High Risk Of Hepatitis C Virus Infection Research Articles

Association of human platelet antigens polymorphisms with susceptibility to hepatitis C virus infection in Chinese population.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis. Previous studies have identified a number of single nucleotide polymorphisms that are associated with HCV infection. Human platelet antigens (HPAs) polymorphisms play an important role in several diseases. Here, we demonstrated the association of the HPA-2, HPA-3, HPA-5 and HPA-15 polymorphisms with susceptibility to HCV infection in Chinese population. Overall, 118 patients with HCV and 167 controls were genotyped for HPAs. There were no significant differences in the allele and genotype frequency distribution for the HPA-3, HPA-5 and HPA-15 systems between the patients with chronic HCV infection and the healthy controls (p>.05). However, the genotype frequency of HPA-2aa was significantly lower, while HPA-2ab/bb was significantly higher in patients than that in the controls (p=.006). The allele frequency of HPA-2a in patients was significantly lower than that in the control group (p=.005). In contrast, HPA-2b in patients was significantly higher than that in the control group (p=.005). We conclude that HPA-2 polymorphism is associated with susceptibility to HCV infection, and individuals carrying the HPA-2b allele may have a higher risk of HCV infection compared with individuals carrying HPA-2a.

Model-based projection of health and economic effects of screening for hepatitis C in Canada.

Because most hepatitis C virus (HCV) infections are asymptomatic and often unrecognized, screening for hepatitis C has been proposed as a plausible public health strategy. We examined the health and economic consequences of a selective one-time hepatitis C screening program for specific populations in the context of current treatment patterns. We used a state-transition model to evaluate 2 general strategies: no screening, and screen and treat with direct-acting antiviral agents. We examined these strategies for 4 different target populations (scenarios): 1) asymptomatic people not at high risk for HCV infection, 2) immigrant populations with high prevalence, 3) a birth cohort of people aged 25-64 years and 4) a birth cohort of people aged 45-64 years of age. We obtained model data from the published literature and expert opinions. We used a payer perspective, a lifetime time horizon and a 5% discount rate. Screening would prevent 49.7%, 57.4%, 64.1% and 49.6% of HCV-related deaths over the lifetime of the cohort for scenarios 1, 2, 3 and 4, respectively. Screening would produce incremental-cost-effectiveness ratios between $31 468/quality-adjusted life-year and $50 490/quality-adjusted life-year. Probabilistic sensitivity analyses indicated that the chance that screening would be cost-effective at $50 000 willingness-to-pay threshold was 39.5%, 63.2%, 58.4% and 58.1% for scenarios 1, 2, 3 and 4, respectively. Our analyses suggest that a one-time hepatitis C screening and treatment program in Canada is likely to be cost-effective for scenarios 2, 3 and 4. The screening programs we have evaluated would identify asymptomatic people with chronic HCV infection and would enable medical treatment to be offered if needed before the development of advanced liver disease.

Urgent action to fight hepatitis C in people who inject drugs in Europe.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and liver cancer, is curable in most people. Injecting drug use currently accounts for 80 % of new HCV infections with a known transmission route in the European Union (EU). HCV has generally received little attention from the public or policymakers in the EU, with major gaps in national-level strategies, action plans, guidelines and the evidence base. Specifically, people who inject drugs (PWID) are often excluded from treatment owing to various patient, healthcare provider and health system factors.All policymakers responsible for health services in EU countries should ensure that prevention, treatment, care and support interventions addressing HCV in PWID are developed and implemented. According to current best practice, PWID should have access to comprehensive, evidence-based multiprofessional harm reduction (especially opioid substitution therapy and clean needles and syringes) and support/care services based in the community and modified with community involvement to accommodate this hard-to-reach population. Other recommended components of care include vaccination against hepatitis B and other infections; peer support interventions; HIV testing, prevention and treatment; drug and alcohol services; psychological care as needed; and social support services. HCV testing should be performed regularly in PWID to identify infected persons and engage them in care. HCV-infected PWID should be considered for antiviral treatment (based on an individualised assessment and delivered within multidisciplinary care/support programmes) both to cure infected individuals and prevent onward transmission. Modelling data suggest that the HCV disease burden can only be cut substantially if antiviral treatment is scaled up together with prevention programmes. Measures should be taken to reduce stigma and discrimination against PWID at the provider and institutional levels.In conclusion, strategic action at the policy level is urgently needed to increase access to HCV prevention, testing and treatment among PWID, the group at highest risk of HCV infection. Such action has the potential to substantially reduce the number of infected persons, along with the disease burden and related care costs.

Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population

Vitamin D and vitamin D receptor (VDR) are involved in multiple immune-mediated disorders including chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between plasma vitamin D level, VDR genetic polymorphisms and risk of HCV infection susceptibility and chronicity. Seven single nucleotide polymorphisms (SNPs) in VDR gene were genotyped and plasma 25-hydroxyvitamin D [25(OH)D] levels were measured in a Han Chinese population of 898 HCV persistent infection cases, 558 spontaneous clearance subjects and 1136 uninfected controls with high risk of HCV infection. In this case–control study, the average plasma 25(OH)D level in persistent infection patients was significantly lower than that in spontaneous clearance cases (P=0.039) and controls (P=0.005). Logistic analyses indicated that rs7975232-C, rs2239185-T and rs11574129-T alleles were significantly associated with a decreased risk of HCV infection susceptibility (all PBonferroni<0.05, in additive/dominant models; Ptrend=9.000×10−4, combined effects in a locus-dosage manner). The protective effects of three favorable alleles were more evident among males, females and subjects aged ≤50years (all P<0.05). Haplotype analyses suggested that compared with the most frequent haplotype Ars7975232Trs731236Crs11574129, CTT was correlated with a reduced risk of HCV infection susceptibility (P=2.200×10−3). These findings implied that low vitamin D levels might be associated with an increased risk for HCV infection and chronicity, and favorable VDR variants (rs7975232-C, rs2239185-T and rs11574129-T) might contribute to a decreased susceptibility to HCV infection in a high-risk Chinese population.

A cross-sectional household cluster serosurvey of hepatitis C virus antibodies in an urban slum of Cairo, Egypt in 2004

BackgroundHepatitis C Virus (HCV) continues to be a burden to the Egyptian population and its economy. Despite all efforts, the prevalence of infection continues to be one of the highest in the world. The high national prevalence has been attributed to unintentional, nosocomial spread during an anti-schistosomiasis campaign conducted in the 1970’s, but that does not fully explain the persistent infection rates. Work is needed to further clarify risk associations. A serosurvey was performed in Manshiet Nasser, a slum in Cairo sometimes referred to as Mokattem Hills where a primary occupation is garbage collection and sorting, to characterize potential risk factors for infection.MethodsFollowing a detailed mapping and census of the area, a cluster sampling was performed and demographic and risk behavior data and a blood sample were collected from subjects older than 6 months. Blood samples were tested using 4th generation anti-HCV EIA kit.ResultsThe slum was estimated to house 45,000 residents. Blood samples were obtained from 2169 subjects. The age adjusted anti-HCV seroprevalence was 9.1 %. Participants with HCV antibodies were more likely to be male, heads of households, subjects without formal education, and those with a lower standard of living. After adjustment of all prevalence ratios (aPR) for age, the following risk factors were significantly associated with higher risk of HCV infection: Garbage collection (aPR 1.5), history of blood transfusion (aPR 2.0), tattooing (aPR 1.4), history of schistosomiasis (aPR 1.5), and use of traditional latrines (aPR 2.0) or pits for sanitation (aPR 1.3). The results of the multivariate analysis indicated that age (p < 0.01), history of schistosomiasis (p < 0.05), garbage sorting (p = 0.05), blood transfusions (<0.001), and the use of traditional latrines for sanitation (p < 0.01) were significantly associated with infection.ConclusionWhile HCV prevalence among those over 30 could be attributed to anti-schistosomiasis injections, the prevalence in younger age indicates ongoing transmission. Although specific behavioral risks were not identified, HCV infection appears to be an occupational hazard of garbage collection and sorting in this environment. Given the large reservoir of HCV infection in the population, further effort needs to be made to identify and mitigate new infections.

Risk factors of hepatitis C virus transmission and genotype distribution in former blood donors from Chinese rural area.

BackgroundIllegal commercial plasma and blood donation activities in the late 1980s and early 1990s caused a large number of hepatitis C virus (HCV) infections in rural areas of China. In the present study, we aimed to elucidate the risk factors of HCV RNA positivity and HCV genotype distribution in former blood donors.MethodsA cross-sectional survey was carried out in a former blood donation village in rural Hebei Province, North China. All residents were invited for a questionnaire interview and testing for HCV antibodies as well as HCV nucleic acids. Questionnaires were administered to collect information about their personal status and commercial blood donation history. Nested PCR was used to amplify HCV nucleic acids in C/E1 region and NS5b region followed by genotyping and phylogenetic analysis. Univariate and multivariate logistic regression were used to analyze the distributions of HCV genotypes in different groups.ResultsA total of 512 blood samples were collected. Anti-HCV positive were 148 (28.5%) whereas RNA positive rate was 13.87%. Residents between 50 and 59 years old had the highest RNA positive rate (27/109, 24.77%) (P = 0.0051). Multivariate logistic regression model analysis revealed that plasma donation (OR = 8.666, 95% CI: 1.390-54.025) was the dominant risk factor of HCV infection. Furthermore, HCV subtypes 1b and 2a were found by genotyping and phylogenetic analysis. 36 samples (53.73%) were subtype 1b and 31 samples (46.27%) were subtype 2a.ConclusionsUnsafe practices during illegal plasma donation led to a high risk of HCV infection. The identification of genotypes 1b and 2a as major HCV genotypes circulating in this region may help to predict the future burden of HCV related diseases and facilitate better medical treatment towards HCV carriers. These results are useful for public healthcare as well as disease control and surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-1535-6) contains supplementary material, which is available to authorized users.

Factors Associated with Hepatitis C Knowledge Before and After an Educational Intervention among Vietnamese Americans.

BACKGROUNDHepatitis C virus (HCV) is a major cause of chronic liver disease and cancer. Vietnamese Americans are at high risk of HCV infection, with men having the highest US incidence of liver cancer. This study examines an intervention to improve HCV knowledge among Vietnamese Americans.STUDYSeven Vietnamese community-based organizations in Pennsylvania and New Jersey recruited a total of 306 Vietnamese participants from 2010 to 2011.RESULTSAverage knowledge scores for pretest and posttest were 3.32 and 5.88, respectively (maximum 10). After adjusting for confounding variables, age and higher education were positively associated with higher pretest scores and having a physician who spoke English or Vietnamese was negatively associated with higher pretest scores. Additionally, after adjusting for confounding variables, household income, education, and having an HCV-infected family member significantly increased knowledge scores.CONCLUSIONSPromotion and development of HCV educational programs can increase HCV knowledge among race and ethnic groups, such as Vietnamese Americans. Giving timely information to at-risk groups provides the opportunity to correct misconceptions, decrease HCV risk behaviors, and encourage testing that might improve timely HCV diagnosis and treatment.

Zasadność realizacji programów przesiewowych w zakresie wczesnego wykrywania HCV

The objective of the study was to collect the data on undetected hepatitis C virus (HCV) in the frequently hospitalized residents of the Kujawsko-Pomorskie Voivodeship. The analysis focused on empirical data. The research was conducted in 2013 among 6332 citizens of the Kujawsko-Pomorskie Voivodeship who had been hospitalized at least twice. The blood was tested for the presence of anti-HCV antibodies. The diagnostic survey with an anonymous questionnaire was developed and used for the purpose of the study. For the statistical analysis Statistica 10.0 was used. The hypothesis was verified using the Mann-Whitney U test and Chi2 test of independence. A level of statistical significance was assumed at α = 0.05. The results were considered to be statistically significant if the probability fulfilled the inequality of p < 0.05. Positive anti-HCV antigens were detected in 91 (1.44%) examined individuals. The relationship was found between blood transfusions provided before 1992, the use of intravenous narcotics and doping, and minor surgical procedures and the infection. Asymptomatic infection was detected in 91 citizens of the Kujawsko-Pomorskie Voivodeship. The highest risk of HCV infection occurs during small surgery and usage of intravenous narcotics and doping. The percentage of positive results is slightly higher in the group of people with cosmetic and beauty treatments. Planning screening programs special attention should be paid to this group of risk. Blood and blood products transfusions before 1992 were associated with a higher risk of HCV infection. People with above-mentioned interventions should become a particular group of screening program participants. Occupational medicine service plays an important role in prevention.

Genetic variants in antigen presentation-related genes influence susceptibility to hepatitis C virus and viral clearance: a case control study.

BackgroundGenes related to antigen presentation pathway, which are in the non-classical class-II region of human leukocyte antigen (HLA), play a vital role during the infection of hepatitis C virus (HCV).MethodsThe current study determined the genotypes of 34 tagging-SNPs (single nucleotide polymorphisms) from 9 candidate genes (HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, TAP1, TAP2, LMP2, LMP7, and tapasin) in a Chinese population of paid blood donors with high risk of HCV infection. The distributions of those SNPs were compared among the 1207 former paid blood donors with different HCV infection outcomes.ResultsHLA-DMA rs1063478 and HLA-DOA rs2284191 were independent factors of acquiring HCV infection. Carrying three favorable alleles of rs1063478-T and rs2284191-G offered the highest protective effect (odds ratio = 0.46, 95% confidence intervals = 0.27-0.78). HLA-DOB rs7383287 and LMP2 rs17587 were independent factors of infection chronicity. Subjects carrying two favorable alleles of rs7383287-G and rs17587-A had a decreased risk of HCV chronicity (odds ratio = 0.42, 95% confidence intervals = 0.26-0.66). The interaction analysis showed that experience of plasma donation interacted with the combined effects of rs1063478 and rs2284191 for HCV susceptibility, and the experience of whole blood donation interacted with the association of rs7383287 with HCV clearance.ConclusionsOur results suggested that genetic variants in antigen presentation pathway had influence on susceptibility to HCV infection and viral clearance. HLA-DMA rs1063478, HLA-DOA rs2284191, and HLA-DOB rs7383287 were identified as novel loci in Chinese population that were involved in HCV infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0716-8) contains supplementary material, which is available to authorized users.

Hepatitis C Virus Vaccines Among People Who Inject Drugs

Most people who inject drugs (PWID) are infected with hepatitis C virus (HCV), and PWID have the highest risk of HCV infection of any risk group. The incidence of HCV infection is 5%-25% per year, demonstrating continued need for HCV infection prevention in PWID. Existing data in chimpanzees and PWID suggest that protective immunity against persistent HCV infection is achievable. Due to the high incidence of infection, PWID are both the most likely to benefit from a vaccine and a population in which vaccine efficacy could be tested. Challenges to testing a vaccine in PWID are significant. However, the first HCV vaccine trial in at-risk HCV-uninfected PWID was initiated in 2012. The results will likely guide future vaccine development and strategies for vaccination of this and other high-risk populations.

Sustained Hyperresponsiveness of Dendritic Cells Is Associated with Spontaneous Resolution of Acute Hepatitis C

Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86(+), programmed death-1 receptor ligand-positive (PDL1(+)), and PDL2(+) pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection.

Frequent Transient Hepatitis C viremia without Seroconversion among Healthcare Workers in Cairo, Egypt

BackgroundsWith 10% of the general population aged 15–59 years chronically infected with hepatitis C virus (HCV), Egypt is the country with the highest HCV prevalence worldwide. Healthcare workers (HCWs) are therefore at particularly high risk of HCV infection. Our aim was to study HCV infection risk after occupational blood exposure among HCWs in Cairo.Methodology/Principal FindingsThe study was conducted in 2008–2010 at Ain Shams University Hospital, Cairo. HCWs reporting an occupational blood exposure at screening, having neither anti-HCV antibodies (anti-HCV) nor HCV RNA, and exposed to a HCV RNA positive patient, were enrolled in a 6-month prospective cohort with follow-up visits at weeks 2, 4, 8, 12 and 24. During follow-up, anti-HCV, HCV RNA and ALT were tested. Among 597 HCWs who reported a blood exposure, anti-HCV prevalence at screening was 7.2%, not different from that of the general population of Cairo after age-standardization (11.6% and 10.4% respectively, p = 0.62). The proportion of HCV viremia among index patients was 37%. Of 73 HCWs exposed to HCV RNA from index patients, nine (12.3%; 95%CI, 5.8–22.1%) presented transient viremia, the majority of which occurred within the first two weeks after exposure. None of the workers presented seroconversion or elevation of ALT.Conclusions/SignificanceHCWs of a general University hospital in Cairo were exposed to a highly viremic patient population. They experienced frequent occupational blood exposures, particularly in early stages of training. These exposures resulted in transient viremic episodes without established infection. These findings call for further investigation of potential immune protection against HCV persistence in this high risk group.

Annual Registry for Hepatitis C and Hepatitis B is Needed for Predicting the Burden of Hepatocellolar Carcinoma in Iran.

Dear Editor, We read with interest the paper entitled “Hepatitis C Virus: The Rising Concerns and Growing Hopes, Report From the HCV Symposium, Fourth Tehran Hepatitis Congress, November 2011, Tehran, Iran”, which is written by Alavian et al. (1). This report highlights the rising concerns for future health burden of hepatitis C virus (HCV) in global scale as well as the necessity of allocating HCV awareness issues in order to control HCV in Iranian high risk populations and patients (1). In contrast to Western countries in which alcoholism remains the most common cause of HCC, in Iranian population the Hepatitis B Virus (HBV) and HCV are the main causes of Hepatocellolar Carcinoma (HCC) (2). Fortunately HCV infectionincidence is low in Iran (3) and available data suggest the prevalence of less than 1% in general population (4). Besides, the burden of HCC is low in Iran and it is predicted that the rate of mortality due to this malignancy is leveled off in recent years (5). Although in Iran the mass vaccination program against HBV started in 1993 and reached 94% coverage in 2005 (6), it is supposed that its decreasing impact on the burden of HCC will expose in future decades (5). The epidemiology and prevalence of HCV infection has changed in Iran (7) and studies indicate that prisoners and drug abusers are at high risk of HCV infection (8, 9). Also statistics show that intravenous drug use (IDU) accounts for 50% of HCV transmission routes in our country (1). On the other hand, there is no update information regarding the annually new cases of HCV in general population in order to draw a picture of the trends of HCV infection in Iran and predicting its share in burden of HCC in future. Since we know that the burden of HCC is still too low in our community to predict the role of HBV and HCV in HCC Burden, there is a need to register the annual prevalence of these infections in Iranian population. In the absence of such data, the estimation of burden for HCV, HBV and HCC could be far from the accuracy.

Risk factors associated with HIV/HCV infection among entrants in methadone maintenance treatment clinics in China: A systematic review and meta-analysis

Background: Methadone maintenance treatment (MMT) has rapidly expanded in China, from 8 pilot sites to 696 clinics covering 27 provinces, during 2004–2010. This study evaluates the demographic characteristics and drug use behaviors associated with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) infections among MMT entrants through a systematic review and meta-analysis of published literature. Methods: Thirty-nine eligible articles (1 in English and 38 in Chinese) were selected for this review. We extracted the relevant indicator information from all eligible studies and performed meta-analyses, by stratifying according to sex of the participants, age groups and drug use behaviors. Five provinces (i.e., Yunnan, Guizhou, Sichuan, Guangxi and Xinjiang) with the population size of HIV-infected drug users greater than 10,000 were defined as high transmission areas (HTAs) for HIV infection; whereas the remaining twenty-six Chinese provinces were considered as low transmission areas (LTAs). Results: The odds of being infected by HIV among male drug users were significantly higher than for females in high transmission areas (OR=1.49, 95% CI: 1.11–1.99, k=9), while the opposite results were observed in low transmission areas (OR=0.46, 0.27–0.79, k=11). In comparison, no significant differences in risk behaviors were found between sexes in HTAs and LTAs. Younger age was not associated with risk of HIV infection, but was associated with higher risk of HCV infection (<30 years OR=1.88; 30–40 years OR=2.21, compared with >40 years, k=17). Risk of HIV infection was higher among injectors than non-injectors (OR=4.29, 2.70–6.79, k=14) and for those who inject, there was greater risk among sharers than non-sharers (OR=2.47, 1.44–4.23, k=4). Similar patterns were also observed in HCV infection (injectors: OR=10.82, 7.60–15.40; sharers: OR=3.41, 2.56–4.54, k=7). Conclusions: Characteristics of MMT entrants positive for HIV or HCV in China vary by disease types, geographical region, sex, age, and injecting behavior. These factors need to be considered in targeted interventions for MMT participants, such as age-specific health education and psychological treatment, antiretroviral therapy and needle-syringe exchange programs.

Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care.

A Polymorphism in IL28B Distinguishes Exposed, Uninfected Individuals From Spontaneous Resolvers of HCV Infection

Background & AimsPolymorphisms in the interleukin-28B (IL28B) gene are associated with outcomes from infection with hepatitis C virus (HCV). However, the role of these polymorphisms in protecting injection drug users who are at high risk for HCV infection but do not have detectable antibodies against HCV or HCV RNA (exposed uninfected) has not been demonstrated. We investigated whether these individuals have the IL28B genotype rs12979860-CC, which protects some individuals against HCV infection.MethodsSeventy-four exposed uninfected individuals, 89 spontaneous resolvers, and 234 chronically infected individuals were genotyped to determine single nucleotide polymorphisms at IL28B.rs12979860.ResultsExposed, uninfected individuals had a significantly lower frequency of the protective genotype (rs12979860-CC) than anti-HCV-positive spontaneous resolvers (41.9% vs 69.7%, respectively; P = .0005; odds ratio [OR], 0.31; 95% confidence interval [CI]: 0.16–0.60) but a similar frequency to patients who were chronically infected (41.9% vs 43.6%, respectively; P = ns). However, exposed, uninfected individuals had a significantly higher frequency of homozygosity for killer cell immunoglobulin-like receptor 2DL3:group 1 HLA-C (KIR2DL3:HLA-C1) than those with chronic infection (31.1% vs 13.3%, respectively; P = .0008; OR, 2.95; 95% CI: 1.59–5.49). For patients who spontaneously resolved infection, IL28B and KIR:HLA protected, independently, against chronic HCV infection, based on logistic regression and synergy analyses (synergy factor, 1.3; 95% CI: 0.37–4.75; P synergy = .6).ConclusionsIL28B and KIR2DL3:HLA-C1 are independently associated with spontaneous resolution of viremia following HCV exposure. Resistance to HCV infection in exposed uninfected cases is associated with homozygosity for KIR2DL3:HLA-C1 but not the single nucleotide polymorphism IL28B.rs12979860. Uninfected individuals are therefore a distinct population from patients who spontaneously resolve HCV infection. Distinct, nonsynergistic innate immune mechanisms can determine outcomes of HCV exposure.

Intrafamilial transmission of hepatitis C virus: Infection of the father predicts the risk of perinatal transmission

The aims of the present study were to evaluate in a cohort of mothers infected with hepatitis C virus (HCV) the prevalence of HCV infection of their sexual partners, the influence of infection of the partners on perinatal transmission, and whether this influence is mediated by other well known risk factors for perinatal transmission. Forty-nine consecutive mothers infected with HCV who transmitted infection to their offspring and, as a control group, 557 consecutive mothers infected with HCV who did not transmit infection, together with their children and the fathers of the children who were also the sexual partners of the mothers were evaluated. History of intravenous drug use was significantly more frequent in women with partners infected with HCV than in women with partners not infected [115/180 (63.9%) vs. 87/401 (21.7%); relative risk (RR): 6.38, 95% confidence intervals (CI): 4.34-9.39, P < 10(-3)]. HCV infection was more frequent in the partners of mothers who transmitted perinatally HCV [23/49 (46.9%) vs. 174/557 (31.2%); RR: 1.95, 95%CI: 1.08-3.51, P = 0.03]. Multivariate analysis demonstrated that paternal HCV infection is not a risk factor per se for perinatal HCV transmission, but its role is dependent on maternal intravenous drug use [adjusted RR: 1.23 (95%CI: 0.44-3.39, P = 0.6)]. In conclusion, the present study shows that partners of mothers infected with HCV with a history of intravenous drug use were at a higher risk of HCV infection. HCV infection of the father seems to be associated with perinatal transmission but this relationship is dependent on maternal history of intravenous drug use.

Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection

Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed-uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27.6% of exposed-uninfected cases compared with 16.7% of healthy controls [chi(2) = 6.3, P = 0.02, odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.2]. CC genotype was found in 10.5% of exposed-uninfected cases compared with 0.9% controls (chi(2) = 9.3, P = 0.01, OR = 12, 95% CI = 1.5-100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed-uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.

Gauging acceptance of a hepatitis C test by family planning clinic attendees in Glasgow, UK

BackgroundIn the UK, pregnant women are not offered and recommended a hepatitis C virus (HCV) test because no effective intervention to prevent vertical transmission of HCV exists following conception. Mother-to-child...

P.141 A large-scale evaluation of a new method for hepatitis C virus (HCV) genotyping based on real-time PCR

Background and aims: The diagnosis of ongoing hepatitis C virus (HCV) infection involves the detection of specific antibodies and of HCV-RNA. We aimed to assess the relationship between these two parameters in a representative sample of a population at high risk for HCV infection. Methods: Plasma and serum samples were respectively tested for HCV-RNA by a qualitative PCR (Cobas Amplicor HCV, Roche) and for HCV antibodies by a MEIA screening assay (AxSYM HCV 3.0, Abbott) and an immunoblot (Inno-LIA-III, Innogenetics). Results and conclusions: Out of 888 samples assayed, 579 (65.2%) were positive for HCV-RNA, while anti-HCV antibodies were detected respectively in 802 sera by AxSYM (90.3%) and in 783 by LIA (706 positive and 77 indeterminate, 88.2%). The anti-core antibodies displayed the best correlation with viremia, since they were present in 97.1% of the PCR+ samples, followed by anti-NS3 (90.2%) and anti-NS4 (89.6%). Only one HCV-RNA positive sample was negative by LIA and MEIA (early seroconversion). The AxSYM sample/cutoff (S/CO) values were directly correlated with the presence of HCV-RNA: a PCR positivity was found in 4.9% of samples with a S/CO ≤10, in 60.8% of samples with a S/CO between 11 and 50 and in 93.6% of cases with a S/CO >50, (P<0.005). The immunoblot adds little, on a single specimen, to the information yielded by the AxSYM screening test. A suitable diagnostic algorithm for HCV in high-risk settings could be the anti-HCV screening by MEIA and a qualitative assay for HCV-RNA on samples with low reactivity.