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Hepatitis C Virus Subtypes Novel 6g-Related Subtype and 6w Could Be Indigenous in Southern Taiwan with Characteristic Geographic Distribution. Viruses 2021; 13:v13071316. [PMID: 34372521 PMCID: PMC8310057 DOI: 10.3390/v13071316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/02/2021] [Accepted: 07/04/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) genotype (GT) 6 is the most genetically diverse GT and mainly distributed in Southeast Asia and south China but not Taiwan. Earlier studies showed the major HCV GTs in Taiwan were GT 1b and 2 with very rare GT 6 except in injection drug users (IDUs), and subtype 6a is the main GT 6 subtype among IDUs. Recently, we reported a much higher prevalence (18.3%) of GT 6 in Tainan City, southern Taiwan. This study was designed to clarify the subtypes of GT 6 in this endemic area. A total of 3022 (1343 men and 1679 women) HCV viremic patients were enrolled. Subtypes of GT 6 were determined by sequencing of core/E1 and nonstructural protein 5B in 322 of 518 GT 6 patients. The overall GT 6 prevalence rate was 17.1% (518/3022), with higher prevalence districts (>25%) located in northern Tainan. A novel 6g-related subtype is the most prevalent subtype (81.0%), followed by 6w (10.8%), 6a (7.5%), and 6n (0.7%). The high GT 6 prevalence in Tainan was mainly due to a novel 6g-related subtype and 6w. These two subtypes could be indigenous in Tainan with characteristic geographic distribution.
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Huang YC, Huang CF, Liu SF, Liu HY, Yeh ML, Huang CI, Hsieh MH, Dai CY, Chen SC, Yu ML, Chuang WL, Huang JF. The performance of HCV GT plus RUO reagent in determining Hepatitis C virus genotypes in Taiwan. PLoS One 2021; 16:e0246376. [PMID: 33513184 PMCID: PMC7845948 DOI: 10.1371/journal.pone.0246376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 01/15/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV) genotyping is a pivotal tool for epidemiological investigation, guiding management and antiviral treatment. Challenge existed in identifying subtypes of genotype-1 (G-1) and genotype (GT) of indeterminate. Recently, the Abbott HCV RealTime Genotype Plus RUO assay (HCV GT Plus) has been developed aiming to overcome the limitations. We aimed to evaluate the performance of the assay compared with 5' UTR sequencing in clinical samples. MATERIALS AND METHODS Eligible individuals were treatment chronic hepatitis C patients that were enrolled consecutively in a medical center and two core regional hospitals in southern Taiwan from Oct 2017 through Aug 2018. The patient with genotype 1 without subtype and indeterminate previously genotyped by Abbott RealTime HCV GT II will further determinate by Abbott HCV RealTime HCV GT Plus. All of the genotype results were validated by 5' UTR sequencing as a reference standard. RESULTS A total of 100 viremic CHC patients were recruited, including 63 G-1 patients (male: 28), and 37 patients (male: 15) of indeterminate genotyped by Abbott RealTime HCV GT II assay (HCV GT II), respectively. The detection rate of 63 GT1 samples without subtype were 93.7% (59/63), 37 indeterminate samples without genotype were 62.2 (23/37) by HCV GT Plus. 5' UTR sequencing confirmed HCV GT Plus characterized results for 84.7% (50/59) of type1, with 100% (4/4), 82.8 (24/29) and 84.6% (22/26) for 1a, 1b and type6; 65.2% (15/23) of indeterminate with 100% (3/3) and 60% (12/20) for 1b and type 6 samples, respectively. CONCLUSIONS The Abbott RealTime HCV GT Plus RUO assay provides additional performance in GT detection.
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Affiliation(s)
- Ying-Chou Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shu-Fen Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hung-Yin Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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The epidemiological profile of chronic hepatitis C with advanced hepatic fibrosis regarding virus genotype in Taiwan: A nationwide study. J Formos Med Assoc 2021; 120:1444-1451. [PMID: 33516585 DOI: 10.1016/j.jfma.2021.01.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 11/19/2020] [Accepted: 01/06/2021] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND/PURPOSE This study aims at investigating the epidemiological profile of chronic hepatitis C (CHC) regarding hepatitis C virus (HCV) genotype in Taiwan. METHODS A total of 29,087 CHC patients with advanced fibrosis who received direct-acting antivirals (DAAs) therapy under Taiwan's National Health Insurance (NHI) during 2017-2018 were recruited. The HCV genotype distribution and its association with patients' demographic factors including age, gender, and geographical areas were examined. RESULTS The most common genotypes were 1b (59.5%) and 2 (30.1%) with characteristics of older age (mean ± standard deviation (SD): 66.5 ± 10.7 years and 67.3 ± 10.9 years) and female gender predominant (57.1% and 59.4%), which were associated with iatrogenic infection decades ago. Most of patients with genotype 1a (5.9%) and 6 (3.7%) infection were relatively younger (59.2 ± 12.0 years and 60.0 ± 13.8 years) and male gender predominant (59.1% and 61.1%), except Liujia and Liuying districts in southern Taiwan. The youngest group (53.2 ± 11.8 years) and most male gender predominant (74.3%) was genotype 3 (0.37%). These genotypes with characteristics of being younger and male gender predominant were highly related to injection drug use in recent years. The number of genotype 4 patients were extremely rare (n = 25) and efficacy of genotype-4-specific-DAA was significantly poorer than non-genotype-4-specific DAA (P value = 0.0411). CONCLUSION The significant differences in demographic characteristics among CHC patients with different HCV genotypes found in this study suggest HCV genotype was highly associated with transmission pattern and may be used as a reference for HCV control.
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High prevalence of genotype 6 hepatitis C virus infection in Southern Taiwan using Abbott genotype assays. J Formos Med Assoc 2019; 119:413-419. [PMID: 31420113 DOI: 10.1016/j.jfma.2019.07.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 07/12/2019] [Accepted: 07/18/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/PURPOSE Abbott RealTime Genotype II assay can effectively identify hepatitis C virus (HCV) genotypes (GTs), but some GT 6 subtypes might not be differentiated from GT 1. Abbott RealTime Genotype II PLUS and sequencing might be needed to resolve these ambiguous results. Unlike the high prevalence of GT 6 in Southeast Asia, GT 6 had rarely been reported in Taiwan except in intravenous drug abusers (IDU). But the prevalence of GT 6 in Taiwan might be underestimated. We conducted this study to determine the GTs in a HCV endemic area in Southern Taiwan. METHODS A total of 1147 patients with hepatitis C viremia for direct acting antivirals (DAA) treatment at the Chi Mei medical system in Tainan were enrolled. Genotype was determined using a working flow consisted of Abbott GT II, PLUS assays and 5' untranslated region (5' UTR)/core sequencing. RESULTS Among the 1147 patients, 883 (77.0%) obtained GT results by GT II, 264 (23.0%) samples with ambiguous results by GT II assay received further tests, including 194 (73.5%) with PLUS assay and 70 (26.5%) with 5'UTR/core sequencing. Nearly three-quarters (73.5%) of ambiguous results by GT II assay were GT 6. Overall, 18.3% of samples were GT 6. Phylogenetic study of 11 samples of GT 6 subtypes showed 7 (63.6%) were 6 g. CONCLUSION GT 6 is the major factor for high ambiguous rate by GT II. Unexpected high prevalence of GT 6 (18.3%) in Southern Taiwan, especially subtype 6 g, closely related to Indonesian strains, is first reported.
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Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, L'Italien G, Chen CJ, Yuan Y. Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma. Int J Cancer 2014; 135:1119-26. [PMID: 24482200 DOI: 10.1002/ijc.28753] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 12/28/2013] [Accepted: 01/13/2014] [Indexed: 12/12/2022]
Abstract
The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case-control and cohort studies. In the case-control study, 397 HCC cases from medical centers were compared with 410 community-based non-HCC controls. All of them were anti-HCV-seropositive, HBsAg-seronegative with serum HCV RNA levels ≥1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti-HCV-seropositive individuals were followed from 1991 to 2008 to assess the long-term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow-up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64 vs. 55%, p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 × 10(6) IU/mL) than those infected with HCV non-1b (1.2 × 10(6) IU/mL, p < 0.001). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.43 (1.02-2.02). After the long-term follow-up, the cumulative lifetime (30-80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non-1b and 1b, respectively (p < 0.001). The multivariate-adjusted hazard ratio (95% CI) was 1.85 (1.06-3.22) for HCV 1b compared to non-1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
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Gladue DP, Holinka LG, Fernandez-Sainz IJ, Prarat MV, O'Donnell V, Vepkhvadze NG, Lu Z, Risatti GR, Borca MV. Interaction between Core protein of classical swine fever virus with cellular IQGAP1 protein appears essential for virulence in swine. Virology 2011; 412:68-74. [PMID: 21262517 DOI: 10.1016/j.virol.2010.12.060] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Revised: 12/28/2010] [Accepted: 12/30/2010] [Indexed: 02/08/2023]
Abstract
Here we show that IQGAP1, a cellular protein that plays a pivotal role as a regulator of the cytoskeleton interacts with Classical Swine Fever Virus (CSFV) Core protein. Sequence analyses identified residues within CSFV Core protein (designated as areas I, II, III and IV) that maintain homology to regions within the matrix protein of Moloney Murine Leukemia Virus (MMLV) that mediate binding to IQGAP1 [EMBO J, 2006 25:2155]. Alanine-substitution within Core regions I, II, III and IV identified residues that specifically mediate the Core-IQGAP1 interaction. Recombinant CSFV viruses harboring alanine substitutions at residues (207)ATI(209) (I), (210)VVE(212) (II), (213)GVK(215) (III), or (232)GLYHN(236) (IV) have defective growth in primary swine macrophage cultures. In vivo, substitutions of residues in areas I and III yielded viruses that were completely attenuated in swine. These data shows that the interaction of Core with an integral component of cytoskeletal regulation plays a role in the CSFV cycle.
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Affiliation(s)
- D P Gladue
- Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY 11944, USA.
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Gladue DP, Holinka LG, Fernandez-Sainz IJ, Prarat MV, O'Donell V, Vepkhvadze N, Lu Z, Rogers K, Risatti GR, Borca MV. Effects of the interactions of classical swine fever virus Core protein with proteins of the SUMOylation pathway on virulence in swine. Virology 2010; 407:129-36. [PMID: 20800867 DOI: 10.1016/j.virol.2010.07.040] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2010] [Revised: 07/21/2010] [Accepted: 07/26/2010] [Indexed: 02/07/2023]
Abstract
Here we have identified host cell proteins involved with the cellular SUMOylation pathway, SUMO-1 (small ubiquitin-like modifier) and UBC9, a SUMO-1 conjugating enzyme that interact with classical swine fever virus (CSFV) Core protein. Five highly conserved lysine residues (K179, K180, K220, K221, and K246) within the CSFV Core were identified as putative SUMOylation sites. Analysis of these interactions showed that K179A, K180A, and K221A substitutions disrupt Core-SUMO-1 binding, while K220A substitution precludes Core-UBC9 binding. In vivo, Core mutant viruses (K179A, K180A, K220A, K221A) and (K220A, K221A) harboring those substitutions were attenuated in swine. These data shows a clear correlation between the disruption of Core protein binding to SUMO-1 and UBC9 and CSFV attenuation. Overall, these data suggest that the interaction of Core with the cellular SUMOylation pathway plays a significant role in the CSFV growth cycle in vivo.
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Affiliation(s)
- D P Gladue
- Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA.
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Molecular and Contextual Markers of Hepatitis C Virus and Drug Abuse. Mol Diagn Ther 2009. [DOI: 10.1007/bf03256323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J Hepatol 2009; 50:1142-54. [PMID: 19395111 DOI: 10.1016/j.jhep.2009.01.019] [Citation(s) in RCA: 159] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2008] [Revised: 01/13/2009] [Accepted: 01/26/2009] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS Hepatitis C virus (HCV) is a known risk factor for hepatocellular carcinoma (HCC), but whether the risk varies among patients infected with different HCV genotypes is still controversial. We performed a meta-analysis to clarify whether the genotype 1b is associated with a higher risk of HCC than other genotypes. METHODS We identified 57 relevant papers through a literature search to December 2007 but, since age could represent a major confounder, we focused the meta-analysis on the 21 studies presenting age-adjusted risk estimates for HCV genotype 1b vs. other genotypes. We used random-effects models with the DerSimonian-Laird method and assessed heterogeneity between studies and publication bias. RESULTS Patients infected with HCV genotype 1b have almost double the risk to develop HCC than those infected with other genotypes (Relative Risk (95% Confidence Intervals) = 1.78(1.36-2.32)). The pooled risk estimate was somewhat lower when we restricted the analysis to the eight studies conducted in patients with liver cirrhosis (1.60;1.07-2.39) or considering the 36 studies presenting only crude data (1.63;1.30-2.06). In seven studies excluding patients with liver cirrhosis, the RR (95% CI) increased to 2.46(1.69-3.59). CONCLUSIONS This meta-analysis suggests that HCV genotype 1b plays an important role in HCC development, especially in patients with early stage liver disease.
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Shapshak P, Somboonwit C, Drumright LN, Frost SDW, Commins D, Tellinghuisen TL, Scott WK, Duncan R, McCoy C, Page JB, Giunta B, Fernandez F, Singer E, Levine A, Minagar A, Oluwadara O, Kotila T, Chiappelli F, Sinnott JT. Molecular and contextual markers of hepatitis C virus and drug abuse. Mol Diagn Ther 2009; 13:153-79. [PMID: 19650670 PMCID: PMC4447498 DOI: 10.2165/01250444-200913030-00002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The spread of hepatitis C virus (HCV) infection involves a complex interplay of social risks, and molecular factors of both virus and host. Injection drug abuse is the most powerful risk factor for HCV infection, followed by sexual transmission and additional non-injection drug abuse factors such as co-infection with other viruses and barriers to treatment. It is clearly important to understand the wider context in which the factors related to HCV infection occur. This understanding is required for a comprehensive approach leading to the successful prevention, diagnosis, and treatment of HCV. An additional consideration is that current treatments and advanced molecular methods are generally unavailable to socially disadvantaged patients. Thus, the recognition of behavioral/social, viral, and host factors as components of an integrated approach to HCV is important to help this vulnerable group. Equally important, this approach is key to the development of personalized patient treatment - a significant goal in global healthcare. In this review, we discuss recent findings concerning the impact of drug abuse, epidemiology, social behavior, virology, immunopathology, and genetics on HCV infection and the course of disease.
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Affiliation(s)
- Paul Shapshak
- Division of Infectious Disease and International Medicine, Department of Internal Medicine, Tampa General Hospital, University of South Florida, College of Medicine, Tampa, Florida, USA.
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Liu J, Lin H, Liu Y, Lee S, Chen Y, Hung C, Ko W, Huang C, Lai C, Chen Y, Shih Y, Chung H, Liang S, Lin J. Extremely High Prevalence and Genetic Diversity of Hepatitis C Virus Infection among HIV‐Infected Injection Drug Users in Taiwan. Clin Infect Dis 2008; 46:1761-8. [DOI: 10.1086/587992] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Lin TJ, Liao LY, Lin SY, Lin CL, Chang TA. Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C. World J Gastroenterol 2006; 12:4897-901. [PMID: 16937477 PMCID: PMC4087629 DOI: 10.3748/wjg.v12.i30.4897] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CHC).
METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Perls’ stain.
RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patients with mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P = 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002).
CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.
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Affiliation(s)
- Tsung-Jung Lin
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Da-an District Taipei City 106, Taiwan, China
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Lee CM, Lu SN, Hung CH, Tung WC, Wang JH, Tung HD, Chen CH, Hu TH, Changchien CS, Chen WJ. Hepatitis C virus genotypes in southern Taiwan: prevalence and clinical implications. Trans R Soc Trop Med Hyg 2006; 100:767-74. [PMID: 16443243 DOI: 10.1016/j.trstmh.2005.10.008] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2005] [Revised: 10/20/2005] [Accepted: 10/21/2005] [Indexed: 12/20/2022] Open
Abstract
The role of hepatitis C virus (HCV) genotypes in the development of hepatocellular carcinoma (HCC) is still controversial. To determine the distribution and clinical implications of HCV genotypes in southern Taiwan, we analysed 418 patients with chronic HCV infections. HCV genotypes were determined using an HCV Line Probe Assay. The predominant HCV genotype was 1b (45.5%), followed by 2a/2c (30.9%) and 2b (6.9%). The prevalence of genotype 1b in HCC patients (60.3%) was significantly higher than in those with liver cirrhosis (38.7%) and chronic hepatitis (38.7%) (P=0.003 and P<0.001, respectively). Patients with chronic HCV 2a/2c infection had higher alanine aminotransferase (ALT) levels than those with chronic HCV 1b infection (P<0.001). Univariate analysis revealed that disease severity was significantly correlated with older age, genotype 1b, lower ALT levels and lower viral load. Based on multiple logistic regression analysis, after adjusting for age and serum HCV RNA levels, HCV 1b infection was still a significant risk factor for HCC. In conclusion, the predominant genotypes in southern Taiwan were 1b and 2a/2c, and disease severity was associated with genotype 1b.
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Affiliation(s)
- Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
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Chuang WL, Yu ML, Dai CY, Chang WY. Treatment of chronic hepatitis C in southern Taiwan. Intervirology 2006; 49:99-106. [PMID: 16166797 DOI: 10.1159/000087271] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection may lead to cirrhosis and hepatocellular carcinoma. Interferon (IFN)-alpha is effective in the treatment of chronic hepatitis C. The rate of response to IFN is enhanced by increasing the IFN dose. Extending the treatment duration can reduce the relapse rate. Addition of ribavirin to IFN increases the sustained virological response (SVR). Thus, combination therapy with IFN and ribavirin was adopted for the treatment of chronic hepatitis C in Kaohsiung Medical University Hospital in 1998. Approximately 60% of patients receiving IFN/ribavirin therapy gained SVR. IFN 6 million units three times per week combined with daily ribavirin for 6 months achieved SVR more frequently than combination therapy with 3 million units. Factors for SVR in these combination regimens were HCV genotype, viral load and early virological response. Long-term follow-up of patients treated with IFN has shown that SVR might reduce the risk of progression to cirrhosis and hepatocellular carcinoma. Pegylated (peg)-IFN has a longer half-life and better efficacy. Combination therapy with peg-IFN and ribavirin accomplished higher SVR than conventional IFN and ribavirin. A multicenter clinical trial was conducted in Taiwan to compare the efficacy of combination therapy between peg-IFN/ribavirin and conventional IFN/ribavirin for 6 months. SVR was higher in patients receiving peg-IFN and ribavirin, especially in those infected with HCV genotype 1b. Based on the results obtained, the national health insurance started to sponsor the combination therapy in October 2003, with a suggested duration for 6 months. Some small-scale studies in Taiwan have postulated higher SVR for treatment duration of 12 than of 6 months in patients with genotype 1b. Further investigation should be conducted in the near future.
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Affiliation(s)
- Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC
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Lee CM, Hung CH, Lu SN, Wang JH, Tung HD, Huang WS, Chen CL, Chen WJ, Changchien CS. Viral etiology of hepatocellular carcinoma and HCV genotypes in Taiwan. Intervirology 2005; 49:76-81. [PMID: 16166793 DOI: 10.1159/000087267] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas of the world. Hepatitis B virus infection is associated with HCC. However, hepatitis C virus (HCV) infection plays an increasingly more important role in the development of HCC and is associated with more than 30% of HCC in Taiwan. The prevalence of HCV infection and HCV genotypes vary in different geographic areas. The prevalence of HCV genotype 1b (HCV-1b) was around 50-70% in Taiwan and even varied in different townships. In addition to host factors, HCV genotypes may be associated with the development of HCC. In our study, the prevalence of HCV-1b in patients with HCC was significantly higher than in those with liver cirrhosis and chronic hepatitis; multivariate analysis revealed that the disease severity was significantly correlated with age and HCV-1b. Furthermore, HCV-1b was associated with a lower response rate to interferon (IFN) therapy than HCV-2. Our study has demonstrated that mutations in the IFN sensitivity-determining region, spanning nucleotides 2,209-2,248 in the NS5A region, correlate with the sustained virological response to combination therapy with IFN and ribavirin in patients with chronic HCV-1b infection in Taiwan. A third-generation enzyme immunoassay for antibody to HCV can be used to predict viremia and monitor the virological response.
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Affiliation(s)
- Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan (ROC).
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16
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Fan X, Lang DM, Xu Y, Lyra AC, Yusim K, Everhart JE, Korber BTM, Perelson AS, Di Bisceglie AM. Liver transplantation with hepatitis C virus-infected graft: interaction between donor and recipient viral strains. Hepatology 2003; 38:25-33. [PMID: 12829983 DOI: 10.1053/jhep.2003.50264] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV. Because of the lack of tissue culture systems and small animal models supporting efficient HCV replication, we explored these issues in the setting of liver transplantation where both recipient and donor were infected with different HCV strains and therefore represent a distinct model for HCV superinfection. Serial serum samples collected at multiple time points were obtained from 6 HCV-positive liver donor/recipient pairs from the National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. At each time point, HCV genotype was determined by both restriction fragment length polymorphism analysis and phylogenetic analysis. Furthermore, we selectively sequenced 3 full-length HCV isolates at the earliest time points after liver transplantation, including both 5' and 3' ends. Detailed genetic analyses showed that only one strain of HCV could be identified at each time point in all 6 cases. Recipient HCV strains took over in 3 cases, whereas donor HCV strains dominated after liver transplantation in the remaining 3 cases. In conclusion, in all 6 cases studied, there was no genetic recombination detected among HCV quasispecies or between donor and recipient HCV strains.
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Affiliation(s)
- Xiaofeng Fan
- Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO, USA
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17
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Yu ML, Chuang WL, Chen SC, Dai CY, Hou C, Wang JH, Lu SN, Huang JF, Lin ZY, Hsieh MY, Tsai JF, Wang LY, Chang WY. Changing prevalence of hepatitis C virus genotypes: molecular epidemiology and clinical implications in the hepatitis C virus hyperendemic areas and a tertiary referral center in Taiwan. J Med Virol 2001. [PMID: 11505444 DOI: 10.1002/jmv.2001] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
To determine the hepatitis C virus (HCV) genotype distribution in Taiwan and to clarify the relationship between genotype and the pathogenesis of HCV infection, 1,164 subjects positive for serum HCV antibodies and HCV RNA from three HCV hyperendemic areas (Masago, Tzukuan, and Taoyuan) and a tertiary referral center in Taiwan were studied during 1995-1997. HCV genotypes and viral loads were determined using Okamoto's method and branched DNA assay, respectively. Genotype 1b was the most prevalent in Tzukuan (61.9%), Taoyuan (76.9%), and the referral center (47.0%). By contrast, genotype 2a was the major HCV type in Masago (63.5%). Prevalence of genotype 1b positively and that of genotype 2a negatively correlated to age, regardless of study populations (P < 0.01). Based on multivariate analysis, the significant factors associated with the presence of cirrhosis, with or without hepatocellular carcinoma, in chronic hepatitis C patients were genotype 1b and age. In conclusion, these results underline that independent HCV outbreaks continue in HCV hyperendemic areas in Taiwan, concomitant with a changing relative prevalence of HCV genotypes in relation to age. Both the correlation of genotype 1b with age (cohort effect) and intrinsic properties of HCV genotypes are probably responsible for the association between genotype and the pathogenesis of HCV infection.
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Affiliation(s)
- M L Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Roffi L, Redaelli A, Colloredo G, Minola E, Donada C, Picciotto A, Riboli P, Del Poggio P, Rinaldi G, Paris B, Fornaciari G, Giusti M, Marin R, Morales R, Sangiovanni A, Belloni G, Pozzi M, Poli G, Mascoli N, Corradi C, Pioltelli P, Scalori A, Mancia G. Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype. Eur J Gastroenterol Hepatol 2001; 13:501-6. [PMID: 11396528 DOI: 10.1097/00042737-200105000-00007] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.
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Affiliation(s)
- L Roffi
- Department of Internal Medicine, Sondrio Hospital, Italy.
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Roffi L, Ricci A, Ogliari C, Scalori A, Minola E, Colloredo G, Donada C, Ceriani R, Rinaldi G, Paris B, Fornaciari G, Morales R, Del Poggio P, Sangiovanni A, Buonocore M, Bellia V, Riboli P, Nava MC, Panizzuti F, Piperno A, Pozzi M, Pioltelli P, Mancia G. HCV genotypes in Northern Italy: a survey of 1368 histologically proven chronic hepatitis C patients. J Hepatol 1998; 29:701-6. [PMID: 9833906 DOI: 10.1016/s0168-8278(98)80249-3] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND/AIMS Hepatitis C virus (HCV) easily undergoes genomic changes, thus accounting for the presence of different genotypes, with different geographic distributions and different outcomes of chronic hepatitis. Type 1b is frequently found in advanced diseases; however, since this genotype is the most prevalent in older patients, the association with advanced age and severity of the disease is confounding. The aim of this study was to assess changes in the prevalence of HCV genotypes by surveying a large population of chronic hepatitis C patients in Northern Italy, and to assess if the high prevalence of genotype 1b in older patients with advanced diseases simply reflects the duration of HCV infection, rather than intrinsic biological properties of HCV. METHODS We studied 1368 HCV-RNA positive patients, with histologically proven chronic hepatitis. Drug addiction, blood transfusions and sporadically acquired infections represented the risk factors. RESULTS Genotype 1b, the most prevalent isolate, and genotype 2a were associated with older age, cirrhosis, sporadically-acquired infections and blood transfusion, while types 1a, 3a, and 4 were associated with younger age, chronic persistent hepatitis and drug addiction. Patients with a history of transfusions were divided into four groups depending on the period of transfusion. The prevalence of genotype 1b decreased with time. Type 3a appeared only after 1979. CONCLUSION The severity of chronic hepatitis C could be related more to the duration of the infection rather than to the intrinsic pathogenicity of HCV genotypes.
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Affiliation(s)
- L Roffi
- S. Gerardo Hospital, Monza, Italy
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20
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Wong DA, Tong LK, Lim W. High prevalence of hepatitis C virus genotype 6 among certain risk groups in Hong Kong. Eur J Epidemiol 1998; 14:421-6. [PMID: 9744672 DOI: 10.1023/a:1007400304726] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The genotype of hepatitis C virus (HCV) of 172 HCV-RNA positive serum specimens taken from patients with chronic liver diseases, thalassaemia major, chronic renal failure (CRF), haemophilia and intravenous drug abusers (IVDA) was determined by analysis of the amplified 5'UTR region by genotype-specific oligonucleotide probes and restriction fragment length polymorphism (RFLP). Six different genotypes and subtypes (1a, lb, 2, 3, 4 and 6) were found. Genotype lb was the predominant genotype among patients with chronic liver diseases (69.6%), followed by genotype 6 (18.8%), which was similar to that reported for blood donors in earlier studies. Pronounced differences in the distribution of genotypes were seen between the four risk groups. Patients with CRF had a similar distribution to those with chronic liver diseases, whilst the greatest diversity of genotypes was seen in patients with haemophilia, which was expected since they were given factor VIII manufactured overseas. Genotype 6 was particularly prominent in patients with thalassaemia major (50%) and IVDA (62.5%). It is possible that clonal spread of HCV genotype 6 has taken place among a closed subset of the population in Hong Kong through intravenous drug abuse.
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Affiliation(s)
- D A Wong
- Government Virus Unit, Queen Mary Hospital, Pokfulam, Hong Kong
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21
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Abstract
The aim of this study was to investigate the prevalence and distribution of hepatitis C virus (HCV) genotypes of blood donors in Taiwan. RNA was extracted from the serum of anti-hepatitis C virus-positive carriers and this was followed by reverse transcriptase-polymerase chain reaction (RT-PCR) using type-specific primers for the presence of HCV genotypes, 1a, 1b, 2a, 2b, 3a and 6a. Of the 604 anti-HCV-positive specimens, the PCR demonstrated that 93.0% (562/604) were positive for at least one HCV genotype. The remaining 42 specimens (7%) were HCV negative. Among the 562 HCV-positive specimens, 505 (89.8%) contained HCV 1a, 1b, 2a, 2b and 3a as the only genotype, with a prevalence of 0.4% (2/562), 60.1% (338/562), 15.5% (87/562), 11.9% (67/562), and 2.0% (11/562), respectively. No HCV genotype 6a was found. Thirty-seven specimens (6.6%) exhibited mixed infections with multiple HCV genotypes that included types 1b, 2a and 2b, while 20 (3.5%) HCV RNA-positive sera remained unclassified. These results confirm that the predominant HCV genotype in Taiwan is 1b. In addition, genotypes 1a and 3a can also be found in Taiwan at low frequency.
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Affiliation(s)
- C H Wu
- Department of Medical Research, Taichung Veterans General Hospital, Taiwan, ROC
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Khan RU, Tong CY, Bloom S, Gilmore IT, Toh CH, Bolton-Maggs PH, Beeching NJ, Hart CA. Evaluation of two simplified methods for genotyping hepatitis C virus. J Med Virol 1997; 52:35-41. [PMID: 9131456 DOI: 10.1002/(sici)1096-9071(199705)52:1<35::aid-jmv7>3.0.co;2-s] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A number of different approaches have been used for genotyping hepatitis C virus (HCV). Two simplified methods were evaluated, both of which used polymerase chain reaction (PCR) to amplify products from the 5' non-coding region of HCV: non-isotopic restriction fragment length polymorphism (RFLP) analysis and type-specific PCR. Sixty-four viraemic patients suffering from chronic HCV infection were studied using these two techniques; 25/64 samples were further tested with a commercial serotyping ELISA based on synthetic NS4 antigen (Murex, U.K.). The results of the three typing methods were generally in agreement with each other. When only the predominant genotype identified by each method was analysed, the 3 methods had 100% agreement. RFLP did not detect any mixed infections and it was unsuccessful in 16/64 (25%) samples. Both type-specific PCR and serotyping ELISA detected mixed infections. However, serotyping ELISA did not give typeable results in 7/25 (28%) samples, whereas type-specific PCR gave typeable results in all 64 samples. Type-specific PCR detected more mixed infections than serotyping ELISA. Direct sequencing of four PCR products with indeterminate RFLP confirmed changes in restriction enzyme recognition sites. The sequences also confirmed the validity of the predominant genotype in cases of apparent mixed infections. It is possible that some of these cases were artefacts as a result of quasispecies.
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Affiliation(s)
- R U Khan
- Department of Medical Microbiology, University of Liverpool, United Kingdom
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Songsivilai S, Dharakul T, Kanistanon D. Hepatitis C virus genotypes in patients with hepatocellular carcinoma and cholangiocarcinoma in Thailand. Trans R Soc Trop Med Hyg 1996; 90:505-7. [PMID: 8944256 DOI: 10.1016/s0035-9203(96)90296-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The prevalences of infections with hepatitis C virus (HCV) and hepatitis B virus (HBV) were determined in 110 Thai patients with liver cancer, of whom 80 and 30 had histological diagnoses of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), respectively. Hepatitis B surface antigen was detected in 63.8% of HCC patients and 16.7% of those with CCA. Antibodies to HCV, detected by a third-generation enzyme immunoassay, were found in 11.3% of HCC patients and in no CCA patient. HCV ribonucleic acid (RNA) was detected by polymerase chain reaction in 6 anti-HCV positive patients, and also in 2 patients who had no detectable anti-HCV antibody. A total of 11 patients had evidence of HCV infection, 8 of whom were infected with HCV alone. HCV genotypes were determined in all 8 patients who had HCV RNA; genotype 3a was the most common (62.5%). These results demonstrate that, in Thailand where both HBV and HCV are endemic, HBV infection is still the most important risk factor for HCC, but HCV also has an important role in those without HBV infection. In addition, the genotypic distribution of HCV in HCC in Thailand is similar to that in the general population. No specific association between genotype 1b and HCC was observed.
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Affiliation(s)
- S Songsivilai
- Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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