HBV/HIV重叠感染的抗病毒治疗

随着人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染率快速增长,乙型肝炎病毒(hepatitis B virus,HBV)/HIV重叠感染成为一种临床易见疾病.HBV/HIV重叠感染使HBV和HIV的生物学行为发生改变,进而相互影响病情进展,使得HBV/HIV重叠感染患者的抗病毒...     

本刊常用英文缩写词汇

正甲型肝炎病毒(hepatitis A virus,HAV)乙型肝炎病毒(hepatitis B virus,HBV)丙型肝炎病毒(hepatitis C virus,HCV)慢性乙型肝炎(chronic hepatitis B,CHB)慢性丙型肝炎(chronic hepatitis C,CHC)肝细胞肝癌(hepatocellular carcinoma,HCC)原发性肝癌(primary hepatocellular carcinoma,PHC)人类免疫缺陷病毒(human immunodeficiency virus,HIV)     

乙型肝炎病毒感染合并丙型肝炎病毒感染直接抗病毒药物治疗的描述性研究

目的 分析乙型肝炎病毒（hepatitis B virus,HBV）合并丙型肝炎病毒（hepatitis C virus,HCV）感染者的流行病学特征及直接抗病毒药物（direct-acting antiviral agents,DAA）抗HCV后HBV再激活的发生和预后。方法 收集2008年10月至2020年5月首都医科大学附属北京地坛医院HCV/HBV合并感染并接受抗HCV治疗的患者进行回顾性分析,分析共感染者的感染途径、是否存在肝硬化及肝细胞癌（hepatocellular carcinoma,HCC）,比较患者治疗前后乙型肝炎病毒表面抗原（hepatitis B virus surface antigen,HBsAg）、丙氨酸氨基转移酶（alaninetransminase,ALT）、天门冬氨酸氨基转移酶（aspirate transaminase,AST）、血清总胆红素（total bilirubin,TBil）、血清直接胆红素（direct bilirubin,DBil）、血清白蛋白（albumin,ALB）的变化情况。统计DAA抗HCV的治疗效果及HBV再激活情况。结果 ...     

乙型肝炎病毒和丙型肝炎病毒在肝癌发生中的作用研究进展

肝细胞癌(hepatocellular carcinoma,HCC)是世界上最常见的十大恶性肿瘤之一,目前全世界每年新增5.O×10~6～1.0×11~6病例。在我国,HCC已占恶性肿瘤死亡的第三位。目前对乙型肝炎病毒(hepatitis B Virus,HBV)和丙型肝炎病毒(hepatitis C virus,HCV)感染与HCC发生的关系最为重视。研究表明,全世界现有4亿慢性HBV携带者,80％以上的HCC患者伴有HBV感染,持续HBV感染者发生HCC的机率比正常人高100～200倍;60％～80％HCV感染者将转为慢性,最终将有20％发展为HCC,而HCV相关肝硬化患者15年     

丙型肝炎病毒非结构蛋白与宿主细胞蛋白相互作用的研究进展

丙型肝炎病毒(hepatitis C virus,HCV)是继乙型肝炎病毒(hepatitis B virus,HBV)之后另一个导致慢性肝炎、肝硬化和肝癌的常见原因.目前HCV致病及致癌机制仍不清楚,也缺乏针对HCV有效的治疗方法及疫苗预防.肝炎病毒蛋白与受染细胞蛋白之间相互作用是肝炎发病机制研究的热点内容.近年研究...     

本刊常用英文缩写词汇

正甲型肝炎病毒(hepatitis A virus,HAV)乙型肝炎病毒(hepatitis B virus,HBV)丙型肝炎病毒(hepatitis C virus,HCV)人类免疫缺陷病毒(human immunodeficiency virus,HIV)巨细胞病毒(CMV)获得性免疫缺陷综合征(AIDS)血压(BP)肝细胞癌(HCC)红细胞(RBC)白细胞(WBC)血小板(PLT)白蛋白(ALB)总蛋白(TP)血红蛋白(Hb)免疫球蛋白(Ig)甲胎蛋白(AFP)白细胞介素(IL)     

酒精合并病毒性肝损伤与肝癌的关系

病毒性肝炎和酒精均是肝细胞癌(肝癌)致病的主要病因, 慢性乙型肝炎病毒(hepatitis Bvirus, HBV)和丙型肝炎病毒(hepatitis C virus,HCV)感染引起肝癌的危险性为正常人10倍以上, 饮酒引起肝癌危险性近2倍, 病毒性肝炎伴饮酒危险性进一步增大. 病毒和酒精协同作用的机制尚未完全清楚, 在多数患者, 两种因素均先通过肝硬化再进展为肝癌. 预防肝炎病毒感染和控制饮酒是预防肝癌的最好手段, 普及乙型肝炎疫苗接种已取得非常好的成绩. 对慢性HBV和HCV感染者应抗病毒治疗, 早期戒酒对预防肝癌的肯定有益, 但尚没有足够证据支持戒酒可减低肝硬化向肝癌发展的风险.     

慢性重型乙肝HCV重叠感染与预后探讨

丙型肝炎病毒(HCV)和乙型肝炎病毒(HBV)存在相似的传播途径．因此HCV和HBV可同时或重叠感染并持续存在于同一患者。有相当数量的重型肝炎可能涉及到HBV、HCV重叠感染，而慢性HBV感染者重叠HCV感染后其肝脏病变在组织学和临床失代偿方面表现更为严重。本文作者经过对比研究，旨在探讨慢性重型乙肝HCV重叠感染与预后的关系，协助了解HCV在其中的作用。     

基因多态性与乙型和丙型肝炎病毒感染的关系

宿主在乙型肝炎病毒(hepatitis B virus,HBV)和丙型肝炎病毒(hepatitis C virus,HCV)感染后不同的临床发展过程,除了与病毒本身的因素有关外,更重要的是由于不同个体对HBV/HCV感染所发生的免疫反应的不同。人白细胞抗原(human leukocyte antigen,HLA)、细胞因子及细胞间粘附分子-1与机体免疫功能状态密切相关,并在乙、丙型肝炎免疫发病机理中起重要作用,其中某些基因的多态性可能导致机体免疫功能状态的差异,因而决定着HBV/HCV感染的不同临床转归。近年国内外有关人体基因多态性与疾病关系的研究成果不断涌现,现将其中有关人体基因多态性与HBV/HCV感染间     

HBV/HCV重叠感染的现状与研究进展

乙型肝炎病毒(HBV)与丙型肝炎病毒(HCV)具有共同的传播途径,因此HBV/HCV重叠感染较为常见。HBV/HCV重叠感染时,两种病毒间存在相互抑制或干扰现象,加速了肝脏疾病的进展,预后不佳。为防止更严重的肝脏损伤,除了进行有效的预防外,应先针对"优势病毒株"及时进行有效的抗病毒治疗,并注意关注"优势病毒株"的转换,针对不同病毒模式的特点,及时调整治疗方案。     

Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment

Because of the shared modes of transmission, hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection is not uncommon in highly endemic areas and among subjects with a high risk of parenteral infections. The worldwide prevalence of HBV/HCV coinfection is unknown and might be underestimated with the phenomenon of silent (occult) HBV infection. HCV superinfection in patients with chronic HBV infection was the most common clinical features of coinfection in Asia-Pacific countries. Further, most, but not all, clinical observations suggested that interference between the two viruses was more frequently characterized by an inhibition of HBV replication exerted by HCV. However, longitudinal follow-up studies have demonstrated that the virological patterns in coinfection cases are widely divergent and have dynamic profiles over time. As compared with monoinfected patients, HBV/HCV coinfected persons tend to have more severe liver injury, a higher probability of liver cirrhosis and hepatic decompensation, and a higher incidence of hepatocellular carcinoma. Detailed serological and virological evaluations are required for coinfected patients before initiation of antiviral therapy. Previous studies demonstrated that HBV/HCV coinfected patients responded poorly to interferon (IFN) monotherapy. Currently, for patients with dominant HCV infection and low level HBV viremia (<10(4) IU/mL), IFN or pegylated IFN plus ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. However, phenomenon of reciprocal viral interference can happen, and resultant "flare" of hepatitis activity may cause liver function deterioration. For coinfected patients with dually-active HBV/HCV, the optimal regimen for therapy remains unclear although adding oral nucleos(t)ide analogs to pegylated IFN and ribavirin seems a reasonable empiric option.     

MiR-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.     

乙型肝炎病毒和丙型肝炎病毒不同模式重叠感染患者临床特征分析

目的 了解HBV和HCV不同模式重叠感染患者临床特征的差异.方法 回顾分析中山大学附属第三医院1999年5月至2010年5月HCV和HBV重叠感染患者186例.统计分析不同病毒学模式重叠感染患者的人口学、流行病学、实验室检查和病理学表现,数据处理采用t检验和x2检验等.结果 186例HBV和HCV重叠感染患者中,HBV...     

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings

The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.     

Hepatitis B virus and hepatitis C virus infection in healthcare workers

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus(HBV) and 1000000 to hepatitis C virus(HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.     

Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study

BACKGROUND/AIMS: This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. METHODS: We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units. RESULTS: Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4% (>30-50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both. CONCLUSIONS: This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy.     

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals

BACKGROUND Current diagnosis of hepatitis C virus(HCV) infection requires two sequential steps: testing for anti-HCV followed by HCV RNA PCR to confirm viremia. We have developed a highly sensitive and specific HCV-antigens enzyme immunoassay(HCV-Ags EIA) for one-step diagnosis of viremic HCV infection.AIM To assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus(HIV)-coinfected individuals.METHODS The study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera: 10 without HCV or HIV infection;54 with viremic HCV monoinfection; 38 with viremic HCV/HIV coinfection; and45 with viremic HCV and non-viremic HIV coinfection.RESULTS Upon decoding, it was 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR test. In five sera with HCV infection, HCV RNA was as low as50-59 IU/mL, and four out of five tested positive for HCV-Ags EIA. Likewise, it was also 100% accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection, regardless if HIV infection was active or not.CONCLUSION The modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/mL. It is highly sensitive and specific in the setting of HIV coinfection, regardless of HIV infection status and CD4 count.These data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.