Treatment of HBV/HCV coinfection

Importance of the field: Hepatitis B (HBV) and hepatitis C (HCV) virus infections are among the most common causes of advanced chronic liver disease worldwide. HBV/HCV coinfection is not uncommon with an estimated 7 – 20 million individuals affected worldwide. Patients with HBV/HCV coinfection have an increased risk for cirrhosis, hepatocellular carcinoma (HCC) and even death.

Areas covered in this review: The pathophysiology of HBV/HCV coinfection is complex, as different patterns of virological dominance may occur, which can even fluctuate over time. Recently, combination of pegylated interferon (PEG-IFN) plus ribavirin has been explored in HBV/HCV coinfected patients who are positive for HCV-RNA. HBV polymerase inhibitors may be indicated if HBV-DNA concentrations are above 2000 IU/ml. In this review, we summarize the epidemiology, viral interaction, its clinical features and the available treatment options.

What the reader will gain: Insights into viral interaction of HBV/HCV coinfection and treatment individualization strategies are provided in the review.

Take home message: Detailed serological and virological evaluations are required for HBV/HCV coinfected patients before initiation of antiviral therapy. At present, PEG-IFN-α plus ribavirin should be the treatment of choice in patients with dominant HCV replication. However, HBV rebound may occur after elimination of HCV, and thus close monitoring for both viruses is recommended even for patients with initially suppressed HBV-DNA.     

艾滋病合并乙型肝炎、丙型肝炎治疗建议

人免疫缺陷病毒(HIV)、乙型肝炎病毒(HBV)及丙型肝炎病毒(HCV)具有相同的传播途径,临床常见HIV/HBV以及HIV/HCV合并感染。合并感染者的临床抗反转录病毒治疗(ART)方案和治疗时机与非合并感染者有一定差异,或患者在接受ART前需筛查HBV和HCV。本文简要综述HIV/HBV以及HIV/HCV合并感染病例的治疗时机、治疗方案选择、停药问题和不良反应处理等。     

An update on the treatment options for HBV/HCV coinfection

Introduction: Despite the reciprocal inhibition exerted by HBV and HCV genomes, dual HBV/HCV infection is associated with more severe forms of liver disease and warrant effective treatment.

Areas covered: A careful evaluation of disease progression to establish the predominance of one virus over another, concomitant HIV infection and comorbidities is essential to make the best therapy choices. In most virological conditions interferon (IFN)-based treatment has been replaced by a combination of different classes of second generation directly acting antivirals (DAAs), which offer better tolerability and HCV eradication in 95% of cases. Tenofovir or entecavir should be part of treatment for patients with active HBV production, for those coinfected with HIV and for those with cirrhosis.

Expert opinion: DAAs have been successfully used to eradicate HCV infection in recent years, but the high cost may limit their use particularly in developing countries. Entecavir and tenofovir have been demonstrated to be effective for long-term inhibition of HBV replication. Careful monitoring of serum ALT and markers of HBV and HCV replication before and during treatment is essential for an early diagnosis and treatment of virus reactivation.     

Influence of HCV or HBV coinfection on adverse drug reactions to antiretroviral drugs in HIV patients

Objective To compare the profile of adverse drug reactions (ADRs) to antiretroviral (ARV) drugs in patients coinfected with hepatitis C virus (HCV) or hepatitis B virus (HBV) versus non-coinfected patients with human immunodeficiency virus (HIV) infection. Methods We used the French Pharmacovigilance Database from 2000 to 2002. Selected patients were classified into four groups: HIV+HCV, HIV+HBV, HIV+HBV+HCV and HIV patients. We compared patients’ characteristics and profiles of ADRs to ARV drugs between the four groups. Results We identified 1,068 HIV, 172 HIV+HCV, 72 HIV+HBV and 26 HIV+HBV+HCV patients with 2,398, 446, 183 and 70 ADRs related to ARV drugs, respectively. The “seriousness” of these ADRs was similar in HIV and coinfected patients but death related to the ADRs was more frequent in HIV+HCV (9.4%) than in HIV (3.6%) patients (p<0.001). “Liver and bile system disorders” were more frequently reported in HIV+HCV and HIV+HBV patients than in HIV patients (17.3% and 20.8%, respectively, versus 8.9%, p<0.001). In HIV+HBV patients, the occurrence of these ADRs was independently associated in a logistic regression model to male gender [odds ratio (OR): 9.28, 95% confidence interval (CI): 2.74–31.36], exposure to zalcitabine (OR: 17.82, 95% CI: 1.49–212.95) or efavirenz (OR: 5, 95% CI: 1.44–17.33). “Red blood cell disorders” were also more frequent in HIV+HCV (7.4%) than in HIV (4.4%) patients (p<0.01). Conclusion Hepatic or haematological (mainly anaemia) ADRs to ARV drugs are more frequent in coinfected patients than in HIV patients. This study underlines the importance of hepatitis B or C in the occurrence of ADRs in HIV patients on ARV drugs.     

Advances in the treatment of HIV/HCV coinfection in adults

Introduction: Direct-acting antivirals (DAA) have revolutionized the modern treatment of chronic hepatitis C (HCV). These highly efficacious, well-tolerated, all-oral HCV regimens allow cure of HCV in over 95% of HCV-monoinfected as well as HIV/HCV-coinfected patients with short treatment durations of 8–12 weeks.

Areas covered: This review will address recent developments of DAA-therapy in HIV/HCV-coinfected patients in clinical trials and real life cohorts and evaluate remaining challenges, particularly resistance, drug-drug interactions, acute HCV infection and liver transplantation focusing on HIV/HCV-coinfected patients.

Expert opinion: Indeed, all available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome. Management, indication of therapy and follow-up of HCV-infection are now the same for both patient populations. HIV/HCV-coinfected patients however, require careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other comedications. The few remaining gaps in DAA-therapy in particular treatment of cirrhotic treatment-experienced genotype 3 infections, decompensated cirrhosis, chronic kidney disease and patients with prior DAA treatment failure have mostly been overcome by the development of new HCV agents recently licensed. Clearly, the biggest challenge globally remains the access to treatment and the inclusion of all patient populations affected in particular people who inject drugs (PWID).     

The impact of parental modeling and permissibility on alcohol use and experienced negative drinking consequences in college

This study examined the impact of parental modeled behavior and permissibility of alcohol use in late high school on the alcohol use and experienced negative drinking consequences of college students. Two-hundred ninety college freshmen at a large university were assessed for perceptions of their parents' permissibility of alcohol use, parents' alcohol-related behavior, and own experienced negative consequences associated with alcohol use. Results indicate that parental permissibility of alcohol use is a consistent predictor of teen drinking behaviors, which was strongly associated with experienced negative consequences. Parental modeled use of alcohol was also found to be a risk factor, with significant differences being seen across the gender of the parents and teens. Discussion focuses on risk factors and avenues for prevention research.     

Recent advances in the treatment of HIV/HBV and HIV/HCV co-infection

Concurrent infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients positive for human immunodeficiency virus (HIV) is relatively common. The treatment of co-infected individuals is rather complex because the anti-viral therapy may be associated with drug-resistance, hepatotoxicity and lack of response. Herein, we present a summary of the available compounds and the recent recommendations concerning the therapeutic management of HIV/HBV and HIV/HCV co-infections.     

某艾滋病治疗示范区HIV/AIDS患者合并HBV/HCV感染调查

目的探讨人免疫缺陷病毒-1(HIV-1)/AIDS患者合并乙型肝炎病毒(HBV)/丙型肝炎病毒(HCV)感染情况及发病特点。方法分析国家"十一五重大专项"课题中河南某获得性免疫缺陷综合征(Acquired immu-nodeficiency syndrome,AIDS)示范区中187例经血液途径感染HIV-1者的血浆,采用酶联免疫吸附试验(ELISA)检测乙型肝炎表面抗原与抗体(HBsAg与抗HBs)、乙型肝炎e抗原与抗体(HBeAg与抗Hbe)、乙型肝炎核心抗体(抗HBc)及丙型肝炎抗体(抗HCV);采用流式细胞仪计数CD4+T淋巴细胞;采用制备膜选择性吸附DNA的方法抽提HBV DNA,并采用巢式PCR法检测HBV DNA。结果 187例HIV-1感染者中,HBsAg阳性9例(4.81%),HBsAg阴性178例(95.19%);抗-HCV阳性143例(76.47%),抗-HCV阴性44例(23.53%);HIV-1/HBV/HCV三重感染者6例(3.21%)。178例HBsAg阴性的HIV感染者中,合并隐匿性HBV感染53例(29.78%)。抗-HCV阳性者合并隐匿性HBV感染42例(29.37%),抗-HCV阴性者合并隐匿性HBV感染11例(25.00%),差异均无统计学意义(P>0.05)。抗-HCV阳性/抗-HCV阴性患者的HbsAg阳性例数、抗-HBs阳性例数、CD4+T淋巴细胞数、单独抗-HBc阳性例数比较差异均无统计学意义(P>0.05)。结论经血传播感染HIV患者中HBsAg阳性率低于普通人群,HCV感染率显著高于普通人群;经输血传播感染HIV患者中存在隐匿性HBV感染,对HBsAg阴性的HIV感染者进行HBV DNA检测是有必要;HIV合并HCV感染不能增加隐匿性HBV感染率。     

122例艾滋病患者合并乙肝病毒 丙肝病毒感染的临床流行病学研究

目的 研究在抗逆转录病毒药物治疗(HAART)状态下HIV/AIDS患者合并乙肝病毒(HBV)、丙肝病毒(HCV)的流行状况以及相关血清生化和病毒学特征。 方法 对122例正在接受HAART治疗的HIV/AIDS患者采集血标本,使用酶免法(MEIA)检测乙肝五项指标(HBs Ag、抗-HBs、HBe Ag、抗-HBe、抗-HBc)、肝功能,应用酶联免疫吸附法(ELISA)检测丙型肝炎病毒抗体,运用RT-PCR法对丙肝病毒抗体阳性标本以及表面抗原和/或核心抗体阳性标本分别进行HCV-RNA以及HBV-DNA测定。以43名单纯HCV感染者作为对照组进行研究。 结果 122名 HIV/AIDS患者,乙肝五项指标全阴性97例(78.86%),表面抗原阳性3例(2.46%),表面抗体阳性者总计19例(15.57%),单纯核心抗体阳性者3例(2.46%)。HCV 抗体阳性84例(68.85%),84例HCV抗体阳性标本中HCV-RNA 阳性58例(69.05%),HIV/HCV/HBV合并感染者为0。HIV/HCV合并感染组 HCV-RNA 水平与感染者性别,CD4⁺ 细胞数水平无明显差异(P>0.05);HIV/HCV合并感染组与单纯HCV感染组 HCV-RNA水平、肝功能异常率无明显差异(P>0.05)。 结论 HIV感染者HBsAg阳性率低于普通人群,HIV/HCV合并感染的比例显著高于普通人群。HIV/HCV合并感染与单纯HCV感染者血清生化及病毒学改变相似。     

The impact of alcohol taxation on liver cirrhosis mortality

OBJECTIVE: The objective of this study is to investigate the impact of distilled spirits, wine, and beer taxes on cirrhosis mortality using a large-panel data set and statistical models that control for various other factors that may affect that mortality. METHOD: The analyses were performed on a panel of 30 U.S. license states during the period 1971-1998 (N = 840 state-by-year observations). Exogenous measures included current and lagged versions of beverage taxes and income, as well as controls for states' age distribution, religion, race, health care availability, urbanity, tourism, and local bans on alcohol sales. Regression analyses were performed using random-effects models with corrections for serial autocorrelation and heteroscedasticity among states. RESULTS: Cirrhosis rates were found to be significantly related to taxes on distilled spirits but not to taxation of wine and beer. Consistent results were found using different statistical models and model specifications. CONCLUSIONS: Consistent with prior research, cirrhosis mortality in the United States appears more closely linked to consumption of distilled spirits than to that of other alcoholic beverages.     

阿德福韦酯治疗失代偿期乙型肝炎肝硬化临床观察

目的观察阿德福韦酯治疗失代偿期乙型肝炎肝硬化的临床效果。方法 40例失代偿期乙型肝炎肝硬化患者,随机分为治疗组和对照组,每组20例。对照组用常规方法治疗,治疗组在常规治疗基础上加用阿德福韦酯10 mg,口服,1次/d,治疗96周。观察治疗前后肝功能变化、HBV-DNA定量、生存时间及不良反应。结果治疗组血清谷丙转氨酶(ALT)、血清谷草转氨酶(AST)、胆红素(TBIL)、白蛋白(ALB)、胆碱酯酶(CHE)等指标均优于对照组,两组之间差异有统计学意义(P<0.01)。治疗组有18例患者HBV-DNA转阴,转阴率为90%,而对照组仅有2例患者转阴,转阴率为10%,两组转阴率比较差异有统计学意义(P<0.01)。治疗组治疗期间未发现与服用阿德福韦酯有关的不良反应。结论阿德福韦酯治疗失代偿期乙型肝炎肝硬化,可以显著改善肝功能,延长患者生存时间,其疗效肯定,不良反应少,患者耐受性好,值得临床推广应用。     

自愿戒毒医院海洛因依赖者HBV、HCV感染的调查与分析

目的：了解上海地区自愿戒毒医院海洛因依赖者HBV、HCV感染状况,为相应的疾病控制提供科学依据。方法：对新入院的1642例海洛因依赖者进行HBV、HCV血清学检测并分类。结果：HBV抗体阳性率7．32％,其中男性阳性率（6．99±2．32）％,女性（6．12±2．41）％;P〉0．05。HCV抗体阳性率41．38％,其中男性阳性率（42．14±3．94）％,女性（45．96±9．57）％;两者之间没有显著差异（P〉0．05）。结论：上海地区自愿戒毒医院海洛因依赖者HCV感染率也远远高于普通人群,但男女之间没有显著差异。