Antiretroviral drugs do not facilitate hepatitis C virus (HCV) infection in vitro

An estimated 4 to 5 million people are co-infected with HIV/HCV worldwide. Recently observed outbreaks of acute HCV infection among HIV-positive men who have sex with men (MSM) have been linked to behavioral factors such as high risk sexual practices and recreational drug use. However, at the molecular level, many drugs such as glucocorticoids or cyclosporine A have been found to modulate viral replication. Thus, it is conceivable that drugs used in highly active antiretroviral therapy (HAART) may heighten susceptibility to HCV infection and contribute to the recent outbreaks. We therefore performed a comprehensive screen of antiretroviral drugs covering all available drug classes both individually and in typical combinations used during HAART to probe for direct effects on HCV cell entry, replication, new particle assembly and release. Importantly, no significant enhancement or inhibition of HCV cell entry, replication or new particle production was detected. While raltegravir and ritonavir boosted atazanavir reduce HCV replication, a tenfold reduction of HCVcc entry by the CCR5 antagonist maraviroc was observed. In conclusion, commonly used HAART agents do not specifically enhance HCV replication. Thus recent epidemic outbreaks of acute HCV in HIV-infected MSM are unlikely to be related to enhancing effects of HAART drugs.     

Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection

Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABA(B) receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some Liver Function Tests (LFTs) (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients.     

广东地区丙型肝炎患者HCV基因亚型分析

目的 了解广东地区丙型肝炎患者HCV的基因亚型分布特征,为丙型肝炎的治疗与预防提供依据.方法 采用巢式逆转录-聚合酶链反应扩增广东省194例丙型肝炎患者HCVNS5B基因区域,特异性PCR产物测序后通过美国洛斯拉莫斯国家实验室HCV数据库的Blast程序进行HCV基因亚型分析.结果 194例丙型肝炎患者中有99例为单纯HCV感染者、95例为HIV/HCV共感染者.丙型肝炎患者HCV共有8种基因亚型,其中1b亚型占42.3％(82/194)、6a亚型占35.0％(68/194)、3a亚型占11.9％(23/194)、3b亚型占6.7％(13/194)、2a亚型占2.6％(5/194)、1a亚型占0.5％(1/194)、4a亚型与0.5％(1/194)、5a亚型占0.5％(1/194).丙型肝炎患者中的单纯HCV感染者HCV有7种基因亚型,以1b亚型为主,占67.7％(67/99);丙型肝炎患者中的HIV/HCV共感染者HCV有5种基因亚型,以6a亚型为主,占53.7％(51/95).结论 广东地区丙型肝炎患者HCV基因亚型呈现多样性,主要基因亚型为1b亚型和6a亚型;丙型肝炎患者中的单纯HCV感染者与HIV/HCV共感染者HCV主要基因亚型不同.     

Short-term injection drug use changes following hepatitis C virus (HCV) assessment and treatment among persons who inject drugs with acute HCV infection

BackgroundIt is unclear whether treatment and care for hepatitis C virus (HCV) infection can help people who inject drugs (PWID) modify their injection drug use behaviours. This study examined changes in injection drug use among PWID with acute HCV systematically referred for HCV clinical assessment and treatment and offered targeted health care services, over the course of one year.MethodsThe study sample included PWID with documented acute HCV infection recruited and followed-up semi-annually at least twice in IMPACT (2007–2015), a longitudinal community-based prospective study in Montréal, Canada. Following enrolment, participants with contra-indications to treatment due to severe co-morbidity were offered targeted health care services. Pegylated interferon-alpha (12–24 weeks) was offered to all other participants who did not spontaneously resolve their infection. At each study visit, data were collected on socio-demographic factors and drug use patterns. Logistic regression was used to assess changes in injection drug use at one-year follow-up.ResultsOf the 87 eligible participants (mean age: 35.6; 78.2% male), 21.8% received treatment [(RT), Sustained virological response: 84.2%], 25.3% spontaneously resolved their infection (SR), 14.9% had contra-indication(s) (CI) and 37.9% chose not to engage in HCV care post-diagnosis (NE). In multivariate analyses adjusting for age, gender and injection drug use at baseline, the RT [Adjusted odds ratio (AOR): 0.18; 95% Confidence interval (CI): 0.04–0.76], SR (AOR: 0.34; 95% CI: 0.08–1.40), and CI (AOR: 0.24; 95% CI: 0.05–1.22) groups were less likely to report injection drug use at follow-up relative to the NE group.ConclusionPWID who received treatment, spontaneously resolved their infection or presented with treatment contra-indication(s) reported reduced injection drug use at one-year follow-up relative to those who did not engage in therapy. Findings suggest that the benefits of HCV assessment and treatment may extent to helping PWID modify their injection drug use patterns.     

Meta-analysis: Effect of hepatitis C virus infection on mortality in dialysis

BACKGROUND: The natural history of hepatitis C virus infection among patients on long-term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life-expectancy is substantially diminished by end-stage renal disease. AIM: To conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus infection on the survival of patients receiving chronic dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. METHODS: We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality with hepatitis C virus across the published studies. RESULTS: We identified four clinical trials (2341 unique patients); three (75%) of them were prospective, cohort studies; the fourth was a case-control study. Pooling of study results demonstrated that presence of antihepatitis C virus antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for relative risk was 1.57 with a 95% confidence interval (CI) of 1.33-1.86. A test for homogeneity of the relative risks across the four studies gave a P-value of 0.77. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among antihepatitis C virus-positive than -negative dialysis patients. CONCLUSIONS: This meta-analysis demonstrates that antihepatitis C virus-positive patients on dialysis have an increased risk of mortality compared with hepatitis C virus-negative patients. The excess risk of death in hepatitis C virus-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. Clinical trials with extended follow-up are currently under way to assess the effect of hepatitis C virus treatment on the excess risk of mortality in this population.     

Acute hepatitis C: clinical aspects, diagnosis, and outcome of acute HCV infection

Acute hepatitis C virus (HCV) infection is often a clinically silent infection, and is therefore rarely detected. A high index of clinical suspicion in addition to careful serological and virological assessment is required to identify the disease, and to determine the eventual clinical outcome after primary infection; the minority of acutely infected individuals spontaneously control viremia in long term whilst the majority become persistently infected. Here, we describe the clinical presentation of acute HCV infection and the patterns of viremia and liver alanine transaminase levels (ALT) observed. We discuss the serological and virological assessment and potential pitfalls in accurately diagnosing acute HCV. Good prospective studies that identify host and virological factors that determine clinical symptoms and disease outcome are difficult to perform due to the asymptomatic nature of infection, but some progress has been made in this field. Host factors including gender, age at time of infection, prior resolution of infection, symptomatic infection and host immune responses, and viral factors such as the nature of the infecting quasispecies and more speculatively viral genotype, are some features that have been correlated with disease outcome. In spite of this, on an individual patient level, it is currently not possible to predict those that will resolve infection. Identifying, in detail therefore, those factors that are responsible for viral control remains an important research goal not only to aid clinical management but also to develop effective treatment and vaccination strategies.     

CYP1A1 MSPI (T6235C) gene polymorphism is associated with mortality in acute coronary syndrome patients

1. The CYP1A1 T6235C polymorphism (rs4646903) gene polymorphism has been linked to the development of coronary heart disease and cigarette smoking‐related lung cancer. The present study investigated associations between survival in acute coronary syndromes (ACS), smoking and the CYP1A1 T6235C polymorphism. 2. Patients with ACS (n = 1251) were genotyped for the CYP1A1 T6235C polymorphism. Patients had a mean age of 67.0 years, 69.8% were male and follow up occurred over a median of 1.9 years. 3. Overall genotype frequencies were CC 2.2%, TC 21.7% and TT 76.1%. The CC genotype was associated with baseline characteristics of a higher incidence of Type 2 diabetes (P = 0.017), elevated body mass index (P = 0.001) and younger age (P = 0.045). Patients with the CC genotype had significantly worse survival than TT/TC patients (P = 0.014), independent of ethnicity and established clinical risk factors. When survival was stratified by smoking history, the T6235C genotype was particularly associated with mortality in past or current smokers (mortality 23.5 vs 9.4% in CC and TT/TC patients, respectively; P = 0.019) compared with those who had never smoked (mortality 11.1 vs 11.5% in CC and TT/TC patients, respectively; P = 0.853). 4. The results indicate that the homozygous CYP1A1 6235C genotype is associated with greater mortality following the onset of ACS, independent of ethnicity and clinical risk factors, but related to smoking history.     

Substance use is independently associated with pneumonia severity in persons living with the human immunodeficiency virus (HIV)

Background: Pneumonia is common in persons living with the human immunodeficiency virus (HIV) (PLWH). Alcohol, cocaine, and marijuana impact pneumonia pathogenesis. We hypothesized that substance use was independently associated with pneumonia severity in PLWH and modified the effect of alcohol on pneumonia severity. Methods: Retrospective data analysis of PLWH admitted with a diagnosis of pneumonia was conducted. Alcohol use disorder was defined by the Alcohol Use Disorders Identification Test score ≥14. Drug use was quantified by self-report. Pneumonia severity was defined by the pneumonia severity index (PSI). Multivariable linear regression was used to test independent associations with pneumonia severity and effect modification by sex. Results: Of 196 PLWH, the mean age was 44?(SD?=?9) years and the majority were men (71%). Ten percent (n?=?19) of subjects met criteria for an alcohol use disorder (AUD). In subjects reporting alcohol use, 25% reported concomitant crack/cocaine use and 16% reported marijuana use. PSI scores were higher with lifetime use of crack/cocaine (mean PSI: 63.1 vs. 57.3, P?=?.06) and/or injection drug use (68.4 vs. 54.9, P?=?.04). PSI scores were lower with active marijuana use (51.5 vs. 62.2, P?=?.01). There was no significant difference in clinical outcomes. Sex modified the effect of drug use on PSI, with greater PSI scores in women with an AUD (β?=?58.1, 95% confidence interval [CI]: 46.7 to 69.5, P?<?.01), whereas active marijuana use mitigated the effect of AUD on PSI in men (β?=??12.7, 95% CI: ?18.8 to ?6.6, P?<?.01). Conclusions: Active alcohol and/or crack/cocaine use was associated with increased pneumonia severity in PLWH, with less severe pneumonia with marijuana use. Alcohol and marijuana effects on pneumonia severity differed by sex, with increased PSI in women and decreased PSI in men with concomitant marijuana and AUD.     

Exploring drug users' attitudes and decisions regarding hepatitis C (HCV) treatment in the U.S

Individuals with a history of injecting drugs are at the highest risk of becoming infected with the hepatitis C virus (HCV), with studies of patients in methadone maintenance treatment programmes (MMTPs) reporting that 60-90 percent of intravenous drug users (IDUs) have the virus. Fortunately, HCV therapy has been shown to be effective in 42-82 percent of all patients with chronic HCV infection, including IDUs. While the decision to start HCV therapy requires significant consideration, little research exists that explores the attitudes of drug users toward HCV therapy. Therefore, this paper examines how drug users perceive the treatment, as well as the processes by which HCV-positive individuals examined the advantages and disadvantages of starting the HCV medications. Interviews were conducted with 164 patients from 14 drug treatment programmes throughout the United States, and both uninfected and HCV-positive drug users described a pipeline of communication among their peers that conveys largely negative messages about the medications that are available to treat HCV. Although many of the HCV-positive individuals said that these messages heightened their anxiety about the side effects and difficulties of treatment, some patients said that their peers helped them to consider, initiate HCV treatment or both. Gaining a better understanding of drug users' perceptions of HCV treatment is important, because so many of them, particularly IDUs, are already infected with HCV and may benefit from support in addressing their HCV treatment needs. In addition, currently uninfected drug users will likely remain at high risk for contracting HCV and may need to make decisions about whether or not to start the HCV medical regimen in the future.     

丙型和乙型肝炎合并感染患者的抗病毒治疗分析

目的：探讨HBV／HCV合并感染患者的临床特征以及对聚乙二醇干扰素α-2a（ PEGIFNα-2a）联合利巴韦林的抗病毒疗效。方法选取收治的HBV／HCV合并感染患者45例（ A组）,单纯HBV感染患者49例（ B组）,单纯HCV感染患者38例（ C组）,比较病毒感染和抗病毒疗效。结果 A组与B组HBeAg阳性率、HBV DNA阳性率、HBV DNA平均值以及HBV DNA量的患者分布差异有统计学意义（ P ＜0貂．05）;A组与C组HCV RNA平均值差异无统计学意义（ P ＞0．05）,HCV RNA量的患者分布差异有统计学意义（ P ＜0．05）;A组与C组基因型分布、HCV RNA和ALT差异无统计学意义（ P ＞0．05）,PLT、WBC、PTA和Alb差异具有统计学意义（ P ＜0．05）;Ⅰ基因型中,A组与C组pEVR、ETVR以及复发率差异有统计学意义（ P ＜0．05）,RVR、cEVR以及SVR差异无统计学意义（ P ＞0．05）;非Ⅰ基因型中,RVR、cEVR、pEVR、ETVR、SVR以及复发率差异均无统计学意义（ P ＞0．05）;A组与C组不良反应例数以及WBC和PLT减少例数差异有统计学意义（ P ＜0．05）,溶血以及甲状腺功能减退差异无统计学意义（ P ＞0．05）;未获得SVR患者和获得SVR患者阳转率差异具有统计学意义（ P ＜0．05）。结论丙型和乙型肝炎合并感染患者以HCV为优势病毒株为主,HBV复制受抑制。合并感染Ⅰ基因型患者复发率、部分早期病毒学应答和治疗结束时病毒学应答高于单纯HCV感染患者,持续病毒学应答相似,但合并感染对非基因Ⅰ型病毒学应答率无影响。