饮酒与原发性肝癌关系的调查--附吉林省1057例原发性肝癌病因学分析

明确饮酒与肝炎病毒感染是否有协同致原发性肝癌的作用.采用病例对照研究的方法对吉林省1057例原发性肝癌患者及3171例非肝病患者的饮用酒精量和HBV/HCV感染状况进行比较.结果表明饮酒可增加患原发性肝癌的危险性,饮酒(40-100)g/d者OR值为1.41,＞100g/d为3.04.饮酒可增加HBV、HCV感染者患原发性肝癌的危险性,饮酒(40-100)g/d的HBV感染者OR值为18.82,＞100g/d为31.15;饮酒(加-100)g/d的HCV感染者OR值为32.02,＞100g/d为47.63;饮酒(40-100)g/d的HBV、HCV重叠感染OR值为79.39,＞100g/d为121.42.452例行HBV-DNA检测的患者中,非嗜酒史者阳性率为26.15%,饮酒(40-100)g/d为49.07%,饮酒＞100g/d为70.56%;特别是HBsAg、抗-HBc、抗-HBe阳性的重度嗜酒者HBV-DNA阳性率最高为78.21%.嗜酒可增加HBV、HCV及重叠感染者患原发性肝癌的危险性,酒精对HBV、HCV在致肝细胞癌方面有协同和加强作用.     

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...     

HBV/HCV重叠感染的抗病毒治疗

从全球范围看,乙型肝炎病毒(hepatitis B virus,HBV)和丙型肝炎病毒(hepatitis C virus,HCV)重叠感染估计约有700-2000万人口感染.重叠感染和单一HBV或HCV感染比较,更易发展为肝硬化、肝细胞癌甚至肝衰竭的比例也高,HBV和HCV重叠感染可有四种不同的临床模式,即HCV活动...     

肝炎病毒基因工程抗体的研究

0引言乙型病毒性肝炎?丙型病毒性肝炎分别是由乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染引起的世界性传染病[1-10].HBV?HCV感染不仅引起急性?慢性病毒性肝炎,而且与肝硬化和肝细胞癌的发生和发展密切相关[11-20].流行病学调查表明,HB V感染的阳性率为10%,抗-HCV的阳性率为3.2%,对我国人民健康危害极大.因此,急需研究有效的针对乙型?丙型病毒性肝炎的防治措施.其中肝炎病毒人源化基因工程抗体及其应用是目前的主要研究方向之一.1乙型肝炎病毒?丙型肝炎病毒基因工程抗体的研究背景目前在我国引起慢性病毒性肝炎的肝炎病毒类型主要是H…     

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     

病毒性肝炎流行病学进展

病毒性肝炎是一个严重的公共卫生问题,全球每年超过100万人死于病毒性肝炎.其感染人数是艾滋病人数的10倍以上[1].全球估计有57％的肝硬化病例和78％的肝细胞癌(HCC)病例与乙型肝炎病毒(HBV)或丙型肝炎病毒(HCV)感染有关.全世界约有20亿人已感染HBV,其中3.5～4亿人为慢性HBV感染者,每年约50～70万人死于与HBV感染相关的疾病.约有1.3～1.7亿人为慢性HCV感染,每年约有35万人死于HCV感染相关疾病[2].2010年5月,世界卫生组织(WHO)第63届世界卫生大会通过一项议案,呼吁采取综合措施来预防和控制病毒性肝炎.尽管目前甲型肝炎(甲肝)和乙型肝炎(乙肝)有有效的预防方法,但在发展中国家,多数慢性乙肝和丙型肝炎(丙肝)患者尚未得到有效的治疗[3].     

乙型肝炎病毒的基因变异及其临床意义

乙型肝炎病毒(hepatitis B virus,HBV)感染仍是世界范围内的公共健康问题.HBV为一嗜肝细胞DNA病毒,不仅可以引起隐匿性、急性和慢性病毒性肝炎,还与肝硬化和肝细胞癌的发生发展密切相关.HBV基因组易发生变异,并在长期进化过程中不断积累,形成了具有种族和地域差异的HBV基因型、基因亚型和准种,与HBV感染的发生、发展和治疗等密切相关.     

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)     

肝炎病毒与肝细胞相互作用的分子生物学机制研究策略

乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染引起的急性和慢性病毒性肝炎、肝硬化、肝细胞癌等,是严重影响中国国民健康的重要传染病。流行病学调查结果表明,在中国HBV表面抗原阳性率为9.75％,HCV抗体的阳性率为3.2％,尽管干扰素、核苷类似物的抗病毒治疗在一部分患者中取得了一定的疗效,中西医结合的综合治疗在终末期肝病的治疗     

HCV HBV感染与肝细胞性肝癌

调查了肝癌高发地区不同肝病患者中丙型肝炎病毒(HCV)感染率。慢性肝病患者绝大多数已被乙型肝炎病毒(HBV)感染。HCV第二代抗体阳性率,肝癌7.3％,肝硬化6.6％,慢性肝炎6.6％和急性肝炎3.4％。两种病毒的复合感染率,肝癌5.1％,肝硬化1.7％,慢性肝炎3.9％和急性肝炎1.1％。在38例HCV抗体阳性的慢性肝病患者中,ALT异常84.2％,有输血史者占57.9％,HCV-RNA阳性率为71.1％。本研究的资料分析提示,在肝癌高发地区尽管HCV抗体阳性率较低,但HCV感染也是肝癌发生的重要病因之一。     

Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment

Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.     

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC)represents 90%of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV),hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.     

Oxidative stress and antioxidants in hepatic pathogenesis

Long term hepatitis B virus (HBV) infection is a major risk factor in pathogenesis of chronic liver diseases,including hepatocellular carcinoma (HCC). The HBV encod-ed proteins,hepatitis B virus X protein and preS,appear to contribute importantly to the pathogenesis of HCC. Both are associated with oxidative stress,which can damage cellular molecules like lipids,proteins,and DNA during chronic infection. Chronic alcohol use is another important factor that contributes to oxidative stress in the liver. Previous studies reported that treatment with antioxidants,such as curcumin,silymarin,green tea,and vitamins C and E,can protect DNA from damage and regulate liver pathogenesis-related cascades by reducing reactive oxygen species. This review summarizes some of the relationships between oxidative stress and liver pathogenesis,focusing upon HBV and alcohol,and suggests antioxidant therapeutic approaches.     

Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.     

Significance of viral status on occurrence of hepatitis B-related hepatocellular carcinoma

Hepatitis B virus (HBV) infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of developing hepatocellular carcinoma (HCC). Interactions that occur among host, environmental, and viral factors determine the natural course and predict the prognosis of patients with chronic HBV infection. In the past decades, several important viral factors of predictive of HCC have been identified, such as high hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high viral load, viral genotype, and specific viral sequence mutations. Identification of certain viral risk factors for HCC development and stratification of patient risk are very important to perform future surveillance programs. In this article, we thus reviewed the risk of viral factors involved in hepatocarcinogenesis.     

Anti-viral therapy to reduce recurrence and improve survival in hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common malignancy and the third leading cause of cancer death worldwide.Chronic infection with hepatitis B virus(HBV)and hepatitis C virus accounts for approximately75%-80%of HCC cases worldwide.In particular,chronic HBV infection is a predominant risk factor for HCC in Asia and Africa.Hepatic resection and radiofrequency ablation are increasingly used for the curative treatment of HCC,and good local control can be achieved.However,the high rate of recurrence is a major obstacle to improving prognosis.A high viral load of HBV DNA is the most important correctable risk factor for recurrence.Furthermore,interferon and/or nucleotide analogues may decrease HBV DNA.Therefore,these drugs may decrease recurrence.In this article,treatment strategies for HBV-related HCC are described in order to reduce recurrence and improve survival.     

丙型肝炎病毒感染个体的准种源于感染过程中的病毒核酸突变

目的研究丙型肝炎病毒(HCV)准种特性与感染慢性化的关系,以及个体准种特性的来源形式。方法收集HCVRNA阳性的10例急性丙肝、20例慢性丙型肝炎(丙肝)和11例肝细胞癌(HCC)患者,采用单链构型多态性分析(SSCP)方法进行HCV准种检测。结果急性丙肝、慢性丙肝和HCC患者中,SSCP电泳条带数分别为2．7±1．16、4．8±1．68和5．2±2．85。慢性丙肝和HCC的条带数显著高于急性丙肝(P＜0．05)。进行DNA序列分析研究发现,准种高变区间的变异性显著低于本地株间和异地株间的变异性(P＜0．01)。结论SSCP是检测准种相对简便而有效的方法。HCV准种特性与其感染慢性化相关。HCV感染个体准种的来源主要为感染过程中的核酸突变。     

各型肝炎病毒单纯及重叠感染的研究

目的 探讨病毒性肝炎患者甲～戊，庚型肝炎病毒(HAV-HEV，HGV)单纯感染及重叠感染情况。方法 采用EIA法检测病毒性肝炎患者血清抗-HAV IgM，HBV标志物、抗-HCV IgM、抗-HDV IgM、抗-HEV IgM、抗-HGV IgM。结果 共检测210例病毒性肝炎患者HAV-HEV、HGV血清标志物，20例未检出(9．5％)，190例患者检出标志物阳性(90．5％)。HBV感染率89，5％(188／210，其中有34例为既往感染，占16．2％，现症感染154例，占73．3％)；HAV感染率29．0％(61／210)，HCV、HDV感染率均为8．1％(17／210)、HEV、HGV感染率依次为10．0％(21／210)、7．1％(15／210)。各临床类型中单纯感染占61．4％(129／210)，二重感染占32．4％(68／210)，以HAV HBV、HBV HDV、HBV HEV感染模式最常见，三重感染占6．2％(13／210)，以HAV HBV HDV感染模式最常见；临床上以肝炎肝硬化、重型肝炎重叠感染常见，急性肝炎最少见。结论 病毒性肝炎中HBV感染最常见，其次为HAV感染；单纯感染、二重感染多见，三重感染少见；重叠感染发生率随病情加重而增加。     

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.     

Genotypes, mutations, and viral load of hepatitis B virus and the risk of hepatocellular carcinoma: HBV properties and hepatocarcinogenesis

Chronic infection with hepatitis B virus (HBV) is the major risk factor for hepatocellular carcinoma (HCC) worldwide. Ten HBV genotypes (A-J) have been discovered so far. Genotypes B and C are endemic in East and Southeast Asia. Genotype C HBV is associated with increased risks of cirrhosis and HCC. Genotype B (B2) is associated with the development of HCC in non-cirrhotic patients younger than 50 years and with relapse of HCC after surgical treatment. It is also associated with earlier hepatitis B e antigen seroconversion than genotype C. High HBV load is independently associated with the occurrence and post-treatment recurrence of HCC. Different genotypes have distinct patterns of mutations. Viral mutations in the core promoter region and in the preS region are frequently found to be significantly associated with an increased risk of HCC. These mutations often occur before the onset of HCC and accumulate during the progression of chronic HBV infection. Multiple such mutations are more frequent in patients with HCC and are specific for HCC. HBV subgenotypes, viral mutations, and viral load can be used for the prediction of HCC. Early identification of HBV-infected individuals who will eventually develop HCC will help to develop active prophylactic protocols to reduce or delay the occurrence of HCC.