A shift in the Hepatitis C virus genotype dominance in blood donor samples from Thailand

Hepatitis C virus (HCV) can be classified into six major genotypes. The HCV genotypes variability accounts for its geographical distribution, its responses to treatments and the clinical outcomes. The aim of this study was to determine the distribution of HCV genotypes among volunteer blood donors in Thailand. Samples from 135 anti-HCV positive blood donors were analyzed. HCV RNA and genotyping was carried out using nested polymerase chain reaction (PCR) and genotype-specific primer PCR for a portion of the core region. HCV RNA was detected in 109 samples (80.7%). Genotype analysis demonstrated four different genotypes. The most common was genotype 3a (36.7%), followed by genotype 6 (29.4%), 1a (19.3%), 1b (6.4%) and mixed infection (1.8%). Seven samples were untyped (6.4%) in the present study. In several previous reports, the prevalence found in Thailand was HCV genotypes 3, 1 and 6. The present results show an increasing importance of the genotype 6 in HCV infections. This study has also described for the first time in Thailand mixed infections of HCV genotypes.     

Hepatitis C virus (HCV) genotypes, human leucocyte antigen expression and monoclonal gammopathy prevalence during chronic HCV infection

Patients with chronic hepatitis C virus (HCV) infection (530 in toto), and 294 individuals with chronic liver disease of different aetiology, were enrolled in this study to investigate the prevalence of monoclonal gammopathies (MG) during chronic liver dysfunction. A monoclonal band was detected in 61 HCV+ patients and in nine HCV subjects only. In both instances, a correlation between MG presence and advanced age or degree of hepatic injury was noted. The prevalence of HCV genotype 2a was higher in HCV+ patients with, rather than in those without, MG. The MG+ HCV+ subjects did not exhibit human leukocyte antigen (HLA)-A33, B8, B65 and DR16 expression, while an increased frequency of DR15 structure was seen in the same group of individuals in comparison with MG- HCV+ patients and healthy donors. These findings suggest a possible relationship between HLA haplotype expression, virus genotypes and the occurrence of MG during the course of chronic HCV infection.     

HCV Genotypes,Characterization of Mutations Conferring Drug Resistance to Protease Inhibitors,and Risk Factors among Blood Donors in S?o Paulo,Brazil

Background

Hepatitis C virus (HCV) infection is a global health problem estimated to affect almost 200 million people worldwide. The aim of this study is to analyze the subtypes and existence of variants resistant to protease inhibitors and their association with potential HCV risk factors among blood donors in Brazil.

Methods

Repeat anti-HCV reactive blood donors are systematically asked to return for retest, notification, and counseling in which they are interviewed for risk factors for transfusion-transmitted diseases. We analyzed 202 donors who returned for counseling from 2007 to 2010 and presented enzyme immunoassay- and immunoblot-reactive results. The HCV genotypes and resistance mutation analyses were determined by the direct sequencing of the NS5b and NS3 regions, respectively. The HCV viral load was determined using an in-house real-time PCR assay targeting the 5′-NCR.

Results

HCV subtypes 1b, 1a, and 3a were found in 45.5%, 32.0%, and 18.0% of the donors, respectively. The mean viral load of genotype 1 was significantly higher than that of the genotype 3 isolates. Subtype 1a was more frequent among young donors and 3a was more frequent among older donors. Protease inhibitor-resistant variants were detected in 12.8% of the sequenced samples belonging to genotype 1, and a higher frequency was observed among subtype 1a (20%) in comparison to 1b (8%). There was no difference in the prevalence of HCV risk factors among the genotypes or drug-resistant variants.

Conclusions

We found a predominance of subtype 1b, with an increase in the frequency of subtype 1a, in young subjects. Mutations conferring resistance to NS3 inhibitors were frequent in treatment-naïve blood donors, particularly those infected with subtype 1a. These variants were detected in the major viral population of HCV quasispecies, have replicative capacities comparable to nonresistant strains, and could be important for predicting the response to antiviral triple therapy.     

Correlation of Viral Loads with HCV Genotypes: Higher Levels of Virus Were Revealed among Blood Donors Infected with 6a Strains

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.     

Prediction of HCV load using genotype,liver biomarkers,and clinical symptoms by a mathematical model in patients with HCV infection

Hepatitis C virus (HCV) infection is a major public health problem with about 1.75 million new HCV cases and 71 million chronic HCV infections worldwide. The study aimed to evaluate clinical, serological, molecular, and liver markers to develop a mathematical predictive model for the quantification of the HCV viral load in chronic HCV infected patients. In this cross‐sectional study, blood samples were taken from 249 recently diagnosed HCV‐infected subjects and were tested for liver condition, viral genotype, and HCV RNA load. Receiver operating characteristics (ROC) curves and multiple linear regression analysis were used to predict the HCV‐RNA load. Genotype 3 followed by genotype 1 were the most prevalent genotypes in Mashhad, Northeastern Iran. The maximum levels of viral load were detected in the mixed genotype group, and the lowest levels in the undetectable genotype group. The log of the HCV viral load was significantly associated with thrombocytopenia and higher serum levels of alanine transaminase (ALT). In addition, the log HCV RNA was significantly higher in patients with arthralgia, fatigue, fever, vomiting, or dizziness. Moreover, genotype 3 was significantly associated with icterus. A ROC curve analysis revealed that the best cut‐off points for serum levels of aspartate aminotransferase (AST), ALT, and alkaline phosphatase (ALP) were >31, >34, and ≤246 IU/L, respectively. Sensitivity, specificity, and positive predictive values for AST were 87.7%, 84.36%, and 44.6%, for ALT they were 83.51%, 81.11%, and 36%, and for ALP were 72.06%, 42.81%, and 8.3%, respectively. A mathematical regression model was developed that could estimate the HCV‐RNA load. Regression model: log viral load = 7.69 ? 1.01 × G3 ? 0.7 × G1 + 0.002 × ALT ? 0.86 × fatigue.     

HCV genotype analysis in HCV-HIV-co-infected Puerto Ricans who are injecting drug users: undetermined and mixed infections.

Direct percutaneous exposure is the main route of HCV transmission. In Puerto Rico half of people infected with HIV use illicit drugs. The effects of HCV in the course of HIV infection and vice versa have been extensively studied, but remain highly controversial. This may be due to HCV genetic heterogeneity. Therefore, a complex classification into genotypes has emerged that prompted us to determined how this impacts a population of intravenous drug users (IDUs) co-infected with HIV-1. Using Inno-LiPa II technique, we analyzed samples from 171 HCV-HIV-1-co-infected IDUs and 375 from a general HCV population of unknown HIV or source of infection status. Similar HCV genotype distribution was detected in these populations. HCV genotype 1a was the most frequently in IDUs-co-infected with HIV-1, followed by 1b and 3a. Twenty mixed infections and 5 undetermined genotypes were reported. A reduced HCV viral load was observed in HIV-1 positives with wasting syndrome. Individuals with a high HIV-1 viral load presented a low HCV viral load. There were no correlation between HCV genotypes and AIDS-related event. Patients with genotype 1b showed a higher HCV viral load. Males presented higher HCV viral load than females. Females were predominantly affected by genotype 1a, and men by 1a and 1b. Neither the HCV viral load nor the frequency of genotypes were influenced by the antiretroviral modality. The importance of continuous genotype monitoring is stressed.     

Hepatitis C virus genotypes in patients with chronic hepatitis C infection in southern Iran from 2016 to 2019

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The treatment of HCV infection has become more complicated due to various genotypes and subtypes of HCV. The treatment of HCV has made significant advances with direct-acting antivirals. However, for the choice of medicine or the combination of drugs for hepatitis C, it is imperative to detect and discriminate the crucial HCV genotypes. The main objective of this study was to determine the pattern of circulating HCV genotypes in southern Iran, from 2016 until 2019. The other aim of the study was to determine possible associations of patients’ risk factors with HCV genotypes. A total of 803 serum samples were collected in 4 years (2016–2019) from patients with HCV antibody positive results. A total of 728 serum samples were HCV-RNA positive. The prevalence of HCV genotypes was detected using the genotype-specific RT-PCR test for serum samples obtained from 615 patients. The HCV genotype 1 (G1) was the most prevalent (48.8%) genotype in the area, with G1a, G1b, and mixed G1a/b representing 38.4%, 10.1%, and 0.3%, respectively. Genotype 3a was the next most prevalent (47.2%). Mixed genotypes 1a/3a were detected in 22 (3.6%) and finally G4 was found in 3 (0.5%) patients. The other HCV genotypes were not detected in any patient. Genotype 1 (1a and 1b alone, 1a/1b and 1a/3a coinfections) is the most prevalent HCV genotype in southern Iran. HCV G1 shows a significantly higher rate in people under 40 years old.     

Liver Fibrosis,Host Genetic and Hepatitis C Virus Related Parameters as Predictive Factors of Response to Therapy against Hepatitis C Virus in HIV/HCV Coinfected Patients

Objective

To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism).

Patients and Methods

A sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, −238 TNF-α and −592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count.

Results

Patients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of −238 TNF-α genotype GG was detected in patients with significant liver fibrosis.

Conclusions

In HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a −238 TNF-α polymorphism in these patients.     

Prospective study of hepatitis C virus infection in hemodialysis patients by monthly analysis of HCV RNA and antibodies

The aims of this study were to (i) evaluate the prevalence and the incidence of hepatitis C virus (HCV) infection in hemodialysis patients in two different centers in S?o Paulo (Brazil), (ii) determine the time required to detect HCV infection among these patients by serology or PCR, (iii) establish the importance of alanine aminotransferase determination as a marker of HCV infection, and (iv) identify the HCV genotypes in this population. Serum samples were collected monthly for 1 year from 281 patients admitted to hospital for hemodialysis. Out of 281 patients, 41 patients (14.6%) were HCV positive; six patients seroconverted during this study (incidence = 3.1/1000 person-month). In 1.8% (5/281) of cases, RNA was detected before the appearance of antibodies (up to 5 months), and in 1.1% (3/281) of cases, RNA was the unique marker of HCV infection. The genotypes found were 1a, 1b, 3a, and 4a. The presence of genotype 4a is noteworthy, since it is a rare genotype in Brazil. These data pointed out the high prevalence and incidence of HCV infection at hemodialysis centers in Brazil and showed that routine PCR is fundamental for improving the detection of HCV carriers among patients undergoing hemodialysis.     

Epidemiological aspects of hepatitis C virus infection among renal transplant recipients in Central Brazil

An investigation was conducted involving 255 renal transplant recipients in the state of Goiás, Central Brazil, to determine the prevalence of hepatitis C virus (HCV), its risk factors, the genotypes involved, and the level of alanine aminotransferase (ALT) present in the patients. All serum samples were tested for anti-HCV antibodies and HCV RNA. Forty-one patients were anti-HCV and/or HCV RNA positive, resulting in an overall HCV infection prevalence of 16.1% (95% CI: 11.9-21.3). A multivariate analysis of risk factors showed that a history of blood transfusions without anti-HCV screening, the length of time spent on hemodialysis, and renal transplantation before 1994 are all associated with HCV positivity. In HCV-positive patients, only 12.2% had ALT levels above normal. Twenty-eight samples were genotyped as genotype 1, subtypes 1a (62.5%) and 1b (31.3%), and two samples (6.2%) were genotype 3, subtype 3a. These data show a high prevalence of HCV infection and low ALT levels in the studied population. The risk factor analysis findings emphasize the importance of public health strategies such as anti-HCV screening of candidate blood and organ donors, in addition to the stricter adoption of hemodialysis-specific infection control measures. The present study also demonstrates that HCV genotype 1 (subtype 1a) is predominant in this population.     

Different HCV Genotype Distributions of HIV-Infected Individuals in Henan and Guangxi,China

Background

Due to shared transmission routes, hepatitis C virus (HCV) infection is highly prevalent among people infected with human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is associated with hepatotoxicity, leading to the negative effects on patients with HIV/HCV co-infection. In order to provide valuable information for HCV management in this particular population, we investigated the HCV genotypes in HIV-infected individuals from Henan and Guangxi, the two provinces with the most HIV-infected cases in China.

Methods

Individuals, who acquired HIV infection through various risk routes, were recruited from Henan and Guangxi. Test of antibodies against HCV (anti-HCV) was conducted, and detection of HCV RNA was performed by PCR amplification. HCV subtypes were determined by direct sequencing of amplicons, followed by phylogenetic analysis.

Results

We recruited a total of 1,112 HIV-infected people in this present study. Anti-HCV was detected from 218 (50.1%) patients from Henan and 81 (12.0%) patients from Guangxi, respectively. The highest prevalence of HIV/HCV co-infection was observed from FBDs (former blood donors) (87.2%) in Henan and IDUs (intravenous drug users) (81.8%) in Guangxi, respectively. The seroprevalence rate of HCV among people with sexual contact was significantly higher in Henan than in Guangxi (18.7% vs. 3.5%, P<0.05). The positive rate of HCV RNA in Henan and Guangxi was 30.6% (133/435) and 11.2% (76/677), respectively. Moreover, we found that 20 anti-HCV negative samples were HCV positive by PCR amplification. HCV subtype 1b (52.7%) was predominant in Henan, followed by subtype 2a (41.9%). The most frequently detected subtypes in Guangxi were 6a (35.6%) and 3b (32.9%).

Conclusion

The HCV genotype distributions were different in HIV-infected people from Henan and Guangxi. HIV/HCV co-infection was not only linked to the transmission routes, but also associated with the geographic position.     

Genotypic Distribution of Hepatitis C Virus in Thailand and Southeast Asia

The majority of hepatitis C virus (HCV) infection results in chronic infection, which can lead to liver cirrhosis and hepatocellular carcinoma. Global burden of hepatitis C virus (HCV) is estimated at 150 million individuals, or 3% of the world’s population. The distribution of the seven major genotypes of HCV varies with geographical regions. Since Asia has a high incidence of HCV, we assessed the distribution of HCV genotypes in Thailand and Southeast Asia. From 588 HCV-positive samples obtained throughout Thailand, we characterized the HCV 5’ untranslated region, Core, and NS5B regions by nested PCR. Nucleotide sequences obtained from both the Core and NS5B of these isolates were subjected to phylogenetic analysis, and genotypes were assigned using published reference genotypes. Results were compared to the epidemiological data of HCV genotypes identified within Southeast Asian. Among the HCV subtypes characterized in the Thai samples, subtype 3a was the most predominant (36.4%), followed by 1a (19.9%), 1b (12.6%), 3b (9.7%) and 2a (0.5%). While genotype 1 was prevalent throughout Thailand (27–36%), genotype 3 was more common in the south. Genotype 6 (20.9%) constituted subtype 6f (7.8%), 6n (7.7%), 6i (3.4%), 6j and 6m (0.7% each), 6c (0.3%), 6v and 6xa (0.2% each) and its prevalence was significantly lower in southern Thailand compared to the north and northeast (p = 0.027 and p = 0.030, respectively). Within Southeast Asia, high prevalence of genotype 6 occurred in northern countries such as Myanmar, Laos, and Vietnam, while genotype 3 was prevalent in Thailand and Malaysia. Island nations of Singapore, Indonesia and Philippines demonstrated prevalence of genotype 1. This study further provides regional HCV genotype information that may be useful in fostering sound public health policy and tracking future patterns of HCV spread.     

Hepatitis G virus (GBV-C) infection among Brazilian patients with chronic liver disease and blood donors

Background: The recently discovered hepatitis G virus (HGV) belongs, as hepatitis C virus (HCV), to the Flaviviridae family. HGV has been isolated from the serum of patients with non A-E hepatitis. However, the association of HGV with hepatitis is uncertain.Objective: To determine the HGV prevalence in blood donors and in patients with liver disease and to evaluate a possible correlation between HGV infection and liver disease.Study design: Sera from a total of 113 consecutive patients with chronic liver disease were submitted to a series of liver enzymes and function tests and analyzed for the presence of HBsAg, anti-HBs, anti-HBc, anti-HCV, HCV RNA and HGV RNA. Prevalence of HGV RNA was determined in a group of 87 blood donors.Results: Nine (10%) sera from blood donors and 15 (13%) sera from patients with chronic liver disease were HGV RNA positive. Some 28 (25%) patients were HCV RNA positive, with genotypes 1a, 1b and 3 present in 10, 12 and 5 patients, respectively. A total of 20 (18%) patients were HBsAg carriers. Five (4%) patients were double infected (one with HBV+HCV, one with HBV+HGV and three with HCV+HGV).Conclusion: The proportion (10%) of HGV-infected blood donors was very high when compared with other countries. The results did not allow to establish HGV as an etiologic agent for chronic liver disease. The parenteral route was the presumed means of HGV transmission for only one-third of the patients.     

HCV genotyping using statistical classification approach

The genotype of Hepatitis C Virus (HCV) strains is an important determinant of the severity and aggressiveness of liver infection as well as patient response to antiviral therapy. Fast and accurate determination of viral genotype could provide direction in the clinical management of patients with chronic HCV infections. Using publicly available HCV nucleotide sequences, we built a global Position Weight Matrix (PWM) for the HCV genome. Based on the PWM, a set of genotype specific nucleotide sequence "signatures" were selected from the 5' NCR, CORE, E1, and NS5B regions of the HCV genome. We evaluated the predictive power of these signatures for predicting the most common HCV genotypes and subtypes. We observed that nucleotide sequence signatures selected from NS5B and E1 regions generally demonstrated stronger discriminant power in differentiating major HCV genotypes and subtypes than that from 5' NCR and CORE regions. Two discriminant methods were used to build predictive models. Through 10 fold cross validation, over 99% prediction accuracy was achieved using both support vector machine (SVM) and random forest based classification methods in a dataset of 1134 sequences for NS5B and 947 sequences for E1. Prediction accuracy for each genotype is also reported.     

502例丙型肝炎患者病毒基因分型及与性别和年龄的关系研究

目的:探讨502例丙型肝炎患者病毒基因分型的情况,分析其与性别和年龄的关系,为丙型肝炎的防治提供参考。方法:收集贵州地区502例丙型肝炎患者的血液标本,采用PCR-荧光探针法检测丙型肝炎病毒基因型,并对检测数据进行统计学分析。结果:共检出4种基因型及5种基因亚型,主要以1b型、3b型为主,其次是6a、3a型,2a型较少。不同性别丙型肝炎病毒(HCV)基因型分布比较,差异有统计学意义(x²=11.029,P=0.026),男、女性患者均以1b型、3b型为主要基因型,但男性感染者明显多于女性。各个年龄组HCV基因型分布比较,差异有统计学意义(x²=102.946,P=0.000),40-59岁组感染者最多,以1b型为主,其次是20-39岁组,以3b型为主,≥60岁组感染人数较少,以1b型为主。结论:贵州地区HCV呈现多基因型分布,1b、3b型为主要流行基因型,6a、3a型次之,其余基因型较少,不同性别、年龄的HCV基因型分布存在差异性。     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

HCV基因型的差异性流行与进化

丙型肝炎病毒(Hepatitis C virus,HCV)是导致慢性肝炎的主要病原体之一,全球感染人数大约为1.7亿。HCV基因组具有高度变异特性,利用现代遗传分类方法,可将HCV分为6个基因型和80多个基因亚型。不同HCV基因型、亚型的分布与流行具有明显地域特性:1型、2型呈全球流行态势,3型主要流行于亚洲、北美及欧洲部分地区,4型主要流行于中非、中东和欧洲地区,5型主要发现于非洲和欧洲部分国家,6型则主要在东南亚和北美地区流行。我国流行的HCV有1、2、3和6四种基因型,北方仍以1b和2a型为主要流行基因型,近年来3型和6型在华南、西南地区快速传播。据推断,云南将可能成为我国HCV流行与传播的重要源头,引起目前HCV基因型/亚型分布的较大变化,并呈现多样化的传播方式。通过溯祖理论和进化分子钟等分析方法,了解HCV不同基因型差异性流行与进化,对研究HCV的分子流行病学特征,对应性制定丙型肝炎的预防控制策略具有重要意义。     

Strain-specific T-cell suppression and protective immunity in patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) frequently persists with an apparently ineffective antiviral T-cell response. We hypothesized that some patients may be exposed to multiple HCV subtypes and that strain-specific T cells could contribute to the viral dynamics in this setting. To test this hypothesis, CD4 T-cell responses to three genotype 1a-derived HCV antigens and HCV antibody serotype were examined in chronically HCV infected (genotypes 1a, 1b, 2, 3, and 4) and spontaneously HCV recovered subjects. Consistent with multiple HCV exposure, 63% of patients infected with genotypes 2 to 4 (genotypes 2-4) and 36% of those infected with genotype 1b displayed CD4 T-cell responses to 1a-derived HCV antigens, while 29% of genotype 2-4-infected patients showed serotype responses to genotype 1. Detection of 1a-specific T cells in patients without active 1a infection suggested prior self-limited 1a infection with T-cell-mediated protection from 1a but not from non-1a viruses. Remarkably, CD4 T-cell responses to 1a-derived HCV antigens were weakest in patients with homologous 1a infection and greater in non-1a-infected patients: proportions of patients responding were 19% (1a), 36% (1b), and 63% (2-4) (P = 0.0006). Increased 1a-specific CD4 T-cell responsiveness in non-1a-infected patients was not due to increased immunogenicity or cross-reactivity of non-1a viruses but directly related to sequence divergence. We conclude that the T-cell response to the circulating virus is either suppressed or not induced in a strain-specific manner in chronically HCV infected patients and that, despite their ability to clear one HCV strain, patients may be reinfected with a heterologous strain that can then persist. These findings provide new insights into host-virus interactions in HCV infection that have implications for vaccine development.     

Prevalence of hepatitis C virus (HCV) genotypes in Balochistan

A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of Balochistan. Forty HCV seropositive samples belonging to seven different locations of Balochistan were collected from different health care centres. Qualitative analysis of these samples using PCR resulted in 28 positive samples. The PCR positive samples were subjected to genotyping using the method described by Ohno et al (J Clin Microbiol 35:201–202, 1997) with minor modifications. Genotyping of 28 samples revealed three different genotypes including 3a, 3b and 1a. The most prevalent genotype was 3a with rate of 50% followed by genotype 3b and 1a, respectively. Nine samples remained untyped, suggesting the need of further investigation of genotypes in this region. It has been proposed that sequencing of these samples may be helpful to unreveal these genotypes and further epidemiology of HCV genotypes. Further more, extensive and large scale studies are needed to understand the epidemiology of HCV genotypes, as no such study has been carried in this province.     

HCV Antibody Response and Genotype Distribution in Different Areas and Races of China

Hepatitis C virus (HCV) heterogeneity accounts for the failure of effective vaccine development and the lack of successful anti-viral therapy in some patients. Little is known about the immune response to HCV peptides and the region or race specific genotypes in China. The objective of this study was to characterize HCV antibody immune response to HCV peptides and HCV genotypes in different regions and races of China. A total of 363 serum samples were collected from HCV carriers in 6 regions in China. The immune response to HCV peptides was evaluated by ELISA. HCV genotypes were examined using nested RT-PCR. We found that the anti-HCV antibody neutralization rates were significantly different among the serum samples from different areas or from different races in the same area. For samples from Tibet and Sinkiang, the rates of neutralization by HCV peptides were only 3.2% and 30.8%, respectively. The genotypes of samples from Tibet and Sinkiang were apparently heterogeneic and included type I, II, III and multiple types (I/II/III, I/II, I/III, II/III). One specific sample with multiple-genotype (I/II/III) HCV infection was found to consist of type I, II, III, II/III and an unclassified genotype. These studies indicate that the anti-HCV antibody immune response to HCV peptides varied across regions and among races. The distribution of HCV genotypes among Tibetans in Tibet and Uighurs in Sinkiang was different from that in the inner areas of China. In addition, a “master” genotype, type II, was found to exist in HCV infection with multiple HCV genotypes.