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Introduction: The significant rise in incidence of Hepatitis C virus (HCV) infection among men-who-have-sex-with-men (MSM) living with HIV-1 suggests that HCV under specific circumstances is transmitted via sexual contact. During sexual transmission HCV has to cross the epithelial barrier to either directly enter the blood stream or indirectly via mucosal immune cells. However, the mechanisms of sexual transmission of HCV remain unclear. We investigated the role of Langerhans cells (LCs) in HCV susceptibility during sexual contact as LCs are among the first cells in mucosal tissues to encounter invading viruses. Methods: We investigated the phenotype of primary LCs in anal biopsies from MSM living with HIV-1. To investigate the role of primary LCs in HCV infection and transmission, we have used both isolated primary skin LCs and the ex vivo tissue transmission model. Results: Our data identified an important role for mucosal LCs in facilitating HCV transmission after HIV-1 exposure or immune activation. LCs were detected within mucosal anal tissues obtained from HIV-1 positive MSM biopsies. In order to perform functional studies, we used primary LCs from skin, which have a similar phenotype as mucosal LCs. Immature LCs were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV-1 significantly increased HCV transmission by LCs in the ex vivo transmission model. HIV-1 replication was crucial for the increased HCV transmission as HIV-1 inhibitors significantly reduced HIV-1-induced HCV transmission. Moreover, tissue immune activation of LCs also increased HCV transmission to target cells. Conclusions: Thus, our data strongly indicate that HIV-1 or immune activation in MSM leads to capture of HCV by mucosal LCs, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LCs also implicates that the activation state of LCs is an important cellular determinant for HCV susceptibility after sexual contact. Keywords: HIV-1; Langerhans Cells; Hepatitis C virus; Immune activation; Viral transmission; Men-who-have-Sex-with-Men, 1 | INTRODUCTION Globally, 115 million people are infected with Hepatitis C virus (HCV) whereas 37 million people are infected with HIV-1, and approximately two million infected with both HIV-1 [...]

Objectives To evaluate Hepatitis C virus (HCV) knowledge and awareness among pregnant women with opioid use disorder (OUD). Methods From May through November 2015, a one-time survey was distributed to a convenience sample of pregnant women with OUD to assess their knowledge and awareness of (a) risk factors for HCV infection, (b) HCV transmission prevention strategies, (c) hepatotoxic risk reduction and (d) perinatal transmission and neonatal implications of HCV infection. Chi square and Fisher's exact tests were used to compare demographic characteristics and HCV knowledge between participants who were HCV positive and negative. Results Of 179 pregnant women with OUD approached, 169 (94%) completed the survey. Of these, 153 (90.5%) reported at least one risk factor for HCV infection, 85 (50.3%) were HCV positive and 38 (44.7%) of HCV positive women were diagnosed with HCV for the first time during pregnancy. When HCV knowledge was evaluated, 114 (66.7%) responded that sharing eating utensils could transmit HCV, 69 (55.0%) responded that there is a vaccine to prevent HCV and 56 (32.7%) did not identify intranasal drug use as a risk factor for HCV transmission. Among HCV positive women, 61 (71.8%) associated breastfeeding with an increased risk for HCV transmission, 33 (38.1%) failed to identify the importance of pediatric follow-up for HCV-exposed children and 16 (18.8%) perceived the risk of HCV vertical transmission as 'likely' or 'very likely.' Conclusions for Practice Gaps in HCV knowledge exist among a rapidly growing population of pregnant women with OUD. Healthcare providers have a unique opportunity to provide HCV education and counseling during pregnancy., Author(s): Elizabeth E. Krans [sup.1] [sup.2] , Scott D. Rothenberger [sup.3] , Penelope K. Morrison [sup.4] , Seo Young Park [sup.3] , Leah C. Klocke [sup.2] , Mary J. Turocy [...]

Purpose We evaluated the preoperative prevalence of risk factors for liver disorders and the relationship between the liver disorders and perioperative outcomes in adult congenital heart disease (ACHD) patients. Methods This retrospective study included 32 ACHD patients who underwent reoperative cardiac surgery. Results Preoperatively, 38% of the study patients had risk factors, including congestive liver (CL) due to right heart failure (31%), chronic hepatitis C (HC) (22%), and both CL and HC (16%). The numbers of patients with Child-Pugh scores 5, 6, 7 and 8 were 22, 7, 2 and 1. Median (range) preoperative platelet count and fibrinogen values were 155 (61-330) x 10.sup.3/[mu]l and 250 (145-367) mg/dl, respectively. The patients with higher Child-Pugh scores tended to have longer duration of anesthesia and surgery (p = 0.078, 0.078, respectively), and had significantly higher platelet transfusion (p = 0.031). Lower platelet count was associated with longer duration of anesthesia, surgery and cardio pulmonary bypass (CPB), and larger amount of blood loss and platelet transfusion (p = 0.01, 0.011, 0.024, 0.033, 0.021). Lower fibrinogen value was associated with longer duration of anesthesia, surgery and CPB, and larger amount of platelet transfusion (p = 0.015, 0.009, 0.009, 0.023). Conclusion ACHD patients who underwent reoperative cardiac surgery had a high prevalence of risk factors for liver disorders preoperatively, and liver disorders aggravated some intraoperative outcomes. These findings suggest that the prevention of liver disorders is important for reducing the occurrence of poor outcomes, and that ACHD patients with liver disorders need attentive perioperative management., Author(s): Koko Adachi [sup.1] [sup.3] , Hiroaki Toyama [sup.1] , Yu Kaiho [sup.1] , Osamu Adachi [sup.2] , Hiroto Hudeta [sup.3] , Masanori Yamauchi [sup.1] Author Affiliations: (1) grid.69566.3aDepartment of [...]

: Introduction: The significant rise in incidence of Hepatitis C virus (HCV) infection among men‐who‐have‐sex‐with‐men (MSM) living with HIV‐1 suggests that HCV under specific circumstances is transmitted via sexual contact. During sexual transmission HCV has to cross the epithelial barrier to either directly enter the blood stream or indirectly via mucosal immune cells. However, the mechanisms of sexual transmission of HCV remain unclear. We investigated the role of Langerhans cells (LCs) in HCV susceptibility during sexual contact as LCs are among the first cells in mucosal tissues to encounter invading viruses. Methods: We investigated the phenotype of primary LCs in anal biopsies from MSM living with HIV‐1. To investigate the role of primary LCs in HCV infection and transmission, we have used both isolated primary skin LCs and the ex vivo tissue transmission model. Results: Our data identified an important role for mucosal LCs in facilitating HCV transmission after HIV‐1 exposure or immune activation. LCs were detected within mucosal anal tissues obtained from HIV‐1 positive MSM biopsies. In order to perform functional studies, we used primary LCs from skin, which have a similar phenotype as mucosal LCs. Immature LCs were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV‐1 significantly increased HCV transmission by LCs in the ex vivo transmission model. HIV‐1 replication was crucial for the increased HCV transmission as HIV‐1 inhibitors significantly reduced HIV‐1‐induced HCV transmission. Moreover, tissue immune activation of LCs also increased HCV transmission to target cells. Conclusions: Thus, our data strongly indicate that HIV‐1 or immune activation in MSM leads to capture of HCV by mucosal LCs, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LCs also implicates that the activation state of LCs is an important cellular determinant for HCV susceptibility after sexual contact., Introduction Globally, 115 million people are infected with Hepatitis C virus (HCV) whereas 37 million people are infected with HIV‐1, and approximately two million infected with both HIV‐1 and HCV. [...]

Although multiple determinants for hepatitis C virus (HCV) infection are known, it remains partly unclear what determines the human specificity of HCV infection. Presumably, the presence of appropriate entry receptors is essential, and this may explain why HCV is unable to infect nonhuman hepatocytes. However, using mice with chimeric human livers, we show in this study that the presence of human hepatocytes, and therefore human entry receptors, is not sufficient for HCV infection. In successfully transplanted SCID/Alb-uPA mice, infection with HCV is reliable only when ~70-80% of the liver consists of human hepatocytes. We show that chimeric mice, which are hard to infect with HCV, have significant groups of human hepatocytes that are readily infected with hepatitis B virus. Thus it is unlikely that the lack of infection with HCV can simply be attributed to low hepatocyte numbers. We investigated whether the humanization of lipoprotein profiles is positively associated with infection success. We show that the lipoprotein profiles of chimeric mice become more human-like at high levels of engraftment of human hepatocytes. This and expression of markers of human lipoprotein biosynthesis, human apolipoprotein B (ApoB) and cholesterol ester transfer protein (CETP), show a strong positive correlation with successful infection. Association of HCV in the blood of chimeric mice to ApoB-containing lipoproteins is comparable to association of HCV in patient serum and provides further support for a critical role for ApoB-containing lipoproteins in the infectious cycle of HCV. Our data suggest that the weakest link in the HCV infection chain does not appear to be the presence of human hepatocytes per se. We believe that HCV infection also depends on the presence of sufficient levels of human lipoproteins. apolipoprotein B; low-density lipoprotein; xenotransplantation; immunodeficient mouse; Flavivirus doi: 10.1152/ajpgi.00200.2010.

Objectives. We sought to identify cross-sectional hepatitis B virus (HBV) and HCV prevalence among Asian Americans at a community health fair and to assess referral rates. Methods. We determined HBV prevalence with hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis B surface antigen (anti-HBs). We determined HCV prevalence with hepatitis C antibodies. Successful referral occurred when participants with HBV or HCV were contacted, medically evaluated, and given contact information of liver specialists for care. Results. Of 202 people screened, 118 were Asian Americans (65 Chinese and 39 Vietnamese). Twelve had chronic HBV with positive HBsAg. However, chronic HBV prevalence increased from 10.2% to 13.6% by concomitant HBsAg, anti-HBc, and anti-HBs testing. Prevalence of HCV was 6% overall but 15.4% among Vietnamese. Overall, 83% of patients with chronic HBV and 100% of patients with occult HBV or HCV were successfully referred. Conclusions. Concomitant HBsAg, anti-HBc, and anti-HBs testing permits diagnosis of chronic, occult HBV infections missed by testing with HBsAg alone. Persons identified with HBV or HCV at community health fairs can be successfully referred. (Am J Public Health. 2010;100:S118-S124. doi: 10.2105/AJPH.2009. 162776)

Injection drug users (IDUs) face an increased risk of acquiring blood borne viral infections, including HIV and the hepatitis C virus (HCV). However, the discrepancy in funding for services to address these two diseases has implications. Although drug treatment programs have played an important role in fighting HIV/AIDS, the HCV-related services offered at these programs remain limited. Research from other countries suggests that drug users view HCV as less important than HIV, yet little is known about the extent to which our society's focus on HIV has been adopted within the drug treatment program culture. This qualitative study examines the perceptions of both staff (n = 165) and clients (n = 215) at these programs with regard to HIV and HCV and presents data on how staffs' attitudes toward HCV changed after participating in an HCV training. Clients described a services landscape at drug treatment programs that favors HIV services over those targeting HCV.

The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)--modified oligonucleotide (SPC3649) complementary to miR-122 leads to long-tasting suppression of HCV viremia, with no evidence of viral resistance or side effects in the treated animals. Furthermore, transcriptome and histological analyses of liver biopsies demonstrated derepression of target mRNAs with miR-122 seed sites, down-regulation of interferon-regulated genes, and improvement of HCV-induced liver pathology. The prolonged virological response to SPC3649 treatment without HCV rebound holds promise of a new antiviral therapy with a high barrier to resistance. 10.1126/science.1178178

Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women's Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV- women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different (p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women. DOI: 10.1089/apc.2009.0111

This retrospective cohort study of HIV/hepatitis C virus (HCV) coinfected patients evaluated time trends and rates of HCV evaluation for patients seen between January 1, 1997 and October 30, 2004. Survival analysis and Cox proportional hazards modeling were used to describe the time to evaluation and covariates associated with this outcome. Patients were predominantly white and male. Of 248 eligible patients, 108 (44%) were evaluated for HCV treatment. The median time to evaluation was 2.98 years. Of 108 evaluated, 17 (16%) received at least one dose of interferon and/or ribavirin. The median time to treatment after being evaluated was 1.39 years. Of the 17 (35%) treated 6 patients had a sustained virologic response, but only 2.4% of the original number of patients were cured. Approximately one half of patients in an HIV-specialty clinic were evaluated for HCV therapy and 16% received treatment, but the median time to treatment from the time of HCV diagnosis was over 4 years. Further efforts to identify and to overcome barriers to HCV treatment are warranted. DOI: 10.1089/apc.2009.0099

Hepatitis C virus (HCV) infection shows clear differences in prevalence among geographic regions, according to World Health Organization data (1). HCV prevalence also varies over time and with behavioral changes [...]

The study examined associations between hepatitis C (HCV) seropositivity and a lifetime history of jail or correctional facility incarceration among injection drug users. The sample consisted of 351 injection drug users recruited in inner-city neighborhoods of Baltimore. Multiple logistic regressions were fit to assess associations between HCV seropositivity and a lifetime history of incarceration for the total sample and stratified by race. Analyses demonstrated HCV nearly two times greater for whites than African Americans. In addition. HCV was 2.6 times greater in participants incarcerated in correctional facilities and HCV was 7. 4 times greater in participants reporting more than 5 years of injection drug use compared to participants reporting less than 1 year of injection drug use. The study findings suggest that incorporating systematic HCV screening, prevention, and treatment programs within correctional systems represents a vital yet under-utilized strategy to reduce HCV transmission in society as a whole.

Liver disease is a leading cause of death among patients with HIV coinfected with hepatitis C (HCV); yet, studies show that less than 10% receive HCV treatment, in part because of limited treatment response, high treatment toxicity, and psychosocial barriers to treatment readiness. Using a process model framework, we sought to explore the factors and processes by which providers make HCV treatment decisions for HIV-coinfected patients. We conducted 22 semistructured interviews with primary care providers and support staff at three HIV clinics in Los Angeles, California, in which rates of HCV treatment uptake varied from 10% to 38%. Providers agreed that stable HIV disease, favorable genotype, and significant signs of liver disease progression are all signs of need for treatment. However, two divergent treatment approaches emerged for genotype 1 and 4 patients with minimal disease, and in definitions of patient readiness. Providers with lower treatment rates preferred to delay treatment in hopes of better future treatment options, and were more conservative in requiring complete mental health screens and treatment and abstinence from substance use. Conversely, providers with higher treatment rates viewed all patients as needing treatment as soon as possible, and defined readiness more leniently, with some willing to treat even in the context of untreated depression and drug use, so long as ability to adhere well was demonstrated. Regardless of whether an aggressive or cautious approach to treatment is used, development of effective programs for promoting patient treatment readiness is critical to ensuring greater treatment uptake.

We report the first reported case of a 61-year-old MSM who was diagnosed with syphilis, primary HIV infection, and acute hepatitis C (HCV) within the same time period who rapidly developed significant liver fibrosis within 6 months of acquisition of both infections. It has been well described that individuals with primary HIV infection have an increase in activated [CD8.sup.+] T cells, which causes a state of immune activation as was evident in this patient. Acquisition of HCV during this time could have further skewed this response resulting in massive hepatocyte destruction, inflammation, and subsequent liver fibrosis. Recent literature suggest that MSM with primary HIV infection have higher rates of acquisition of HCV than other HIV-positive cohorts and HCV acquisition can occur very soon after acquiring HIV. This case of rapid hepatic fibrosis progression coupled with the increasing incidence of HCV in individuals with primary HIV infection demonstrates a need for this phenomenon to be studied more extensively.

Objectives. We sought to investigate independent contributions of risky sexual behaviors and bleeding caused by intimate partner violence to prediction of HCV infection. Methods. We conducted a case-control study of risk factors among patients of a sexually transmitted disease clinic with and without HCV antibodies, group-matched by age. Results. Multivariate analyses indicated that Black race (odds ratio [OR]=2.4; 95% confidence interval [Cl]=1.3, 4.4), injection drug use (OR=20.3; 95% Cl=10.8, 37.8), sharing straws to snort drugs (OR=1.8; 95% Cl=1.01, 3.0), sharing razors (OR=7.8; 95% Cl=2.0, 31.0), and exposure to bleeding caused by intimate partner violence (OR=5.5; 95% Cl=1.4, 22.8) contributed significantly to the prediction of HCV infection; risky sexual behavior and exposure to blood or sores during sexual intercourse did not. Conclusions. HCV risk among patients of a sexually transmitted disease clinic can be explained by direct blood exposure, primarily through injection drug use. Exposure to bleeding caused by intimate partner violence may be a previously unrecognized mechanism for HCV transmission associated with risky sexual behavior. (doi:10.2105/AJPH.2007.126383)

Objectives. We compared the effects of 2 interventions on alcohol use, use of a new syringe at last injection, and condom use at last sexual encounter in a community sample of injection drug users. Methods. Between 2003 and 2006, 851 out-of-treatment injection drug users were recruited in Raleigh, NC, and Durham, NC, through street outreach and were randomly assigned to either a 6-session educational intervention or a 6-session motivational intervention. Intervention effects were examined at 6 and 12 months after enrollment. Results. In multiple logistic regression analyses adjusted for baseline alcohol use and HCV status, participants assigned to the motivational intervention were significantly less likely than were participants in the educational intervention to be drinking at the 6-month follow-up (odds ratio=0.67; 95% confidence interval=0.46, 0.97). There were no significant between-group differences in use of a new syringe at last injection or condom use at last sexual encounter at either follow-up. Conclusions. Reducing alcohol use among persons with HCV may slow disease progression and provide important health benefits. Additional strategies are needed for slowing HCV disease progression until more effective HCV treatments are available. (doi:10.2105/AJPH.2007.126854)

Chronic infection with hepatitis C virus (HCV) affects 130 million people worldwide and is a major cause of liver cirrhosis and liver cancer. After translation of the HCV RNA genome into a polyprotein, 2 viral proteases process its non-structural protein (NS) region. While the essential chymotrypsin-like serine protease NS3-4A mediates all cleavages downstream of NS3, the NS2-3 cysteine protease catalyzes a vital cleavage at the NS2/3 site. Protease activity of NS2-3 has been described to require, besides NS2, the N-terminal 181 aa of NS3. The latter domain corresponds to the NS3 serine protease domain and contains a structural [Zn.sup.2+]-binding site with functional importance for both viral proteases. The catalytic triad of the NS2-3 protease resides in NS2; the role of the NS3 part in proteolysis remained largely undefined. Here we report a basal proteolytic activity for NS2 followed by only 2 amino acids of NS3. Basal activity could be dramatically enhanced by the NS3 [Zn.sup.2+]-binding domain (NS3 amino acids 81-213) not only in cis but also in trans which, however, required a more extended N-terminal part of NS3 downstream of NS2 in cis. Thus, this study defines for the first time (i) NS2 as a bona fide protease, (ii) NS3 as its regulatory cofactor, and (iii) functional subdomains in NS3 that cooperate in NS2 protease activation. These findings give new mechanistic insights into function and regulation of the NS2 protease and have important implications for the development of anti-HCV therapeutics. autoprotease | hepacivirus/HCV | protease cofactor | zinc binding domain

There is an association between expression of the MHC class I molecule HLA-B27 and protection following human infection with either HIV or HCV. In both cases, protection has been linked to HLA-B27 presentation of a single immunodominant viral peptide epitope to [CD8.sup.+] T cells. If HIV mutates the HLA-B27-binding anchor of this epitope to escape the protective immune response, the result is a less-fit virus that requires additional compensatory clustered mutations. Here, we sought to determine whether the immunodominant HLA-B27-restricted HCV epitope was similarly constrained by analyzing the replication competence and immunogenicity of different escape mutants. Interestingly, in most HLA-B27-positive patients chronically infected with HCV, the escape mutations spared the HLA-B27-binding anchor. Instead, the escape mutations were clustered at other sites within the epitope and had only a modest impact on replication competence. Further analysis revealed that the cluster of mutations is required for efficient escape because a combination of mutations is needed to impair T cell recognition of the epitope. Artificially introduced mutations at the HLA-B27-binding anchors were found to be either completely cross-reactive or to lead to substantial loss of fitness. These results suggest that protection by HLA-B27 in HCV infection can be explained by the requirement to accumulate a cluster of mutations within the immunodominant epitope to escape T cell recognition., Introduction HCV, a positive-strand RNA virus of the Flaviviridae family, is a major cause of chronic liver disease. More than 170 million people worldwide are chronically infected and are at [...]

Hepatitis C virus (HCV) is a common RNA virus that causes hepatitis and liver cancer. Infection is treated with IFN-[alpha] and ribavirin, but this expensive and physically demanding therapy fails in half of patients. The genomic sequences of independent HCV isolates differ by approximately 10%, but the effects of this variation on the response to therapy are unknown. To address this question, we analyzed amino acid covariance within the full viral coding region of pretherapy HCV sequences from 94 participants in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C) clinical study. Covarying positions were common and linked together into networks that differed by response to therapy. There were 3-fold more hydrophobic amino acid pairs in HCV from nonresponding patients, and these hydrophobic interactions were predicted to contribute to failure of therapy by stabilizing viral protein complexes. Using our analysis to detect patterns within the networks, we could predict the outcome of therapy with greater than 95% coverage and 100% accuracy, raising the possibility of a prognostic test to reduce therapeutic failures. Furthermore, the hub positions in the networks are attractive antiviral targets because of their genetic linkage with many other positions that we predict would suppress evolution of resistant variants. Finally, covariance network analysis could be applicable to any virus with sufficient genetic variation, including most human RNA viruses., Introduction HCV chronically infects about 3.8 million Americans and causes 8,000-10,000 deaths each year in the United States by inducing liver failure or hepatocellular carcinoma (1). HCV infection is treated [...]

The aim of this study was to examine the incidence and factors associated with the severity of liver fibrosis in 234 coinfected patients in Brazil. Patients were cared for in our clinic, from 1996 to 2004. Eligible patients were defined as patients with documented HIV and hepatitis C virus (HCV) infections and had previously undergone a liver biopsy. Patients with persistently normal alanine aminotransferase (ALT) were also included. The variables selected for study were age, gender, risk category, history of high alcohol consumption, CD[4.sup.+] T cell count, antiretroviral therapy usage, HCV genotype and duration of HCV infection. Stage of fibrosis was scored as follows: F0, no fibrosis; F1, portal fibrosis with no septa; F2, portal fibrosis with few septa; F3, bridging fibrosis with many septa; and F4, cirrhosis. The liver fibrosis stage was F3 in 39 (16.6%) and F4 in 20(8.5%) patients. Among patients with normal ALT, the liver fibrosis stage was F3-F4 in three patients (5.6%). Predictors of severe liver fibrosis (F3-F4) by multivariate analysis were age (older patients) and genotype 3 (genotype 1 = odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12 0.65). In summary, in the present study severe liver fibrosis was found in 25% of our patients and was associated with an age of more than 38 years at the time of liver biopsy as well as, HCV genotype 3. No differences were found with respect to CD[4.sup.+] T cell counts although patients with a CD[4.sup.+] T cell count greater than 50 were excluded.

We examined the impact of methadone maintenance treatment (MMT) on risk behaviors for transmission of blood-borne diseases in polydrug users who had tested positive or negative for hepatitis C virus (HCV). At intake, HCV-positive participants (n = 362) engaged in more human immunodeficiency virus (HIV) risk behaviors (as measured by the HIV Risk-Taking Behavior Scale) than HCV-negative participants (n - 297; p < .001). This difference was specific to injection-related behaviors and decreased significantly within the first few weeks of MMT (p < .0001 ). Where needles continued to be used, HCV-positive participants became more likely over time to engage in safer injecting practices. Furthermore, HCV-positive participants became more likely to use condoms than HCV-negative participants. These findings demonstrate that both drug- and sex-related risk behaviors decrease during MMT and emphasize the benefits of methadone programs for public health and HIV/HCV prevention. Keywords: Hepatitis C; Risk behaviors; Methadone maintenance; Injection drug use; Substance abuse

Transgenic mice expressing HCV core protein develop hepatic steatosis and hepatocellular carcinoma (HCC), but the mechanism underlying this process remains unclear. Because PPAR[alpha] is a central regulator of triglyceride homeostasis and mediates hepatocarcinogenesis in rodents, we determined whether PPAR[alpha] contributes to HCV core protein--induced diseases. We generated PPAR[alpha]-homozygous, -heterozygous, and -null mice with liver-specific transgenic expression of the core protein gene (Ppara+/+:HCVcpTg, Ppara+/-:HCVcpTg, and Ppara-/-:HCVcpTg mice. Severe steatosis was unexpectedly observed only in Ppara+/+:HCVcpTg mice, which resulted from enhanced fatty acid uptake and decreased mitochondrial [beta]-oxidation due to breakdown of mitochondrial outer membranes. Interestingly, HCC developed in approximately 35% of 24-month-old Ppara+/+: HCVcpTg mice, but tumors were not observed in the other genotypes. These phenomena were found to be closely associated with sustained PPAR[alpha] activation. In Ppara+/-:HCVcpTg mice, PPAR[alpha] activation and the related changes did not occur despite the presence of a functional Ppara allele. However, long-term treatment of these mice with clofibrate, a PPAR[alpha] activator, induced HCC with mitochondrial abnormalities and hepatic steatosis. Thus, our results indicate that persistent activation of PPAR[alpha] is essential for the pathogenesis of hepatic steatosis and HCC induced by HCV infection., Introduction HCV is one of the major causes of chronic hepatitis, whereas patients with persistent HCV infection have a high incidence of hepatocellular carcinoma (HCC) (1), (2). Occurrence of HCC [...]

Hepatitis C prevention counselling and education are intended to increase knowledge of disease, clarify perceptions about vulnerability to infection, and increase personal capacity for undertaking safer behaviours. This study examined the association of drug equipment sharing with psychosocial constructs of the AIDS Risk Reduction Model, specifically, knowledge and perceptions related to hepatitis C virus (HCV) among injection drug users (IDUs). Active IDUs were recruited between April 2004 and January 2005 from syringe exchange and methadone maintenance treatment programs in Montreal, Canada. A structured, interviewer-administered questionnaire elicited information on drug preparation and injection practices, self-reported hepatitis C testing and infection status, and AIDS Risk Reduction Model constructs. Separate logistic regression models were developed to examine variables in relation to: (1) the sharing of syringes, and (2) the sharing of drug preparation equipment (drug containers, filters, and water). Among the 321 participants, the mean age was 33 years, 70% were male, 80% were single, and 91% self-identified as Caucasian. In the multivariable analyses, psychosocial factors linked to syringe sharing were lower perceived benefits of safer injecting and greater difficulty to inject safely. As with syringe sharing, the sharing of drug preparation equipment was associated with lower perceived benefits of safer injecting but also with low self-efficacy to convince others to inject more safely. Interventions should aim to heighten awareness of the benefits of risk reduction and provide IDUs with the skills necessary to negotiate safer injecting with their peers. Keywords: Knowledge; Serf-efficacy; Risk perceptions; Hepatitis C; Injection drug use; Canada