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Background: Two receptor chains, IL-10RA and IL-10RB, are known to mediate the functions of interleukin-10 (IL-10), which has been shown to be involved in the progression of persistent hepatitis C virus (HCV) infection. Little information is available on the role of host genetic variation in IL-10 receptor genes and outcome of HCV infection. IL-22, an IL-10 homologue, shares the IL-10RB receptor chain with IL-10 and has antiviral properties. We investigated the possible role of polymorphisms in the IL-10RA and IL-22 genes in hepatitis C disease pathogenesis. Methods: This study population consisted of 631 HCV patients, recruited from several hepatology clinics across Europe. We genotyped four singlenucleotide polymorphisms (SNPs) in the IL-10RA and six SNPs in the IL-22 gene by ligation detection reaction or restriction fragment length polymorphism. Outcome of HCV infection was assessed according to viral clearance, treatment response, severity of fibrosis and overall inflammation. Conclusions: Variation in IL-10RA appeared to be correlated with response to treatment and inflammation. Two SNPs in IL-22 affected treatment response and viral clearance respectively. We furthermore report on allele and haplotype frequencies and linkage disequilibrium for IL-10RA and IL-22. Our results indicate that genetic variation in these genes may play a modulatory role in the outcome of hepatitis C infection. The prevalence of Hepatitis C is approximately 3% worldwide and an estimated 80% of individuals infected by the hepatitis C virus (HCV) suffer from persistent infection (1). The rate of disease progression is variable and the determinants of the clinical outcome of the disease long-term remain poorly understood. Multiple factors affect the outcome of infectious diseases, including environmental factors and interactions with both pathogens and host genetic factors. There is an increasing body of evidence for the involvement of polymorphic variation in the outcome of persistent HCV infection, influencing the degree of inflammation, severity of fibrosis and response to interferon (IFN) therapy (2‐6). HCV infection may be treated with IFN-a or in combination with ribavirin, but the response to current treatment is variable. Only approximately 20% of infected individuals spontaneously clear the virus (self-limiting infection), whereas the remaining 80% proceed to persistent HCV infection (7). These patients have varying degrees of hepatic inflammation and fibrosis at presentation. Long-term, up to 30% of carriers develop cirrhosis with annual risks of 1‐6% of developing hepatocellular carcinoma and 2‐5% of dying from liver disease (8). The investigation of host genetic factors should help us gain a better understanding of the possible molecular mechanisms underlying susceptibility and differences in disease outcome of HCV infection.

Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR.Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication.

The dynamics of the viral decline immediately after the start of therapy for chronic hepatitis C virus (HCV) infection may have prognostic potential for ultimate sustained virologic response. Considerable interindividual variability in the decline has been reported, including differences by race. The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in the immune response to viral infections. We examined whether carriage of specific human MHC alleles are associated with the rate of the early viral decline. Longitudinal viral level data (baseline and days 1, 2, 7, 14, and 28 of treatment), medium resolution MHC genotyping, and random coefficients models were used to examine associations between MHC class I and class II allele carriage and the dynamics of the viral decline in 180 African-Americans (AAs) and 194 Caucasian Americans (CAs) with genotype-1 HCV infection over the first 28 days of treatment with peginterferon α2a plus ribavirin. Baseline viral levels were similar by race, irrespective of allele carriage. However, the rate of change in the viral decline was associated with both allele and race. Among the four subgroups defined by race and specific allele, the fastest rates of decline were observed (in terms of estimated mean viral declines log 10 IU/ml during the first four weeks) in CA noncarriers for A*03 (2.75; P = 0.018), in CA carriers for Cw*03 (2.99; P = 0.046), and in CA noncarriers for DQA1*04 (2.66; P = 0.018) or DQB1*0402 (2.65; P = 0.018). MHC alleles are associated with the viral decline during the first 28 days of peginterferon therapy.

Hepatic steatosis is the accumulation of fat in liver cells. Insulin resistance (IR) occurs when normal amounts of insulin do not stimulate insulin activity in cells. Both conditions have been described in hepatitis C virus (HCV) infection and are thought to be biologically related. This study examined the association of genetic variants with steatosis and IR among 167 African Americans and 184 Caucasian Americans with HCV genotype-1. Steatosis was defined as at least 5% of fat in cells on liver biopsy. IR was quantified as a score greater than 2 from the Homeostasis Model Assessment, version 2.2 (HOMA2-IR). Associations were investigated by estimating odds ratios separately by race. Statistically significant associations (p < 0.05) were observed for variants in interleukin-10 (IL10), leptin receptor (LEPR), interleukin-6 (IL6) and transforming growth factor beta-1 (TGF-β1) for both outcomes. Some significant interactions were observed between IL10,LEPR and TGF-β1 polymorphisms and HOMA2-IR scores when examining steatosis. The interaction of HOMA2-IR and IL10 was consistent in both races whereas for LEPR and TGF-β1 the interactions were statistically significant in only one of the racial groups.These results could imply that some IL10,LEPR and TGF-β1 polymorphisms may modify an association between steatosis and IR.

Background: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. Aim: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. Methods: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. Results: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. Conclusions: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.

Health departments, community-based organizations (CBOs), and AIDS service organizations (ASOs) in the United States and abroad distribute large quantities of free condoms to sexually active individuals; however, little is known about where individuals who use condoms actually acquire them. This community-based participatory research (CBPR) study was designed to identify factors associated with the use of free condoms during most recent anal intercourse among self-identifying gay and bisexual men who reported condom use. Data were collected using targeted intercept interviewing during North Carolina Pride Festival events in Fall 2006, using the North Carolina Condom Acquisition and Preferences Assessment (NC-CAPA). Of the 606 participants who completed the assessment, 285 met the inclusion criteria. Mean age of participants was 33 (+/-10.8) years. The sample was predominantly white (80%), 50% reported being single or not dating anyone special, and 38% reported the use of free condoms during most recent anal intercourse. In multivariable analysis, participants who reported using free condoms during most recent anal sex were more likely to report increased age; dating someone special or being partnered; and having multiple male sexual partners in the past 3 months. These participants were less likely to report ever having had a sexually transmitted disease. Despite being in the third decade of the HIV epidemic, little is known about condom acquisition among, and condom preferences of, gay and bisexual men who use condoms. Although more research is needed, our findings illustrate the importance of free condom distribution.

Crystal methamphetamine is a highly addictive stimulant that initially gained popularity in the western region of the United States and has spread to all regions of the country. This study was designed to identify factors associated with methamphetamine use among men who have sex with men (MSM) in North Carolina. Participants were recruited in five gay bars and in five geographically defined Internet chat rooms concurrently in 2005 to complete a brief assessment of drug use and other risk behaviors. Of the 1189 MSM who completed the assessment, mean age was 29 years. Two thirds self-identified as black/African American or other minorities, and 25% as bisexual. Nearly 6% reported using methamphetamines during the past 30 days. In multivariable analysis, MSM who reported using methamphetamines were more likely to report higher education; health insurance coverage; inconsistent condom use during anal sex within the past 3 months; a history of sexually transmitted disease (STD) infection; positive HIV serostatus; and use of medications designed to treat erectile dysfunction. A lack of data exists on methamphetamine use among MSM in the southeastern United States, particularly in nonurban regions. Because the southeastern United States carries a disproportionate HIV, AIDS, and STD burden, our findings underscore the need for further research and intervention.

Chat room-based human immunodeficiency virus (HIV) prevention interventions are being implemented to reduce the risk of HIV exposure, infection and reinfection among men who have sex with men (MSM). However, little is known about how participants in chat room-based prevention interventions differ from their online non-participating peers. This analysis compared the baseline risk profiles of participants in an HIV prevention intervention ('active recruitment') to their chat room peers who did not participate in the intervention ('passive recruitment'). Data were collected using an online brief risk assessment from MSM (N = 448) who were recruited within Internet chat rooms. Mean age was 30 years. Half self-identified as Black or African American, 29% as White and 64% as gay. Compared with participants, non-participants were more likely to report: spending higher mean number of hours in online chat rooms; using condoms inconsistently during anal intercourse with a man met online during the past 3 months; having had an sexually transmitted disease; being HIV seropositive; using methamphetamines during the past 30 days and using drugs to enhance sexual satisfaction during the past 30 days. Although risk among MSM who use chat rooms remains high, those at greater risk may be those who are less likely to engage in online HIV prevention interventions.

While the gold standard in the assessment of liver fibrosis remains liver biopsy, non-invasive methods have been increasingly used for chronic hepatitis B (CHB). This study aimed to evaluate the performance of two commonly used non-invasive scoring systems (aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)) to predict fibrosis stage in CHB patients.Demographic, histologic and clinical laboratory data from two trials investigating tenofovir disoproxil fumarate in CHB were analyzed. Predicted fibrosis stage, based on established scales and cut-off values for APRI and FIB-4 scores, was compared with Ishak scores obtained from liver biopsy at baseline and at 240 week follow-up.In the 575 patients with a baseline liver biopsy, APRI and FIB-4 scores correlated with Ishak stage (p0.01); however extensive overlap in the distribution of both scores across Ishak stages prevented accurate determination of fibrosis. The majority (81-89%) of patients with advanced fibrosis or cirrhosis were missed by the scores. Similarly, 71% patients without fibrosis were misclassified as having clinically significant fibrosis. APRI and FIB-4 scores at week 240 tended to be low and underestimate fibrosis stage in the patients with liver biopsies after 240 weeks of therapy. APRI or FIB-4 reduction did not correlate with fibrosis regression after 240 weeks of antiviral therapy.APRI and FIB-4 scores are not suitable for use in clinical practice in CHB patients for assessment of hepatic fibrosis according to Ishak stage, especially in gauging improvements in liver fibrosis following therapy.

Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF. Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy-diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis. After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0 % achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9 % had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2 % developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3 % of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss. This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients. Gilead Sciences Robert W. Storr bequest University of Sydney National Health and Medical Research Council (NHMRC) of Australia (1053206) Sydney West Translational Cancer Research Centre Partner Program - Cancer Institute NSW

Efficacy trials have shown that antiviral therapy improves the outcomes of patients with chronic hepatitis B virus (HBV) infection. However, prospective data regarding the effect of antiviral therapy on the incidence of hepatocellular carcinoma (HCC), especially among patients without cirrhosis, are limited. The authors examined the impact of tenofovir disoproxil fumarate (TDF) on the incidence of HCC using a validated prediction model.The incidence of HCC in patients treated with TDF was obtained in the pivotal TDF registration studies after 384 weeks of follow-up. The predicted risk of HCC in individual patients was calculated using the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model, which estimates HCC incidence for up to 10 years based on age, sex, alanine aminotransferase level, hepatitis B e antigen status, and HBV-DNA. Standardized incidence ratios (SIRs) were calculated comparing the observed and predicted numbers of HCC cases in the study cohort.Among 634 patients with evaluable baseline biopsies, 152 had cirrhosis (Ishak fibrosis score of 5 or 6) and 482 did not. During the 384 weeks of study, 14 cases of HCC were reported, with 4 occurring within the first year. The incidence of HCC was 0.37% per year in the study as a whole (0.28% among patients without cirrhosis and 0.65% among patients with cirrhosis). Among patients without cirrhosis, the observed incidence of HCC was significantly lower than predicted (SIR, 0.40; 95% confidence interval, 0.199-0.795). The last HCC case in a patient with cirrhosis occurred around week 192 with an SIR of 0.51 (95% confidence interval, 0.231-1.144) reported at week 384.Based on the REACH-B risk calculator, long-term therapy with TDF was associated with a reduced incidence of HCC among patients without cirrhosis who met treatment criteria.

Because the southeastern USA is experiencing a disproportionate HIV infection rate compared to other regions of the country, we explored HIV behavioural risk disparities by race/ethnicity among self-identifying gay men. Conceived and implemented as a community-based participatory research (CBPR) study, this rapid assessment collected demographic and HIV risk-behaviour data from men in five gay bars in the northwestern part of the state of North Carolina, using an assessment available in English and Spanish. Of 719 participants, 34.8% reported inconsistent condom use during anal intercourse in the past three months, 11.4% reported ever having had a sexually transmitted disease (STD), 3.6% reported being HIV-seropositive and 26% reported illicit drug use during the past 30 days. Compared to white participants, African American/black and Hispanic/Latino participants were more likely to report inconsistent condom use during anal intercourse with multiple partners during the past three months. African American/black participants were more likely to report illicit drug use during the past 30 days. Hispanic/Latino participants were more likely to have never been tested for HIV. Rates of HIV risk behaviours among gay men remain high and racial/ethnic differences indicate the need for targeted and tailored prevention strategies.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.

Inducible nitric oxide synthase (iNOS) is an important molecule involved in the host defense against infectious agents. iNOS is encoded by the NOS2A gene and well-defined haplotypes exist with respect to this gene. We examined whether these haplotypes were associated with the outcome of hepatitis C virus (HCV) infection in 619 Caucasian patients from seven European liver centres. We observed five major haplotypes: (-277A)+(-1026G)+(-1659C): haplotype 1; (-277G)+(-1026T)+(-1659C): haplotype 2; (-277G)+(-1026G)+(-1659C): haplotype 3; (-277G)+(-1026T)+(-1659T): haplotype 4; and (-277A)+(-1026T)+(-1659C): haplotype 5. Distributions of these haplotypes are comparable with those of previous studies. Homozygotes for haplotype 2 or those with haplotypes 2/4 were more likely than those with the 1/1 (wild type) combination to have self-limiting infections (odds ratios (OR)=3.43; 95% confidence intervals (95% CI): 1.10-8.0; P=0.0206 and OR=5.15; 95% CI: 1.32-14.32; P=0.0018, respectively). Conversely, carriage of haplotype 1 was associated with the lack of self-limiting disease (OR=0.48; 95% CI: 0.27-0.83; P=0.009). The effect was mainly among males (OR=0.41; 95% CI: 0.182-0.942; P=0.031 for males, and OR=0.55; 95% CI: 0.24-1.37; P=0.136 for women). Carriage of haplotype 1 was not associated with initial response (P=0.268) or sustained response (P>0.171). Combinations of haplotypes 1/4 were more likely to respond to interferon monotherapy in comparison of initial responders to nonresponders (OR=2.25; 95% CI: 1.05-5.68; P=0.0275).

Using a bar-based sample, we identified factors associated with hepatitis B virus (HBV) vaccination among young African American men who have sex with men (MSM). The mean (+/- standard deviation [SD]) age of the 170 participants was 26 +/- 6.5 years. Nearly 40% reported at least one dose of vaccine; the remainder were completely unvaccinated. Approximately 22% (37) reported having never heard of HBV. Less than 7% of participants reported using condoms the majority of the time during oral intercourse within the past 3 months, and approximately 50% reported using condoms the majority of the time during anal intercourse within the past 3 months. In multivariable analysis, variables associated with vaccination were younger age (odds ratio [OR], 0.44 per 10-year increase in age; 95% confidence interval [CI]: 0.21-0.93, p = 0.032), higher educational attainment (OR, 4.6; 95% CI: 1.17-12.59, p = 0.003), homosexual as opposed to bisexual behavior (OR, 0.15; 95% CI: 0.06-0.41, p = 0.0001), and recent visits to a health care provider (OR, 4.31; 95% CI: 2.08-8.94, p = 0.0001). Our findings underscore the need to reach MSM for HBV vaccination. Innovative approaches are necessary to ensure the prevention of infection, transmission and disease among individuals with limited education, bisexual MSM, and men who have limited access to health care.

Objectives: Hepatitis B infection (HBV) is prevalent among men who have sex with men (MSM) and may lead to significant morbidity and death. Although an effective vaccine exists vaccination rates among MSM are low. We conducted a systematic review to synthesise the various findings from empirical correlational studies to understand HBV vaccination and series completion among MSM. Methods: We systematically searched the Medline, PubMed, EMBASE, CINAHL, ERIC, and Web of Science databases to identify the breadth of published studies pertaining to HBV vaccination among MSM and to synthesise findings from these studies to better identify common themes that may direct future research and intervention approaches. Results: Eight papers specifically addressed correlates of HBV vaccination among MSM. Six domains were identified as predictors of vaccination: (1) demographic variables such as younger age and higher education level; (2) knowledge of the vaccine; (3) access to health care; (4) level of "outness" regarding one's same sex sexual orientation; (5) behavioural factors including sexual and drug use behaviour; and (6) psychosocial variables. Three papers addressed predictors of vaccine series completion among MSM, observing two main domains: (1) demographic variables such as younger age and higher income level; and, (2) behavioural factors including sexual and health promotion behaviours. Conclusions: Continued educational efforts, creation of environments that facilitate proper risk factor evaluation, and access to low cost vaccine may facilitate vaccine uptake. Although we observed important trends in the studies we reviewed, there is a lack of empirical research regarding this important public health issue.

This study compared the demographics and risk behaviors of two samples of men who have sex with men (MSM), using cross-sectional data that were collected via the Internet and through conventional bar-based outreach. The Internet sample was significantly older, more likely to identify as "bisexual," and less educated than the bar sample. After controlling for age and education, few differences were observed between the samples. However, three variables that markedly differentiated the samples were history of sexually transmitted disease infection, HIV serostatus, and sources utilized to obtain health information. No difference in Internet use was found. Based on the possible decreased social desirability promoted by the use of electronic data collection methodologies, these findings provide preliminary evidence that Internet and bar respondents are similar and that the Internet may serve as an expedient as well as reliable methodology to increase understanding of risk among MSM.

We explored the influence of the major CCR5 promoter or coding region variants as haplotypes and genotypes in a cohort of 250 chronically infected HCV patients receiving combined interferon/ ribavirin therapy. No haplotype, including the D32-bearing haplotype (G*2) reportedly associated in homozygotes with high HCV viral load (VL), showed a similar effect. Patients with genotype C/G*2 showed slightly lower median VL (p = 0.05). Neither the G*2 haplotype nor the C/G*2 genotype influenced viral dynamics during the initial 12 wk of treatment (p = 0.53). The genotype E/E was more frequent among sustained responders (15.5%) than non-responders (7.8%), and VL declined further among E/E homozygotes during the initial 12 wk of treatment, particularly those with HCV genotype 1 (p = 0.016). Differential receptor expression due to E/E homozygosity in HCV infection remains to be confirmed.

Background: Nearly 4 million individuals in the United States (1.8%) have been infected with hepatitis C virus, yet few are aware of their infection. Goal: To identify correlates associated with hepatitis C virus testing among a sample of men who have sex with men. Study Design: Internet communications were used for solicitation and collection of data, using a 31-question survey. Results: When the study was restricted to men who have sex with men in the United States (n = 381), 95% of the respondents (n = 361) reported at least one risk factor for hepatitis C virus transmission, 39% of these respondents (n = 140) reported having been tested for hepatitis C virus. Testing was associated with a history of nonsexual risk behavior, increased knowledge of the hepatitis C virus, and healthcare provider communication. Conclusion: A significant proportion of at-risk respondents had not been tested. Interventions are needed to increase hepatitis C virus knowledge in the community of men who have sex with men, and to encourage providers to communicate about hepatitis to the men in this group who screen as high risk on the basis of their risk behaviors.

Chronic hepatitis B (CHB) patients with high pretreatment viral load (HVL) represent a clinical challenge. Higher levels of hepatitis B virus (HBV) DNA are associated with an increased risk for hepatocellular carcinoma (HCC) and cirrhosis.1 In addition, available evidence suggests that CHB patients with HVL are less likely to respond to interferon (IFN)-based regimens than those with lower viral load. In hepatitis B e antigen (HBeAg)-positive patients, having baseline HBV DNA

Little is known about the intersections of immigration, masculinity, and sexual risk behaviours among recently arrived Latino men in the United States (USA). Nine immigrant Latino men from three urban housing communities in the South-eastern USA used photovoice to identify and explore their lived experiences. From the participants’ photographs and words, thirteen themes emerged within four domains. The immigration experience and sociocultural norms and expectations of masculinity were factors identified decreasing Latino men’s sense of power and increasing stress, which lead to sexual risk. Latino community strengths and general community strengths were factors that participants identified as promoting health and preventing risk. These themes influenced the development of a conceptual model to explain risk among immigrant Latino men. This model requires further exploration and may prove useful in intervention development.

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; approximately 30%) compared to Caucasian Americans (CA; approximately 50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-alpha-2a and ribavirin. We observed carriage of A(*)02 (RR=1.33(1.08-1.64); P=0.008), B(*)58 (RR=1.84(1.24-2.73); P=0.002) and DPB1(*)1701 (RR=1.57(1.09-2.26); P=0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

Candidate genes, including myxovirus resistance-1 (Mx1), protein kinase (PKR), transforming growth factor-β1 (TGF-β), interleukin-10 (IL-10), and interferon-gamma (IFN-γ), were evaluated for associations with liver fibrosis in 374 treatment-naive patients with genotype-1 chronic HCV infection [194 Caucasian Americans (CAs) and 180 African Americans (AAs)], using a genetic haplotype approach. Among the 18 haplotypes that occurred with a frequency ≥5% in the cohort overall, the Mx1-(-123C)-(+6886A)-(+19820G(379V))-(+38645T) (abbreviated Mx1-CAGT), and PKR-(+110T)-(+7949G)-(+13846A)-(+22937T)-(+40342T) (abbreviated PKR-TGATT) haplotypes were independently associated with less severe hepatic fibrosis (Ishak ≥ 3 versus

Background: An understanding of vaccine acceptance and uptake is imperative for successful vaccination of populations that will be primary targets for vaccination after a vaccine against HIV is developed and ready for dissemination. Experiences with vaccination against vaccine-preventable hepatitis (VPH) among men who have sex with men (MSM) may offer key insights to inform future HIV vaccination strategies. The purpose of this analysis was to explore what is known currently about vaccination among MSM, using knowledge gained from vaccination against VPH, and to identify important considerations from these experiences that must be explored further as a vaccine against HIV is promoted among MSM. Because cultural and political differences make it difficult to extrapolate findings from studies in one country to another, we have focused our analyses on studies conducted in the USA. Methods: Through a qualitative systematic review of published reports, we identified eight studies that reported correlates of VPH among MSM in the USA. Results: Six major domains of variables associated with vaccination against VPH were identified, including: demographics (e.g. younger age, higher educational attainment); increased vaccine knowledge; increased access to health care; provider recommendation; behaviours (e.g. same-sex behaviour, health-promoting and disease-preventing behaviours); and psychosocial factors (e.g. openness about one’s sexual orientation, reduced barriers to being vaccinated, self-efficacy). Conclusions: Further research is needed to understand vaccination behaviour among MSM and to maximise acceptance and uptake after a vaccine exists. Experiences with VPH provide a real-world model on which to base preliminary assumptions about acceptance and uptake of a vaccine against HIV.

Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position -88 in the MxA gene promoter in self-limiting HCV infection (OR=0.56; 95% CI: 0.35-0.8; P=0.010) and in nonresponders to therapy (OR=0.49; 95% CI: 0.25-0.95; P=0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR=0.22 95% CI: 0.07-0.67; P=0.002). A polymorphism in the 3'-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR=0.43; 95% CI: 0.21-0.86; P=0.010). A polymorphism at position -168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR=2.75; 95% CI: 1.45-5.24; P=0.002). Further associations were found with a CGG trinucleotide repeat in the 5'UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.

Cytotoxic T lymphocyte antigen-4 (CTLA4) suppresses cytotoxic T lymphocyte activity. We examined the associations of CTLA4 single-nucleotide polymorphisms (SNPs) at promoter site -318 and exon-1 site 49 with clearance of hepatitis C virus (HCV) after treatment with combination interferon-alpha plus ribavirin (IFN-alpha+R) therapy in 79 white sustained responders (SRs) and 79 nonresponders (NRs). SRs had higher frequencies of 49G, alone (odds ratio [OR], 2.3; P=.042) and tightly linked with -318C in a haplotype (OR, 2.4; P=.030). Homozygosity for the -318C-49G haplotype was even more frequent among SRs (OR, 5.2; P=.049). Comparably strong associations persisted after multivariable analysis. Relationships were not seen with non-1 genotype viruses (OR, 0.93-1.25; P>.25). Virus load also declined more rapidly in carriers of both 49G (P=.0095) and the -318C-49G haplotype. CTLA4 49G in exon 1 alone and in a haplotype with -318C promoter is associated with sustained IFNalpha+R response in white patients with HCV genotype 1 infection.

Background Transmission of hepatitis C vims (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. Methods Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. Results Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. Conclusion One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors.

PURPOSE: We sought to identify factors associated with hepatitis B virus vaccination, including knowledge and attitudes about hepatitis vaccination, and sexual and nonsexual risk behaviors among at-risk homosexual and bisexual men. SUBJECTS AND METHODS: Internet electronic communications were used to collect data from homosexual and bisexual men from the United States, using a 31-item online questionnaire accessible for 1 month. RESULTS: The mean (± SD) age of the 336 respondents was 38 ± 11 years. Nearly 42% (142) reported at least one dose of vaccine; the remainder were completely unvaccinated. About 21% (n = 71) reported having no information about hepatitis. Approximately 72% (242) of respondents reported never using condoms during oral intercourse, and 26% (n = 87) reported using condoms during less than half of their episodes of anal intercourse. In multivariate analysis, variables associated with vaccination were younger age (odds ratio [OR] 0.7 per 10-year increase in age; 95% confidence interval [CI] 0.59 to 0.84, P = 0.002), high level of knowledge about the vaccine (OR 1.4; 95% CI: 1.03 to 1.83, P = 0.007), communication with a health-care provider about hepatitis (OR 1.98; 95% CI 1.31 to 2.98, P = 0.006), and professional training that included hepatitis education (OR 2.77; 95% CI 1.7 to 4.5, P = 0.001). CONCLUSIONS: Our findings underscore the need for health care providers to emphasize vaccine efficacy and safety, and to encourage high-risk patients to receive vaccination, particularly among men at high risk based on sexual and drug use behaviors.

Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin alpha and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (-238A) and TNF3 (-308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the -238G/A and -308G/A dimorphic sequences. Polymorphisms in the TNF alpha promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.

Editor,—Estimates of the prevalence of hepatitis B virus (HBV) markers among men who have sex with men (MSM) range from 5% to 81%, and the prevalence of HBV surface antigen varies from 1% to 11%.1,2 Despite a safe and effective vaccine against HBV, sexually active MSM are not vaccinated adequately.2–5 Few empirical data describe the factors associated with HBV vaccination among MSM. We conducted a study to identify correlates of HBV vaccination among MSM that could inform future interventions designed to enhance HBV …

Background & AimsLong-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB).MethodsLAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA