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Steffen G, Sperle I, Leendertz SA, Sarma N, Beermann S, Thamm R, Bremer V, Zimmermann R, Dudareva S. The epidemiology of Hepatitis B, C and D in Germany: A scoping review. PLoS One 2020; 15:e0229166. [PMID: 32150561 PMCID: PMC7062254 DOI: 10.1371/journal.pone.0229166] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 01/23/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Germany is considered to be a low prevalence country for viral Hepatitis B, C and D (HBV, HCV, HDV). However, the burden of disease can be high among subpopulations. To meet the world Health Organization (WHO) viral hepatitis (VH) elimination goals, a national strategy was developed by the German government in 2016. We performed a scoping review to understand the baseline epidemiological situation in Germany regarding burden of disease, sequelae and care of HBV, HCV and HDV as a reference to monitor the progress of the national VH elimination and to identify further knowledge gaps and research needs. METHODS The protocol of the systematic review was prepared following the PRISMA statement guidelines for scoping reviews. Relevant search terms were used to identify eligible studies according to the research questions. We searched six online databases for original work published between January 2005 and March 2017. Based on the identified references, a matrix was developed presenting the eligible literature by targeted population group and outcome category. RESULTS 104 publications were eligible for extraction covering 299 outcome results. The population groups targeted in the identified studies included the general population and proxy populations, a range of clinical populations, people who inject drugs, men who have sex with men, healthcare workers, people in prisons and different migrant/mobile populations. Other vulnerable populations (e.g. sex workers) were not targeted. Overall, good evidence was found for HBV and HCV prevalence and HBV vaccination coverage in the GP and proxy populations. Evidence for these outcomes was weaker in populations at risk for VH. For HBV and HCV incidence and mortality, we identified large evidence gaps in all population groups. Outcomes on VH sequelae and care were mainly covered by studies in clinical populations of people living with viral hepatitis. For HDV the overall evidence available was scarce. CONCLUSIONS We created a comprehensive evidence-based overview on the current epidemiological situation of viral hepatitis in Germany. We identified knowledge gaps for further research and established a baseline for future monitoring of viral hepatitis elimination goals in Germany.
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Affiliation(s)
- Gyde Steffen
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
| | - Ida Sperle
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Siv Aina Leendertz
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
| | - Navina Sarma
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Epidemiology and Health Monitoring, Robert Koch Institute Berlin, Berlin, Germany
| | - Sandra Beermann
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany
| | - Roma Thamm
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Department of Infectious Disease Epidemiology, Translational Infrastructure Epidemiology of the German Centre for Infection Research, Robert Koch Institute, Berlin, Germany
- Department of Epidemiology and Health Monitoring, Robert Koch Institute Berlin, Berlin, Germany
| | - Viviane Bremer
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Ruth Zimmermann
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Sandra Dudareva
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
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Bhatia M, Gupta E. Emerging resistance to directly-acting antiviral therapy in treatment of chronic Hepatitis C infection-A brief review of literature. J Family Med Prim Care 2020; 9:531-538. [PMID: 32318377 PMCID: PMC7113931 DOI: 10.4103/jfmpc.jfmpc_943_19] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 12/16/2019] [Accepted: 12/24/2019] [Indexed: 12/13/2022] Open
Abstract
Hepatitis caused by Hepatitis C virus (HCV) is a major cause of chronic liver disease. HCV is transmitted by injection drug use, blood transfusion, hemodialysis, organ transplantation and less frequently sexual intercourse. It has been recognized as a global health problem because of the progression to cirrhosis and hepatocellular carcinoma. Globally, about 170 million people are infected with HCV. Since the discovery of this virus in 1989, the clinical management of chronic hepatitis C infection has undergone a paradigm shift from alpha interferon to direct-acting antiviral (DAA) therapy. However, resistance to many of these antiviral agents has been reported increasingly from all over the globe. This review article focuses on the emerging HCV resistance to DAAs and the relevance of in vitro DAA resistance testing in clinical practice.
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Affiliation(s)
- Mohit Bhatia
- Department of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Ekta Gupta
- Department of Virology, Institute of Liver and Biliary Sciences, New Delhi, India
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3
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Mettikanont P, Bunchorntavakul C, Reddy KR. Systematic review: epidemiology and response to direct-acting antiviral therapy in genotype 6 chronic hepatitis C virus infection. Aliment Pharmacol Ther 2019; 49:492-505. [PMID: 30687952 DOI: 10.1111/apt.15100] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 10/07/2018] [Accepted: 11/27/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) genotype 6 (GT6) is predominantly encountered in Southeast Asia and data on GT6 response to direct-acting antiviral (DAA) therapy are relatively limited. AIM To review the epidemiology and virologic outcome of DAA regimens in HCV GT6 patients. METHODS Electronic literature search of PubMed, EMBASE, and The Cochrane Library databases were conducted. RESULTS Hepatitis C virus genotype 6 is the most genetically diverse, has a prevalence of 19.9%-95.6% in HCV infected patients in Southeast Asia and has been associated with a higher risk of HCC in those with cirrhosis. After an extensive literature review, a total of 20 studies were selected to assess study population and treatment outcomes (total of 938 GT6 patients were included); 12 were clinical trials and eight were observational studies. Sustained virologic response at week 12 (SVR 12) following glecaprevir/pibrentasvir (n = 4; 108 patients), ledipasvir/sofosbuvir (n = 8; 427 patients), sofosbuvir/velpatasvir with or without voxilaprevir (n = 5; 171 patients), sofosbuvir/daclatasvir (n = 3; 172 patients) and sofosbuvir with ribavirin (n = 3; 60 patients) was 98%-100%, 64%-100%, 100%, 88%-94% and 100%, respectively. Failure was mostly in those with cirrhosis and prior treatment experience. DAA therapy was well tolerated and with a serious adverse event rate of <5%. CONCLUSIONS Hepatitis C virus genotype 6 is genetically diverse and is highly prevalent in Asia. While SVR rates have been high, cirrhosis and prior treatment experience marginally compromise response to DAAs. Large scale and exclusive studies in HCV genotype 6 prevalent areas are needed, while the current evidence suggests that DAAs are highly effective and safe.
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Affiliation(s)
| | - Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Singh A, Mankotia DS, Irshad M. A Single-step Multiplex Quantitative Real Time Polymerase Chain Reaction Assay for Hepatitis C Virus Genotypes. J Transl Int Med 2017; 5:34-42. [PMID: 28680837 PMCID: PMC5490960 DOI: 10.1515/jtim-2017-0010] [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] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND AND OBJECTIVES The variable response of hepatitis C virus (HCV) genotypes towards anti-viral treatment requires prior information on the genotype status before planning a therapeutic strategy. Although assays for typing or subtyping of HCV are available, however, a fast and reliable assay system is still needed. The present study was planned to develop a single-step multiplex quantitative real time polymerase chain reaction (qPCR) assay to determine HCV genotypes in patients' sera. METHODS The conserved sequences from 5' UTR, core and NS5b regions of HCV genome were used to design primers and hydrolysis probes labeled with fluorophores. Starting with the standardization of singleplex (qPCR) for each individual HCV-genotype, the experimental conditions were finally optimized for the development of multiplex assay. The sensitivity and specificity were assessed both for singleplex and multiplex assays. Using the template concentration of 102 copies per microliter, the value of quantification cycle (Cq) and the limit of detection (LOD) were also compared for both singleplex and multiplex assays. Similarly, the merit of multiplex assay was also compared with sequence analysis and restriction fragment length polymorphism (RFLP) techniques used for HCV genotyping. In order to find the application of multiplex qPCR assay, it was used for genotyping in a panel of 98 sera positive for HCV RNA after screening a total number of 239 patients with various liver diseases. RESULTS The results demonstrated the presence of genotype 1 in 26 of 98 (26.53%) sera, genotype 3 in 65 (66.32%) and genotype 4 in 2 (2.04%) sera samples, respectively. One sample showed mixed infection of genotype 1 and 3. Five samples could not show the presence of any genotype. Genotypes 2, 5 and 6 could not be detected in these sera samples. The analysis of sera by singleplex and RFLP indicated the results of multiplex to be comparable with singleplex and with clear merit of multiplex over RFLP. In addition, the results of multiplex assay were also found to be comparable with those from sequence analysis. The sensitivity, specificity, Cq values and LOD values were compared and found to be closely associated both for singleplex and multiplex assays. CONCLUSION The multiplex qPCR assay was found to be a fast, specific and sensitive method that can be used as a technique of choice for HCV genotyping in all routine laboratories.
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Affiliation(s)
- Akanksha Singh
- Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Dhananjay Singh Mankotia
- Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Mohammad Irshad
- Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi-110029, India
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Assessment of HCV genotypes in Yunnan Province of Southwest China. Virus Genes 2016; 53:190-196. [PMID: 28012010 DOI: 10.1007/s11262-016-1420-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 12/07/2016] [Indexed: 01/30/2023]
Abstract
Recently, we reported that the frequency of hepatitis C virus (HCV) genotypes and subtypes has rapidly changed among intravenous drug users (IDUs) in Yunnan Province over the last 5 years; this is especially true for subtype 6a which has increased in frequency from 5 to 15%. Here, we assessed 120 HCV-positive plasma samples from the general population (GP). HCV NS5B fragments were amplified and sequenced by PCR. We identified four HCV genotypes (1, 2, 3 and 6) and seven HCV subtypes (1b, 2a, 3a, 3b, 6a, 6n, and 6k) in this population. Genotype 3 was predominant, with a distribution frequency of 0.484, followed by genotype 1 (0.283), genotype 6 (0.133) and genotype 2 (0.100). HCV subtypes 3b (frequency 0.292) and 1b (frequency 0.283) were the most common subtypes. A comparison of the current data with previous results reported for IDUs showed that the distribution frequencies of genotypes 1, 2 and 6 were significantly different between patients in the GP and IDUs (P < 0.05). Among the HCV subtypes, the distribution frequencies of 1b, 2a, 6a, and 6n were significantly different between patients in the GP and IDU groups (P < 0.05). Moreover, Phylogenetic analyses showed that HCV subtype 6a strains isolated from IDUs and the GP were intermixed and not separately clustered. HCV subtype 6a was predominant not only among IDUs but also among those in the GP in the Guangdong Province and Vietnam. However, HCV subtype 6a was predominant only among IDUs and not among those in the GP in the Yunnan and Guangxi Provinces. Our results indicate that the HCV subtype 6a could rapidly spread across China.
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Alberti A, Lacoin L, Morais E, Lefevre C, Abogunrin S, Iheanacho I. Literature review of the distribution of hepatitis C virus genotypes across Europe. J Med Virol 2016; 88:2157-2169. [DOI: 10.1002/jmv.24573] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2016] [Indexed: 12/21/2022]
Affiliation(s)
- Alfredo Alberti
- Department of Molecular Medicine; University of Padova; Padua Italy
| | | | - Edith Morais
- Bristol-Myers Squibb; Rueil-Malmaison; Paris France
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Thong VD, Poovorawan K, Tangkijvanich P, Wasitthankasem R, Vongpunsawad S, Poovorawan Y. Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis. Intervirology 2016; 58:373-381. [PMID: 27010195 DOI: 10.1159/000444366] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 01/31/2016] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). METHODS Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11. RESULTS Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24-week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates. CONCLUSIONS Treatment outcomes for HCV-6 patients are superior to those for HCV-1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome.
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Affiliation(s)
- Vo Duy Thong
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Stahmeyer JT, Krauth C, Bert F, Pfeiffer-Vornkahl H, Alshuth U, Hüppe D, Mauss S, Rossol S. Costs and outcomes of treating chronic hepatitis C patients in routine care - results from a nationwide multicenter trial. J Viral Hepat 2016; 23:105-15. [PMID: 26411532 DOI: 10.1111/jvh.12471] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 08/18/2015] [Indexed: 12/14/2022]
Abstract
Viral hepatitis is a major public health problem affecting millions of people worldwide. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The aim of the study was to assess outcomes and costs of treating patients with chronic hepatitis C in clinical practice in Germany. We carried out a prospective noninterventional study. Information on treatment outcomes, resource utilization and quality of life was provided by 281 physicians throughout Germany. Data of 3708 monoinfected HCV-patients treated between 2008 and 2011 were analysed. Therapy consisted of peginterferon/ribavirin. Mean age of patients was 43.7 years, 60.3% were male and estimated duration of infection was 13.6 years. Predominantly genotype 1 (61.3%) or 3 (28.5%) infections were observed. Sustained viral response (SVR)-rates in most frequently observed genotypes were 49.2% in GT-1 and 61.9% in GT-3 treatment-naive patients (Relapser: GT-1: 35.3% and GT-3: 57.3%; Nonresponder: GT-1: 25.0% and GT-3: 33.3%). Average treatment costs were lowest in treatment-naive patients (€18 965) and higher in patients who failed previous treatments (relapsers: €24 753; nonresponders: €19 511). Differences according to genotype were observed. Average costs per SVR in treatment-naive patients were €44 744 for GT-1 and €22 218 for GT-3. Treatment was associated with a decrease in quality of life; post-treatment quality of life was higher in patients achieving SVR. Our insight on real-life treatment outcomes and costs can serve as a reference for a comparison with other treatments. There is high need for short-term and long-term cost-effectiveness analysis in real-life settings as newly introduced treatment strategies with direct acting antivirals result in high SVR-rates but are more costly.
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Affiliation(s)
- J T Stahmeyer
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School, Hannover, Germany
| | - C Krauth
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School, Hannover, Germany
| | - F Bert
- Department of Internal Medicine, Krankenhaus Nordwest, Frankfurt/M, Germany
| | - H Pfeiffer-Vornkahl
- Factum - Company for Statistics, Scientific Information and Communication mbH, Offenbach, Germany
| | - U Alshuth
- Virology, Roche Pharma AG, Grenzach-Wyhlen, Germany
| | - D Hüppe
- Center of Gastroenterology, Herne, Germany
| | - S Mauss
- Center for HIV and Hepatogastroenterology, Duesseldorf, Germany
| | - S Rossol
- Department of Internal Medicine, Krankenhaus Nordwest, Frankfurt/M, Germany
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Yee BE, Nguyen NH, Zhang B, Lin D, Vutien P, Wong CR, Lutchman GA, Nguyen MH. Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis. BMJ Open Gastroenterol 2015; 2:e000049. [PMID: 26462288 PMCID: PMC4599167 DOI: 10.1136/bmjgast-2015-000049] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 05/31/2015] [Accepted: 06/02/2015] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Pegylated interferon and ribavirin (PEG-IFN+RBV) may be more cost-effective than direct-acting antivirals in resource-limited settings. Current literature suggests sustained virological response (SVR) in hepatitis C virus genotype 4 (HCV-4) is similar to genotype 1 (HCV-1), but worse than 2 and 3 (HCV-2/3). However, few studies have compared treatment response between these groups and these have been limited by small sample sizes with heterogeneous designs. We performed a meta-analysis of SVR predictors in HCV-4 versus HCV-1, 2, and 3 patients treated with PEG-IFN+RBV. METHODS In November 2013, we searched for 'genotype 4' in MEDLINE/EMBASE databases and scientific conferences. We included original articles with ≥25 treatment-naïve HCV-4 and comparisons to HCV-1, 2, and/or 3 patients treated with PEG-IFN+RBV. Random effects modelling was used with heterogeneity defined by Cochrane Q-test (p value<0.10) and I(2) statistic (>50%). RESULTS Five studies with 20 014 patients (899 HCV-4; 12 033 HCV-1; and 7082 HCV-2/3 patients) were included. SVR was 53% (CI 43% to 62%) for HCV-4, 44% (CI 40% to 47%) for HCV-1; and 73% (CI 58% to 84%) for HCV-2/3. SVR with EVR (early virological response) was 75% (CI 61% to 86%) in HCV-4; 64% (CI 46% to 79%) in HCV-1; and 85% (CI 71% to 93%) in HCV-2/3. SVR without EVR was 10% (CI 6% to 17%) for HCV-4; 13% (CI 12% to 15%) for HCV-1; and 23% (CI 16% to 33%) for HCV-2/3. CONCLUSIONS SVR rates are similar in HCV-4 (∼50%) and HCV-1 (∼40%). Lack of EVR is a good stopping rule for HCV-4 and HCV-1 since only 10% subsequently achieve SVR. In HCV-4 patients with EVR, three-quarters can expect to achieve SVR with PEG-IFN+RBV.
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Affiliation(s)
- Brittany E Yee
- School of Medicine, University of California, San Diego, California, USA
| | - Nghia H Nguyen
- School of Medicine, University of California, San Diego, California, USA
| | - Bing Zhang
- School of Medicine, University of California, San Diego, California, USA
| | - Derek Lin
- Department of Internal Medicine, Stanford University Medical Centre, Palo Alto, California, USA
| | - Philip Vutien
- Department of Internal Medicine, Rush University Medical Centre, Chicago, Illinois, USA
| | - Carrie R Wong
- Department of Medicine, North Shore-Long Island Jewish Health System, Manhasset, New York, USA
| | - Glen A Lutchman
- Division of Gastroenterology and Hepatology, Stanford University Medical Centre, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Centre, Palo Alto, California, USA
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Prediction of long-term treatment outcome in HCV following 24 day PEG-IFN alpha-2b therapy using population pharmacokinetic-pharmacodynamic mixture modeling and classification analysis. J Theor Biol 2015; 382:91-8. [PMID: 26163367 DOI: 10.1016/j.jtbi.2015.06.041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 06/23/2015] [Accepted: 06/26/2015] [Indexed: 11/21/2022]
Abstract
Mathematical models have been widely used for understanding the dynamics of the hepatitis C virus (HCV). We propose a method to predict final clinical outcome for 24 HIV-HCV - coinfected patients with the help of a mathematical model based on the first two weeks of PEG-IFN therapy. Applying a pharmacokinetic-pharmacodynamic (PKPD) approach, together with mixture models, to the adapted model of viral dynamics developed by Neumann et al., we have analyzed the influence of PEG-IFN on the kinetics and interaction of target cells, infected cells and virus mRNA. It was found that PEG-IFN pharmacokinetic parameters were similar in sustained virological responders and nonresponders, while the plasma PEG-IFN concentration that decreases HCV production by 50% (EC50) and the rate of infected cell death were different. The treatment outcome depended mainly on the initial viral mRNA concentration and the rate of infected cell death. The population PKPD approach with a mixture model enabled the determination of individual PKPD parameters and showed high sensitivity (93.5%) and specificity (97.4%) for the prediction of the treatment outcome.
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Devaki P, Jencks D, Yee BE, Nguyen MH. Sustained virologic response to standard interferon or pegylated interferon and ribavirin in patients with hepatitis C virus genotype 5: systematic review and meta-analysis of ten studies and 423 patients. Hepatol Int 2015; 9:431-7. [DOI: 10.1007/s12072-015-9635-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Accepted: 04/27/2015] [Indexed: 11/29/2022]
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Papastergiou V, Karatapanis S. Current status and emerging challenges in the treatment of hepatitis C virus genotypes 4 to 6. World J Clin Cases 2015; 3:210-20. [PMID: 25789294 PMCID: PMC4360493 DOI: 10.12998/wjcc.v3.i3.210] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 11/01/2014] [Accepted: 12/29/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminary data, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.
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13
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Nguyen NH, McCormack SA, Vutien P, Yee BE, Devaki P, Jencks D, Nguyen MH. Meta-analysis: superior treatment response in Asian patients with hepatitis C virus genotype 6 versus genotype 1 with pegylated interferon and ribavirin. Intervirology 2015; 58:27-34. [PMID: 25592813 PMCID: PMC4351719 DOI: 10.1159/000369097] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 10/09/2014] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Our goal was to systematically and quantitatively assess treatment response between Asian patients with hepatitis C virus genotype 6 (HCV-6) and hepatitis C virus genotype 1 (HCV-1) treated for 48 weeks with pegylated interferon and ribavirin. METHODS We performed a literature search in MEDLINE and EMBASE for 'genotype 6' in August 2013. Additional abstracts from major international scientific conferences from 2012 to 2013 were reviewed. Studies included were original articles with ≥10 treatment-naïve Asian HCV-6 patients. Exclusion criteria were coinfections with hepatitis B virus, HIV and/or other liver diseases. Heterogeneity was defined as a Cochrane Q test with a p value of 0.10 and an I(2) statistic of >50%. RESULTS of a random-effects model are reported. RESULTS A total of 1,046 (503 HCV-6; 543 HCV-1) patients from 12 studies were included in the analysis. The pooled sustained virologic response (SVR) rate was 80.2% (95% CI 74.3-85.0, Q statistic = 20.87, p < 0.035; I(2) = 47.3%) for HCV-6 and 62.5% (95% CI 41.9-79.4, Q statistic = 52.41, p < 0.001; I(2) = 92.37) for HCV-1 patients. HCV-6 patients had a significantly higher SVR rate compared to HCV-1 patients (odds ratio 2.73, 95% CI 1.69-4.41, p < 0.001). Approximately one fourth of patients without early virologic response (EVR) achieved SVR, regardless of genotype (HCV-1, n = 6/23; HCV-6, n = 4/21). CONCLUSIONS Asian patients with HCV-6 can expect higher SVR rates (∼80%) than HCV-1 patients (∼63%). EVR as a stopping rule is less clear in Asian patients with HCV-6 and HCV-1.
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Affiliation(s)
- Nghia H. Nguyen
- School of Medicine at the University of California, San Diego, CA
| | | | - Philip Vutien
- Department of Medicine, Rush University Medical Center, Chicago, IL
| | - Brittany E. Yee
- School of Medicine at the University of California, San Diego, CA
| | - Pardha Devaki
- Department of Medicine, Detroit Medical Center/Wayne State University, Detroit, MI
| | - David Jencks
- Department of Medicine, Stanford University, Palo Alto, CA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA
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Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin. Eur J Gastroenterol Hepatol 2014; 26:1189-201. [PMID: 25171028 PMCID: PMC4180769 DOI: 10.1097/meg.0000000000000147] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ∼20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive literature search in MEDLINE and EMBASE for 'genotype 4' was conducted in November 2013. Abstracts from American Association for the Study of Liver Diseases, Asian Pacific Study of the Liver, Digestive Disease Week, and European Association for the Study of the Liver in 2012/2013 were reviewed. Inclusion criteria were original studies with at least 25 treatment-naive HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were coinfection with HIV, hepatitis B virus, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (P<0.05) and I statistic (>50%). We included 51 studies (11 102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% [95% confidence interval (CI): 50-55%] (Q-statistic=269.20, P<0.05; I=81.43). On subgroup analyses, SVR was significantly associated with lower viral load, odds ratio (OR) 3.05 (CI: 1.80-5.17, P<0.001); mild fibrosis, OR 3.17 (CI: 2.19-4.59, P<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI: 2.87-7.69, P<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI: 2.31-11.73, P<0.001). HCV-4 patients treated with PEG IFN+RBV may expect SVR rates of ∼50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.
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Meta-analysis of patients with hepatitis C virus genotype 6: 48 weeks with pegylated interferon and ribavirin is superior to 24 weeks. Hepatol Int 2014. [PMID: 26202759 DOI: 10.1007/s12072-014-9570-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis C virus genotype 6 (HCV-6) is common in patients from Southeast Asia and the surrounding regions. Optimal treatment duration for HCV-6 is unknown given the inconclusive evidence from studies with varying methodologies and small sample sizes. METHODS A literature search for 'genotype 6' in MEDLINE and EMBASE in October 2013 produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/liver conferences in 2012/2013. Inclusion criteria were original studies with ≥10 HCV-6 treatment-naïve patients treated with pegylated interferon + ribavirin (PEG IFN+RBV). Exclusion criteria were coinfections with HBV, HIV, other HCV genotypes, and/or other liver diseases. Primary outcome was pooled sustained virologic response (SVR). Heterogeneity was defined by Cochrane Q test (p value of 0.10) and I (2) statistic (≥50 %). RESULTS A total of 13 studies with 641 patients were included. The pooled SVR estimate was 77 % (CI 70-83 %) (Q value = 38.4, p value <0.001, I (2) = 68.7 %) overall, 79 % (CI 73-84 %) for the 48-week group and 59 % (CI 46-70 %) for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 versus 24 weeks, OR 1.9 (CI 1.08-3.2, p = 0.026). In studies with direct comparison of patients with rapid virologic response (RVR), there was no difference in SVR between 48 versus 24 weeks, OR 1.74 (CI 0.65-4.64, p = 0.27). CONCLUSION Hepatitis C virus genotype 6 patients should be treated for 48 weeks, and those who achieve RVR may receive the shorter 24-week treatment duration. The high SVR (~80 %) with 48 weeks of PEG IFN+RBV therapy may be a cost-effective option for HCV-6 patients from resource-poor regions.
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Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G. Hepatitis C virus in the new era: Perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol 2014; 20:9633-9652. [PMID: 25110404 PMCID: PMC4123355 DOI: 10.3748/wjg.v20.i29.9633] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 04/18/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Despite the great successes achieved in the fields of virology and diagnostics, several difficulties affect improvements in hepatitis C virus (HCV) infection control and eradication in the new era. New HCV infections still occur, especially in some of the poorest regions of the world, where HCV is endemic and long-term sequelae have a growing economic and health burden. An HCV vaccine is still no available, despite years of researches and discoveries about the natural history of infection and host-virus interactions: several HCV vaccine candidates have been developed in the last years, targeting different HCV antigens or using alternative delivery systems, but viral variability and adaption ability constitute major challenges for vaccine development. Many new antiviral drugs for HCV therapy are in preclinical or early clinical development, but different limitations affect treatment validity. Treatment predictors are important tools, as they provide some guidance for the management of therapy in patients with chronic HCV infection: in particular, the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets, representing a chance for modulated and personalized treatment management, when also very potent therapies will be available. In the present review we discuss the most recent data about HCV epidemiology, the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis, therapy and predictors of response to it.
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Efficacy and safety of pegylated interferon plus ribavirin therapy for chronic hepatitis C genotype 6: a meta-analysis. PLoS One 2014; 9:e100128. [PMID: 24963667 PMCID: PMC4070902 DOI: 10.1371/journal.pone.0100128] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 05/21/2014] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis C genotype 6 (HCV-6) is prevalent in Southeast Asia. Data on the efficacy of direct-acting antiviral agents in chronic HCV-6 patients is limited and pegylated interferon (Peg-IFN) plus ribavirin (RBV) combination therapy remains standard therapy for those patients. Aim Meta-analysis was performed to assess the efficacy and safety of Peg-IFN plus RBV combination therapy for chronic HCV-6 patients. Methods Relevant studies were found by database search through Medline, Embase, Web of Science and The Cochrane Library. All published clinical trials assessing the efficacy of Peg-IFN plus RBV combination therapy for chronic HCV-6 patients were included. Sustained virological response rate (SVR) was pooled. We performed additional meta-analyses to compare the SVR outcomes of 24 versus 48 weeks of treatment in four head-to-head trials. Another second meta-analysis was also conducted to compare the efficacy of combination Peg-IFN plus RBV therapy in HCV-6 versus HCV-1 patients. Results Thirteen studies met the inclusion criteria. The pooled SVR of all single arms was 75% (95% CI: 0.68–0.81). The SVR of 24 weeks treatment was significantly lower than that at 48 weeks, with a risk difference of −14% (95% CI: −0.25 to −0.02, p = 0.02). However, when restricted to the patients with rapid virological response (RVR), there was no significant effect on SVR between these two treatment groups, with a risk difference of −1% (95% CI: −0.1 to 0.07, p = 0.67). The SVR in HCV-6 patients was significantly higher than that in HCV-1 patients, with a relative risk of 1.35 (95% CI: 1.16–1.57, p<0.001). Side effects were common, but rarely caused treatment discontinuation. Conclusions The results of this meta-analysis suggest that Peg-IFN plus RBV is effective and safe for HCV-6 patients. Shortening treatment seems to be feasible in HCV-6 patients with RVR when tolerance to treatment is poor. However, this decision should be made cautiously.
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Bruggmann P, Berg T, Øvrehus ALH, Moreno C, Brandão Mello CE, Roudot-Thoraval F, Marinho RT, Sherman M, Ryder SD, Sperl J, Akarca U, Balık I, Bihl F, Bilodeau M, Blasco AJ, Buti M, Calinas F, Calleja JL, Cheinquer H, Christensen PB, Clausen M, Coelho HSM, Cornberg M, Cramp ME, Dore GJ, Doss W, Duberg AS, El-Sayed MH, Ergör G, Esmat G, Estes C, Falconer K, Félix J, Ferraz MLG, Ferreira PR, Frankova S, García-Samaniego J, Gerstoft J, Giria JA, Gonçales FL, Gower E, Gschwantler M, Guimarães Pessôa M, Hézode C, Hofer H, Husa P, Idilman R, Kåberg M, Kaita KDE, Kautz A, Kaymakoglu S, Krajden M, Krarup H, Laleman W, Lavanchy D, Lázaro P, Marotta P, Mauss S, Mendes Correa MC, Müllhaupt B, Myers RP, Negro F, Nemecek V, Örmeci N, Parkes J, Peltekian KM, Ramji A, Razavi H, Reis N, Roberts SK, Rosenberg WM, Sarmento-Castro R, Sarrazin C, Semela D, Shiha GE, Sievert W, Stärkel P, Stauber RE, Thompson AJ, Urbanek P, van Thiel I, Van Vlierberghe H, Vandijck D, Vogel W, Waked I, Wedemeyer H, Weis N, Wiegand J, Yosry A, Zekry A, Van Damme P, Aleman S, Hindman SJ. Historical epidemiology of hepatitis C virus (HCV) in selected countries. J Viral Hepat 2014; 21 Suppl 1:5-33. [PMID: 24713004 DOI: 10.1111/jvh.12247] [Citation(s) in RCA: 182] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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Affiliation(s)
- P Bruggmann
- Arud Centres for Addiction Medicine, Zurich, Switzerland
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Wantuck JM, Ahmed A, Nguyen MH. Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6. Aliment Pharmacol Ther 2014; 39:137-47. [PMID: 24251930 DOI: 10.1111/apt.12551] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 06/23/2013] [Accepted: 10/27/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes. AIM To review characteristics of patients infected with HCV genotypes 4, 5 and 6. METHODS PubMed search for 'hepatitis C' AND 'genotype 4', 'hepatitis C' AND 'genotype 5', and 'hepatitis C' AND 'genotype 6' was conducted and relevant articles were reviewed. RESULTS Intravenous drug use is generally responsible for HCV genotype 4 infection in developed countries, but unsafe medical practices cause most cases of HCV genotypes 4, 5 and 6 in endemic countries. The sustained virological response (SVR) rate for patients with HCV genotype 4 who receive pegylated interferon and ribavirin for 48 weeks ranges from 40% to 70% in various small studies. The SVR rate is in the 60-70% range for HCV genotype 5 and 70-80% range for HCV genotype 6 following 48 weeks with pegylated interferon and ribavirin. Preliminary data suggest that a shorter course of 24 weeks of pegylated interferon and ribavirin may be acceptable for HCV genotype 6, with an SVR rate of approximately 70%. CONCLUSIONS The current standard-of-care therapy for HCV genotypes 4, 5 and 6 is pegylated interferon and ribavirin for 48 weeks. A shorter course with 24 weeks of therapy may be considered for patients with genotype 6. Newer and much more effective therapies may be forthcoming in the next few years.
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Affiliation(s)
- J M Wantuck
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
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Bunchorntavakul C, Chavalitdhamrong D, Tanwandee T. Hepatitis C genotype 6: A concise review and response-guided therapy proposal. World J Hepatol 2013; 5:496-504. [PMID: 24073301 PMCID: PMC3782687 DOI: 10.4254/wjh.v5.i9.496] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Revised: 08/05/2013] [Accepted: 08/13/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C genotype 6 is endemic in Southeast Asia [prevalence varies between 10%-60% among all hepatitis C virus (HCV) infection], as well as also sporadically reported outside the area among immigrations. The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5’-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred. Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response (SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4 (RVR). In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic direct-acting antivirals have completed phase II/III studies (sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype 6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR (representing > 70% of patients) are suitable for 24-wk treatment with expected SVR rates > 80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy, and a detectable HCV RNA at week 12 (with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia, wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.
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Seong MH, Kil H, Kim JY, Lee SS, Jang ES, Kim JW, Jeong SH, Kim YS, Bae SH, Lee YJ, Lee HC, Yun H, Kang BH, Kim K. Clinical and epidemiological characteristics of Korean patients with hepatitis C virus genotype 6. Clin Mol Hepatol 2013; 19:45-50. [PMID: 23593609 PMCID: PMC3622855 DOI: 10.3350/cmh.2013.19.1.45] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Revised: 11/20/2012] [Accepted: 12/04/2012] [Indexed: 12/14/2022] Open
Abstract
Background/Aims The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2. Methods This was a prospective, multicenter HCV cohort study that enrolled 1,173 adult patients, of which 930 underwent HCV genotype analysis, and only 9 (1.0%) were found to be infected with genotype 6 HCV. The clinical and epidemiological parameters of the genotypes were compared. Results The patients with genotype 6 HCV had a mean age of 41.5 years, 77.8% were male, and they had no distinct laboratory features. A sustained virologic response (SVR) was observed in four (67%) of six patients who received antiviral therapy. Risk factors such as the presence of a tattoo (n=6, 66.7%), more than three sexual partners (n=3, 33.3%), and injection drug use (n=3, 33.3%) were more common among genotype 6 patients than among genotypes 1 or 2. Conclusions The epidemiology and treatment response of patients infected with genotype 6 HCV differed significantly from those with genotypes 1 or 2, warranting continuous monitoring.
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Affiliation(s)
- Mun Hyuk Seong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Rong X, Lu L, Wang J, Xiong H, Huang J, Chen J, Huang K, Xu R, Wang M, Zhang X, Guo T, Liu Y, Gao G, Fu Y, Nelson KE. Correlation of viral loads with HCV genotypes: higher levels of virus were revealed among blood donors infected with 6a strains. PLoS One 2012; 7:e52467. [PMID: 23285053 PMCID: PMC3524124 DOI: 10.1371/journal.pone.0052467] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2012] [Accepted: 11/13/2012] [Indexed: 12/18/2022] Open
Abstract
Background Both HCV genotypes and viral loads are predictors of therapeutic outcomes among patients treated with α-interferon plus ribavirin; however, such correlation has only been studied for genotypes 1, 2, and 3 but not for genotype 6. Methodology/Findings 299 voluntary blood donors were recruited who were HCV viremic. Their mean age was 31.8; the male/female ratio was 3.82 (225/59). The viral loads of HCV were measured using the COBAS AmpliPrep/COBAS TaqMan test (CAP/CTM) while HCV genotypes were determined by direct sequencing the partial NS5B region. HCV genotypes 1, 2, 3, and 6 were determined in 48.9%, 8.7%, 12.3%, and 30.1% of the donors, respectively, and the levels of mean viral loads in genotype 1 and 6 significantly higher than that of 2 and 3 (P<0.001). As a whole, the viral loads in male donors were higher than in female (P = 0.006). Moreover, the donors' gender and HCV genotypes are independently correlated with the measured viral loads. Conclusion HCV genotype 1 and 6 had significantly higher viral loads than genotype 2 and 3.
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Affiliation(s)
- Xia Rong
- Department of Biochemistry, Medical College of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Ling Lu
- Center for Viral Oncology, University of Kansas Medical Center, Kansas City, Kansas, United States of America
| | - Junzhi Wang
- National Institutes for Food and Drug Control, Beijing, China
| | | | | | - Jinyan Chen
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Ke Huang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Ru Xu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Min Wang
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Xuemei Zhang
- Department of Biochemistry, Medical College of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Tai Guo
- National Institutes for Food and Drug Control, Beijing, China
| | - Yueyue Liu
- National Institutes for Food and Drug Control, Beijing, China
| | - Guoquan Gao
- Department of Biochemistry, Medical College of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yongshui Fu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
- * E-mail:
| | - Kenrad E. Nelson
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
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Wartelle-Bladou C, Le Folgoc G, Bourlière M, Lecomte L. Hepatitis C therapy in non-genotype 1 patients: the near future. J Viral Hepat 2012; 19:525-36. [PMID: 22762136 DOI: 10.1111/j.1365-2893.2012.01634.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Worldwide, 50-70 million subjects are infected with an hepatitis C virus (HCV) genotype 2, 3, 4, 5 or 6. In these patients, the combination of PEG-INF-α and ribavirin remains the currently approved standard-of-care treatment. The identification of different potential therapeutic targets in the HCV life cycle has led to the development of both direct antiviral agents (DAAs) and reagents targeting host functions essential for viral replication. DAAs comprise so far first-generation, second-wave and second-generation NS3/4A protease inhibitors (PIs), nucleos(t)ide (NIs) and non-nucleoside inhibitors of the NS5B RNA polymerase and NS5A complex inhibitors. The main host-protein-directed antiviral agents are cyclophilin inhibitors and silibinin. Whereas the launch of first-generation PIs was a major landmark in the management of genotype 1 (GT-1)-infected patients, these drugs are inactive in most non-GT-1-infected patients. Several of these and other drugs have now reached phase II and even phase III clinical stage development. The purpose of this article is to provide an overview of the clinical results recently reported for the treatment for non-GT-1 HCV infection with a focus on the most promising new compounds and combinations.
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Affiliation(s)
- C Wartelle-Bladou
- Department of Hepatology, Saint Luc Hospital, CHUM, Montréal, Canada
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