Importance of markers of hepatitis B virus in alcoholic liver disease.

To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg.     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

Hepatitis B and Delta Virus Are Prevalent but Often Subclinical Co-Infections among HIV Infected Patients in Guinea-Bissau,West Africa: A Cross-Sectional Study

BackgroundCo-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) may lead to accelerated hepatic disease progression with higher rates of liver cirrhosis and liver-related mortality compared with HBV mono-infection. Co or super-infection with hepatitis Delta virus (HDV) may worsen the liver disease and complicate treatment possibilities.MethodsIn this cross-sectional study we included HIV-infected individuals who had a routine blood analysis performed at an HIV clinic in Bissau, Guinea-Bissau between the 28^th of April and 30^th of September 2011. All patients were interviewed, had a clinical exam performed and had a blood sample stored. The patients'' samples were tested for HBV and HDV serology, and HBV/HDV viral loads were analyzed using in-house real-time PCR methods.ResultsIn total, 576 patients (417 HIV-1, 104 HIV-2 and 55 HIV-1/2) were included in this study. Ninety-four (16.3%) patients were HBsAg positive of whom 16 (17.0%) were HBeAg positive. In multivariable logistic regression analysis, CD4 cell count <200 cells/ µl and animist religion were significantly associated with HBsAg positivity. Due to scarcity of available plasma, virological analyses were not performed for eight patients. HBV DNA was detected in 42 of 86 samples (48.8%) positive for HBsAg and genotyping was performed in 26 patients; 25 of whom had genotype E and one genotype D. Among 9 patients on antiretroviral treatment (ART), one patient had the [L180M, M204V] mutation associated with lamivudine resistance. Among the HBsAg positive patients 25.0% were also positive for anti-HDV and 4/9 (44.4%) had detectable HDV RNA.ConclusionHBV and HDV were frequent co-infections among HIV positive patients in Guinea-Bissau and chronic infection was associated with severe immunosuppression. Lamivudine was widely used among HBsAg positive patients with the risk of developing resistant HBV.     

Detection of hepatitis B virus DNA by polymerase chain reaction in HBsAG negative Senegalese patients suffering from cirrhosis or primary liver cancer

The polymerase chain reaction was used to search for hepatitis B virus (HBV)-DNA sequences in the sera of HBsAg-negative Senegalese patients suffering from liver cirrhosis or liver cancer. Amplified HBV-DNA sequences were detected by hybridization with a digoxigenin-labelled HBV-DNA probe. HBV-DNA was detected in 17% of HBsAg negative Senegalese subjects from the general population and in 44% and 58% of the patients suffering from cirrhosis or primary hepatocellular carcinoma (PHCC) respectively. In the control group, amplified HBV-DNA was detected in 25% of the subjects without HBsAg and anti-HBs antibodies, and in 6% of subjects positive for anti-HBs antibodies. This study confirmed the hypothesis that there is an etiologic link between HBV and PHCC in HBsAg-negative patients.     

Hepatitis B virus surface and core antigens in the liver of primary hepatocellular carcinoma cases in Virginia

Zenker-fixed paraffin-embedded sections of biopsy liver tissue from 64 cases of primary hepatocellular carcinoma (PHC) were stained for hepatitis B surface antigen (HBsAg) and for hepatitis B core antigen (HBcAg) by histochemical and/or immunohistochemical techniques in a retrospective study. PHC arose in livers with postnecrotic cirrhosis in 30 (46.9%) cases. Controls included liver biopsy sections from 123 miscellaneous liver disorders and from 67 randomly selected autopsy specimens, none of which were known to be associated with hepatitis B virus (HBV) infection. HBsAg was detected in tumorous hepatocytes in only one of the 64 cases of PHC. HBsAg was identified in nontumorous hepatocytes of 8 (20%) of 40 specimens that contained adequate nontumorous liver tissue. All of these HBsAg positive cases of PHC were associated with cirrhosis. Thus HBsAg was detected in 8 (33.3%) of 24 cases of PHC with cirrhosis, but in none of the remaining 16 cases without cirrhosis. HBcAg was not detected in the hepatocytes of those HBsAg positive PHC cases tested. Our results suggest that HBV infection may successively lead to chronic hepatitis, cirrhosis and ultimately PHC.     

Hepatitis G virus (GBV-C) infection among Brazilian patients with chronic liver disease and blood donors

Background: The recently discovered hepatitis G virus (HGV) belongs, as hepatitis C virus (HCV), to the Flaviviridae family. HGV has been isolated from the serum of patients with non A-E hepatitis. However, the association of HGV with hepatitis is uncertain.Objective: To determine the HGV prevalence in blood donors and in patients with liver disease and to evaluate a possible correlation between HGV infection and liver disease.Study design: Sera from a total of 113 consecutive patients with chronic liver disease were submitted to a series of liver enzymes and function tests and analyzed for the presence of HBsAg, anti-HBs, anti-HBc, anti-HCV, HCV RNA and HGV RNA. Prevalence of HGV RNA was determined in a group of 87 blood donors.Results: Nine (10%) sera from blood donors and 15 (13%) sera from patients with chronic liver disease were HGV RNA positive. Some 28 (25%) patients were HCV RNA positive, with genotypes 1a, 1b and 3 present in 10, 12 and 5 patients, respectively. A total of 20 (18%) patients were HBsAg carriers. Five (4%) patients were double infected (one with HBV+HCV, one with HBV+HGV and three with HCV+HGV).Conclusion: The proportion (10%) of HGV-infected blood donors was very high when compared with other countries. The results did not allow to establish HGV as an etiologic agent for chronic liver disease. The parenteral route was the presumed means of HGV transmission for only one-third of the patients.     

Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections.

Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.     

A case of hepatitis B reactivation due to the hepatitis B virus escape mutant in a patient undergoing chemotherapy

A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient’s virologic markers were positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc), while antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine (LMV) therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin (TB) were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C (HBsAg subtype adw) with immune escape mutations, F8L, S34L, F41S, G44V, F93C, V96G, L110I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.     

Prevalence of occult hepatitis B virus infection in kidney transplant recipients

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.     

Hepatitis B Surface Antigen Concentrations in Patients with HIV/HBV Co-Infection

HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss.     

HBV感染中抗-(抗-HBs)独特型抗体的研究

1.75％聚乙二醇(MW6000)沉淀血清免疫复合物后,采用ELISA法检测上清中抗独特型抗体〔抗-(抗-HBs)〕。56例急性HBV感染患者血清IgM抗-(抗-HBs),第一周检出率最高(60.00％),1个月后大部分阴性,IgG抗-(抗-HBs)维持时间略长。IgM抗-(抗-HBs)较HBsAg/IgM和IgM抗-HBc消失早,将有利于急性HBV感染的诊断。27例CAH和29例CPH,IgM和IgG抗-(抗-HBs)阳性率约为38～52％,两型间无显著差异(p>0.5)。3例无症状HBsAg携带者和12例HBsAg血清疫苗接受者血清,抗-(抗-HBs)阴性。115例HBV感染者中,IgM抗-(抗-HBs)阳性者HBsAg阳性率(93.62)显著高于IgM抗-(抗-HBs)阴性者(52.31％),p<0.005;反之,HBsAg阳性血清IgM抗-(抗-HBs)阳性率(55.5S％)显著高于HBsAg阴性血清(9.68％),p<0.005;IgM抗-(抗-HBs)阳性和阴性血清的HBVDNA阳性率有显著差异(p<0.025),IgG反应到类似的结果。以上资料表明,抗-(抗-HBs)提示了一些HBV感染患者体内可能存在一种缺陷的反馈机制,导致抗-HBs产生不足而容许更活跃的HBV复制。本文证明了HBV感染患者血清中存在的抗-(抗-HBs)可能是共同决定簇“a”特异性的,还表明抗-HBs人抗-Id反应可能被纯化人血清HBsAg抑制,提示人抗-(抗-HBs)与抗-HBs结合的位点可能在HBsAg与抗-HBs结合位点内或在其附近,这和一些动物抗-(抗-HBs)的研究结果是一致的。     

Clinicopathologic features and genotyping of patients with chronic HBV infection in the Upper Egypt

The aim of this study was to determine the clinicopathologic features and Hepatitis B virus genotypes in HBV-infected patients in the Upper Egypt. Eighty-three HBsAg-positive patients (28 carriers, 14 with chronic hepatitis, 32 with liver cirrhosis and 9 with hepatocellular carcinoma) were enrolled. Blood was collected and serum samples obtained were screened for Hepatitis markers genotyping was conducted for 6 HBV genotypes (A through F) using a method for genotyping HBV by primer specific polymerase chain reaction. Genotype D was the only genotype detected in different clinical forms of chronic HBV infection (carriers, chronic hepatitis, cirrhosis and hepatocellular carcinoma) and, in all patients who had elevated or normal alanine aminotransferase levels and in all ages. HBeAg was absent in 78 patients suggesting the presence of pre-core or core mutations. Positive correlation was found among serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), histological activity index and grade of hepatitis. This study provides the first indication about the clinicopathologic features of HBV-infected patients in the Upper Egypt. It also reports the predominance of genotype D in this region.     

Prognosis for the patients with alcoholic and nonalcoholic liver disease

The purpose of this investigation was to determine the role of alcohol in development of progressive liver disease. For this purpose, 41 alcoholic patients were followed up for 5 years. Criteria for alcohol abuse was that the patients were enjoying 20 g alcohol daily in a period of 5 years for females and respectively 60 g daily for males. In the same time a group of 51 nonalcoholic patients with histologically proven chronic liver disease were investigated. In all 92 patients chronic liver disease and progression of the disease was proven by liver biopsy during a 5-years follow-up. In sera of all patients the markers of hepatitis viruses B, D and C were continuously determined and chronic viral hepatitis was excluded. Also, autoimmune chronic hepatitis was excluded. The results of the investigation showed that alcoholics develop cirrhosis hepatitis, in most cases 78.04%. The most progressive chronic liver diseases--cirrhosis and hepatocellular carcinoma--are significantly present among nonalcoholics (p < or = 0.05). In the mentioned investigation a large group of 51 patients with severe chronic hepatitis without a proven etiology of disease was found and it deserves priority in future research.     

Hepatitis B viral factors and clinical outcomes of chronic hepatitis B

Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of hepatitis flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favorable outcome. In contrast, late or absent HBeAg seroconversion after multiple hepatitis flares accelerates the progression of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors predictive of clinical outcomes have been identified. For example, serum HBV DNA level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, hepatitis B viral factors such as serum HBV DNA level, genotype and mutants have already been clarified to influence disease progression of chronic hepatitis B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.     

Immunopathogenesis of hepatitis B virus infection

Hepatitis B virus (HBV) infection is a non-cytopathic hepatotropic virus that can lead to severe liver disease including acute hepatitis, cirrhosis and hepatocellular carcinoma. Successful clearance of the virus as well as the establishment of liver disease is largely driven by a complex interaction between the virus and the host immune response. In this review, the immunological events, including both the innate and adaptive immune response are discussed in the setting of both acute and chronic HBV infection and liver disease.     

肝硬化患者乙肝表面抗原的定量检测及意义

目的:探讨HBsAg定量测定在乙肝相关性肝硬化病程中的变化和意义。方法:选择乙肝相关性肝硬化患者60例纳入实验对象,根据2000年9月(西安)第10次全国病毒性肝炎学术会议修订的《病毒性肝炎防治方案》中的诊断标准分为代偿期组和失代偿期组,其中代偿期组35例,失代偿期组25例。另选取20例乙型肝炎病毒携带者作为对照组。应用电化学发光免疫分析法测定患者血清中HBsAg和HBeAg滴度,免疫荧光定量PCR法检测HBVDNA载量。结果:对照组、肝硬化代偿期组和肝硬化失代偿期组HBsAg滴度分别为:2574.73±3252.27COI、5494.35±2129.84COI和6921.25±1957.60COI,三组之间差别均有统计学意义(P<0.05)。肝硬化代偿期组中,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性(P<0.05()r=-0.350;r=-0.514)。肝硬化失代偿期组中,HBsAg滴度与HBVDNA及HBeAg水平均无明显相关性(r=-0.020;r=0.154)。结论:肝硬化失代偿期HBsAg滴度明显高于肝硬化代偿期,代偿期HBsAg滴度高于HBV携带者组,即HBsAg滴度随肝脏疾病进展呈阶梯型递增。肝硬化代偿期,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性,HBsAg水平可以作为评估病毒复制的参考指标。肝硬化失代偿期,HBsAg滴度与HBVDNA和HBeAg无相关性,不能反映病毒复制水平,不能作为评估病毒复制的参考指标。     

Occult hepatitis B demonstrated by anti-HBc and HBV DNA in HIV-positive patients

Background:

In patients who are hepatitis B virus (HBV) DNA-positive, but HBV surface antigen (HBsAg) -negative, the infection is referred to as occult hepatitis B infection (OBI). Occult HBV infection is harmful when other liver diseases are present, and can aggravate liver damage in in patients with chronic liver diseases. In human immunodeficiency virus (HIV) infection the suppression of viral replication by the immune system might be inactivated, and classical HBV infection in OBI patients may occur. Health care professionals should be aware of OBI in HIV patients. The routine test for HBV infection in Iran is the enzyme-linked immunosorbent assay for the HBV surface antigen (ELISA HBsAg); therefore, the aim of this study was to evaluate the prevalence of OBI in Iranian HIV patients.

Methods:

This cross-sectional study was conducted in 2012 on sera from all the known and accessible HIV patients in Jahrom and Fassa, two cities in southern Iran. All samples were tested for the HBsAg, HBV core antibody (HBcAb). All the results were analyzed using SPSS.

Results:

Of the 91 patients, seven (7.7%) were HBsAg-positive and forty-five (49.5%) were HBcAb-positive. In patients with negative HBsAg (84 patients), 39 (46.4%) were HBcAb positive and 53 (63%) were positive for HBV DNA.

Conclusion:

The prevalence of HBV infection is relatively high in HIV patients, and more accurate tests than those presently in use should be used for diagnosis.Key Words: Hepatitis B, HIV infection, Occult hepatitis     

2型糖尿病患者乙型肝炎病毒感染率分析

目的：通过调查糖尿病患者乙型肝炎病毒（HBV）的携带率,阐明糖尿病发生是否与HBV感染有关,并观察糖尿病合并HBV感染时是否加重对肝功能的损害。方法：用ELISA方法检测533例2型糖糖尿病患者和1440例普通人群乙型肝炎表面抗原（HBsAg）以及HBV其他血清学标志,同时常规测定肝功能和血糖等。结果：2型糖尿病HBsAg阳性24例,阳性率4.50%,普通人群HBsAg阳性70例,阳性率4.86%,两组间阳性率差异无统计学意义（x2=0.110,P=0.740）。糖尿病患者感染HBV后的抗体应答与普通人群相似。糖尿病合并HBV感染者与无糖尿病HBV感染者的肝功能异常差异无统计学意义。糖尿病患者中83例（16.3%）谷氨酰转肽酶升高,在肝功能异常指标中最常见,这与HBV感染后丙氨酸转氨酶升高为主不同。结论：糖尿病发生与HBV感染无关,糖尿病合并HBV感染时不加重对肝脏的损害。     

Antibodies against HBV, HCV and HAV detected by using microparticle enzyme immunoassay in hepatitis outpatients

The presence of the hepatitis B surface antigen (HBsAg), of the antibodies against HBc, HCV and HAV was determined in outpatients in the period September 2005 - December 2006. The serum samples were analyzed by using Enzyme Immunoassay microparticles (Abbott AxSYM System). At least one test was positive in 238 patients (15.4%) of the total of 1547 patients. Of the 238 positive subjects, in 130 positive subjects (54.6%) the existence of HBV infection could be ascertained based on the presence of HBsAg or of the antibodies against HBc or of their association; 83 patients (34.9%) presented antibodies against HCV and in other 12 patients the antibodies against HCV were associated with HBsAg or with antibodies against HBc, suggesting the coexistence of HCV and HBV infection. The antibodies against HCV and the associations between HCV and HBV were mostly detected in subjects with the diagnosis of cirrhosis, liver failure or chronic hepatitis. Of the 13 (5.46%) patients with antibodies against HAV, 6 patients presented the associations: in 2 cases antibodies anti-HAV with positive HBsAg, in 1 case antibodies anti-HAV and anti-HBc with positive HBsAg, in 2 cases antibodies anti-HAV and anti-HBc and in 1 case antibodies anti-HAV and anti-HCV.     

Liver-cell-membrane autoantibody specific for inflammatory liver diseases.

With an immunofluorescence technique using rabbit hepatocytes isolated by a non-enzymatic method an autoantibody directed against liver-cell-membrance was identified. Sera from 361 patients with various liver diseases and 274 patients with primary non-hepatic diseases-many associated with non-organ-specific auto-antibodies-were examined. The antibody (LMA) was found in 27 out of 72 patients with hepatitis-B-surgace antigen (HBsAg)-negative chronic active hepatitis and in 17 out of 28 patients with HBsAg-negative non-alcoholic cirrhosis. Only two patients had LMA and HBsAg, and both had chronic active hepatitis. One patient with extrhepatic disease was found to have LMA, and this patient had biochemical evidence of liver disease. Hence there is a close correlation between the presence of LMA and HBsAg-negative chronic inflammatory liver diseases and its detection may help in diagnosis.