Infection Frequency of Hepatitis C Virus and IL28B Haplotypes in Papua New Guinea,Fiji, and Kiribati

It has been estimated that there are more than 60 million Hepatitis C virus (HCV) carriers in the World Health Organisation''s Western Pacific region (WHO-WPR), where liver cancer is among the top three causes of cancer death. WHO and the US Centres for Disease Control and Prevention report the prevalence of HCV in the South Pacific islands (countries within the WHO-WPR) to be high (5–10% and >2% respectively). However, since HCV is not tested for in many of these countries, there is sparse data available to support this assertion. We screened ∼2000 apparently healthy individuals from Papua New Guinea, Fiji and Kiribati and found a sero-prevalence of 2.0%, 0.1% and 0%, respectively. All sero-positive samples tested negative for HCV RNA. Curious as to why all the sero-positive individuals were negative for HCV-RNA, we also screened them for the HCV protective IL28B SNP markers rs12979860 and rs8099917. All antibody-positive participants bar one had HCV protective haplotypes. Our results suggest that HCV is present in these Pacific island countries, albeit at a prevalence lower than previous estimates. As none of our participants had undergone antiviral treatment, and therefore must have cleared infection naturally, we hypothesise that genotypes 1 and/or 4 are circulating in South Pacific Island people and that these peoples are genetically predisposed to be more likely to spontaneous resolve HCV infection than to become chronic carriers.     

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.     

Review of ”Bioinformatics for vaccinology“ edited by Darren R. Flower

The aim of this study was to determine the seropositivity of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) dual infection among blood donors in Nyala Teaching Hospital, which is the biggest (400 beds) hospital in great Dar Fur of Western Sudan. 400 blood donors were tested serologically for the detection of HBsAg and anti-HCV antibodies. Only one (0.25%) out of the 400 examined blood donors was detected reactive for both HBsAg and anti-HCV antibodies. The study concluded that the seropositivity of HBV and HCV dual infection among population studied is uncommon.     

Distribution of hepatitis C virus serotypes and duration of infection in HCV infected subjects from a geographical area in Southeast Italy

Hepatitis C virus serotypes and the duration of infection HCV positive subjects from a restricted geographical area in Italy, were evaluated. HCV serotypes were determined by Murex serotyping assay. Serotypes were detected in 592 (88.0%) of 669 samples. Type 1 proved to be the most frequent (48.9%), followed by types 2 (29%), 3(4.5%) and 4 (2.1%). The transmission of HCV 3 and 4 were observed only in the past 20 years whilst those of other types were recorded during 40 or more years. The results support the view that the prevalence of different HCV types of infection in one restricted geographical area may be associated with the source and duration of infection.     

Evidence for a dominant major gene conferring predisposition to hepatitis C virus infection in endemic conditions

Hepatitis C virus (HCV), infecting 170 million people worldwide, is a major public health problem. In developing countries, unsafe injections and blood transfusions are thought to be the major routes of transmission. However, our previous work in a population from Egypt, endemic for HCV, revealed highly significant familial correlations, strongly suggesting the existence of both familial transmission of the virus and genetic predisposition to HCV infection. We investigated the hypothesis of genetic predisposition by carrying out a segregation analysis of HCV infection in the same population. We used a logistic regression model simultaneously taking into account a major gene effect, familial correlations and relevant risk factors. We analyzed 312 pedigrees (3,703 subjects). Overall HCV seroprevalence was 11.8% and increased with age. The main associated risk factors were previous parenteral treatment for schistosomiasis and blood transfusions. We found strong evidence for a dominant major gene conferring a predisposition to HCV infection. The frequency of the predisposing allele was 0.013, reflecting a strong predisposition to HCV infection in 2.6% of the subjects, particularly those under the age of 20. This study provides evidence for the involvement of host genetic factors in susceptibility/resistance to HCV infection in endemic conditions.     

Hepatitis B and C in the hemodialysis unit of Tocantins,Brazil: serological and molecular profiles

A survey was conducted in the hemodialysis population of the state of Tocantins, Brazil, aiming to assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, to analyze associated risk factors, and also to investigate these viruses genotypes distribution. During January and March 2001, all patients (n = 100) were interviewed at the unique dialysis unit in Tocantins. Blood samples were collected and serum samples were screened for HBV serological markers. Hepatitis B surface antigen positive samples were tested for HBV DNA. All samples were also tested for anti-HCV antibodies and HCV RNA. An overall prevalence of 45% was found for HBV infection (4% were HBsAg/anti-HBc positive, 2% were anti-HBc only and 39% had anti-HBc/anti-HBs markers). Concerning HCV infection, anti-HCV and HCV RNA were detected in 13% and 14% of the subjects, respectively. Three patients were HCV RNA positive and anti-HCV negative, resulting in an overall HCV prevalence of 16%. Univariate analysis of risk factors showed that only shift and length of tile on hemodialysis were associated with HBV and HCV positivity respectively. Among the four HBsAg-positive samples, HBV DNA was detected in three of them, which were identified as genotype A by restriction fragment length polymorphism (RFLP) analysis. All 14HCV RNA-positive samples were genotyped by INNO-LiPA. Genotypes la and 3a were found in 85% and 15%, respectively. The present data show low HBsAg and HCV prevalence rates. The risk factors associated with HBV and HCV positivity suggest that nosocomial transmission may influence in spreading these viruses in the dialysis unit studied.     

Prevalence of hepatitis B and C virus markers among malaria-exposed gold miners in Brazilian Amazon

Hepatitis B and C virus markers were assessed during a survey on malaria in gold mine camps in southern Brazilian Amazon in order to identify risk factors associated to these viral diseases. The study comprised 520 subjects, most of them were gold miners. Missing subjects totaled 49 (8.6%). Among these 520, 82.9% had HBV markers and 7.1% were HBsAg positive. Previous hospitalization, surgery, sexually transmitted diseases and incarceration were quite common among surveyed people, but there is no association between total HBV markers and these factors. On other hand, HBsAg was independently associated to history of sexually transmitted diseases and history of surgery after adjustment. The most frequent HBsAg subtypes identified, adw2 (59%), predominates in populations of Northeast Brazil. The most surveyed people were immigrants coming from that area suggesting that immigrants carried HBV themselves to the study area. Immunoblot (RIBA) confirmed-anti-HCV were found in 2.1%. The only variable associated to anti-HCV in multivariate analysis was illicit intravenous drug. Lack of HCV infection in subjects with such a high HBV markers prevalence reinforces the opinion that HCV is transmitted by restricted routes when compared to HBV. Furthermore, gold miners in Amazon may be considered as a risk group for HBV infection, but not for HCV.     

Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance

Hepatitis C virus (HCV) infection significantly increases the prevalence of type 2 diabetes mellitus (T2DM). Insulin receptor substrate 1 (IRS-1) plays a key role in insulin signaling, thus enabling metabolic regulation in mammalian cells. We have previously shown that HCV infection modulates phosphorylation of Akt, a downstream target of IRS-1. In this study, we further examined the status of total IRS-1 and the downstream regulation of the Akt pathway in understanding mTOR/S6K1 signaling using HCV genotype 2a (clone JFH1)-infected hepatocytes. Inhibition of IRS-1 expression was observed in HCV-infected hepatocytes compared to that in a mock-infected control. The status of the tuberous sclerosis complex (TSC-1/TSC-2) was significantly decreased after HCV infection of human hepatocytes, showing a modulation of the downstream Akt pathway. Subsequent study indicated an increased level of Rheb and mTOR expression in HCV-infected hepatocytes. Interestingly, the phosphoS6K1 level was higher in HCV-infected hepatocytes, suggesting a novel mechanism for IRS-1 inhibition. Ectopic expression of TSC-1/TSC-2 significantly recovered the IRS-1 protein expression level in HCV-infected hepatocytes. Further analyses indicated that HCV core protein plays a significant role in modulating the mTOR/S6K1 signaling pathway. Proteasome inhibitor MG 132 recovered IRS-1 and TSC1/2 expression, suggesting that degradation occurred via the ubiquitin proteasome pathway. A functional consequence of IRS-1 inhibition was reflected in a decrease in GLUT4 protein expression and upregulation of the gluconeogenic enzyme PCK2 in HCV-infected hepatocytes. Together, these observations suggested that HCV infection activates the mTOR/S6K1 pathway in inhibiting IRS-1 function and perturbs glucose metabolism via downregulation of GLUT4 and upregulation of PCK2 for insulin resistance.     

HCV and HBV infection in 3 communities in the Neapolitan area

Using the antibody to HCV and HBc (anti-HCV, anti-HBc), we studied the prevalence of Hepatitis C and B virus in three groups: intravenous drug abusers, subjects lodging in huts and elderly clergymen. Statistical analysis was carried out by chi-square and Fisher's exact tests. Our results show statistical significance for anti-HCV seroprevalence among the three groups, while anti-HBc doesn't differ. These preliminary data seem to show that the two viruses have different ways of transmission.     

Regulation of insulin resistance and type II diabetes by hepatitis C virus infection: A driver function of circulating miRNAs

Hepatitis C virus (HCV) infection is a serious worldwide healthcare issue. Its association with various liver diseases including hepatocellular carcinoma (HCC) is well studied. However, the study on the relationship between HCV infection and the development of insulin resistance and diabetes is very limited. Current research has already elucidated some underlying mechanisms, especially on the regulation of metabolism and insulin signalling by viral proteins. More studies have emerged recently on the correlation between HCV infection‐derived miRNAs and diabetes and insulin resistance. However, no studies have been carried out to directly address if these miRNAs, especially circulating miRNAs, have causal effects on the development of insulin resistance and diabetes. Here, we proposed a new perspective that circulating miRNAs can perform regulatory functions to modulate gene expression in peripheral tissues leading to insulin resistance and diabetes, rather than just a passive factor associated with these pathological processes. The detailed rationales were elaborated through comprehensive literature review and bioinformatic analyses. miR‐122 was identified to be one of the most potential circulating miRNAs to cause insulin resistance. This result along with the idea about the driver function of circulating miRNAs will promote further investigations that eventually lead to the development of novel strategies to treat HCV infection‐associated extrahepatic comorbidities.     

慢性肝炎中乙型和丙型病毒混合感染的重症化研究

在慢性肝炎中,乙、丙型病毒性肝炎混合感染相当多见,可使肝炎慢性化、重症化,肝组织损伤加重,肝硬化(LC)和肝癌(HCC)发生率增加[1]。本文应用血清学和分子生物学方法对196例肝病患者的血清进行检测,初步探讨了乙型肝炎病毒(Hepatitis B virus,HBV)、丙型肝类病毒(Hepatitis C virus,HCV)的复制状况以及两者间的相互作用与预后的关系。1材料和方法1.1病例受检的196例病例均为2004年1月至2005年7月我院住院及门诊病人,男149例,女47例,年龄15~82岁,其中慢性肝炎(CH)患者139例,肝硬化(LC)患者42例,肝癌(HCC)患者15例。所有病例诊断符合…     

Hepatitis C Virus Co-Infection Increases the Risk of Anti-Tuberculosis Drug-Induced Hepatotoxicity among Patients with Pulmonary Tuberculosis

Background

The country of Georgia has a high prevalence of tuberculosis (TB) and hepatitis C virus (HCV) infection.

Purpose

To determine whether HCV co-infection increases the risk of incident drug-induced hepatitis among patients on first-line anti-TB drug therapy.

Methods

Prospective cohort study; HCV serology was obtained on all study subjects at the time of TB diagnosis; hepatic enzyme tests (serum alanine aminotransferase [ALT] activity) were obtained at baseline and monthly during treatment.

Results

Among 326 study patients with culture-confirmed TB, 68 (21%) were HCV co-infected, 14 (4.3%) had chronic hepatitis B virus (HBV) infection (hepatitis B virus surface antigen positive [HBsAg+]), and 6 (1.8%) were HIV co-infected. Overall, 19% of TB patients developed mild to moderate incident hepatotoxicity. In multi-variable analysis, HCV co-infection (adjusted Hazards Ratio [aHR]=3.2, 95% CI=1.6-6.5) was found to be an independent risk factor for incident anti-TB drug-induced hepatotoxicity. Survival analysis showed that HCV co-infected patients developed hepatitis more quickly compared to HCV seronegative patients with TB.

Conclusion

A high prevalence of HCV co-infection was found among patients with TB in Georgia. Drug-induced hepatotoxicity was significantly associated with HCV co-infection but severe drug-induced hepatotoxicity (WHO grade III or IV) was rare.     

Prevalence of hepatitis C virus (HCV) genotypes among positive UAE patients

A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of UAE. 67 HCV seropositive samples were collected from different health care centres. Quantitative analysis of these samples using PCR resulted in 67 positive samples. The PCR positive samples were subjected to genotyping using the method described by Simmonds et al. (J Gen Virol 74: 2391–2399, 1993). HCV genotype 4 was the predominant genotype (46.2%) followed by genotype 3a (23.8%) and 1a (15%). The predominant genotype among the female patients was genotype 4 (65.6%), while genotype 3a was the predominant among the male patients (42.8%). The predominance of HCV genotype 4 in our population confirms the predominance of HCV genotype 4 in UAE and most of the Arab countries in the Middle East. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.     

Removal of cell-bound lipoproteins: a crucial step for the efficient infection of liver cells with hepatitis C virus in vitro.

Hepatitis C virus (HCV) is of major social, medical and economic importance. The prevalence of HCV is approximatively 1% in most developed countries, and much higher in developing countries. HCV infection is the second major cause, after hepatitis B virus infection, for the generation of chronic liver disease and hepatocellular carcinoma. To date, the only reliable model for the study of HCV infection is the chimpanzee. Indeed, there is no robust in vitro infection system, yet. There is thus an urgent need for such an in vitro infection system in order to evaluate therapeutic agents. Here, a process is provided for infecting hepatocyte cell lines with hepatitis C virus in vitro. It is strongly suggested that cell-bound lipoproteins are playing a crucial role during the infection process. In order to obtain a robust infection, the cell-bound lipoproteins have first to be removed from their cellular receptor prior to the addition of viral inocula originating from human sera, the latter being made originally of a virus-lipoprotein complex.     

Occurrence of hepatitis viruses in wild-born non-human primates: a 3 year (1998-2001) epidemiological survey in Gabon

Hepatitis B and C infections are endemic in human population in central Africa, particularly in Gabon. The aim of this study was to determine the prevalence of hepatitis B virus (HBV) and eventual occurrence of hepatitis C virus (HBC)-related strains in a variety of wild-born non-human primates living in Gabon and Congo. Plasma samples were screened for HBV and HCV markers. A non-invasive method of DNA extraction from faeces followed by specific HBV-DNA amplification was developed to study this infection in wild troops of chimpanzees and gorillas. No HCV infection in non-human primates, wild-born or captive, was detected among 596 samples tested. No HBV infection could be detected in samples tested and obtained from Cercopithecidae. In contrast, 14.7 and 42.2% of wild-born chimpanzees in Gabon and Congo were infected with HBV or had evidence of past HBV infection. At Centre International de Recherches Médicales (CIRMF) Primate Centre, 32.1% of chimpanzees and gorillas were HBV positive or had evidence of past infection. In the cases with past infection, 5.9% wild-born and 8.3% at CIRMF harboured HBV-DNA despite the presence of neutralizing HbsAb. Together with previous findings, we confirm the high HBV prevalence not only in humans but also in chimpanzees and gorillas in Gabon and Congo.     

Frequent recovery and broad genotype 2 diversity characterize hepatitis C virus infection in Ghana,West Africa

Hepatitis C virus (HCV) infection is thought to mostly become chronic and rarely resolves. HCV infection was serologically screened in 4,984 samples from Ghanaian blood donors, and 1.3% prevalence was found. At least 53% of confirmed anti-HCV carriers had no detectable viral RNA and were considered to have cleared the virus and recovered from the infection. Confirmation was authenticated by the presence of antibodies specific to at least two viral antigens, mostly NS3 and E2. Reactivity to HCV core antigens was lower in Ghanaian than United Kingdom blood donors. The minority of chronically infected donors carried a viral load significantly lower than an unselected comparative group of United Kingdom blood donors (2.5 x 10(5) versus 2.9 x 10(6) IU/ml; P = 0.004). HCV genotype 2 was largely predominant (87%). Sequence clustering was similarly broad in the E1/E2 and NS5 regions. The phylogenetic diversity and the incapacity to distinguish subtypes within genotype 2 in our and others' West African strains suggested that West Africa may be the origin of HCV genotype 2. The genetic diversity extended to the identification of strains clearly separated from known subtypes of genotype 2 and genotype 1. One strain appears to be part of a new HCV genotype. HCV infection in Ghana is characterized by a high rate of recovery and the predominance of broadly divergent genotype 2 strains.     

In Silico Screening for Potent Anti-HCV Compounds with Inhibitory Activities Toward the NS3/4A Protease

International Journal of Peptide Research and Therapeutics - Hepatitis C virus (HCV) infection is a global health problem and the vaccine for this infection is currently unavailable. The HCV NS3...     

High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai

Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.     

Co-infections with hepatitis G and TT virus in patients with chronic hepatitis C in Hungary

The significance of co-infections with novel hepatitis viruses Hepatitis G (GBV-C, HGV) and TT virus (TTV) in chronic hepatitis C is not clear. We determined the prevalence of HGV RNA and TTV DNA in chronic hepatitis C patients and in asymptomatic hepatitis C virus (HCV) carriers, and assessed the influence of these agents on the course of HCV infection. Seventy-seven patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. Previous HBV infection was detected by testing serum HBsAg and aHBc. HGV RNA and TTV DNA were detected by PCR. In the healthy population, the prevalence of anti-HCV was 0.3%, HGV RNA 8.0% and TTV DNA 18.5%. In chronic hepatitis C HGV RNA occurred in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of HGV RNA was 9.09% and TTV DNA 75.7%. Neither HGV RNA nor TTV DNA had apparent effect on the HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.     

HCVE2／NS1相对保守区多肽体外诱导慢丙肝患者PBMC增殖反应的研究

为了解ＨＣＶ感染后细胞免疫在其中的作用,对３１例慢丙肝及２０例正常献血员以ＭＴＴ法检测外周血单核细胞（ＰＢＭＣ）对ＨＣＶＥ２／ＮＳ１相对保守区多肽抗原及Ｃ２２、ＮＳ５的增殖反应。结果表明与正常人相比,慢性丙型肝炎患者ＰＢＭＣ对ＨＣＶＣ２２、Ｅ２／ＮＳ１抗原有明显的增殖反应（Ｐ＜００５）,而对ＮＳ５无明显增殖,其中以Ｃ２２抗原性最强。作者认为慢性丙型肝炎患者存在针对与ＨＣＶ相关抗原的细胞免疫,这种细胞免疫不能消除ＨＣＶ感染,而且与疾病的状态无关。