Serum hepatitis B virus DNA in acute hepatitis type B

Sera obtained within 7 days after clinical onset of acute hepatitis type B were positive for hepatitis B virus (HBV) DNA by spot hybridization only in 4 out of 45 patients who subsequently recovered, but in 10 out of 10 patients who instead developed chronic infection. These results indicate that in uncomplicated acute hepatitis B, virus replication is limited to an early phase of infection, often preceding the onset of clinical symptoms, and suggest that serum HBV-DNA may represent an early and predictive marker of chronicity.     

Isoniazid-rifampin-induced hepatitis in hepatitis B carriers

From January 1984-December 1987, 1783 patients received combination therapy of isoniazid, rifampin, and ethambutol for the control of tuberculosis. Forty-two developed symptomatic hepatitis during the period of treatment. Fifteen were hepatitis B virus carriers, and the remaining 27 were noncarriers. The peak serum transaminase and bilirubin levels were higher in carriers. Seven carriers died of fulminant or subacute hepatic failure, and only 1 noncarrier died. Eleven carriers had detectable serum hepatitis B virus deoxyribonucleic acid during the acute stage of hepatitis. The roles of isoniazid-rifampin combination therapy and hepatitis B virus in the adverse outcomes of carriers were discussed.     

Profile of hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Although chronic hepatitis B occurs in hepatitis B e antigen (HBeAg)-negative patients, its prevalence and clinical significance are not known. AIM: To determine the prevalence and profile of HBeAg-negative chronic hepatitis B virus (HBV) infection. METHODS: A retrospective analysis of 363 consecutive patients (mean age 36 y; 288 men) with chronic HBV infection was performed. All patients were HBsAg-positive. Tests for liver profile, HBeAg and anti-HBe antibody were performed in all patients. Serum HBV DNA was tested using branched DNA assay in 245 patients. The patients were classified into three groups: no cirrhosis with normal ALT levels, no cirrhosis with elevated ALT levels, and clinical or histological evidence of cirrhosis. RESULTS: Of 363 patients, 141 (39%) were HBeAg-positive and 222 (61%) HBeAg-negative. Of HBeAg-negative patients, 120 (54%) had normal ALT, 45 (20%) had elevated ALT and 57 (26%) had evidence of cirrhosis; corresponding figures in the HBeAg-positive patients were 40 (28%), 66 (47%) and 35 (25%). HBV DNA was positive in 53 of 131 (40%) HBeAg-negative patients tested; of these 53 patients, 9 (17%) had normal ALT, 20 (38%) had elevated ALT and 24 (45%) had cirrhosis. Thus, 72% of HBeAg-positive and 46% of HBeAg-negative patients had elevated ALT and/or cirrhosis. Among the latter group, 83% of HBV DNA-positive patients had elevated ALT and/or cirrhosis. Overall, 18% of HBsAg-positive patients had HBeAg-negative, HBV DNA-positive liver disease. CONCLUSION: HBeAg-negative chronic hepatitis B is not an uncommon and benign entity and chronic liver disease develops in a significant proportion of such patients.     

Viral hepatitis B

More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.     

Occult hepatitis B

Worldwide, chronic hepatitis B virus (HBV) infection is the primary cause of cirrhosis and hepatocellular carcinoma and is one of the ten leading causes of death. Traditionally, people with chronic HBV infection have been identified with blood tests for HBV antigens and antibodies. Recently, another group of patients with chronic HBV infection has been identified by sensitive, molecular testing for HBV DNA. Members of this group are often referred to as having occult hepatitis B because they are HBV-DNA positive, but hepatitis B surface antigen negative. Occult hepatitis B occurs in a number of clinical settings. In this review, we examine occult hepatitis B in people co-infected with hepatitis C, in whom occult hepatitis B has been associated with advanced fibrosis and diminished response to interferon alpha. Although much more research is needed, existing reports justify a heightened awareness of the medical importance and means of testing for occult hepatitis B.     

Chronic hepatitis B

Opinion statement  

Chronic hepatitis B

Opinion statement Interferon alpha, lamivudine, and adefovir are the three drugs currently approved for the treatment of chronic hepatitis B virus (HBV). There are pros and cons associated with the use of each drug. Individualization of therapy, based upon factors such as patient comorbidities, response to prior therapies, and stage of disease, is recommended. Patients with abnormal liver enzymes, indices of active viral replication (HBV DNA positive ± hepatitis B early antigen [HB_eAg] positive) or evidence of necroinflammatory activity on liver biopsy, and compensated liver disease are potential candidates for treatment with interferon, lamivudine, or adefovir. Patients with abnormal liver enzymes, indices of active viral replication (HBV DNA positive ± HB_eAg positive), and decompensated liver disease are candidates for treatment with lamivudine or adefovir. Consideration of liver transplantation should occur concurrently. Interferon alpha treatment results in hepatitis B surface antigen [HB_eAg] loss and sustained suppression of HBV DNA replication in 30% to 40% of treated patients. Loss of HBsAg occurs in nearly 10% of patients and a higher than expected frequency of HBsAg loss occurs long-term. The main limitation of therapy is the side effects and the need for parenteral administration. Additionally, interferon therapy is not applicable to all patient groups. Lamivudine achieves HB_eAg seroconversion in 15% to 20% of patients treated for 12 months, but (HBsAg) loss is rare. Reduction in HBV DNA to undetectable levels (by hybridization assay) during treatment is nearly universal, and histologic improvement is seen in about 55% of patients. The main limitation of lamivudine therapy is the development of drug resistance, which occurs in 20% of patients after 12 months and increases with duration of therapy (55% at 3 years). Adefovir achieves HB_eAg seroconversion in 12% of patients treated for 12 months, but HBsAg loss is rare. An average 3.5 log reduction in HBV DNA levels is and histologic improvement occurs in 50% to 60% of patients. It is effective against both wild-type and lamivudine-resistant HBV. The risk of drug resistance is low and estimated to be approximately 2% to 3% after 2 years of treatment. Several new antiviral agents are currently under evaluation in clinical trials. In addition, there are two drugs (tenofovir and emtricitabine) that have been approved for HIV infection and that have anti-HBV activity. In the future, combination therapy for chronic HBV infection can be anticipated. Utilization of two or more anti-HBV drugs would be predicted to enhance efficacy and reduce the likelihood of emergence of drug resistance.     

乙型肝炎e抗原阴性和阳性慢性乙型肝炎患者临床转归的回顾性分析

目的 随访HBeAg阴性和HBeAg阳性慢性乙型肝炎的临床转归，为比较两者的预后提供佐证。方法 采用回顾性分析，随访6～18年，平均（11．8±4．1）年，经肝穿刺病理组织学诊断，HBeAg阴性65例、HBeAg阳性118例慢性乙型肝炎患者的临床转归。统计学处理采用t检验和Х^2检验。结果 HBeAg阴性慢性乙型肝炎患者累计发展为肝硬化7例，占10．8％，肝癌4例，占6．2％，死亡8例，占12．3％；HBeAg阳性慢性乙型肝炎患者累计发展为肝硬化15例，占12．7％，肝癌8例，占6．8％，死亡12例，占10．2％。两组相比，肝硬化、肝癌和死亡的发生率差异均无统计学意义（均P〉0．05）。结论 HBeAg阴性和HBeAg阳性慢性乙型肝炎患者的远期临床转归差异无统计学意义。     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.     

一种新的HBeAg阴性慢性乙型肝炎病毒变异机制

目的 检测HBV核心启动子区(CP)基因变异方式.方法 自HBV慢性感染患者血清中提取HBV DNA,扩增CP区域序列,克隆入pMD19 T载体,选择阳性克隆进行DNA测序,与已知HBV基因相应序列比较患者体内HBV基因变异位点以及变异形式.结果 自21例患者中共挑选74个克隆测序,54个克隆中病毒基因序列CP区发生大段缺失突变,长度达234个核苷酸,另有1个克隆发生245个核苷酸缺失突变.缺失突变区域包括CP区、HBeAg起始密码子和直接重复序列(DR)Ⅰ区,命名为CP缺失突变,发生CP缺失突变的病毒株同时存在A1585T替换突变,这两个部位的突变具有联动特征.结论 观察到一种导致HBeAg阴性慢性乙型肝炎的新方式,即CP、HBeAg起始密码子缺失突变,并提出一种简明的CP缺失检测方式.     

乙型肝炎e抗原阴性与阳性慢性重型乙型肝炎临床分析

目的 分析乙型肝炎e抗原(HBeAg)阴性与HBeAg阳性慢性重型乙型肝炎患者的临床特点.方法 2001年1月至2006年9月在重庆医科大学附属二医院收治的353例慢性重型乙型肝炎患者分为HBeAg阴性组236例(66.8%),HBeAg 阳性组117例(33.2%),HBeAg阴性患者平均年龄高于HBeAg阳性患者,分别为(43.5±12.4)岁和(40.8±11.3)岁,两组比较差异有统计学意义(t=-1.988,P=0.048).对两组生化指标、HBV DNA、肝硬化基础、并发症、预后等进行分析.结果 HBeAg阴性患者血清HBV DNA低于HBeAg阳性患者,分别为(5.49±2.02)log10拷贝/mL、(6.64±1.41)log10拷贝/mL,两组比较差异有统计学意义(t=6.46,P<0.001);且HBeAg阴性患者血清HBV DNA<5 log10拷贝/mL的病例教比例为41.8%,远高于HBeAg阳性患者(11.9%),两组比较差异有统计学意义(X2=30.055,P<0.001).两组在肝脏生化指标、肝硬化基础及发生感染、腹水、肝性脑病、消化道出血等并发症及近期预后方面比较,差异均无统计学意义.结论 HBeAg阴性患者血清HBV DNA低于HBeAg阳性患者.HBeAg阴性慢性重型肝炎的肝脏生化指标、并发症发生率及近期预后与HBeAg阳性的慢性重型肝炎相似.应重视低水平病毒复制的HBeAg阴性慢性乙型肝炎患者的治疗、随访,早期抗病毒治疗,减少重型肝炎的发生率.