Update on chronic viral hepatitis

Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely. Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly. The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial. Hepatitis D virus infection occurs on a background of hepatitis B virus infection and can also cause liver damage. The response to antiviral therapy is poor. The newer "hepatitis" viruses G and TT do not cause significant liver injury.     

核苷类药物在慢性乙型病毒性肝炎中的应用

慢性乙型肝炎治疗的根本目标是清除乙型肝炎病毒(HBV),阻断HBV复制,只有清除HBV才能阻止慢性乙型病毒性肝炎向肝脏失代偿、肝硬化、肝癌发展,减少并发症。国内外医学界公认的抑制乙型病毒性肝炎复制的药物主要有干扰素和核苷类似物两大类。近年来核苷类似物成为抗病毒药物的研究热点,该类药物抗HBV作用较强。现主要对拉米夫定、阿德福韦酯、恩替卡韦和替比夫定的疗效比较、联合用药、安全性等进行简要的介绍。     

Efficacy of interferon alpha-2b and lamivudine therapy for chronic hepatitis B in children

Objective To evaluate the efficacy of interferon (IFN) alpha-2b and lamivudine therapy in children with chronic hepatitis B virus (HBV) infection.Method Ten children who developed chronic hepatitis B infection received IFN alpha-2b 10 million intemational units (IU)/m^2 body surface area, subcutaneously three times a week for six months. IFN lamivudine therapy began to be used in the cases who were unresponsive to IFN treatment.Results Among 27 HBsAg ( ) subjects in this study, interferon treatment was given to 11 subjects who developed chronic hepatitis. One case was excluded from the study due to detection of Herpes type 1 encephalitis. At the end of six months of follow-up, complete response was obtained in three(30%) patients and partial response in four (40%) patients, whereas no response was detected in three (30%) patients. Fifty percent of the cases experienced serological response, 70% biochemical response, and all (100%) had histological response. In three cases started concomitant IFN lamivudine therapy, HBV-DNA became negative at the second month of treatment.Conclusions IFN-alpha and lamivudine can be used for the treatment of chronic hepatitis B infection in children.     

拉米夫定联合干扰素治疗慢性乙型肝炎的疗效观察

目的:观察拉米夫定与干扰素联合用药治疗慢性乙肝的疗效。方法:将150例慢性乙肝患者随机分为三组,每组50例。联合组予拉米夫定和重组人干扰素α-2b治疗,拉米夫定组单予拉米夫定治疗;干扰素组单予干扰素治疗,疗程均为1年。结果:治疗1年后,联合组HBV-DNA转阴率为86%,血清HBeAg/抗HBe转换率为48%,均优于拉米夫定组和干扰素组(P<0.05)。联合组仅出现1例YMDD变异(2%),而拉米夫定组出现8例YMDD变异(16%)。结论:拉米夫定联合干扰素应用的治疗效果优于单独应用组,并且能减少病毒YMDD变异,防止耐药发生。     

HBeAg阳性B、C基因型乙肝患者使用拉米夫定治疗的病毒抑制效应对比分析

目的探讨拉米夫定对B、C基因型乙型肝炎（乙肝）患者治疗作用。方法观察未用、使用拉米夫定治疗的慢性乙肝患者随时间延长血清病毒标志物HBV DNA水平、HBeAg血清转换率及随拉米夫定疗程延长乙肝病毒聚合酶及转录酶区酪氨酸-蛋氨酸-门冬氨酸-门冬氨酸基序（HBV YMDD）耐药变异率等的变化,对比分析拉米夫定抗病毒治疗对B、C基因型乙肝患者的病毒抑制效应。结果（1）未用拉米夫定治疗的乙肝患者, B基因型者HBV DNA水平低于C基因型者,而自发HBeAg血清转换率高于C基因型者。（2）使用拉米夫定治疗的乙肝患者,B、C基因型者之间HBV DNA水平、HBeAg血清转换率及YMDD变异率没有明显差异。（3） B、C基因型患者均随拉米夫定疗程延长HBV DNA水平下降,HBeAg血清转换率增加,但YMDD变异率也增加。结论（1）未用拉米夫定治疗的自然状况下C基因型乙肝患者携带的乙肝病毒复制能力强于B基因型患者者且不易清除。（2）使用拉米夫定疗程相同时B、C基因型患者之间拉米夫定的病毒抑制效应及HBV YMDD耐药变异率相似。（3）C基因型HBV感染的乙肝患者及早使用拉米夫定抗病毒治疗意义更大。     

乙型肝炎病毒C基因启动子变异与基因型和肝硬化的关系

目的 研究HBV C基因启动子(CP)和前C基因变异与HBV基因型和病情的关系。方法 通过DNA扩增、基因序列分析检测44例慢性乙型肝炎(CH)，29例肝硬化(LC)患者的血清HBV S基因序列以确定其基因型，测定HBVCP和前C区序列以确定其变异状况。结果 (1)CP双变异(nt 1762A→T和1764G→A)的发生率肝硬化组为75．9％，慢性乙型肝炎组为45.5%，两组间差别有显著性意义(P＜0.05)。(2)LC患者的C基因型检出率为69．0%，CH患者的C基因型检出率为43.2％，二者间差别有显著性意义(P＜0.05)。(3)C基因型HBV感染者CP双变异发生率为69.2％，B基因型HBV感染者CP双变异发生率为44．1％，二者间差别有显著性意义(P＜0.05)。结论 CP双变异与C基因型密切相关，并且导致病情向肝硬化发展。     

Epidemiology of Hepatitis B and Associated Liver Diseases in China

Hepatitis B virus (HBV) infection has long been a critical public health challenge in China. National surveys revealed a prevalence of approximate 10% for chronic HBV infection in general population. HBV has been the leading cause of chronic hepatitis, cirrhosis, and liver cancers in Chinese population and a common pathogen of acute viral hepatitis. Meanwhile, the epidemic provided important opportunities to research the natural history, public health impact, and therapeutic and preventive interventions for HBV in China. In this review, we summarized the selected key epidemiological studies since 1970s regarding HBV infection and its associated liver diseases in China, and provided considerations for future research, prevention and treatment of HBV.     

干扰素-α与拉米夫定配伍治疗对慢性乙型肝炎预后的影响

目的:研究干扰素-α和拉米夫定治疗对慢性乙型肝炎(CHB)预后的影响。方法:回顾性研究456例慢性乙型肝炎病毒感染相关肝病住院患者,分析干扰素-α和拉米夫定治疗对CHB进展至终末期肝病(ESLD)包括肝硬化、重型肝炎、原发性肝癌的影响。结果:分别有68例、55例和365例患者曾接受干扰素-α、拉米夫定和未接受抗病毒治疗,其中32例患者曾接受干扰素-α和拉米夫定治疗。365例未抗病毒治疗者中116例进展为ESLD,68例干扰素-α治疗者中10例进展为ESLD,差异有统计学意义,其中30例治疗结束时获得病毒学和生化学联合应答者仅2例进展至ESLD;55例拉米夫定治疗者(平均疗程15.8月)中有13例进展为ESLD,与未接受抗病毒治疗者相比,差异无统计学意义;32例曾接受拉米夫定和干扰素-α治疗,7例进展为ESLD,与未接受抗病毒治疗者相比,差异无统计学意义。结论:干扰素-α治疗能减少慢性乙型肝炎进展至ESLD,尤其是治疗结束时获得病毒学和生化学联合应答者;短疗程拉米夫定治疗未能明显影响其预后。     

Hepatitis C. An update

Hepatitis C is a long-term viral infection affecting the liver caused by the hepatitis C virus HCV. Hepatitis C can be silent for years before symptoms appear, and liver damage occurs. The hepatitis C virus is extremely infectious, which means that only a tiny amount of HCV can cause illness. Hepatitis C is a major public health problem worldwide with far-reaching implications because of the chronicity of the infection that leads to chronic liver disease, cirrhosis, and primary hepatocellular carcinoma.     

我国乙型病毒性肝炎防治研究新进展和面临的挑战

乙型病毒性肝炎目前仍然是威胁我国广大人民群众的严重传染病之一,但自1992年乙肝疫苗纳入计划免疫规划以来,乙肝病毒感染流行率已明显下降,尤其是5岁以下儿童的HBsAg阳性率已降到1%以下。成人易感者乙肝疫苗接种也越来越广泛。HBV DNA的检测进入了高灵敏度时代,检测下限已低至10~20 IU/mL,因此为临床治疗决策点提供了更准确的依据和预后判断支持。新型核苷类等药物的研制和序贯或联合聚乙二醇干扰素等治疗方案使人们看到了实现乙肝"功能性治愈"新希望。乙肝患者通过规范化抗病毒治疗,可有效抑制其体内HBV DNA病毒复制,显著降低失代偿肝硬化和肝癌等不良转归风险。《中国热带医学》这期乙肝防治专栏重点刊登了5篇针对我国乙肝相关疾病的早期诊断、母婴传播的发生机制、临床患者的治疗和转归等方面的最新研究成果。相信通过大家的共同努力,在我国消除乙肝的夙愿已为期不远。     

甘肃省1～59岁人群乙型肝炎疫苗接种率调查分析

目的了解甘肃省1～59岁人群乙型肝炎疫苗（HepB）接种情况,为乙肝预防控制策略提供依据。方法采用多阶段随机抽样方法确定1～59岁调查对象,对抽样人群HepB接种情况进行调查。结果甘肃省1～59岁人群HepB接种率为48.18%,其中1～4岁儿童为89.37%,10～14岁儿童为55.40%,15～59岁人群仅为10.99%,HepB接种率呈现随年龄年龄增加而降低;托幼儿童接种率高于散居儿童,农民最低,医务人员接种率为46.15%;不同职业人群HepB接种率差异具有统计学意义。1～14岁儿童HepB首针及时接种率为46.79%,2岁儿童最高为72.81%;HepB首针及时接种率随年龄增长而降低。结论乙肝疫苗纳入计划免疫后出生的儿童乙肝疫苗接种率高,15岁以上人群接种率低,要加速我国控制乙肝步伐,必须提高重点和高危人群乙肝疫苗接种率。     

柔肝煎联合拉米夫定对慢性乙型肝炎患者E抗原及乙型肝炎病毒复制指标的影响

目的：观察自拟中药方剂柔肝煎对慢性乙型肝炎患者E抗原及乙型肝炎病毒复制的影响。方法：将65例慢性乙型肝炎患者随机分为治疗组和对照组,治疗组35例以柔肝煎联合应用拉米夫定治疗,对照组30例单纯应用拉米夫定治疗,疗程均为6个月,观察治疗前后E抗原及乙型肝炎病毒复制等指标的变化。结果：两组血清乙型肝炎病毒阴转率未见显著差别（P〉0.05）,但治疗组HBeAg阴转率及ALT复常率均显著高于对照组（两组P值均小于0.01,有统计学差异）,且未发现明显不良反应。结论：柔肝煎联合应用拉米夫定对慢性乙型肝炎患者病毒血清学指标及肝功能指标的控制总体效果好于单纯应用拉米夫定,且安全性好。     

1997～2007年天津市急性病毒性肝炎流行病学分析

目的分析天津市急性病毒性肝炎流行现状、发展趋势及探讨控制对策。方法回顾性统计1997-2007年急性病毒性肝炎病例,数据用Excel整理,采用描述性流行病学分析方法。结果报告急性病毒性肝炎9455例,其中以乙型肝炎和戊型肝炎所占比例为高,分别为36．28％和27．94％,其次为未定型肝炎（20．95％）、甲型肝炎和丙型肝炎所占比例为最低,分别为12．98％和1．85％;戊型和未定型以中老年（31-60a）为主,分别占78．8％（2082／2642）、64．0％（1267／1981）,甲型以青少年（11-30a）为主,占59．8％（734／1227）,乙型、丙型以中青年（21～50a）为主,分别占80．85％（2773,3430）、70．86％（124／175）;各型肝炎男性所占比例均显著高于女性;甲型肝炎以1-4月为发病高峰期,戊型肝炎以12～6月为发病高峰期,未定型肝炎以12～5月为发病高峰期,乙型及丙型肝炎发病无明显季节性;感染途径甲、戊、未定型肝炎传播途径以消化道感染为主,乙型肝炎传播途径以性接触为主,丙型肝炎传播途径多数有不洁注射史。结论急性病毒性肝炎以乙型、戊型及未定型肝炎为主,近2年总体发病例数呈减少趋势。防治仍需从饮食卫生、注射用具的管理、加强宣传教育及健康人群保护入手。     

Epidemiology and prevention of hepatitis B virus in China

Hepatitis B virus （HBV） infection is prevalent in China. Approximately 600 million people have ever been infected by HBV. About 130 million are HBV chronic carders and 30 million HB patients. Among them, 50% of HBV carriers are caused by carrier mothers to born infants. Around 300 000 people died of liver disease including liver cirrhosis and primary hepatocellular carcinoma each year and 50% of them died of primary hepatocellular carcinoma. HBV infection is not only the health problem but also becoming a social problem. HBV chronic carriers and patients have endured the great pressure from disease burden and social discrimination. According to the report of the national screening program of HBV released by the ministry of health in 2008, China has taken many effective measures to control the HBV infection, including vaccine immunization program, strengthening the management of blood sources and blood productions, prevention of nosocomial HBV infection, strengthening health education on HBV infection and safe injection techniques. The implementation of HB vaccine immunization program, which China officially introduced into the national immunization program since 1992, has dramatically reduced the incidence of HBV infection among infants and children. Integrated with other interventions, the rate of HBV infection decreased gradually. According to the survey of the national screening program of HBV in 2006, compared with the incidence of HBV in 1992, the incidence rate of HBsAg positive has decreased 26.36%, the number of children who have ever been infected by HBV decreased 80 million since 1992. However some problems are still existing. The solutions of low rate of vaccination in rural areas and migration population, lacking of practical measures on management of hepatitis B patients, the occurrence of health care acquired HBV infection, and low rate of vaccination among high risk groups have also been recommended.     

拉米夫定联合干扰素治疗慢性乙型肝炎的疗效观察

目的：观察拉米夫定与干扰素联合用药治疗慢性乙型肝炎的疗效。方法：将150例慢性乙型肝炎患者随机分为三组,各50例。联合组给予拉米夫定和重组人干扰素α-2b治疗,拉米夫定组单给予拉米夫定治疗;干扰素组单给予干扰素治疗,疗程均为1年。结果：治疗1年后,联合组HBV-DNA转阴率为86%,血清HBeAg/抗HBe转换率为48%,均优于拉米夫定组和干扰素组（P〈0.05）。联合组仅出现1例YMDD变异（2%）,而拉米夫定组出现8例YMDD变异（16%）。结论：拉米夫定联合干扰素治疗效果优于单独应用组,并且能减少病毒YMDD变异,防止耐药发生。     

乙型肝炎病毒基因型与拉米夫定疗效关系研究

目的 探讨乙型肝炎病毒（HBV）基因型与拉米夫定治疗疗效的关系及其机理。方法 收集拉米夫定治疗的51例慢性乙型肝炎患者的临床资料，分析HBV基因型与拉米夫定治疗疗效的关系。结果 HBV基因型B型对拉米夫定的应答率为45．4％（10／22），C基因型的应答率为20．7％（6／29），两组应答率差异有显著性（P〈0．05）；B基因型的HBeAg的血清转换率为31.8％（7／22），C基因型为13．8％（4／29），经统计学处理差异有显著性（P〈0．05）。结论 拉米夫定治疗慢性乙型肝炎患者，B基因型疗效较C基因型好，HBV基因型可能是预测拉米夫定治疗效果的因素之一。     

小儿急性乙型肝炎86例6年追踪观察报告

目的探讨小儿急性乙型肝炎(AHB)临床治愈后的病情演化、肝组织病理学改变和预后。方法86例AHB患儿于出院后追踪观察6年,每半年检测1次常规肝功、血清HBV标志物,部分患儿进行肝组织活检。结果本组小儿AHB乙肝慢转率为18.60%。结论乙肝病毒持续感染是乙肝慢转及肝组织病理改变的重要因素。     

Hepatitis C in childhood

The prevalence of hepatitis C virus (HCV) infection is relatively low in childhood. Blood transfusion has been the principal route of acquisition in children but vertical transmission is gradually occupying primacy in the developed world. The risk of vertical transmission increases with higher maternal viraemia and human immuno-deficiency virus (HIV) co-infection but current international guidelines do not suggest avoidance of vaginal delivery and breastfeeding to minimise the risk of vertical transmission. The diagnosis of perinatal transmission is different from that in older child or adult and detection of HCV-RNA is essential. Although the natural history of HCV infection in children is not well characterised, almost 50-80% will progress to chronic hepatitis among vertically infected and blood transfusion acquired hepatitis C cases. Children have a lower viral load, lower ALT values and milder histological derangement as compared to adults with chronic hepatitis C cases. Experience of treatment of chronic hepatitis C in children is limited and still evolving. Few patients achieve spontaneous remission and progression to a more severe liver disease might occur in adult life. Here, the natural history, diagnosis and management of HCV infection in children are discussed with special emphasis on features which are different from adults.     

拉米夫定与阿德福韦酯联合治疗应答不佳的慢性乙型肝炎患者的抗病毒治疗

目的观察重组人干扰素α-2b（INFα-2b）单药治疗及恩替卡韦（ETV）与阿德福韦酯（ADV）联合治疗拉米夫定（LAM）与
ADV联合治疗应答不佳的慢性乙型肝炎患者的疗效和安全性。方法选择我院2008年6月~2011年1月LAM与ADV联合治疗
应答不佳的慢性乙型肝炎患者161例,随机分为A、B两组,A组给予INFα-2b 5×106,每周3次;B组ETV（0.5 mg,1次/d）与ADV
（10 mg,1 次/d）联合应用。所有病例治疗48 周为观察终点。采用化学发光法定量检测HBsAg和HBeAg,采用实时荧光定量
PCR检测HBV DNA水平,采用PCR产物直接测序法检测病毒耐药基因。组间比较采用配对t检验,率的比较采用χ2检验。结
果治疗48 周,A组与B 组患者血清HBV DNA水平中位数均明显下降,下降幅度分别为2.06±1.15log10 拷贝/ml 与1.77±
1.28log10 拷贝/ml;A组与B组血清病毒学应答率、血清学应答率、生化学应答率分别为：48.15%（39/81）与53.75%（43/80）、
61.70%（50/81）与53.75%（43/80）、49.38%（40/81）与60.00%（48/80）,两组间差异均无统计学意义（P>0.05）;基因耐药变异率分
别为30.95%（13/42）与64.86%（24/37）,差异有统计学意义（P<0.05）。结论LAM联合ADV治疗应答不佳的慢性乙型肝炎患者,
选择改用INF或改用ETV与ADV联合治疗,均能获得较好的临床疗效。若患者无干扰素禁忌证,尽可能选择干扰素治疗。
     

Spectrum of Acute Viral Hepatitis in Southern India

Background

The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented.

Methods

A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features.

Result

Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11-20 and 21-30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A.

Conclusion

Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India.Key Words: Viral hepatitis, Hepatitis A