DERMATOLOGIC THERAPY, Issue 2009
Antonio Giovanni Richetta
ABSTRACT Erythrodermic psoriasis is a severe and disabling variant of psoriasis. The authors present the case of a 48-year-old man with psoriasis and hemophilia presented with a history of hepatitis C virus (HCV) infection treated with pegylated interferon alpha-2a and ribavirin therapy. At the end of antiviral therapy, skin manifestation progressively worsened, becoming erythrodermic, with lack of efficacy of steroid therapy. The authors decided to start biological therapy with induction dose of adalimumab (Humira, Abbott Laboratories, Abbott Park, Chicago, IL) 80 mg at Week 0 and 40 mg weekly. In our case, this resulted in a highly effective and safe treatment. [source]

The impact of diabetes and obesity on liver histology in patients with hepatitis C

DIABETES OBESITY & METABOLISM, Issue 3 2003
F. Friedenberg
Aim:, An association between diabetes mellitus and HCV has been recognized previously. No study has examined whether there is an independent association between the degree of hepatic fibrosis and the incidence of diabetes in HCV patients when controlling for other risk factors. Methods:, We reviewed the charts of 264 consecutive patients with chronic HCV infection at a referral liver centre from January 1991 to December 1999. Demographic background, medical history, laboratory and liver biopsy results were retrieved. Results:, The prevalence of diabetes was 16.3%. Gender, intravenous drug use, steatosis scores, aminotransferase levels and iron studies were similarly distributed in patients with and without diabetes (all p > 0.05). In contrast, mean age was greater in the diabetic group (49.8 vs. 44.3, p = 0.003). The prevalence of diabetes was substantially higher in African-Americans (p = 0.001) and those with BMI > 30 (p = 0.015). Although the fibrosis score was higher in diabetics (, = 0.14, p = 0.03), that association did not remain significant when controlling for diabetes risk factors (p > 0.3). The degree of steatosis and fibrosis both tended to increase with increasing BMI (, = 0.47, p < 0.001 and , = 0.13, p = 0.03, respectively). Even after controlling for diabetes, age, gender, race, and current alcohol use, those associations remained (both p < 0.001). Conclusions:, The prevalence of diabetes in our group of HCV patients was high, consistent with other studies. Diabetes is not an independent predictor of degree of fibrosis. Body mass index is an independent predictor of both fibrosis and steatosis in HCV patients. [source]

NO EVIDENCE FOR PATIENT-TO-PATIENT TRANSMISSION OF HEPATITIS C VIRUS DURING UPPER GASTROINTESTINAL ENDOSCOPY: MOLECULAR STUDIES ON THREE ACUTE HEPATITIS C PATIENTS

DIGESTIVE ENDOSCOPY, Issue 3 2009
Takayuki Toda
Background:, The risk of patient-to-patient transmission of hepatitis C virus (HCV) during endoscopy remains controversial. Using molecular approaches, we examined the possibility of patient-to-patient transmission of HCV in three patients who developed acute hepatitis C 1,6 months after examination by upper gastrointestinal endoscopy (UGIE) in a hospital endoscopy unit in Japan. Methods:, For the source of HCV infection, we used frozen sera obtained from potential candidates who underwent UGIE earlier than three index patients on the same days in the same unit. HCV genotype was determined by multiplex polymerase chain reaction (PCR) with genotype-specific primers. The 1087-nucleotide (nt) sequence of the NS5B region of the HCV genome was compared between index patients and their HCV-viremic candidates. Results:, The three index patients were exclusively infected with HCV of genotype 1b. Among a total of 60 candidate patients who underwent UGIE earlier than the index patients, 14 were positive for anti-HCV, of whom 12 had detectable HCV-RNA (1b, n = 9; 2a, n = 1; 2b, n = 2) on sera collected during each UGIE. Shared identity within the 1087-nt NS5B sequence was less than 95.0% between index patients and HCV/1b-infected candidates (n = 3, 1 and 5, respectively). None of the remaining 46 candidates who were negative for anti-HCV at UGIE examination tested positive for HCV-RNA, nor seroconverted to anti-HCV on their sera, which most likely excludes the possibility of HCV viremia despite the anti-HCV-negative serology at UGIE examination. Conclusion:, The present study suggests that patient-to-patient transmission of HCV during UGIE is infrequent. [source]

Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment

DRUG AND ALCOHOL REVIEW, Issue 3 2007
BIANCA WATSON
Abstract Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study. [source]

Viral proteinases: targets of opportunity

DRUG DEVELOPMENT RESEARCH, Issue 6 2006
Chelsea M. Byrd
Abstract During antiviral drug development, any essential stage of the viral life cycle can serve as a potential drug target. Since most viruses encode specific proteases whose cleavage activity is required for viral replication, and whose structure and activity are unique to the virus and not the host cell, these enzymes make excellent targets for drug development. Success using this approach has been demonstrated with the plethora of protease inhibitors approved for use against HIV. This discussion is designed to review the field of antiviral drug development, focusing on the search for protease inhibitors, while highlighting some of the challenges encountered along the way. Protease inhibitor drug discovery efforts highlighting progress made with HIV, HCV, HRV, and vaccinia virus as a model system are included. Drug Dev. Res. 67:501,510, 2006. © 2006 Wiley-Liss, Inc. [source]

Hepatitis C virus risk behaviors within the partnerships of young injecting drug users

ADDICTION, Issue 7 2010
Judith A. Hahn
ABSTRACT Aims Young injection drug users (IDU) are at high risk for hepatitis C virus (HCV). We sought to determine whether perceiving one's injecting partner to be HCV positive was associated with decreased odds of engaging in receptive needle/syringe sharing (RNS) or ancillary equipment sharing (AES) with that partner. Design Cross sectional study. Setting 2003 to 2007 in San Francisco. Participants 212 young (under age 30) IDU who were HCV antibody negative reported on 492 injecting partnerships. Measurements Self-reported RNS and AES within injecting partnerships. Findings RNS and AES (in the absence of RNS) occurred in 23% and 64% of injecting partnerships in the prior month. The odds of engaging in RNS were significantly lower for relationships in which the participant reported that his/her partner was HCV positive (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.25,0.95). This association was attenuated when adjusted for reusing one's own needle/syringe (adjusted OR 0.57; 95% CI 0.28,1.15). The odds of engaging in AES were lower for participants who did not know the HCV status of their partner, only among non-sexual partnerships (OR 0.47; 95% CI 0.29,0.76). Conclusions Because perceiving one's partner to be HCV positive was associated with decreased RNS, increased HCV testing and partner disclosure may be warranted. AES was common and was decreased only among non-sexual partnerships in which the HCV status of the partner was not known. This suggests that interventions to reduce AES in young IDU must be widespread. [source]

Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia

ADDICTION, Issue 6 2010
Rudi Wisaksana
ABSTRACT Background There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Methods Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan,Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. Result A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12,111] cells/mm3 compared to 84 (IQR, 28,224) cells/mm3 in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts <25, 25,99, 100,199, respectively, ,200/mm3 had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35,1.23], loss to follow-up (HR = 0.85, 95% CI 0.51,1.41) and virological failure (HR = 0.47, 95% CI 0.19,1.13) were not significantly different in IDUs and non-IDUs. Conclusion Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy. [source]

Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviews

ADDICTION, Issue 5 2010
Norah Palmateer
ABSTRACT Aims To review the evidence on the effectiveness of harm reduction interventions involving the provision of sterile injecting equipment in the prevention of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). The interventions assessed were needle and syringe programmes (NSP), alternative modes of needle/syringe provision (pharmacies, vending machines and outreach) and the provision of injecting equipment other than needles/syringes. Methods Systematic searches of the English language literature to March 2007 were undertaken to identify systematic, narrative or meta-analytical reviews (also known as a review of reviews) of the impact of interventions on HCV transmission, HIV transmission or injecting risk behaviour (IRB). Critical appraisal criteria classified the reviews as either high quality (,core') or supplementary: a framework based on the quality of reviews, the reviewers' conclusions and the designs/findings of the primary studies was used to derive evidence statements. Results Three core and two supplementary reviews of injecting equipment interventions were identified. According to the proposed framework, this study found (a) insufficient evidence to conclude that any of the interventions are effective in preventing HCV transmission; (b) tentative evidence to support the effectiveness of NSP in preventing HIV transmission; (c) sufficient evidence to support the effectiveness of NSP (and tentative evidence of an additional impact of pharmacy NSP) in reducing self-reported IRB; and (d) little to no evidence on vending machines, outreach or providing other injecting equipment in relation to any of the outcomes. Conclusions The evidence is weaker than given credit for in the literature. The lack of evidence for effectiveness of NSP vis-à-vis biological outcomes (HCV and HIV incidence/prevalence) reflects the limitations of studies that have been undertaken to investigate these associations. Particularly for HCV, low levels of IRB may be insufficient to reduce high levels of transmission. New studies are required to identify the intervention coverage necessary to achieve sustained changes in blood-borne virus transmission. [source]

Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population-based cohort study

ADDICTION, Issue 3 2010
Mette V. Larsen
ABSTRACT Objectives To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. Design Population-based, nation-wide prospective cohort study in Denmark (the Danish HIV Cohort Study). Methods A total of 4578 HIV-infected patients were followed from 1 January 1997 or date of HIV diagnosis. We calculated mortality rates stratified on IDU. One-, 5- and 10-year survival probabilities were estimated by Kaplan,Meier methods, and Cox regression analyses were used to estimate mortality rate ratios (MRR). Results Of the patients, 484 (10.6%) were categorized as IDUs and 4094 (89.4%) as non-IDUs. IDUs were more likely to be women, Caucasian, hepatitis C virus (HCV) co-infected and younger at baseline; 753 patients died during observation (206 IDUs and 547 non-IDUs). The estimated 10-year survival probabilities were 53.2% [95% confidence interval (CI): 48.1,58.3] in the IDU group and 82.1% (95% CI: 80.7,83.6) in the non-IDU group. IDU as route of HIV infection more than tripled the mortality in HIV-infected patients (MRR: 3.2; 95% CI: 2.7,3.8). Adjusting for potential confounders did not change this estimate substantially. The risk of HIV-related death was not increased in IDUs compared to non-IDUs (MRR 1.1; 95% CI 0.7,1.7). Conclusions Although Denmark's health care system is tax paid and antiretroviral therapy is provided free of charge, HIV-infected IDUs still suffer from substantially increased mortality in the HAART era. The increased risk of death seems to be non-HIV-related and is due probably to the well-known risk factors associated with intravenous drug abuse. [source]

Can hepatitis C virus prevalence be used as a measure of injection-related human immunodeficiency virus risk in populations of injecting drug users?

ADDICTION, Issue 2 2010
An ecological analysis
ABSTRACT Background Human immunodeficiency virus (HIV) outbreaks occur among injecting drug users (IDUs), but where HIV is low insight is required into the future risk of increased transmission. The relationship between hepatitis C virus (HCV) and HIV prevalence among IDUs is explored to determine whether HCV prevalence could indicate HIV risk. Methods Systematic review of IDU HIV/HCV prevalence data and regression analysis using weighted prevalence estimates and time,series data. Results HIV/HCV prevalence estimates were obtained for 343 regions. In regions other than South America/sub-Saharan Africa (SAm/SSA), mean IDU HIV prevalence is likely to be negligible if HCV prevalence is <30% (95% confidence interval 22,38%) but increases progressively with HCV prevalence thereafter [linearly (, = 0.39 and R2 = 0.67) or in proportion to cubed HCV prevalence (, = 0.40 and R2 = 0.67)]. In SAm/SSA, limited data suggest that mean HIV prevalence is proportional to HCV prevalence (, = 0.84, R2 = 0.99), but will be much greater than in non-SAm/SSA settings with no threshold HCV prevalence that corresponds to low HIV risk. At low HCV prevalences (<50%), time,series data suggest that any change in HIV prevalence over time is likely to be much smaller (<25%) than the change in HCV prevalence over the same time-period, but that this difference diminishes at higher HCV prevalences. Conclusions HCV prevalence could be an indicator of HIV risk among IDUs. In most settings, reducing HCV prevalence below a threshold (30%) would reduce substantially any HIV risk, and could provide a target for HIV prevention. [source]

The outcome of a rapid hepatitis B vaccination programme in a methadone treatment clinic

ADDICTION, Issue 2 2010
Parameswaran Ramasamy
ABSTRACT Aim Injecting drug users are a high-risk population for hepatitis B (HBV), but are difficult to engage in vaccination programmes. This study examines the completion rates of a HBV vaccination schedule and seroconversion in a group of patients in methadone maintenance treatment. Methods Patients at a public methadone maintenance programme in Sydney, Australia, were screened for viral hepatitis (hepatitis A, B and C) and offered a rapid HBV vaccination schedule (0, 1 and 2 months). Hepatitis B surface antibody (antiHBs) was retested on completion of the vaccination schedule. Results A total of 143 patients [71.3% male, mean age 33.1 (standard deviation ± 8.3)] enrolled in the project. Forty-nine per cent of patients were HAV antibody (Ab) positive, 81.1% hepatitis C virus (HCV) antibody (Ab) positive and 38.9% antiHBs positive. Exposure to multiple hepatitis viruses was common, with 24.5% testing positive for all three viruses. Seventy-three (83%) of the 88 antiHBs negative patients completed the vaccination schedule. Post-vaccination serology indicated a seroconversion rate of 75.4% (55 of 73) of completors, or 62.5% of eligible participants (55 of 88). Conclusion While there was a high rate of completion of the rapid vaccination schedule in this population, a moderate seroconversion rate was achieved. Further work is required to identify an optimal vaccination schedule in opioid substitution patients. [source]

Determinants of successful chronic hepatitis C case finding among patients receiving opioid maintenance treatment in a primary care setting

ADDICTION, Issue 12 2009
Oliver Senn
ABSTRACT Aims Injection drug users are at high risk for chronic hepatitis C virus infection (CHC). Opioid maintenance treatment (OMT) offers a unique opportunity to screen for CHC. This study proposed the hypothesis that a general practitioner (GP) with special interest in addiction medicine can achieve CHC screening rates comparable to specialized centres and aimed to investigate determinants for a successful CHC case finding in a primary care setting. Design and participants Retrospective medical record analysis of 387 patients who received opioid maintenance therapy between 1 January 2002 and 31 May 2008 in a general practice in Zurich, Switzerland. Measurements Successful CHC assessment was defined as performance of hepatitis C virus (HCV) serology with consecutive polymerase chain reaction-based RNA and genotype recordings. The association between screening success and patient characteristics was assessed using multiple logistic regression. Findings Median (interquartile range) age and duration of OMT of the 387 (268 males) patients was 38.5 (33.6,44.5) years and 34 (11.3,68.0) months, respectively. Fourteen patients (3.6%) denied HCV testing and informed consent about screening was missing in 13 patients (3.4%). In 327 of 360 patients (90.8%) with informed consent a successful CHC assessment has been performed. Screening for HCV antibodies was positive in 136 cases (41.6%) and in 86 of them (63.2%) a CHC was present. The duration of OMT was an independent determinant of a successful CHC assessment. Conclusions In addicted patients a high CHC assessment rate in a primary care setting in Switzerland is feasible and opioid substitution provides an optimal framework. [source]

Estimating population attributable risk for hepatitis C seroconversion in injecting drug users in Australia: implications for prevention policy and planning

ADDICTION, Issue 12 2009
Handan Wand
ABSTRACT Objective To determine risk factors and estimate their population-level contribution to hepatitis C virus (HCV) burden. Methods Established and potentially modifiable risk factors were estimated using partial population attributable risk (PARp) in a cohort of new injecting drug users (IDUs) in Sydney, Australia. Results A total of 204 hepatitis C seronegative IDUs were recruited through street-based outreach, methadone clinics and needle and syringe programmes (NSPs) and followed-up at 3,6-monthly intervals. A total of 61 HCV seroconversions were observed during the follow-up [overall incidence rate of 45.8 per 100 person-years (95% confidence interval: 35.6,58.8)]. Overall, five potentially modifiable risk factors (sharing needles/syringes, sharing other injecting equipment, assisted injecting, frequency of injection and not being in drug treatment) accounted for approximately 50% of HCV cases observed. Conclusion While sharing needles/syringes or other injecting equipment were associated most strongly with increased risk of HCV infection, the PARp associated with these behaviours was relatively modest (12%) because they are relatively low-prevalence behaviours. Our analyses suggest that more HCV infection could be avoided by changing more common, but less strongly associated behaviours such as assisted injecting or daily injecting. Results suggest that to have a very substantial effect on HCV, a range of risk factors need modifying. The most efficient use of scarce resources in reducing HCV infections will require complex balancing between the PAR for a given risk factor(s), the efficacy of interventions to actually modify the risk factor, and the cost of these interventions. [source]

Hepatitis C virus infection among drug injectors in St Petersburg, Russia: social and molecular epidemiology of an endemic infection

ADDICTION, Issue 11 2009
Elijah Paintsil
ABSTRACT Aims To understand the epidemiology and transmission patterns of hepatitis C virus (HCV), the predominant blood borne-pathogen infecting injection drug users (IDUs), in a part of the former Soviet Union. Design Cross-sectional respondent-driven sample of IDUs. Setting St Petersburg, Russia. Participants A total of 387 IDUs were recruited in late 2005 and throughout 2006. Measurements Participants were surveyed to collect demographic, medical and both general and dyad-specific drug injection and sexual behaviors. A blood sample was collected to detect antibodies to hepatitis C and to amplify viral RNA for molecular analysis. The molecular data, including genotypes, were analyzed spatially and linkage patterns were compared to the social linkages obtained by respondent-driven sampling (RDS) for chains of respondents and among the injection dyads. Findings HCV infection was all but ubiquitous: 94.6% of IDUs were HCV-seropositive. Among the 209 viral sequences amplified, genotype 3a predominated (n = 119, 56.9%), followed by 1b (n = 61, 29.2%) and 1a (n = 25, 11.9%). There was no significant clustering of genotypes spatially. Neither genotypes nor closely related sequences were clustered within RDS chains. Analysis of HCV sequences from dyads failed to find associations of genotype or sequence homology within pairs. Conclusions Genotyping reveals that there have been at least five unique introductions of HCV genotypes into the IDU community in St Petersburg. Analysis of prevalent infections does not appear to correlate with the social networks of IDUs, suggesting that simple approaches to link these networks to prevalent infections, rather than incident transmission, will not prove meaningful. On a more positive note, the majority of IDUs are infected with 3a genotype that is associated with sustained virological response to antiviral therapy. [source]

Doing harm reduction better: syringe exchange in the United States

ADDICTION, Issue 9 2009
Don C. Des Jarlais
ABSTRACT Objective To trace the growth of syringe exchange programs (SEPs) in the United States since 1994,95 and assess the current state of SEPs. Methods Annual surveys of US SEPs known to North American Syringe Exchange Network (NASEN). Surveys mailed to executive directors with follow-up interviews by telephone and/or e-mail. Response rates have varied between 70% and 88% since surveys were initiated in 1996. Results The numbers of programs known to NASEN have increased from 68 in 1994,95 to 186 in 2007. Among programs participating in the survey, numbers of syringes exchanged have increased from 8.0 million per year to 29.5 million per year, total annual budgets have increased from $6.3 to $19.6 million and public funding (from state and local governments) has increased from $3.9 to $14.4 million. In 2007, 89% of programs permitted secondary exchange and 76% encouraged it. Condoms, referrals to substance abuse treatment, human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) counseling and testing and naloxone for overdose were among the most commonly provided services in addition to basic syringe exchange. Each of these services was provided by 40% or more of SEPs in 2007. Conclusions While syringe exchange has remained controversial in the United States, there has been very substantial growth in numbers of programs, syringes exchange and program budgets. Utilizing secondary exchange to reach large numbers of injecting drug users and utilizing SEPs as a new platform for providing health and social services beyond basic syringe exchange have been the two major organizational strategies in the growth of SEPs in the United States. [source]

Use of supervised injection facilities and injection risk behaviours among young drug injectors

ADDICTION, Issue 4 2009
María J. Bravo
ABSTRACT Aims To study the use of supervised injection facilities (SIFs) as a predictor of safer injecting practices. Design Cross-sectional study conducted with face-to-face interview using a structured questionnaire with computer-assisted personal interviewing. Dried blood spot samples were collected for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) antibody testing. Setting All participants were street-recruited by chain referral methods in Madrid and Barcelona. Participants A total of 249 young heroin drug injectors recruited by the ITINERE cohort study in two Spanish cities with SIFs. Measurements The main outcome measures were self-reported injecting behaviours and SIFs attendance. Results SIF users were more marginalized socially than non-users. They were also more often regular injectors (weekly or more versus sporadic) [odds ratio (OR) = 4.9, 95% confidence interval (CI): 2.7,8.8], speedball users (OR = 2.5, 95% CI: 1.5,4.3) and anti-HCV-positive (OR = 3.1, 95% CI: 1.4,7.1). In the logistic regression analysis, using SIFs was associated independently with not borrowing used syringes (OR = 3.3, 95% CI: 1.4,7.7). However, no significant association was found between SIF use and not sharing injection equipment indirectly (OR = 1.1, 95% CI: 0.5,2.2). Conclusions SIFs attract highly disadvantaged drug injectors who engage none the less in less borrowing of used syringes than non-users of these facilities. The risks of indirect sharing should be emphasized when counselling SIF attendees. [source]

Psychopathological changes and quality of life in hepatitis C virus-infected, opioid-dependent patients during maintenance therapy

ADDICTION, Issue 4 2009
Arne Schäfer
ABSTRACT Aims To examine among maintenance patients (methadone or buprenorphine) with and without hepatitis C virus (HCV) infection (i) the frequency of psychopathological symptoms at baseline and 1-year follow-up; (ii) the association between antiviral interferon (IFN) treatment and psychopathological symptoms; and (iii) to explore whether IFN therapy has an effect on 1-year outcome of maintenance treatment. Design Naturalistic prospective longitudinal cohort design. Setting A total of 223 substitution centres in Germany. Participants A nationally representative sample of 2414 maintenance patients, namely 800 without and 1614 with HCV infection, of whom 122 received IFN therapy. Measures HCV infection (HCV+/HCV - ), IFN (IFN+/IFN - ) treatment status and clinical measures. Diagnostic status and severity (rated by clinician), psychopathology (BSI,Brief Symptom Inventory) and quality of life (EQ-5D,EuroQol Group questionnaire). Findings HCV+ patients revealed indications for a moderately increased psychopathological burden and poorer quality of life at baseline and follow-up compared to HCV - patients. HCV+ patients showed a marked deterioration over time only in the BSI subscale somatization (P = 0.002), and the frequency of sleep disorders almost doubled over time (12.8% at baseline; 24.1% at follow-up; P < 0.01). IFN treatment, received by 10% of HCV+ patients, did not impair efficacy or tolerability of maintenance therapy and was associated overall with neither increased psychopathological burden nor reduced quality of life. Conclusions Findings suggest no increased risk among HCV+ patients on maintenance therapy for depressive or other psychopathological syndromes. In our patient sample, IFN treatment was not associated with increased psychopathological burden, reduced quality of life or poorer tolerability and efficacy of maintenance treatment. [source]

Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients

ADDICTION, Issue 6 2008
David M. Novick
ABSTRACT Aims Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. Methods Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990,present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. Results Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53,96%) and in patients enrolled in methadone maintenance programs (67,96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28,94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72,100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. Conclusion High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them. [source]

Drug injecting and syringe use in the HIV risk environment of Russian penitentiary institutions: qualitative study

ADDICTION, Issue 12 2006
Anya Sarang
ABSTRACT Background Evidence highlights the prison as a high risk environment in relation to human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmsission associated with injecting drug use. Methods We undertook qualitative studies among 209 injecting drug users (IDUs) in three Russian cities: Moscow (n = 56), Volgograd (n = 83) and Barnaul in western Siberia (n = 70). Results Over three-quarters (77%) reported experience of police arrest related to their drug use, and 35% (55% of men) a history of imprisonment or detention. Findings emphasize the critical role that penitentiary institutions may play as a structural factor in the diffusion of HIV associated with drug injection in the Russian Federation. While drugs were perceived to be generally available in penitentiary institutions, sterile injection equipment was scarce and as a consequence routinely shared, including within large groups. Attempts to clean borrowed needles or syringes were inadequate, and risk reduction was severely constrained by a combination of lack of injecting equipment availability and punishment for its possession. Perceptions of relative safety were also found to be associated with assumptions of HIV negativity, resulting from a perception that all prisoners are HIV tested upon entry with those found HIV positive segregated. Conclusion This study shows an urgent need for HIV prevention interventions in the Russian penitentiary system. [source]

Prevalence of HIV, hepatitis C and syphilis among injecting drug users in Russia: a multi-city study

ADDICTION, Issue 2 2006
Tim Rhodes
ABSTRACT Objectives To estimate the prevalence of HIV, hepatitis C virus (HCV) and syphilis in injecting drug users (IDUs) in Russia. Methods Unlinked anonymous cross-sectional survey of 1473 IDUs recruited from non-treatment settings in Moscow, Volgograd and Barnaul (Siberia), with oral fluid sample collection for HIV, HCV antibody (anti-HIV, anti-HCV) and syphilis testing. Results Prevalence of antibody to HIV was 14% in Moscow, 3% in Volgograd and 9% in Barnaul. HCV prevalence was 67% in Moscow, 70% in Volgograd and 54% in Barnaul. Prevalence of positive syphilis serology was 8% in Moscow, 20% in Volgograd and 6% in Barnaul. Half of those HIV positive and a third of those HCV positive were unaware of their positive status. Common risk factors associated with HIV and HCV infection across the cities included both direct and indirect sharing of injecting equipment and injection of home-produced drugs. Among environmental risk factors, we found increased odds of anti-HIV associated with being in prison in Moscow, and some association between official registration as a drug user and anti-HIV and anti-HCV. No associations were found between sexual risk behaviours and anti-HIV in any city. Conclusions HIV prevalence among IDUs was markedly higher than city routine surveillance data suggests and at potentially critical levels in terms of HIV prevention in two cities. HCV prevalence was high in all cities. Syphilis prevalence highlights the potential for sexual risk and sexual HIV transmission. Despite large-scale testing programmes, knowledge of positive status was poor. The scaling-up of harm reduction for IDUs in Russia, including sexual risk reduction, is an urgent priority. [source]

HCV viremia is associated with drug use in young HIV-1 and HCV coinfected pregnant and non-pregnant women,

ADDICTION, Issue 5 2005
Georgia B. Nikolopoulou
ABSTRACT Aims Vertical transmission of HCV is increased among HIV-1/HCV coinfected women and is related to HCV viral load. In this study we assessed clinical and demographic factors associated with HCV viremia in a cohort of young pregnant and non-pregnant mothers coinfected with HIV-1. Design A cross-sectional clinic-based study nested within a prospective cohort study. Methods From 1988 to 2000, HIV-1 + pregnant and non-pregnant women with children followed in a large maternal, child and adolescent HIV-1 clinic were evaluated for HCV infection using EIA 3.0. HCV RNA levels were determined for HCV antibody + women using polymerase chain reaction. Demographic and clinical characteristics between HCV-RNA(+) and HCV-RNA(,) women and between pregnant and non-pregnant HIV-1/HCV coinfected women were compared using univariate and multivariate analyses. Findings Among 359 HIV-1(+) women, 84 (23%) were HCV-ab + and 49/84 (58%) had detectable HCV-RNA in plasma. Median age was 31. CD4 counts, HIV-1 RNA levels and demographic characteristics were similar for viremic and non-viremic women and pregnant and non-pregnant women. However, viremic women were more likely to report a history of (88% versus 43%; P < 0.001) or active injection drug use (AIDU) (83% versus 29%; P < 0.001). Logistic regression analysis showed that HCV viremia was associated significantly with AIDU (adjusted OR: 15.17; 95% CI: 3.56, 64.56) after adjusting for age, race, number of sexual partners, pregnancy status, CD4 counts and HIV-1 viral load. Conclusion In this cohort of young HIV-1 and HCV coinfected women, HCV viremia was associated strongly with active injection drug use, perhaps due to reinfection or reactivation of HCV. Thus, careful evaluation for HCV infection and counseling related to drug use may be necessary. [source]

The recent breakthroughs in the understanding of host genomics in hepatitis C

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2010
Andri Rauch
Eur J Clin Invest 2010; 40 (10): 950,959 Abstract Background, Hepatitis C Virus (HCV) infection is spontaneously resolved in about 30% of acutely infected individuals. In those who progress to chronic hepatitis C, HCV therapy permanently eradicates infection in about 40% of cases. It has long been suspected that host genetic factors are key determinants for the control of HCV infection. Design, We will review in this study four genome-wide association studies (GWAS) and two large candidate gene studies that assessed the role of host genetic variation for the natural and treatment-induced control of HCV infection. Results, The studies consistently identified genetic variation in interleukin 28B (IL28B) as the strongest predictor for the control of HCV infection. Importantly, single nucleotide polymorphisms (SNPs) in IL28B strongly predicted both spontaneous and treatment-induced HCV recovery. IL28B is located on chromosome 19 and encodes interferon-,, a type III interferon with antiviral activity, which is mediated through the JAK-STAT pathway by inducing interferon-stimulated genes. The SNPs identified in the GWAS are in high linkage disequilibrium with coding or functional non-coding SNPs that might modulate function and/or expression of IL28B. The role of the different IL28B alleles on gene expression and cytokine function has not yet been established. Conclusions, These findings provide strong genetic evidence for the influence of interferon-, for both the natural and treatment-induced control of HCV infection, and support the further investigation of interferon-, for the treatment of chronic hepatitis C. Furthermore, genetic testing before HCV therapy could provide important information towards an individualized HCV treatment. [source]

Natural killer cells in viral hepatitis: facts and controversies

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010
Mario U. Mondelli
Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source]

NF,B, cytokines, TLR 3 and 7 expression in human end-stage HCV and alcoholic liver disease

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010
Peter Stärkel
Eur J Clin Invest 2010; 40 (7): 575,584 Abstract Background/aims, Conflicting observations exist concerning the role of nuclear factor kappa B (NF,B) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll-like receptors (TLRs) expressions in conjunction with NF,B activation in non-active end-stage human ALD compared with normal livers and hepatitis C virus (HCV) related end-stage disease. Methods, mRNA and protein expression were examined by quantitative PCR and Western blotting, DNA-binding by electrophoretic mobility shift assays and NF,B sub-cellular localization by immunofluorescent staining of livers. Results, NF,B mRNA and protein expression as well as strong DNA-binding were preserved in ALD but significantly down-regulated in HCV compared with normal livers. P50 immunofluorescence was found in hepatocytes and bile ducts in ALD and normal livers, whereas a shift was observed in p65 staining from non-parenchymal cells in normal livers to hepatocytes in ALD. NF,B responsive genes mRNA levels IkB, and interleukin 6 were significantly higher in ALD compared with HCV. Tumour necrosis factor alpha (TNF,), TLRs 3 and 7 mRNA were up-regulated in ALD and HCV compared with normal liver with TNF, and TLR7 being the highest in HCV. Strong induction of interferon beta was found in HCV but not in ALD or normal liver tissue. Conclusions, Persistent NF,B activation together with high pro-inflammatory cytokine expression and upregulation of TLR3 and TLR7 is associated with end-stage ALD in humans and could contribute to disease progression even in absence of alcohol intake. [source]

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008
Omer Dizdar
Abstract Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV(+) patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels. [source]

HIV+ MALT lymphoma remission induced by highly active antiretroviral therapy alone

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2005
Thomas Girard
Abstract:, MALT lymphoma is usually described in association with Helicobacter pylori, HCV, HHV8, Campylobacter jejuni or in a setting of overreactive immunity. In HIV+ patients, MALT lymphoma is most commonly described in children. We describe here an original case of HIV+ MALT lymphoma with bronchial, conjuctival and laryngeal involvement for which a clinical and histopathological remission has been obtained with HAART alone. We conclude that HIV, as well as H. pylori, C. jejuni and HCV can target lymphogenesis in MALT lymphoma. [source]

Interleukin-4 downregulates CD127 expression and activity on human thymocytes and mature CD8+ T cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010
Angela M. Crawley
Abstract Signaling via the IL-7 receptor complex (IL-7R,/CD127 and IL-2R,/CD132) is required for T-cell development and survival. Decreased CD127 expression has been associated with persistent viral infections (e.g. HIV, HCV) and cancer. Many IL-2R,-sharing (,C) cytokines decrease CD127 expression on CD4+ and CD8+ T cells in mice (IL-2, IL-4, IL-7, IL-15) and in humans (IL-2, IL-7), suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8+ T cells is unknown and was therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested and only on naïve (CD45RA+) CD8+ T cells, without altering membrane-bound CD127 mRNA expression. Pre-treatment of thymocytes or CD8+ T cells with IL-4 inhibited IL-7-mediated phosphorylation of STAT5 and decreased proliferation of CD8+ T cells. By downregulating CD127 expression and signaling on developing thymocytes and CD8+ T cells, IL-4 is a potential contributor to impaired CD8+ T-cell function in some anti-viral and anti-tumor responses. These findings are of particular consequence to diseases such as HIV, HCV, RSV, measles and cancer, in which CD127 expression is decreased, IL-7 activity is impaired and IL-4 concentrations are elevated. [source]

Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2008
Donatella Ciuffreda
Abstract HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-, and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-, and single IFN-,-producing CD4+ and dual IL-2/IFN-, and single IFN-,-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-,-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation. [source]

Increased natural cytotoxicity receptor expression and relevant IL-10 production in NK cells from chronically infected viremic HCV patients

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007
Andrea De Maria M. D.
Abstract Hepatitis C virus (HCV) readily establishes high-level lifelong persistent infection in the majority of immunocompetent adults with failure of HCV-specific CD8+ CTL to clear viral replication. Virus-induced conditioning of innate immune responses is a possible mechanism that may contribute to the impairment of virus-specific CD8+ CTL responses. Here, we analyzed whether triggering of NK cell receptor expression and function is affected during chronic viremic HCV infection. Flow cytometric analysis of purified resting peripheral NK cells showed no evidence of NK cell activation, while analysis of natural cytotoxicity receptors (NCR) showed that NK cells from HCV-infected patients had selective increased expression of NKp30 and NKp46. NK cells had corresponding conserved cytotoxic activity against all targets with the exception of HepG2 hepatoma cells. Freshly separated NK cells from HCV patients showed significant production of IL-10 and normal concentrations of IFN-, upon cell-mediated triggering. Thus, increased expression of NKp30 during HCV infection with increased IL-10 production could contribute, once NK cells localize in the liver, to a NK-DC crosstalk leading to skewing of subsequent adaptive immune responses and lack of virus control. [source]

T cell costimulation by the hepatitis C virus envelope protein E2 binding to CD81 is mediated by Lck

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2003
Elisabetta Soldaini
Abstract Binding of the hepatitis C virus (HCV) envelope protein E2 to CD81 provides a costimulatory signal for human T cells. This phenomenon may play a role in liver damage and autoimmune manifestations associated with HCV infection. Here we show that cross-linking of CD81 by HCV E2 induced a calcium flux in T cells that depends on Lck since it was blocked by PP1 and absent in Lck-deficient Jurkat T cells. In wild-type Jurkat cells, Lck was activated by CD81 cross-linking, and CD81, like Lck, was found in lipid rafts. Indeed, the integrity of the raft compartment was required for the induction of a calcium flux by E2, since methyl-,-cyclodextrin abolished this response. A requirement for TCR/CD3 expression was indicated by the absence of a calcium flux following E2 stimulation of TCR/CD3-deficient Jurkat cells. CD81 cross-linking increased and prolonged the anti-CD3-induced tyrosine phosphorylation of TCR, and of other proteins, indicating that the CD81-mediated signal converges with the TCR/CD3 signaling cascade at its most upstream step. In conclusion, we propose that the costimulatory effects of HCV E2 on T cells depend on CD81 cross-linking that activates Lck through raft aggregation and thus leads to enhanced TCR signaling. [source]