Challenges in the treatment of chronic hepatitis C in the HIV/HCV-coinfected patient

Hepatitis C virus (HCV) and HIV are common coinfections that convey a shortened lifespan, mostly related to liver disease. Treatment against HCV in the coinfected patient is notoriously more complex and challenging. There are no optimal treatment algorithms for HIV/HCV coinfected patients as efficacy of approved anti-HCV therapies is low with relevant side effects. The use of direct-acting antivirals for anti-HCV therapy has the potential to improve therapeutic efficacy, but also increase side effects and drug–drug interactions. In spite of all of this, the most important and significant fact is that chronic hepatitis C is potentially curable, and the eradication of the HCV infection is a crucial outcome in this population. The establishment of a productive collaboration among the regulatory agencies, the medical community and the pharmaceutical industry could lead to faster access to more effective HCV therapies for the coinfected patient and eventually stop the progression of liver disease in these patients.     

Hepatitis C virus--biology, host evasion strategies, and promising new therapies on the horizon

Hepatitis C reduces the quality of life for some 170 million people around the globe and is one of the most prevalent diseases on the planet. It is caused by the hepatitis C virus (HCV) that is replicated by an error-prone polymerase and therefore undergoes rapid evolution. To date, although much has been learned about the biology of HCV, only a partially effective combination therapy comprised of ribavirin and pegylated-interferon-alpha is available to hepatitis C sufferers. Given the prevalence of hepatitis C, together with the fact that almost half the chronically infected HCV patients are refractory to current therapy, there is an urgent need for an efficacious immunoprophylactic that protects individuals from HCV infection, as well as drugs that impede the viral life cycle effectively and eradicate infection. Herein, I provide an overview of the molecular biology of HCV, highlighting the functions of different virally encoded proteins in terms of how they alter signaling pathways of host cell to establish an infection and discuss whether a more promising therapy for treating hepatitis C is anywhere in sight.     

Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers

This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.     

Direct-acting antiviral treatment of acute hepatitis C virus infections

Introduction: Hepatitis C contributes to significant morbidity and mortality worldwide. AHCV is defined as documented infection within 6 months of exposure. Treating acute hepatitis C virus (AHCV) with direct-acting antiviral agents in persons who inject drugs, HIV-positive men who have sex with men, and patients who acquire HCV nosocomially can contribute to the elimination of disease globally, preclude the morbidity and mortality of chronic disease, and prevent further transmission.

Areas covered: In this review, we describe the epidemiology of AHCV, its natural history, the considerations involved in the decision of whether to treat AHCV, and the most current DAA therapy guidelines. PubMed was queried using key words and bibliographies were evaluated for relevant articles.

Expert commentary: Despite the obvious benefits of AHCV treatment, clinical management is limited by the ability to identify asymptomatic cases and the absence of fully supported guidelines. However, clinical research is advancing and identifying specific regimens, decreasing treatment durations, and creating strategies to target at risk groups and screen for AHCV.     

HCV-IgG、HCV-cAg与HCV-RNA对丙型肝炎诊断的评价

目的评价丙型肝炎病毒核心抗原(HCV-cAg)、丙型肝炎病毒抗体(HCV-IgG)及丙型肝炎病毒RNA(HCV-RNA)3种检测方法在丙型肝炎实验室诊断中的意义。方法收集84例丙型肝炎疑似患者和87例健康对照者血清,采用ELISA法检测HCV-cAg和HCV-IgG,实时荧光定量聚合酶链式反应法(RT-PCR)检测HCV-RNA。结果 84例丙型肝炎疑似患者中HCVIgG阳性率为84.5%,HCV-cAg阳性率为13.1%,HCV-RNA阳性率为52.4%;71例HCV-IgG阳性患者中HCV-RNA阴性35例,假阳性率为49.3%,11例HCV-cAg阳性患者中HCV-RNA阴性5例,假阳性率为45.5%;44例HCV-RNA阳性的丙型肝炎确诊患者中HCV-IgG假阴性率为18.2%,HCV-cAg假阴性率为86.4%;HCV-cAg和HCV-IgG联合检测的假阴性率为13.6%,真阳性率为100.0%。结论 HCV-cAg和HCV-IgG在丙型肝炎的实验室诊断中均存在一定的假阴性和假阳性,将二者联合检测或在必要时与HCV-RNA三者联合检测可降低漏诊率。     

Sofosbuvir (GS-7977), a pan-genotype,direct-acting antiviral for hepatitis C virus infection

Given the global importance of chronic hepatitis C virus infection as a major health burden, there is still a need for treatment options that are more efficient, safer, simpler, more convenient and preferably interferon-free. Sofosbuvir (GS-7977; formerly PSI-7977) is a direct-acting antiviral agent that has met many of these attributes. This novel nucleotide analogue has demonstrated a consistently potent antiviral activity across several hepatitis C virus genotypes, and has been found to be safe and well tolerated when administered alone or with ribavarin +/? pegylated interferon. The clinical data evaluating the safety, tolerability and antiviral activity of sofosbuvir in various treatment regimens are presented in this article. Sofosbuvir is a major breakthrough in the care of HCV infection, making it possible that thousands of HCV infected patients around the world achieve cures, and preventing HCV associated morbidity and mortality.     

不同喂养方式对HBV母婴传播的影响

目的探讨母乳喂养对HBV母婴传播的影响。方法2002年1月—2004年12月江苏地区HBsAg阳性的281例孕妇及其子女,其中30.2%孕妇乙肝病毒e抗原阳性。婴儿母乳喂养222例,人工喂养59例。所有儿童均接种过乙肝疫苗,37.0%同时注射HBIG。2009年10月—2010年3月随访采血,检测HBV血清学标志。结果母乳喂养组和人工喂养组孕妇年龄、分娩方式,儿童年龄、性别比及HBIG注射情况差异均无统计学意义(P>0.05)。281例儿童中,HBsAg阳性和乙肝表面抗体阳性分别为3.2%和58.0%。人工喂养组和母乳喂养组HBsAg阳性率分别为5.1%和2.7%(P>0.05),进一步比较85例乙肝病毒e抗原阳性母亲的子女感染情况,两组孕妇HBVDNA水平相近(2.285×106 Vs 2.350×106,P>0.05),人工和母乳喂养的儿童HBsAg阳性率分别为11.1%(3/27)和10.3%(6/58),差异无统计学意义(P>0.05)。结论慢性HBV感染母亲的婴儿经免疫预防后,母乳喂养并不增加HBV母婴传播风险。因此,新生儿注射HBIG和乙肝疫苗后,医务人员应鼓励包括HBeAg阳性在内的HBV感染产妇进行母乳喂养。     

丙肝病毒核心总抗原定量检测的临床应用

目的 探讨定量检测丙型肝炎病毒核心总抗原（total HCV-cAg,tHCV-cAg）在丙型肝炎诊断中的作用及与病毒载量的相关性.方法 随机选取广州军区武汉总医院2010年10月-2013年3月丙肝患者血清标本66例,分别采用化学发光法检测血清tHCV cAg,酶联免疫法（ELISA）检测血清丙型肝炎游离核心抗原（free HCV-cAg,fHCV-cAg）及丙型肝炎抗体（hepatitis C virus antibody,HCV-Ab）,实时荧光定量PCR方法检测血清HCV-RNA,全自动生化分析仪检测血清谷氨酸氨基转移酶（ALT）.比较HCV-RNA,tHCV-cAg及fHCV-cAg阳性率差异,同时分析tHCV-cAg与HCV-RNA及ALT相关性,探讨tHCV-cAg联合检测HCV-Ab与HCV-RNA检测符合率.结果 66例丙型肝炎患者血清中,tHCV-eAg阳性率与HCV-RNA阳性率差异无统计学意义（χ^2=0.165,P＞0.05）;tHCV-cAg量与HCV-RNA呈正相关：logHCV Ag=0.81 log HCV RNA-1.31（γ=0.83,P＜0.05）.tHCV-cAg阳性率与fHCV cAg阳性率差异有统计学意义（χ^2 =12.53,P＜0.05）.HCV-cAg阳性组ALT值异常率与HCV-eAg阴性组ALT值异常率差异有统计学意义（P＜0.05,χ^2=17.47）.tHCV-cAg联合检测HCV-Ab符合率与HCV-RNA检测达100.00％.结论 化学发光法定量检测血清tHCV-cAg阳性率显著高于fHCV-cAg,与HCV RNA阳性符合率达96.08％ （49/51）,是丙型肝炎早期诊断的特异性指标.tHCV-cAg和HCV-RNA呈正相关性,与肝功能损害相关,是反映病毒的复制指标.tHCV-cAg联合检测HCV-Ab可减低丙型肝炎的漏诊率.     

Real life experiences in HCV management in 2018

Introduction: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Treatment of chronic hepatitis C has considerably improved in the last few years thanks to the introduction of direct-acting antivirals able to achieve sustained virological response in more than 95% of patients. Successful anti-HCV treatment can halt liver disease progression and solve the HCV-related extra-hepatic manifestations, eventually reducing liver-related and overall mortality.

Areas covered: With the aim to respond to unmet needs in patient’s identification, universal access to antiviral therapy and treatment optimization in specific setting of HCV-infected patients, a group of Italian experts met in Stresa in May 2018. The summary of the considerations arising from this meeting and the final statements are reported in this paper.

Expert commentary: All the advances on HCV cure may have a real clinical impact not only in individual patients but also at the social health level if they are applied to all infected patients, independently from the stage of liver disease. Further improvements are needed in order to attain HCV elimination, such as the development of an enhanced screening program working in parallel to the present treatment options.     

丙型肝炎病毒感染者自身抗体的检测及临床研究

目的 检测丙型肝炎患者血清肝特异性自身抗体并分析其临床意义。方法 采用间接免疫荧光法，对220例丙型肝炎病毒感染者血清进行肝特异性自身抗体的检测；应用聚合酶链反应定量检测血清HCV-RNA含量，HCV抗体的检测用ELISA法；结果 220例丙型肝炎患者总自身抗体检出率为34．55％；单纯Ant-HCV阳性的检出率为29．57％；HCVRNA和Ant-HCV均阳性自身抗体检出率为40．59％，单纯Ant-HCV阳性与HCV-RNA和Ant-HCV均阳性组比较差异显著（P〈0．01）。各组与正常对照比较差异均非常显著（P〈0．01）；自身抗体以低滴度为主，主要为抗核抗体。自身抗体阳性的检出与性别无关（P〉0．05）而与年龄关系密切（P〈0．01），且自身抗体随年龄的增加检出率升高。结论 HCV感染可诱导自身免疫反应，使患者血清中出现多种自身抗体，检测其自身抗体及滴度对丙型肝炎患者的诊断和治疗有一定的参考价值。     

丙型肝炎病毒总抗原检测用于病程监测的研究

目的探讨丙型肝炎病毒(HCV)总抗原检测方法在丙肝病程监测方面的临床意义。方法对来本院就诊的40位丙肝患者于治疗前、治疗1个月时、治疗3个月时、治疗6个月(停药)时,停药6个月后等不同时期进行采血,收集血清或血浆标本,用抗-HCV检测试剂盒(酶联免疫法)、HCV核酸(RNA)扩增(PCR)荧光定量检测试剂盒、HCV总抗原检测试剂盒(酶联免疫法)进行检测。结果从患者确认感染丙肝到治疗结束抗-HCV检测均呈阳性,而HCV-RNA检测和HCV总抗原检测会随着病程的变化而变化。本次共检测了189例标本(40位患者不同时期标本总例数),其中HCV-RNA阳性51例,该51例阳性标本中,HCV总抗原检测阳性44例,阳性检出率为86.27%;138例HCV-RNA阴性标本,有3例HCV总抗原检测为阳性(2.2%)。2种方法比较,差异无统计学意义(χ2=1.6,P>0.05)。HCV总抗原检测其OD值会随着病程的变化而相应改变,可以较好地反应丙肝患者的病程状况。结论 HCV总抗原检测方法在丙肝病程监测方面具有很好的临床意义,适合在缺少荧光定量PCR检测能力的中小医院使用,可在一定程度上替代HCV-RNA检测,对抗-HCV阳性患者作进一步的验证检测或补充,更好地应用于丙肝患者的病程监测。     

Role of Ribavirin in the Era of Direct–Acting Antiviral Therapies of Chronic Hepatitis C

ABSTRACT

Background

The efficacy of adding ribavirin (RBV) to direct antivirals (DAAs) in HCV treatment is still debatable, with allegations of insecure profiles.     

Lichen planus and hepatitis C virus in the Northern Kyushu region of Japan

Abstract. Oral lichen planus (OLP) is a common oral disorder that manifests a mucosal reaction to a variety of aetiological factors, including liver disorder. This study investigated the relationship between OLP and hepatitis C virus (HCV) infection by studying the prevalence of hepatitis B and C virus infection or liver disease in 45 patients with OLP in the Northern Kyushu region of Japan where the prevalence of HCV infection is the highest in the country. Serum hepatitis B virus surface antigen (HBsAg) was positive in only four patients. Serum anti-HCV or serum HCV RNA was positive in 28 (62%) and 27 (60%) of 45 OLP patients, respectively. The majority (35 of 45, 78%) of OLP patients suffered from liver disease, including chronic hepatitis C (22/45, 49%), HCV-related liver cirrhosis (two), and HCV-related hepatocellular carcinoma (two). These results suggest that HCV is a major cause of OLP.     

拔牙术中乙型、丙型肝炎病毒污染的调查及对策

目的对常规拔牙术中乙型、丙型肝炎病毒污染情况进行调查,进一步控制医源性感染。方法随机抽取500例门诊拔牙患者的术中止血棉球,分别浸入2个（A、B）盛有1ml生理盐水的无菌试管内,其浸出液分别用两种方法进行肝炎病毒检测。结果A组（HBsAg）检测到40例阳性（8．00％）,B组（IgG）检测到12例阳性（2．40％）,HBsAg和IgG检测到A组和B组同时阳性2例（0．40％）;500例门诊拔牙患者中检测到被肝炎病毒感染的有54例,占调查总人数的10．8％。结论口腔门诊乙型、丙型肝炎感染率很高,迫切要求口腔医务工作者要加强职业防护,有效防治肝炎病毒通过口腔科诊疗传播。     

Pharmacokinetics,Safety, and Tolerability of the Direct-acting Hepatitis C Antiviral Sofosbuvir in HealthyChineseSubjects

Purpose

The purpose of this study was to investigate the safety, tolerability, and pharmacokinetic profile of sofosbuvir and its metabolites after a single dose of sofosbuvir 400mg and once daily dosing of sofosbuvir 400mg for 7days in healthy Chinese subjects.

丙型病毒性肝炎与性传播关系的临床研究

目的　研究丙型病毒性肝炎与性传播的关系。方法　应用逆转录巢式聚合酶链反应 (RT PCR)检测丙型病毒性肝炎患者、性病患者精液以及阴道分泌物中HCVRNA。应用ELISA法检测其配偶的抗 HCV ,并与正常健康夫妇 18对作对照观察。结果　① 3 3例男性丙型病毒性肝炎患者精液中HCVRNA阳性 6例 (18 18% ) ,2 5例女性丙型病毒性肝炎患者阴道分泌物中HCVRNA阳性 9例 (3 6 0 % )。② 6例男性丙型病毒性肝炎患者精液HCVRNA阳性者配偶抗 HCV阳性1例 (16 67% ) ,9例女性丙型病毒性肝炎患者阴道分泌物HCVRNA阳性者配偶抗 HCV阳性 7例 (77 78% )。③ 72例性病患者生殖道分泌物HCVRNA阳性 4例 (5 5 % )。④对照组配偶抗 HCV均为阴性。结论　①丙型病毒性肝炎患者精液、阴道分泌物中可检出HCVRNA ,丙型病毒性肝炎病毒存在性传播的可能性。②女性丙型病毒性肝炎患者性传播丙型病毒性肝炎病毒可能性比男性丙型病毒性肝炎患者要大。③性乱人群通过性接触感染丙型病毒性肝炎病毒的可能性高于正常人群