核苷类似物治疗失代偿期乙型肝炎肝硬化临床分析

目的通过核苷类似物治疗乙型肝炎肝硬化失代偿期患者，对比观察临床疗效。方法在病人知情同意情况下随机分组，进行核苷类似物抗病毒治疗，并设立常规护肝治疗组。结果抗病毒治疗1年，拉米夫定治疗患者HBVDNA全部转阴，HBeAg血清转换率为26％，肝功能明显好转，疗效显著；阿德福韦酯组疗效相对较慢，只出现3例HBVDNA转阴，HBeAg血清转换率为13％，两组无1例患者死亡；未抗病毒组疗效最差，2例死亡，3组疗效差异性显著（P〈0．05）。结论乙型肝炎肝硬化失代偿期患者应进行抗病毒治疗，并应首先选用起效快的拉米夫定迅速控制病情。     

慢性乙型肝炎的免疫调节治疗：挑战与机遇

慢性乙型肝炎的抗病毒治疗药物主要包括核苷类似物和干扰素，其中核苷类似物主要抑制HBV复制；普通干扰素以抑制病毒为主，兼有免疫调节作用。值得关注的是长效干扰素（PEG—IFNOt2a）在5％-8％的HBeAg转阴并发生HBeAb转换的慢性乙型肝炎患者治疗中，出现HBsAg血清转换，显示其可能具有通过诱导免疫应答来清除病毒的作用。由于目前应用的抗病毒治疗药物不能彻底清除病毒，而且在停药后易复发，     

原发性肝癌局部化疗后肝炎及乙型肝炎抗病毒治疗的临床研究

目的分析肝癌化疗后肝炎发生的病因,探讨核苷类似物抗病毒治疗对化疗后乙肝病毒再激活肝炎疗效。方法收集明确诊断乙型肝炎后肝细胞癌患者120例,男108例,女12例,年龄28~85岁,平均（53.88±12.16）岁。肝癌患者均接受1次经导管肝动脉化疗栓塞（TACE）治疗;并分为抗病毒治疗组35例;未行抗病毒治疗组85例。抗病毒组中TACE前2周23例服拉米夫定;12例服阿德福韦酯,维持抗病毒治疗TACE后4周为观察终点。随访4周后,监测2组患者TACE前后肝功能及HBV载量水平变化和肝炎发生情况,观察核苷类似物抗病毒治疗HBV再激活肝炎的疗效。结果肝细胞癌患者化疗后HBV再激活33例,化疗后未再激活87例,HBV再激活发生率为27.50%。HBV再激活肝炎23例,发生率为69.70%;化疗药物性肝炎11例,发生率为12.64%,2种肝炎的发生之间差异有统计学意义（P=0.00）。抗病毒治疗组与未抗病毒组之间HBV再激活肝炎的发生差异有统计学意义（2χ=5.78,P〈0.05）,2组间药物性肝炎的发生差异无统计学意义。结论肝细胞癌化疗后发生HBV再激活肝炎和化疗药物性肝炎;HBV再激活肝炎的发生较化疗药物性肝炎多。核苷类似物（拉米夫定/阿德福韦酯）抗病毒治疗可明显降低肝细胞癌患者化疗后HBV再激活肝炎的发生。     

重型病毒性肝炎病原学特点及转归

探讨重型病毒尾肝炎的病原学特点。收集各型重型病毒性肝炎418例，分析其病原学分型及乙型肝炎病毒不同病原学模式与重型肝炎预后的关系。急性重型肝炎以甲型、戊型及乙型病毒性肝炎为主，乙型肝炎病毒感染治愈后病毒阴转率较高。亚急性有慢性重型肝炎以乙型肝炎病毒毒感染居首，占92．8％。在乙型肝炎病毒感染的病原学模式中，以HBsAgHBeAbHBcAb阳性的重型肝炎发病及死亡率最高。乙型肝炎病毒与其他肝炎病毒重叠感染与单独感染比较，死亡率无显著差异。单纯TTV感染可导致重型肝炎。重型肝炎发病后HBVDNA可自然阴转，阴转率可达53．6％。重型肝炎仍以乙型肝炎病毒病毒感染为主。乙型肝炎病毒前C区发生基因突变可能较易发生重型肝炎。     

多次抗病毒治疗无效的慢性乙型肝炎患者停用抗病毒药物后的联合治疗

目的 对于干扰素治疗无效、核苷类似物耐药后停用抗病毒药物治疗的慢性乙型肝炎患者,探讨其停药的后果及再联合应用核苷类似物长期治疗的必要性.方法 先后用干扰素α-2b、核苷类似物抗病毒治疗均无效的42例慢性乙型肝炎患者,其自动停用抗病毒药物一段时间后,再联用拉米夫定(100 mg/d)(或替比夫定600 mg/d、恩替卡韦...     

核苷(酸)类似物治疗慢性乙型肝炎存在的问题与对策

目前用于慢性乙型肝炎抗病毒治疗的药物主要有干扰素或聚乙二醇化干扰紊及核苷（酸）类似物两类，其中核苷（酸）类似物具有高效、低毒、使用方便等优点，在临床应用范围广泛。已批准用于乙型肝炎抗病毒治疗的核苷（酸）类似物有拉米夫定、阿德福韦酯和恩替卡韦；此外正在进行临床试验和开发的还有特比夫定、依曲他滨和克拉夫定等。随着新的核苷（酸）类似物不断问世及治疗方案的优化，其疗效已得到肯定。但核苷（酸）类似物抗乙型肝炎病毒（HBV）治疗开始容易，治疗过程中医师会面临众多难题：如疗程难以确定；停药难，可能出现停药反弹，不停药也难，继续治疗部分患者有出现耐药的可能；一旦出现耐药（基因型耐药或者表型耐药），在什么时机加用或改用其它药物治疗等。这些是任何现有核苷类药物都无法回避的问题。作为有责任和合格的肝病专科医师，在确定使用核苷（酸）类似物治疗后，需与患者进行充分和必要的沟通，将这些有关核苷（酸）类似物的重要信息告知患者。本文对核苷（酸）类似物治疗慢性乙型肝炎中常见的几个主要问题进行讨论。     

重型病毒性肝炎病原学与预后的关系探讨

目的探讨重型病毒性肝炎的病原学特点。方法收集各型重型病毒性肝炎418例,分析其病原学分型及乙型肝炎病毒不同病原学模式与重型肝炎预后的关系。结果急性重型肝炎以甲型和戊型病毒性肝炎为主,乙型肝炎病毒感染治愈后病毒阴转率较高。亚急性及慢性重型肝炎以乙型肝炎病毒感染居首位,占92.8％。在乙型肝炎病毒感染的病原学模式中,以HBsAg、HBeAb、HBcAb阳性的重型肝炎发病及死亡率最高。乙型肝炎病毒与其他肝炎病毒重叠感染与单纯感染比较死亡率无显著差异。单纯TTV感染可导致重型肝炎。重型肝炎发病后HBV DNA可自然阴转,阴转率可达53.6％。结论重型肝炎仍以乙型肝炎病毒感染为主。乙型肝炎病毒前C区发生基因突变可能较易发生重型肝炎。     

核苷(酸)类似物耐药变异对乙型肝炎病毒生物学特性的影响

目前,所有口服核苷(酸)类似物抗病毒药物,包括拉米夫定、阿德福韦、恩替卡韦、替比夫定等,在长期抗乙型肝炎病毒(HBV)治疗过程中都可能出现耐药。随着核苷(酸)类似物抗病毒药物在临床上广泛应用于治疗慢性乙型肝炎,HBV耐药问题日益凸显,成为制约慢性乙型肝炎抗病毒疗效的主要因     

拉米夫定耐药的慢性乙型肝炎抗病毒治疗

全球慢性HBV感染者多达3．6亿，我国有1．2亿，其中有3000万是慢性乙型肝炎患者，慢性乙型肝炎最关键的处理应是抗病毒治疗，以拉米夫定（lamivudine，LAM）为代表的核苷（酸）类似物开创了慢性乙型肝炎治疗的新时代。LAM是被批准的第一个治疗慢性乙型肝炎的抗病毒口服药，随着其在国内、外临床的广泛应用，HBV耐药突变（resistant mutation）已成为令临床医师棘手的问题。LAM耐药后的抗病毒治疗是临床面临的一个新课题，为此，许多学者进行了有益探讨。     

176例急性乙型肝炎临床特点分析

目的探讨急性乙型肝炎的流行病学及临床特征。方法以同期的慢性乙型肝炎(急性发作型)作为对照,观察176例急性乙型肝炎的临床症状、体征、生化指标,病毒学标志及治疗结果,并调查其传播途径。结果急性乙型肝炎除有少部分(19%)发热外,其发病时症状、体征、生化指标均与慢性乙型肝炎(急性发作型)极为相似,经常规护肝治疗后,急性乙型肝炎肝功能均较慢性乙型肝炎(急性发作型)恢复快(P<0.05),其HBsAg及HBV DNA均在四个月内阴转。176例急性乙型肝炎患者,经性接触传播者为98例,占55.7%。结论成人急性乙型肝炎一般预后好,是否应抗病毒治疗有待进一步研究。杜绝不洁性交,注射乙型肝炎疫苗,是阻止目前急性乙型肝炎发病率上升的主要措施。     

散发型戊型肝炎与急性乙肝临床特征比较

目的比较散发型急性戊型肝炎与乙肝临床特征。方法分析戊肝和急性乙肝间年龄、性别、肝脏损伤、症状体征以及病程的差异。结果急性肝炎病例中,戊型肝炎最常见（28.0%）,急性乙肝次之（9.2%）;戊肝平均发病年龄为56.3±13.1岁,急性乙肝为43.0±12.5岁,平均发病年龄戊肝较急性乙肝大（t=4.4723, P<0.0001）,均为男性多发;两者常见的临床症状和体征基本相当,但戊肝患者黄疸症状更多见（P<0.05）;戊肝病程较急性乙肝长（t=3.7249, P=0.0003）;通过年龄性别进行1∶1匹配分析,戊肝比急性乙肝对肝脏的损伤程度严重（t=3.5978, P=0.0019）。结论戊肝多见于中老年,急性乙肝多见于中青年,均为男性多于女性。临床特征比较戊肝较急性乙肝更为严重。     

Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults

We prospectively followed up 821 adults with acute viral hepatitis hospitalized at the Athens Hospital for Infectious Diseases between May 1981 and May 1983. Radioimmunoassays for the detection of serologic markers of hepatitis A virus, hepatitis B virus, and hepatitis delta virus, and molecular hybridization techniques for the detection of serum hepatitis B virus deoxyribonucleic acid and hepatitis delta virus ribonucleic acid were used. Based on the results of an enzyme immunoassay for the detection of immunoglobulin M antibody to hepatitis B core antigen (Corzyme-M), 563 cases were diagnosed as acute hepatitis B and 45 as acute hepatitis superimposed on hepatitis B surface antigen carriage. Development of the hepatitis B surface antigen carrier state was observed in only 1 (0.2%) of the 507 cases with acute hepatitis B that were followed. In contrast, hepatitis B surface antigen persisted in all the latter cases. Acute hepatitis superimposed on hepatitis B surface antigen carriage was attributed to hepatitis A virus superinfection in 2 (4.4%), hepatitis delta virus superinfection in 22 (48.9%), reactivation of chronic type B hepatitis in 12 (26.7%), seroconversion from hepatitis B e antigen-positive to anti-hepatitis B e antibody-positive in 2 (4.4%), presumed superinfection by non-A, non-B agent(s) in 6 (13.4%), and the first clinical manifestation of chronic active hepatitis in 1 (2.2%) case. These data show that acute clinical hepatitis B in adults seems to be a self-limited disease and rarely leads to the development of the carrier state in this epidemiologic setting and hepatitis delta virus superinfection and spontaneous reactivation of chronic hepatitis B are the principal causes of acute hepatitis superimposed in hepatitis B surface antigen carriers in an area with a moderately high prevalence of hepatitis B virus infections.     

乙型肝炎患者血清中抗HBc-IgM的临床意义

抗HBc-IgM在鉴别急性乙肝、慢性乙肝及慢性乙肝急性发作中的意义。应用亚培试剂盒检测抗HBc-IgM,追溯120例抗体阳性患者的临床诊断和各临床类型的抗体滴度水平分布,同时统计急性乙肝、慢性乙肝和慢性乙肝急性发作共240例患者的抗HBc-IgM检测结果,比较其抗体阳性率和滴度水平之间的差异。抗HBc-IgM阳性率,急乙肝组明显高于慢乙肝组和慢乙肝急性发作组。抗体滴度<2.0者,慢乙肝组和慢乙肝急性发作组的百分率明显高于急肝组。抗体滴度的检测对鉴别急乙肝和慢乙肝急性发作有较大的意义。     

Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C

BACKGROUND AND AIMS: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. RESULTS: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). CONCLUSION: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B.     

A biphasic pattern of anti-pre-S responses in acute hepatitis B virus infection

The clinical relevance of the immune response to the translation products of the pre-S1 and pre-S2 regions of hepatitis B virus was examined by testing sequential serum samples from 17 patients with acute self-limited hepatitis B and from two patients in whom chronic liver disease developed. Anti-pre-S antibodies were determined by enzyme immunoassays based on the inhibition of binding of monoclonal antibodies to epitopes in the pre-S1 and pre-S2 sequence. In acute, self-limited infection, anti-pre-S antibodies appeared in a biphasic pattern. The early antibodies were detected at the time of clinical signs of acute disease when HBsAg and often HBeAg were present, but hepatitis B virus DNA was no longer detectable in serum. Anti-pre-S levels then fell, but subsequently reappeared as the late antibody during the recovery phase, after development of anti-HBe, but before anti-HBs. Anti-pre-S responses were detected in 15 of 17 patients who recovered (88.2%) and in both patients with acute hepatitis B virus infection evolving to chronic liver disease. Although the early antibodies to pre-S1 and pre-S2 proteins appeared at the time of decreasing levels of infectious virus in serum in cases of self-limited infection, these antibodies also were transiently or continuously present with high levels of serum hepatitis B virus DNA in patients in whom chronic hepatitis B infection developed. Thus the anti-pre-S response in acute hepatitis is not a prognostic marker for clinical resolution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute delta hepatitis without circulating HBsAg.

Infection with the delta agent can only occur in the context of coexistent hepatitis B virus infection. We describe a patient in whom the clinical features of acute delta hepatitis developed when seroconversion from hepatitis B surface antigen to antibody had already occurred and diagnosis of recent acute hepatitis B was based on high titre IgM antibody to hepatitis B core antigen. We discuss the significance of such a serological profile, not previously described.     

Lamivudine treatment failure in preventing fatal outcome of de novo severe acute hepatitis B in patients with haematological diseases

BACKGROUND: Patients with malignant haematological diseases administered or no longer receiving immunosuppressive therapy are at high risk of reactivation or de novo hepatitis B infection and fulminant hepatitis. Despite promising results in the treatment of chronic hepatitis and its use in selected patients with acute hepatitis B, there is no consensus on lamivudine treatment in severe acute hepatitis portending a fatal clinical outcome. CASE REPORTS: Of the ten patients with malignant haematological disorders who became infected with the same strain of hepatitis B virus during hospitalisation in a haematology ward, five received lamivudine (and in some cases, ganciclovir and famciclovir). The other patients received only supportive therapy, since deteriorating clinical conditions hampered specific treatment efforts. Eight patients died from acute liver failure and one from a fatal course of the haematological disease; one had a favourable outcome from the therapy. There was no significant difference in terms of survival between the treated and untreated patients. CONCLUSIONS: Although lamivudine has proved promising in the therapy of chronic hepatitis B and of recurrent hepatitis after liver transplantation, its use in de novo severe acute hepatitis should be investigated further, particularly in immunocompromised patients.     

Significance of IgM antibody to hepatitis B core antigen for the differential diagnosis of acute and chronic hepatitis B virus infection and for the evaluation of the inflammatory activity of type B chronic liver diseases

IgM antibody to hepatitis B core antigen (anti-HBc) was assayed using a commercial kit in acute and chronic hepatitis B virus (HBV) infection and evaluated for its diagnostic and clinical significance. IgM anti-HBc was positive in all of 21 cases with type B acute hepatitis in the acute phase, and was also detected in 5 of 20 cases with type B chronic persistent hepatitis, in 4 of 20 patients with type B chronic active hepatitis and in one of 10 with type B liver cirrhosis. The absence of this marker was noted in all of 20 asymptomatic hepatitis B surface antigen (HBsAg) carriers and in 50 with HBsAg-negative patients with liver disease and in 200 healthy blood donors. The cut-off index of IgM anti-HBc was greater than 2.0 in all serum samples obtained in the acute phase of type B acute hepatitis, but was below 2.0 in type B chronic liver disease. A close relationship was found between the presence of IgM anti-HBc and the degree of inflammatory activity in patients with HBsAg-positive chronic liver disease. These data show that examination of IgM anti-HBc is useful in distingushing type B acute hepatitis from type B chronic liver disease, and also in evaluating the severity of disease in type B chronic liver disease.     

Changing aetiologic patterns of acute viral hepatitis in Taiwanese children

During 1981-86, 76 children were diagnosed as having acute viral hepatitis at the Department of Pediatrics, National Taiwan University Hospital, which is a major referral centre for hepatitis in children in northern Taiwan. The majority (64%) of children had acute hepatitis B which had occurred mainly during infancy. Perinatal transmission from a hepatitis B e negative surface antigen (HBsAg) carrier mother or infection through blood transfusion from a donor who had escaped notice by a less sensitive screening test (reverse passive haemagglutination test) for HBsAg were the two important modes of transmission of hepatitis B virus. The number of cases of acute hepatitis B declined after 1984, with the beginning of the nation-wide hepatitis B vaccination programme. Due to an outbreak of hepatitis A in northern Taiwan in 1982, the number of cases of hepatitis A peaked that year. Subsequently, cases of acute hepatitis A decreased remarkably. Better socio-economic conditions and improved hygiene might have contributed to the marked decrease of viral hepatitis A. The frequency of non-A, non-B hepatitis remained stable during the study period. It is possible to conclude that the aetiologic pattern of acute hepatitis in Taiwanese children changed during the past 6 years: clinical cases of hepatitis A and B decreased, probably because of more effective control of hepatitis A and B virus infections, whereas the control of non-A, non-B virus apparently requires further efforts.     

Hepatitis B virus replication in acute hepatitis B, acute hepatitis B virus-hepatitis delta virus coinfection and acute hepatitis delta superinfection

To evaluate the effect of hepatitis delta virus on the level of replication of hepatitis B virus and to assess the clinical significance that such an effect might have on the final outcome of the infection, the serological profile of hepatitis B virus DNA was investigated in 153 patients with acute or chronic hepatitis B virus infection with or without associated delta infection. Serum hepatitis B virus DNA was detected in 57% of patients with acute hepatitis B, 67% of those with acute hepatitis B virus-hepatitis delta virus coinfection and 25% of HBsAg carriers with hepatitis delta virus superinfection during the first week after the onset of symptoms. Patients with acute hepatitis B and those with acute hepatitis B virus-hepatitis delta virus coinfection did not differ significantly with respect to the serological profile of hepatitis B virus DNA and final clinical outcome. Within the group of HBsAg carriers with hepatitis delta virus superinfection, all patients who were initially negative for hepatitis B virus DNA developed chronic hepatitis delta virus infection, whereas 3 of the 4 patients with active hepatitis B virus infection at the time of superinfection showed transient inhibition of hepatitis B virus replication followed by termination of hepatitis delta virus infection in two patients. Therefore, although delta virus may inhibit the replication of hepatitis B virus among chronic HBsAg carriers, this effect is not readily apparent among patients with hepatitis B virus-hepatitis delta virus coinfection.