3 and 6 were concentrated in the population aged 30 to 50 years, and male carriers had lower proportions of subtypes 1b and 2a than female carriers (P < 0.01). Genotypes 3 and 6 were more prevalent in southern parts of Chinese mainland. Nationwide spreads of subtypes 1b and 2a were associated with sequences from northern parts of Chinese mainland, while subtypes 3a, 3b and 6a were associated with sequences from southern parts of Chinese mainland. CONCLUSIONS HCV subtypes 1b and 2a remained the most common subtypes in Chinese mainland, and their proportions decreased over the past years, while the proportions of genotypes 3 and 6 increased. Our investigation provided an accurate epidemiological picture of the circulating viral strains in Chinese mainland, contributing to the prevention, diagnosis and treatment of HCV infection. TRIAL REGISTRATION Not applicable.
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Affiliation(s)
- Qiao Tang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Zhiwei Chen
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Hu Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Li Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Mingli Peng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Yi Zeng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Xiaoqing Liu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China
| | - Zubi Liu
- Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, Zhejiang, China.
- Zhejiang University School of Medicine, Hangzhou, 310000, China.
| | - Peng Hu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing, 400000, China.
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful. J Viral Hepat 2023; 30:148-159. [PMID: 36461645 DOI: 10.1111/jvh.13778] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/07/2022] [Accepted: 11/26/2022] [Indexed: 12/04/2022]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is one of the most serious complications of hepatitis C virus (HCV) infection. Recently, effective antiviral medications have made sustained viral response (SVR) or cure a realistic therapeutic goal for most chronic HCV patients. Given HCV's tumorigenic propensity, it is not surprising that achieving SVR is helpful in preventing HCC. This review briefly summarizes and discusses the existing evidence on the relationship between hepatic carcinogenesis and viral eradication by antivirals, which is mainly divided into interferon-based and direct-acting antivirals (DAAs) based therapy. DAAs have changed the treatment landscape of chronic HCV, reaching high rates of SVR even in patients with advanced cirrhosis, with few contraindications and little side effects. Although some early reports suggested that DAA treatment increased the chance of HCC occurrence, more subsequent observational studies have refuted this theory. The probability of HCC recurrence after HCV eradication appears to be decreasing over time following SVR. Despite virological suppression/cure, individuals with liver cirrhosis are still at risk of HCC and should be monitored. There is a considerable need for markers/scores to predict the long-term risk of HCC in patients with HCV-related liver disease who attain SVR with direct-acting antivirals.
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Affiliation(s)
- Walaa Abdelhamed
- Endemic Medicine Department, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Tian Z, Xu C, Yang P, Lin Z, Wu W, Zhang W, Ding J, Ding R, Zhang X, Dou K. Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma. Front Immunol 2022; 13:984728. [PMID: 36189208 PMCID: PMC9520190 DOI: 10.3389/fimmu.2022.984728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 08/31/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.
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Affiliation(s)
- Zelin Tian
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Chen Xu
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Peijun Yang
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Zhibin Lin
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Wenlong Wu
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Wenjie Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
- Chinese Education Ministry’s Key Laboratory of Western Resources and Modern Biotechnology, Key Laboratory of Biotechnology Shaanxi Province, College of Life Sciences, Northwest University, Xi’an, China
| | - Jian Ding
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Rui Ding
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
| | - Xuan Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
- *Correspondence: Xuan Zhang, ; Kefeng Dou,
| | - Kefeng Dou
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China
- *Correspondence: Xuan Zhang, ; Kefeng Dou,
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Chen JJ, Chiu YC, Lee PL, Tung HD, Chiu HC, Chien SC, Cheng PN. Real-world effectiveness and safety of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for genotype 6 chronic hepatitis C. J Formos Med Assoc 2022; 121:2265-2272. [PMID: 35581112 DOI: 10.1016/j.jfma.2022.04.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 04/25/2022] [Accepted: 04/28/2022] [Indexed: 12/29/2022] Open
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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: 04/02/2022] [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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Sun HY, Cheng CY, Lin CY, Yang CJ, Lee NY, Liou BH, Tang HJ, Liu YM, Lee CY, Chen TC, Huang YC, Lee YT, Tsai MJ, Lu PL, Tsai HC, Wang NC, Hung TC, Cheng SH, Hung CC. Real-world effectiveness of direct-acting antivirals in people living with human immunodeficiency virus and hepatitis C virus genotype 6 infections. World J Gastroenterol 2022; 28:1172-1183. [PMID: 35431505 PMCID: PMC8985481 DOI: 10.3748/wjg.v28.i11.1172] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/26/2021] [Accepted: 01/29/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) genotype 6 (HCV-6) infection is prevalent predominantly in Southeast Asia, and the data on the virologic response of HCV-6 to direct-acting antivirals (DAAs) are sparse in people living with human immunodeficiency virus (HIV) (PLWH).
AIM To assess the virologic response of HCV-6 to DAAs in PLWH.
METHODS From September 2016 to July 2019, PLWH coinfected with HCV-6 initiating DAAs were included. Laboratory investigations were performed at baseline, the end of treatment, and 12 wk off-therapy.
RESULTS Of the 349 PLWH included (mean age 48.9 years, 82.5% men), 80.5% comprised people who inject drugs, 18.1% men who have sex with men, and 1.4% heterosexuals. Coexistent hepatitis B virus infection was present in 12.3% of the included PLWH, liver cirrhosis 10.9%, hepatocellular carcinoma 0.9%, and previous HCV treatment experience 10.9%. The mean baseline plasma HCV RNA was 6.2 log10 IU/mL. Treatment with glecaprevir/pibrentasvir was initiated in 51.9%, sofosbuvir/ledipasvir 41.5%, sofosbuvir/velpatasvir 6.3%, and sofosbuvir/daclatasvir 0.3%. At DAA initiation, antiretroviral therapy containing tenofovir alafenamide was given in 26.4%, tenofovir disoproxil fumarate 34.4%, non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%, non-nucleoside reverse-transcriptase inhibitors 30.4%, protease inhibitors 4.0%, and integrase strand transfer inhibitors 66.8%; 94.8% of the included patients had CD4 counts ≥ 200 cells/mm3 and 96.0% had plasma HIV RNA < 50 copies/mL. Overall, 96.8% achieved undetectable plasma HCV RNA (< 30 IU/mL) at end of treatment; and 92.3% achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis (93.5% in patients receiving sofosbuvir-based DAAs and 91.2% in those receiving glecaprevir/pibrentasvir).
CONCLUSION Similar to the observation made in HIV-negative patients, sustained virologic response 12 wk off-therapy with DAAs is high in PLWH coinfected with HCV-6.
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Affiliation(s)
- Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100225, Taiwan
| | - Chien-Yu Cheng
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330215, Taiwan
- School of Public Health, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Chi-Ying Lin
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin County 640203, Taiwan
| | - Chia-Jui Yang
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City 220216, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Nan-Yao Lee
- Department of Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan
| | - Bo-Huang Liou
- Department of Internal Medicine, Hsinchu MacKay Memorial Hospital, Hsin-Chu 300044, Taiwan
| | - Hung-Jen Tang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan 710402, Taiwan
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Sciences, Tainan 717301, Taiwan
| | - Yuang-Meng Liu
- Department of Internal Medicine, Changhua Christian Hospital, Changhua 500209, Taiwan
| | - Chun-Yuan Lee
- Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Tun-Chieh Chen
- Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801735, Taiwan
| | - Yi-Chia Huang
- Department of Internal Medicine, National Taiwan University Hospital Biomedical Park Branch, Hsin-Chu 302058, Taiwan
| | - Yuan-Ti Lee
- Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402306, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan
| | - Ming-Jui Tsai
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin County 640203, Taiwan
| | - Po-Liang Lu
- Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
| | - Hung-Chin Tsai
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
| | - Ning-Chi Wang
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, Taiwan
| | - Tung-Che Hung
- Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 600566, Taiwan
| | - Shu-Hsing Cheng
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330215, Taiwan
- School of Public Health, Taipei Medical University, Taipei 110301, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100225, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, 404332, Taiwan
- China Medical University, Taichung 406040, Taiwan
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12
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Inukai Y, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia. Ann Hepatol 2022; 27:100545. [PMID: 34571264 DOI: 10.1016/j.aohep.2021.100545] [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: 05/01/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. PATIENTS AND METHODS The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. RESULTS Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. CONCLUSION Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.
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Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine.
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Shuichi Okamoto
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine
| | | | - Nobuaki Suzuki
- Department of Transfusion Medicine, Nagoya University Hospital
| | - Tadashi Matsushita
- Department of Clinical Laboratory, Nagoya University Hospital; Department of Transfusion Medicine, Nagoya University Hospital
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
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13
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Shiha G, Mikhail NNH, Soliman R, Hassan A, Eslam M. Predictive performance and clinical utility of HCC risk scores in chronic hepatitis C: a comparative study. Hepatol Int 2022; 16:159-170. [PMID: 35034266 DOI: 10.1007/s12072-021-10284-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Many HCC risk prediction scores were developed to guide HCC risk stratification and identify CHC patients who either need intensified surveillance or may not require screening. There is a need to compare different scores and their predictive performance in clinical practice. We aim to compare the newest HCC risk scores evaluating their discriminative ability, and clinical utility in a large cohort of CHC patients. PATIENTS AND METHODS The performance of the scores was evaluated in 3075 CHC patients who achieved SVR following DAAs using Log rank, Harrell's c statistic, also tested for HCC-risk stratification and negative predictive values. RESULTS HCC developed in 212 patients within 5 years follow-up. Twelve HCC risk scores were identified and displayed significant Log rank (p ≤ 0.05) except Alonso-Lopez TE-HCC, and Chun scores (p = 0.374, p = 0.053, respectively). Analysis of the remaining ten scores revealed that ADRES, GES pre-post treatment, GES algorithm and Watanabe (post-treatment) scores including dynamics of AFP, were clinically applicable and demonstrated good statistical performance; Log rank analysis < 0.001, Harrell's C statistic (0.66-0.83) and high negative predictive values (94.38-97.65%). In these three scores, the 5 years cumulative IR in low risk groups be very low (0.54-1.6), so screening could be avoided safely in these patients. CONCLUSION ADRES, GES (pre- and post-treatment), GES algorithm and Watanabe (post-treatment) scores seem to offer acceptable HCC-risk predictability and clinical utility in CHC patients. The dynamics of AFP as a component of these scores may explain their high performance when compared to other scores.
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Affiliation(s)
- Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt.
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Nabiel N H Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
- Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
| | - Ayman Hassan
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
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14
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Shi X, Li N. Research Progress in Infectious Agents of Malignant Tumors. PROGRESS IN CHINA EPIDEMIOLOGY 2022:215-241. [DOI: 10.1007/978-981-19-2199-5_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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15
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Elpek GO. Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update. World J Clin Cases 2021; 9:4890-4917. [PMID: 34307543 PMCID: PMC8283590 DOI: 10.12998/wjcc.v9.i19.4890] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 03/14/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of cancer among primary malignant tumors of the liver and is a consequential cause of cancer-related deaths worldwide. In recent years, uncovering the molecular mechanisms involved in the development and behavior of this tumor has led to the identification of multiple potential treatment targets. Despite the vast amount of data on this topic, HCC remains a challenging tumor to treat due to its aggressive behavior and complex molecular profile. Therefore, the number of studies aiming to elucidate the mechanisms involved in both carcinogenesis and tumor progression in HCC continues to increase. In this context, the close association of HCC with viral hepatitis has led to numerous studies focusing on the direct or indirect involvement of viruses in the mechanisms contributing to tumor development and behavior. In line with these efforts, this review was undertaken to highlight the current understanding of the molecular mechanisms by which hepatitis B virus (HBV) and hepatitis C virus (HCV) participate in oncogenesis and tumor progression in HCC and summarize new findings. Cumulative evidence indicates that HBV DNA integration promotes genomic instability, resulting in the overexpression of genes related to cancer development, metastasis, and angiogenesis or inactivation of tumor suppressor genes. In addition, genetic variations in HBV itself, especially preS2 deletions, may play a role in malignant transformation. Epigenetic dysregulation caused by both viruses might also contribute to tumor formation and metastasis by modifying the methylation of DNA and histones or altering the expression of microRNAs. Similarly, viral proteins of both HBV and HCV can affect pathways that are important anticancer targets. The effects of these two viruses on the Hippo-Yap-Taz pathway in HCC development and behavior need to be investigated. Additional, comprehensive studies are also needed to determine these viruses' interaction with integrins, farnesoid X, and the apelin system in malignant transformation and tumor progression. Although the relationship of persistent inflammation caused by HBV and HCV hepatitis with carcinogenesis is well defined, further studies are warranted to decipher the relationship among inflammasomes and viruses in carcinogenesis and elucidate the role of virus-microbiota interactions in HCC development and progression.
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Affiliation(s)
- Gulsum Ozlem Elpek
- Department of Pathology, Akdeniz University Medical School, Antalya 07070, Turkey
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16
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Wei MT, Le MH, Landis C, Trinh H, Wong G, Le A, Zhang J, Cheung R, Nguyen MH. Evaluation of ethnic influence in the application of a hepatocellular carcinoma predictive model for chronic hepatitis C. J Med Virol 2021; 93:6257-6266. [PMID: 34219250 DOI: 10.1002/jmv.27168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 06/26/2021] [Indexed: 01/10/2023]
Abstract
Currently, there is no well-established algorithm predicting hepatocellular carcinoma (HCC) development in untreated hepatitis C virus (HCV) patients. We aimed to validate an algorithm (risk evaluation of viral load elevation and associated liver disease/HCV [REVEAL-HCV]: age, AST, ALT, HCV RNA, HCV genotype, and cirrhosis) developed in Taiwanese patients. We analyzed 1381 (50.1% White, 14.7% Hispanic, 13.8% Asian of diverse origin, and 7.8% African American) adult treatment-naïve HCV patients (no viral co-infection, no HCC within 6 months) at 4 U.S. and one Hong Kong centers (11/1994-10/2017). Compared to the non-Asian cohort, the Asian cohort had a higher percentage of patients in the low-risk group (46.1% vs. 26.1%) and a lower percentage in the high-risk group (12.0% vs. 20.3%, p < 0.01). Overall, 5-year HCC incidence were 1.75%, 4.71%, and 24.4% for low, medium, and high-risk patients, respectively (p < 0.0001). For the overall cohort, area under receiving operating characteristic curve (AUROC) for HCC prediction were 0.83 (95% confidence interval [CI]: 0.72-0.93), 0.82 (95% CI: 0.75-0.88), and 0.84 (95% CI: 0.77-0.89) for 1-, 3-, and 5-year HCC risk, respectively. There was a slightly lower AUROC for Asians compared to the non-Asian cohort at 3 years (0.75 vs. 0.83) and 5 years (0.78 vs. 0.84), though this was not statistically significant. In multivariable analysis, we found male sex, presence of metabolic syndrome as well as the risk score categories to be independently associated with HCC but not ethnicity. The REVEAL-HCV risk score has good validity for both Asian and non-Asian populations. Further studies should consider additional factors, such as sex, metabolic syndrome, and treatment status.
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Affiliation(s)
- Mike T Wei
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Michael H Le
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Charles Landis
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Huy Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | - Grace Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - An Le
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Jian Zhang
- Chinese Hospital, San Francisco, California, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
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17
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Tang Q, Wei L, Liu X, Hu P. Sofosbuvir-Based Therapies Achieved Satisfactory Virological Response in Chinese Individuals with Genotypes 3 and 6 Infections: A Real-World Experience. Infect Drug Resist 2021; 14:2297-2307. [PMID: 34188496 PMCID: PMC8233542 DOI: 10.2147/idr.s312902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/28/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection. METHODS This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12). RESULTS Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred. CONCLUSION Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.
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Affiliation(s)
- Qiao Tang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Li Wei
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Xiaoqing Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
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18
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Jang TY, Liang PC, Liu TW, Wei YJ, Yeh ML, Hsu CT, Hsu PY, Lin YH, Hsieh MH, Huang CI, Huang CF, Lin ZY, Chen SC, Huang JF, Dai CY, Yu ML, Chuang WL. Genotype distribution, clinical characteristics, and racial differences observed in chronic hepatitis C patients in Pingtung, Taiwan. J Chin Med Assoc 2021; 84:255-260. [PMID: 33433134 DOI: 10.1097/jcma.0000000000000478] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The World Health Organization (WHO) set out to eliminate hepatitis C virus (HCV) infection by 2030, a goal Taiwan might achieve before 2025. Using effective direct antiviral agents (DAAs) against chronic hepatitis C (CHC) in Taiwan, the treatment of CHC has been initiated in rural areas. Here, we aimed to elucidate the clinical and virological characteristics of HCV infection, and the treatment efficacy of DAAs in patients from Pingtung county in southern Taiwan. METHODS A total of 152 chronic hepatitis patients treated with DAAs were consecutively enrolled. Baseline characteristics and therapeutic efficacy were evaluated. RESULTS HCV genotype 2 was the most common viral genotype (39.5%), followed by 1b (36.8%), 6 (10.5%), and 1a (9.2%). The sustained virological response (SVR) rate was 98.7%. Hakka patients accounted for 22.4% of the study cohort, of which 14.7% had HCV genotype 6. There were no differences in clinical characteristics between Hakka and non-Hakka patients. Patients with HCV genotype 6 were younger in age (OR/CI: 0.95/0.91-1.00, p = 0.04) and composed of more people who inject drugs (PWID) (OR/CI: 17.6/3.6-85.5, p <0.001), when compared with other patients. CONCLUSION We demonstrated that DAA therapy can achieve a 98.7% SVR rate among CHC patients in Pingtung county of southern Taiwan, with a relative higher prevalence of genotype 6. The most important factor attributed to genotype 6 infection was PWID.
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Affiliation(s)
- Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Ping-Tung, Taiwan, ROC
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ta-Wei Liu
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, ROC
| | - Yu-Ju Wei
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, ROC
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Cheng-Ting Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
- Hepatobiliary Laboratory, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC
- Center For Intelligent Drug Systems and Smart Bio-devices (IDS B) and Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, ROC
- Center for Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
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19
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Ji F, Li J, Liu L, Liang J, Wang X, Liu J, Cai D, Huang R, Zhang J, Wang Q, Nan Y, Li J, Ye Q, Zhang M, Xu Q, Guo F, Zhao C, Liu L, He C, Li Y, Wang W, Kam LY, Tran S, Maeda M, Mizuta A, Li Z, Dang S, Ren W, Zhu Q, Cheung R, Niu J, Xie W, Pan H, Ren H, Wu C, Shang J, Wang F, Nguyen MH. High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b. J Gastroenterol Hepatol 2021; 36:767-774. [PMID: 32840326 DOI: 10.1111/jgh.15192] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/04/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.
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Affiliation(s)
- Fanpu Ji
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jie Li
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Li Liu
- Department of Hepatology, The Third People's Hospital of Kunming, Kunming, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China
| | - Xiaozhong Wang
- Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Junping Liu
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Jiajie Zhang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Qi Wang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Department of Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
| | - Junyi Li
- Department of Hepatology, The Third People's Hospital of Kunming, Kunming, China
| | - Qing Ye
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China
| | - Mingyuan Zhang
- Department of Hepatology, First Hospital of Jilin University, Changchun, China
| | - Qiang Xu
- Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Feng Guo
- Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T. C. M., Shanghai, China
| | - Lingdi Liu
- Department of Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
| | - Caini He
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yu Li
- Department of Infectious Diseases, Shaanxi Provincial People's Hospital, Xi'an, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Leslie Y Kam
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Sally Tran
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Akiko Mizuta
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Zongfang Li
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wanhua Ren
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Veteran Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Junqi Niu
- Department of Hepatology, First Hospital of Jilin University, Changchun, China
| | - Wen Xie
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongying Pan
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Fengmei Wang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
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Risk of hepatocellular carcinoma and fibrosis evolution in hepatitis C patients with severe fibrosis or cirrhosis treated with direct acting antiviral agents. Acta Gastroenterol Belg 2021; 84:25-32. [PMID: 33639690 DOI: 10.51821/84.1.420] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background and study aims Cirrhosis associated to chronic hepatitis C virus (HCV) is one of the leading cause of hepatocellular carcinoma (HCC). The goal of our study was to evaluate first the risk and determinants of HCC and second the evolution of fibrosis in patients treated for HCV with advanced fibrosis stages who achieved sustained virological response (SVR) after direct-acting antivirals (DAA) treatment. Patients and methods We conducted a prospective study on HCV patients with F3 or F4 Metavir fibrosis scores treated with DAA between October 2014 and February 2017. The annual incidence rate for HCC was calculated. We used Cox regression model in order to identify factors associated with HCC. Transient elastography (TE) was performed 12 and 24 months after the end of DAA treatment and non-invasive liver fibrosis biomarkers were performed twice a year during follow-up. Results 143 patients with severe fibrosis or cirrhosis were enrolled in the study. 6 patients developed HCC. The annual incidence rate of HCC in our cohort was 2.7 per 100 patients. Risk factors associated with HCC after DAA were genotype 2 and steatosis. Overall TE values significantly decreased after DAA treatment with a median value prior to treatment of 16.9 kPa to a median of 10.8 kPa 24 months after the end of the treatment. Biological fibrosis scores also significantly decreased following viral eradication. Conclusions DAA treatment does not seem to be associated with HCC promotion after HCV eradication in patients with severe fibrosis stages. DAA-induced SVR is associated with a reduced estimation of fibrosis.
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Muzica CM, Stanciu C, Huiban L, Singeap AM, Sfarti C, Zenovia S, Cojocariu C, Trifan A. Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy: A debate near the end. World J Gastroenterol 2020; 26:6770-6781. [PMID: 33268960 PMCID: PMC7684455 DOI: 10.3748/wjg.v26.i43.6770] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/27/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
Direct acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, achieving high rates (≥ 95%) of sustained virological response, with a good safety profile and high compliance rates. Consequently, it had been expected that viral clearance will reduce morbidity and mortality rates, as well as the risk of hepatocellular carcinoma (HCC). However, since 2016, concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy, which led to an avalanche of studies with contradictory results. We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.
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Affiliation(s)
- Cristina Maria Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
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22
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Abstract
Liver cancer is a global problem and hepatocellular carcinoma (HCC) accounts for about 85% of this cancer. In the USA, etiologies and risk factors for HCC include chronic hepatitis C virus (HCV) infection, diabetes, non-alcoholic steatohepatitis (NASH), obesity, excessive alcohol drinking, exposure to tobacco smoke, and genetic factors. Chronic HCV infection appears to be associated with about 30% of HCC. Chronic HCV infection induces multistep changes in liver, involving metabolic disorders, steatosis, cirrhosis and HCC. Liver carcinogenesis requires initiation of neoplastic clones, and progression to clinically diagnose malignancy. Tumor progression associates with profound exhaustion of tumor-antigen-specific CD8+T cells, and accumulation of PD-1hi CD8+T cells and Tregs. In this chapter, we provide a brief description of HCV and environmental/genetic factors, immune regulation, and highlight mechanisms of HCV associated HCC. We also underscore HCV treatment and recent paradigm of HCC progression, highlighted the current treatment and potential future therapeutic opportunities.
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23
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Mei YY, Chen YM, Wu YK, Zhang XH, Xu WX. Efficacy and Safety of Sofosbuvir-Based Direct-Acting Antiviral Agents Treatment for Patients with Genotype 3/6 Hepatitis C Virus Infection. Can J Gastroenterol Hepatol 2020; 2020:8872120. [PMID: 33194875 PMCID: PMC7648714 DOI: 10.1155/2020/8872120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 10/12/2020] [Accepted: 10/16/2020] [Indexed: 02/07/2023] Open
Abstract
Aims The aim is to evaluate the efficacy and safety of Sofosbuvir- (SOF-) based direct-acting antiviral agents (DAAs) treatment for patients with genotype (GT) 3/6 hepatitis C virus (HCV) infection. Methods Patients infected with GT 3/6 HCV and treated with SOF-based DAAs were enrolled in this prospective, open, single-center, and real-world study. Drugs included Sofosbuvir (SOF), Velpatasvir (VEL), Daclatasvir (DCV), and Ribavirin (RBV). The treatment regimens included SOF + RBV for 24 weeks, SOF + DCV ± RBV for 12/24 weeks, and SOF/VEL ± RBV for 12 weeks. Results A total of 54 patients were included. Age was 42.5 ± 10.4 years. Baseline HCV RNA was 6.29 ± 0.89log10 IU/mL. The numbers of GT 3a, 3b, and 6a patients were 10, 12, and 32, respectively. The numbers of chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis patients were 39, 9, and 6, respectively. In patients with chronic hepatitis C and liver cirrhosis, sustained virological response 12 weeks after the end of treatment (SVR12) was 97.4% and 96.7%, respectively, and rapid virological response (RVR) was 75.0% and 57.1%, respectively. SVR12 of GT3a, GT3b, and GT6a was 100%, 83.3%, and 97%, respectively. ALT normality rate in chronic hepatitis group is higher than that in cirrhosis group at 4 weeks of treatment (89.7% versus 60.0%, p = 0.033) and at 12 weeks after EOT (94.9% versus 66.7%, p = 0.021). The overall incidence rate of adverse events was 44.4%, with fatigue being the most common (13.0%). Conclusion SOF-based DAAs regimen can achieve ideal SVR12 for Chinese patients with both GT3a and GT6a HCV infection. The tolerance and safety of SOF-based DAAs regimen are good.
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Affiliation(s)
- Yong-yu Mei
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - You-ming Chen
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - Yuan-kai Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - Xiao-hong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - Wen-xiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
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Rao H, Xie Q, Shang J, Gao Z, Chen H, Sun Y, Jiang J, Niu J, Zhang L, Wang L, Zhao L, Li J, Yang R, Zhu S, Li R, Wei L. Real-world clinical outcomes among individuals with chronic HCV infection in China: CCgenos study. Antivir Ther 2020; 24:473-483. [PMID: 31566575 DOI: 10.3851/imp3334] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status. METHODS Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression. RESULTS 281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not (P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m2, HCV GT1, platelet count <100×109/l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100×109/l (multivariate Cox regression, P<0.05). CONCLUSIONS Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.
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Affiliation(s)
- Huiying Rao
- Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Beijing, China
| | - Qing Xie
- Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China
| | - Jia Shang
- Henan Provincial People's Hospital, Zhengzhou, China
| | - Zhiliang Gao
- The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hong Chen
- The First Affiliated Hospital of Lanzhou University, Lanzhou, China
| | | | - Jianning Jiang
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Junqi Niu
- The First Hospital of Jilin University, Changchun, China
| | - Lunli Zhang
- The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Lei Wang
- The Second Hospital of Shandong University, Jinan, China
| | - Longfeng Zhao
- The First Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Li
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruifeng Yang
- Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Beijing, China
| | - Siyun Zhu
- Bristol-Myers Squibb, Shanghai, China
| | - Runqin Li
- Bristol-Myers Squibb, Shanghai, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
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D'souza S, Lau KCK, Coffin CS, Patel TR. Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma. World J Gastroenterol 2020; 26:5759-5783. [PMID: 33132633 PMCID: PMC7579760 DOI: 10.3748/wjg.v26.i38.5759] [Citation(s) in RCA: 146] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/03/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.
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Affiliation(s)
- Simmone D'souza
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
| | - Keith CK Lau
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
| | - Carla S Coffin
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
| | - Trushar R Patel
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
- Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, Lethbridge T1K3M4, AB, Canada
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Chen JJ, Lee PL, Chiu HC, Tung HD, Chiu YC, Cheng PN. Real-world effectiveness and safety of ledipasvir/sofosbuvir for genotype 6 chronic hepatitis C patients in Taiwan. J Gastroenterol Hepatol 2020; 35:467-472. [PMID: 31445507 DOI: 10.1111/jgh.14845] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 08/20/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Infection with hepatitis C virus (HCV) genotype (GT) 6 is uncommon in Taiwan, and reports of ledipasvir/sofosbuvir (LDV/SOF) treatment for GT6 are few. This study evaluates the effectiveness and safety of LDV/SOF in treating chronic hepatitis C (CHC) patients with GT6 infection. METHODS CHC patients that were infected with GT6 and treated for 12 weeks with LDV/SOF at two hospitals were enrolled. All patients were followed for an additional 12 weeks after the completion of LDV/SOF treatment. Demographics, HCV viral load, lipid and sugar profiles, and adverse events were recorded and reviewed. RESULTS A total of 127 patients were enrolled. Cirrhosis was found in 68.2% of them. Sustained virological response (SVR), determined by per-protocol analysis, was 97.6%. The SVR rates for cirrhosis versus non-cirrhosis (96.5% vs 100%, P = 0.229) and low versus high viral load (cutoff value: 106 IU/mL; 100% vs 95.6%, P = 0.108) were similar. Following HCV clearance, significantly lower glycosylated hemoglobin was present both in patients with or without diabetes mellitus. Twenty-three (18.1%) patients exhibited adverse events, and each adverse event presented with an incidence of 0.8% to 3.1%. Neuropsychiatric symptoms were the most common. During treatment, 18 patients (14.2%) had alanine aminotransferase elevations consistent with more than grade 1 abnormalities, and none had signs of decompensation. Renal function remained unchanged. CONCLUSION The high SVR and excellent safety of LDV/SOF treatment for GT6 CHC patients suggest that LDV/SOF is a favorable option for treating GT6 CHC patients in Taiwan and Asia.
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Affiliation(s)
- Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Hung-Chih Chiu
- Division of Gastroenterology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Da Tung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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27
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Jasirwan COM, Hasan I, Sulaiman AS, Lesmana CRA, Kurniawan J, Kalista KF, Nababan SH, Gani RA. Risk factors of mortality in the patients with hepatocellular carcinoma: A multicenter study in Indonesia. Curr Probl Cancer 2020; 44:100480. [PMID: 31130257 DOI: 10.1016/j.currproblcancer.2019.05.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 05/07/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is considered a significant burden, and its associated rate of mortality is increasing. Therefore, a population-based cancer registry is considered an essential element in the baseline and comprehensive analysis of the risk factors associated with HCC. We present a multicenter analysis of HCC registry from 2 hospitals in Indonesia. METHODS We performed a follow-up on patients with HCC who were admitted between January 2015 and November 2017 in Cipto Mangunkusumo National General Hospital and Dharmais Hospital, Jakarta, Indonesia. Patient's death was considered the primary outcome of the study. A multivariate analysis was conducted using logistic regression, and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS A total of 282 patients with HCC included. At the last follow-up, 136 (48.2%) patients had died. Mortality rate was not significantly affected by sex, age, etiology, the presence of cirrhosis, nor surveillance of HCC. Based on the Child-Pugh (CP) classification, the OR increased progressively in CP C patients (OR 1.95; 95% CI 1.08-3.53; P = 0.026). The progressive increase was also found in patients with a higher Barcelona Clinic Liver Cancer stage, and the OR for CP C and D patients were 3.50 (95% CI 1.18-10.38; P = 0.024) and 3.41 (95% CI 1.02-11.41; P = 0.047), respectively. Supportive treatment was the most common treatment modality with an OR of 2.17 (95% CI 1.14-4.16; P = 0.019), and it was associated with the mortality rate of HCC. CONCLUSIONS The CP classification, Barcelona Clinic Liver Cancer staging system, and treatment modality might predict mortality in patients with HCC. Moreover, other parameters must be further evaluated.
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MESH Headings
- Adult
- Aged
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/statistics & numerical data
- Female
- Follow-Up Studies
- Hepatectomy/statistics & numerical data
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/pathology
- Hepatitis B, Chronic/therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/therapy
- Hepatitis C, Chronic/virology
- Humans
- Indonesia/epidemiology
- Kaplan-Meier Estimate
- Liver/pathology
- Liver/surgery
- Liver/virology
- Liver Cirrhosis/diagnosis
- Liver Cirrhosis/epidemiology
- Liver Cirrhosis/pathology
- Liver Cirrhosis/therapy
- Liver Neoplasms/diagnosis
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Liver Neoplasms/therapy
- Male
- Middle Aged
- Neoplasm Staging
- Palliative Care/statistics & numerical data
- Radiofrequency Ablation/statistics & numerical data
- Registries/statistics & numerical data
- Retrospective Studies
- Risk Assessment/statistics & numerical data
- Risk Factors
- Severity of Illness Index
- Sorafenib/administration & dosage
- Treatment Outcome
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Affiliation(s)
- Chyntia Olivia Maurine Jasirwan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
| | - Irsan Hasan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Andri Sanityoso Sulaiman
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Cosmas Rinaldi A Lesmana
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Juferdy Kurniawan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Kemal Fariz Kalista
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Saut Horas Nababan
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Rino Alvani Gani
- Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
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Gundala R, Balutia H, Lavanya R, Velayutham R, Roy KK. HCV NS3 serine protease as a drug target for the development of drugs against hepatocellular carcinoma (liver cancer). CANCER-LEADING PROTEASES 2020:243-263. [DOI: 10.1016/b978-0-12-818168-3.00009-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Pronier C, Fontaine H, Dorival C, Carrat F, Pol S, Thibault V. Genetic diversity of genotype 6 HCV infections in France: Epidemiology and consequences for treatment strategy. J Viral Hepat 2019; 26:1276-1283. [PMID: 31273896 DOI: 10.1111/jvh.13171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/28/2019] [Accepted: 05/30/2019] [Indexed: 01/12/2023]
Abstract
Genotype-6 hepatitis C virus (GT6-HCV) exhibits a high genetic diversity. GT6 prevalence, diversity and real-life response to treatment were studied among 14 603 HCV mono-infected patients from the French ANRS-CO22-Hepather cohort. NS3, NS5A and NS5B-HCV genes were amplified and sequenced for all GT6-infections identified in the database. Following phylogenic characterization, resistance-associated substitution polymorphisms were identified. GT6-infected patients (n = 36; 0.25%) did not differ from patients infected with other genotypes with regard to gender, age or liver fibrosis. GT6e was the most prevalent (27.8%), followed by 6a (22.2%), 6q (11.1%) and 6o (8.3%). Each subtype p and xc were found in two patients (5.6%) and subtypes f/h/r and t were each detected in one patient. Four strains (11.1%) clustered with unclassified reference sequences. Concordant genotype determination throughout NS3, NS5A and NS5B-genes is consistent with lack of recombination within this genomic region. All, but three patients were born in Asia, Cambodia (44.4%), Vietnam (38.9%) or Laos (8.3%). GT6a were found in 42.8% of Vietnamese and 6e in 37.5% of Cambodian. GT6q, 6p and 6r were only found in Cambodian patients. Resistance-associated polymorphisms for each DAA classes were identified in baseline sequences. Twenty-seven patients were treated with sofosbuvir-based combinations and 3 with glecaprevir/pibrentasvir. All treated patients, whether naïve or previously treated, achieved a sustained viral response. In conclusion, GT6-infections are uncommon in France and their genetic diversity likely reflects infection within the country of origin. Despite residue variability at DAA resistance-associated positions, sustained viral response was obtained in all treated patients.
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Affiliation(s)
- Charlotte Pronier
- CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Virology Univ Rennes, Rennes, France
| | - Hélène Fontaine
- Hepatology, Hôpital Cochin, AP-HP, Inserm U1223 Institut Pasteur, Paris Descartes University, Paris, France
| | - Céline Dorival
- UMR S 1136-IPLESP, INSERM, Sorbonne University, Paris, France
| | - Fabrice Carrat
- UMR S 1136-IPLESP, INSERM, Sorbonne University, Paris, France
| | - Stanislas Pol
- Hepatology, Hôpital Cochin, AP-HP, Inserm U1223 Institut Pasteur, Paris Descartes University, Paris, France
| | - Vincent Thibault
- CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Virology Univ Rennes, Rennes, France
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30
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Hsu SJ, Yang SS, Kao JH. Risk of hepatocellular carcinoma development after hepatitis C virus eradicated by direct-acting antivirals: Fact or fiction? J Formos Med Assoc 2019; 119:3-11. [PMID: 31627984 DOI: 10.1016/j.jfma.2019.09.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 09/08/2019] [Accepted: 09/18/2019] [Indexed: 12/18/2022] Open
Abstract
Although interferon (IFN)-based therapy has been shown to reduce hepatocellular carcinoma (HCC) development once patients with chronic hepatitis C virus (HCV) infection achieve sustained virologic response (SVR), IFN-based therapy is limited by its multiple adverse effects, non-oral administration, and unsatisfactory SVR rate. In recent years, IFN-free all-oral direct-acting antivirals (DAAs) have replaced IFN-based therapy as the standard of care for HCV infection worldwide because of the higher SVR rate and lower incidence of adverse effects. By using currently approved DAA regimens, HCV can be eradicated in more than 95% of infected hosts, regardless of their disease severity. Since 2016, the risk of de novo occurrence or recurrence of HCC in hepatitis C patients receiving DAAs has been debatable because of a report addressing an unexpected high early tumor recurrence rate. To solve this important, interesting, yet controversial issue, we thus reviewed the latest and most relevant articles on this subject and proposed recommendations to manage such patients for healthcare providers.
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Affiliation(s)
- Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Nursing, Central Taiwan University of Science and Technology, Taichung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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31
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Wong GLH, Chan HLY, Loo CK, Hui YT, Fung JYY, Cheung D, Chung C, Chim AML, Wong VWS. Change in treatment paradigm in people who previously injected drugs with chronic hepatitis C in the era of direct-acting antiviral therapy. J Gastroenterol Hepatol 2019; 34:1641-1647. [PMID: 30707777 DOI: 10.1111/jgh.14622] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 12/28/2018] [Accepted: 01/27/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs but is often undiagnosed. The treatment paradigm for HCV patients has been changing since the availability of direct-acting antiviral (DAA) treatment. We aimed to evaluate the change in treatment paradigm of people who previously injected drugs (ex-PWID) in Hong Kong before and after the availability of DAA. METHOD Consecutive ex-PWID referred from various nongovernmental organizations attended education talks at rehabilitation centers and received point-of-care rapid test for HCV antibody (anti-HCV) at the same session. Subjects tested positive for anti-HCV were invited to undergo further assessment. Afterwards, the patients were referred to the regional hospitals for follow-up and/or treatment. RESULTS Three hundred sixty-five ex-PWID received HCV rapid test; 268 (73.4%) were found to be anti-HCV positive. Among these 268 HCV-positive ex-PWID, 234 (87.3%) attended the assessment session (mean age 52 years, 90.2% male, 45.5% genotype 1b, 41.1% genotype 6a, and median liver stiffness 5.9 kPa); 187 (69.8%) attended follow-up visits at regional hospitals. Seventy-one patients received antiviral treatment for HCV; 69 first received peginterferon and ribavirin (PegIFN/RBV), whereas 10 patients (eight PegIFN/RBV-treated patients) received DAA treatment. Fifty-two patients achieved sustained virologic response at 12 or 24 weeks. Treatment uptake rates of PegIFN/RBV and DAA treatment in the pre-DAA versus post-DAA era were 22.3% versus 48.5% and 0% versus 15.6%, respectively. CONCLUSIONS Targeted screening in ex-PWID is effective in identifying patients with HCV infection in the community. To improve treatment uptake, further improvements in the referral system and treatment regimens are needed.
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Affiliation(s)
- Grace Lai-Hung Wong
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | | | - Yee-Tak Hui
- Department of Medicine, Queen Elizabeth Hospital, Hong Kong
| | | | | | | | - Angel Mei-Ling Chim
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
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Shui J, Liu W, Liang Y, Zhang J, Wan Z, Wang H, Qu X, Tang S. Infection of human pegivirus 2 (HPgV-2) is associated with hepatitis C virus but not hepatitis B virus infection in people who inject drugs. J Gen Virol 2019; 100:968-974. [PMID: 31090532 DOI: 10.1099/jgv.0.001266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We evaluated the association between human pegivirus-2 (HPgV-2) infection and hepatitis C virus (HCV)/hepatitis B virus (HBV) co-infection in 745 plasma samples collected from HCV-positive but human immunodeficiency virus type one (HIV-1)-negative people who inject drugs in Hunan, China. The prevalence of anti-HPgV-2 was 4.43 % (33/745) and, within this, the HCV 6a genotype showed significantly higher prevalence as compared with the HCV non-6a genotypes, 6.29 % (18/286) vs. 1.69 % (4/236), respectively (P=0.009). HPgV-2 RNA was detected in 2.15 % (16/745), and was not significantly different between the HCV 6a and non-6a genotypes, 2.45 % (7/286) vs. 2.54 % (6/236), respectively (P =0.945). HBV single infection did not increase the risk of HPgV-2 infection. Compared with HCV single infection, HCV/HBV co-infection increased the risk of HPgV-2 infection by about three-fold: odds ratio (OR)=3.24 [95 % confidence interval (CI) 1.34-7.82, P=0.014] according to anti-HPgV-2 positivity or OR=3.51 (95 % CI 1.15-10.74, P=0.051) according to HPgV-2 viraemia. HPgV-2 infection did not increase the levels of liver-specific enzymes. Our study provides new findings regarding the association between HPgV-2 and HCV genotypes as well as HCV/HBV co-infection.
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Affiliation(s)
- Jingwei Shui
- 1 Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China
| | - Wenpei Liu
- 2 Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, PR China
| | - Yuanhao Liang
- 1 Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China
| | - Jian Zhang
- 2 Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, PR China
| | - Zhengwei Wan
- 1 Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China
| | - Haiying Wang
- 1 Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China
| | - Xiaowang Qu
- 2 Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, PR China
| | - Shixing Tang
- 1 Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China
- 3 Dermatology Hospital, Southern Medical University, Guangzhou, PR China
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33
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Chen M, Zheng F, Yuan G, Duan X, Rong L, Liu J, Feng S, Wang Z, Wang M, Feng Y, Zhou Q, Li J, Deng K, Li C, Xia J, Rao G, Zhou Y, Fu Y, Li YP. Development of an Infectious Cell Culture System for Hepatitis C Virus Genotype 6a Clinical Isolate Using a Novel Strategy and Its Sensitivity to Direct-Acting Antivirals. Front Microbiol 2018; 9:2950. [PMID: 30564209 PMCID: PMC6288186 DOI: 10.3389/fmicb.2018.02950] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 11/16/2018] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) is classified into seven major genotypes, and genotype 6 is commonly prevalent in Asia, thus reverse genetic system representing genotype 6 isolates in prevalence is required. Here, we developed an infectious clone for a Chinese HCV 6a isolate (CH6a) using a novel strategy. We determined CH6a consensus sequence from patient serum and assembled a CH6a full-length (CH6aFL) cDNA using overlapped PCR product-derived clones that shared the highest homology with the consensus. CH6aFL was non-infectious in hepatoma Huh7.5 cells. Next, we constructed recombinants containing Core-NS5A or 5′UTR-NS5A from CH6a and the remaining sequences from JFH1 (genotype 2a), and both were engineered with 7 mutations identified previously. However, they replicated inefficiently without virus spread in Huh7.5 cells. Addition of adaptive mutations from CH6a Core-NS2 recombinant, with JFH1 5′UTR and NS3-3′UTR, enhanced the viability of Core-NS5A recombinant and acquired replication-enhancing mutations. Combination of 22 mutations in CH6a recombinant with JFH1 5′UTR and 3′UTR (CH6aORF) enabled virus replication and recovered additional four mutations. Adding these four mutations, we generated two efficient recombinants containing 26 mutations (26m), CH6aORF_26m and CH6aFL_26m (designated “CH6acc”), releasing HCV of 104.3–104.5 focus-forming units (FFU)/ml in Huh7.5.1-VISI-mCherry and Huh7.5 cells. Seven newly identified mutations were important for HCV replication, assembly, and release. The CH6aORF_26m virus was inhibited in a dose- and genotype-dependent manner by direct-acting-antivirals targeting NS3/4A, NS5A, and NS5B. The CH6acc enriches the toolbox of HCV culture systems, and the strategy and mutations applied here will facilitate the culture development of other HCV isolates and related viruses.
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Affiliation(s)
- Mingxiao Chen
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Fuxiang Zheng
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Guosheng Yuan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaobing Duan
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Liang Rong
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Junwei Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shengjun Feng
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Ziting Wang
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Min Wang
- Guangzhou Blood Center, Guangzhou, China
| | - Yetong Feng
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Qing Zhou
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Jinqian Li
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Kai Deng
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Chunna Li
- Program of Pathobiology, The Fifth Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China
| | - Jinyu Xia
- Program of Pathobiology, The Fifth Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China
| | - Guirong Rao
- Key Laboratory of Liver Disease, Center of Infectious Diseases, PLA 458 Hospital, Guangzhou, China
| | - Yuanping Zhou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | | | - Yi-Ping Li
- Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Program of Pathobiology, The Fifth Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China
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Paboriboune P, Vial T, Sitbounlang P, Bertani S, Trépo C, Dény P, Babin FX, Steenkeste N, Pineau P, Deharo E. Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients. Virol Sin 2018; 33:295-303. [PMID: 29948850 DOI: 10.1007/s12250-018-0039-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 05/25/2018] [Indexed: 12/29/2022] Open
Abstract
Hepatitis C virus (HCV) is a global health concern, notably in Southeast Asia, and in Laos the presentation of the HCV-induced liver disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients, their infection status (viral load: VL), liver function (aminotransferases) and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6 years for women (13-86 years). The majority of patients (72%) were confirmed positive (VL > 50 IU/mL) and 28% of them had high VL (> 6log10). About 23% of patients had level of aminotransferases indicative of liver damage (> 40 IU/mL); but less than 20% of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff, without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines. However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.
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Affiliation(s)
| | - Thomas Vial
- UMR 152 PHARMADEV, IRD, Université de Toulouse, UPS, 31062, Toulouse, France
| | | | - Stéphane Bertani
- UMR 152 PHARMADEV, IRD, Université de Toulouse, UPS, 31062, Toulouse, France
| | - Christian Trépo
- INSERM U1052, CNRS, UMR 5286, Cancer Research Centre of Lyon, 69008, Lyon, France
| | - Paul Dény
- INSERM U1052, CNRS, UMR 5286, Cancer Research Centre of Lyon, 69008, Lyon, France.,Université Paris 13, Sorbonne Paris Cité, Hôpitaux Universitaires Paris Seine Saint Denis, 93000, Bobigny, France
| | | | | | - Pascal Pineau
- INSERM U993, Institut Pasteur Unité "Organisation Nucléaire et Oncogenèse", 75015, Paris, France
| | - Eric Deharo
- UMR 152 PHARMADEV, IRD, Université de Toulouse, UPS, 31062, Toulouse, France.
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Pham LV, Ramirez S, Gottwein JM, Fahnøe U, Li YP, Pedersen J, Bukh J. HCV Genotype 6a Escape From and Resistance to Velpatasvir, Pibrentasvir, and Sofosbuvir in Robust Infectious Cell Culture Models. Gastroenterology 2018; 154:2194-2208.e12. [PMID: 29454794 DOI: 10.1053/j.gastro.2018.02.017] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 01/24/2018] [Accepted: 02/08/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS Chronic liver diseases caused by hepatitis C virus (HCV) genotype 6 are prevalent in Asia, and millions of people require treatment with direct-acting antiviral regimens, such as NS5A inhibitor velpatasvir combined with the NS5B polymerase inhibitor sofosbuvir. We developed infectious cell culture models of HCV genotype 6a infection to study the effects of these inhibitors and the development of resistance. METHODS The consensus sequences of strains HK2 (MG717925) and HK6a (MG717928), originating from serum of patients with chronic HCV infection, were determined by Sanger sequencing of genomes amplified by reverse-transcription polymerase chain reaction. In vitro noninfectious full-length clones of these 6a strains were subsequently adapted in Huh7.5 cells, primarily by using substitutions identified in JFH1-based Core-NS5A and Core-NS5B genotype 6a recombinants. We studied the efficacy of NS5A and NS5B inhibitors in concentration-response assays. We examined the effects of long-term culture of Huh7.5 cells incubated with velpatasvir and sofosbuvir singly or combined following infection with passaged full-length HK2 or HK6a recombinant viruses. Resistance-associated substitutions (RAS) were identified by Sanger and next-generation sequencing, and their effects on viral fitness and in drug susceptibility were determined in reverse-genetic experiments. RESULTS Adapted full-length HCV genotype 6a recombinants HK2cc and HK6acc had fast propagation kinetics and high infectivity titers. Compared with an HCV genotype 1a recombinant, HCV genotype 6a recombinants of strains HK2 and HK6a were equally sensitive to daclatasvir, elbasvir, velpatasvir, pibrentasvir, and sofosbuvir, but less sensitive to ledipasvir, ombitasvir, and dasabuvir. Long-term exposure of HCV genotype 6a-infected Huh7.5 cells with a combination of velpatasvir and sofosbuvir resulted in clearance of the virus, but the virus escaped the effects of single inhibitors via emergence of the RAS L31V in NS5A (conferring resistance to velpatasvir) and S282T in NS5B (conferring resistance to sofosbuvir). Engineered recombinant genotype 6a viruses with single RAS mediated resistance to velpatasvir or sofosbuvir. HCV genotype 6a viruses with RAS NS5A-L31V or NS5B-S282T were however, able to propagate and escape in Huh7.5 cells exposed to the combination of velpatasvir and sofosbuvir. Further, HCV genotype 6a with NS5A-L31V was able to propagate and escape in the presence of pibrentasvir with emergence of NS5A-L28S, conferring a high level of resistance to this inhibitor. CONCLUSIONS Strains of HCV genotype 6a isolated from patients can be adapted to propagate in cultured cells, permitting studies of the complete life cycle for this important genotype. The combination of velpatasvir and sofosbuvir is required to block propagation of original HCV genotype 6a, which quickly becomes resistant to single inhibitors via the rapid emergence and persistence of RAS. These features of HCV genotype 6a could compromise treatment.
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Affiliation(s)
- Long V Pham
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Santseharay Ramirez
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Judith M Gottwein
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ulrik Fahnøe
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Yi-Ping Li
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jannie Pedersen
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Bukh
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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Axley P, Ahmed Z, Ravi S, Singal AK. Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review. J Clin Transl Hepatol 2018; 6:79-84. [PMID: 29607308 PMCID: PMC5863002 DOI: 10.14218/jcth.2017.00067] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/14/2017] [Accepted: 11/20/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of liver-related death worldwide. Hepatitis C virus (HCV) infection is a major cause of advanced hepatic fibrosis and cirrhosis, with significantly increased risk for development of HCC. The morbidity and mortality of HCV-related HCC remains high, as rates of HCV cirrhosis continue to increase. The long-term goal of antiviral therapy for chronic HCV is to reduce complications from cirrhosis, including HCC. The advent of new direct-acting antivirals with high rates of virological clearance has revolutionized cure of HCV infection. While the development of HCC in HCV patients who achieve disease sustained virologic response is reduced, these patients remain at risk for HCC, particularly those patients with advanced fibrosis and cirrhosis. This review outlines the epidemiology of HCC in chronic HCV, various mechanisms, risk factors and pathophysiology that contribute to this disease process, screening recommendations, and the available data on the impact of new direct-acting antiviral treatment on the development on HCC.
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Affiliation(s)
- Page Axley
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Zunirah Ahmed
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sujan Ravi
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, AL, USA
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37
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Open Label Study of 8 vs. 12 Weeks of Ledipasvir/Sofosbuvir in Genotype 6 Treatment Naïve or Experienced Patients. Am J Gastroenterol 2017; 112:1824-1831. [PMID: 29087397 DOI: 10.1038/ajg.2017.399] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 09/15/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatitis C genotype 6 (HCV-GT6) is one of the most prevalent genotypes in Southeast Asia. Ledipasvir and sofosbuvir fixed-dose combination (LDV/SOF FDC) for 12 weeks has been shown to be effective for multiple HCV genotypes including treatment-naïve HCV-6. Our goal was to examine treatment outcomes in a diverse HCV-6 population. METHODS We prospectively enrolled 60 HCV-GT6 patients at four US centers. Treatment -naïve without cirrhosis patients received open-labeled LDV/SOF FDC orally once a day for 8 weeks; All cirrhotic and/or treatment-experienced patients received LDV/SOF FDC for 12 weeks. The primary outcome was sustained virological response 12 weeks after therapy (SVR12). Secondary outcomes were adverse events (AEs) and/or serious adverse events (SAEs). All patients gave written consent. RESULTS Overall mean age was 58±10 and 58% were male. All patients were Asian and foreign born. The 8-week group included 20 patients (33.3%) and the 12-week included 40 patients (66.7%). There were 2 (5%) patients with decompensation, 3 with liver cancer (7.5%), and 14 with prior treatment (35%) in the 12-week group. SVR12 was 95.0% for the 8-week group (19/20) and 95.0% for the 12-week group (38/40). AEs included fatigue (5%), insomnia (3.3%), headache (1.7%), and nausea (1.7%); however, all patients completed the intended treatment duration. There were two treatment-unrelated SAEs. CONCLUSIONS LDV/SOF FDC for 8 or 12 weeks was safe and effective for patients without cirrhosis or prior treatment failure as well as for patients with cirrhosis and/or prior treatment failure, respectively.
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