Evaluation of micro particle enzyme immunoassay technique (MEIA)-IMx for the detection of IgM class antibody to hepatitis B core antigen]

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBc-M, Abbott) had been recently introduced for the detection of IgM class antibody to hepatitis B core antigen (IgM anti-HBc). To evaluate the feasibility of using the IMx HBc-M, we carried out comparison tests between this method. RIA and EIA using sera from acute hepatitis B and type B chronic liver disease. Results obtained were as follows: In the test of 98 sera from acute hepatitis B patients, 92 (93.9%) were positive for IgM anti-HBc by IMx HBc-M, 96 (98.0%) by RIA and 82 (83.7%) by EIA. The four sera which were positive by RIA, but not by IMx were ones obtained from 5 to 12 month after onset. In the test of 267 sera from B type chronic liver disease patients, 93 (34.8%) were positive by IMx HBc-M, 109 (40.8%) by RIA and 23 (8.6%) by EIA. There was a difference in the positive rate between IMx HBc-M and RIA among type B chronic liver disease: the positive rate was higher in RIA than in IMx HBc-M among type B active chronic hepatitis, but only a little higher in IMx HBc-M than RIA among hepatocellular carcinoma. IgM anti-HBc titer was significantly higher in acute hepatitis type B than in chronic liver disease, and was so even in the phase of HBsAg negative in acute hepatitis. IgM anti-HBc was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of acute type B hepatitis by a solid phase u-antibody capture radioimmunoassay for IgM class antibody to hepatitis B core antigen: a diagnostic proposal based on a prospective study

The diagnostic and prognostic significance of IgM anti-HBc, studied by a solid phase u-antibody capture radioimmunoassay at a serum dilution of 1:4000, was prospectively evaluated in 73 adult patients with acute hepatitis seropositive for hepatitis B surface antigen (HBsAg). Of the 73 cases, 20 (27.4%) cleared their HBsAg within 6 months, while the remaining 53 (72.6%) did not. HBsAg seroconversion to its antibody occurred in 15 (93.8%) of the 16 patients positive for IgM anti-HBc with S/N ratios above 5.0, as did 5 (26.3%) of the 19 with S/N ratios between 2.1 to 5.0, and none (0%) of the 38 negative for IgM anti-HBc (S/N ratios less than 2.1). Therefore, a S/N ratio of IgM anti-HBc above 5.0 is diagnostic for acute type B hepatitis. However, low S/N ratios (2.1-5.0) of IgM anti-HBc were observed in the early stage of some patients with acute type B hepatitis, and would increase to a level greater than 5.0 when assayed again 1-2 weeks later. It was therefore suggested that repeated testing of anti-HBc IgM is mandatory for accurate diagnosis of acute type B hepatitis in patients whose initial serum specimens showed low S/N ratios of IgM anti-HBc. According to this criterion, only 22 (30.1%) of the 73 patients with acute hepatitis seropositive for HBsAg in Taiwan were true acute type B hepatitis, of whom 2 (9.1%) subsequently became chronic HBsAg carriers, while the remaining 51 (69.9%) were chronic HBsAg carriers with other superimposed forms of acute hepatic injury.     

Anti-HBc of IgM-class,HBeAg and anti-HBe in acute and chronic hepatitis B

ABSTRACT— The presence and persistence of IgM antibody against hepatitis B core antigen (anti-HBc IgM) and the correlation with other HBV markers were studied in 42 patients, all of whom had acute HBsAg-positive hepatitis but whose subsequent diseases differed. All patients initially had anti-HBc IgM. In 13 out of 15 patients with uncomplicated acute hepatitis, anti-HBc IgM disappeared within 6 months after onset of the disease. In five out of 12 patients, who in spite of transient HBsAg developed chronic liver disease, the anti-HBc IgM persisted for more than 2 years. Among 15 patients with persistent HBsAg, anti-HBc IgM was present from 7 months to more than 8 years. Seroconversion from HBeAg to anti-HBe was observed in seven patients and in five of these anti-HBc IgM disappeared during the follow-up period. These results indicate that anti-HBc IgM can be used as a serological marker of recent or ongoing HBV infection.     

Low-molecular-weight IgM antibody to hepatitis B core antigen in chronic infections with hepatitis B virus

IgM antibody to hepatitis B virus core antigen (IgM anti-HBc) develops during acute hepatitis B but frequently persists in chronic infections. To characterize persistent IgM anti-HBc better, 7-8S and 19S immunoglobulin fractions were prepared by rate-zonal centrifugation of sera from 17 patients with persistent hepatitis B (chronic active hepatitis) and were tested for IgM anti-HBc by a specific radioimmunoassay. In 16 sera peak activity was found in 7-8S fractions, although in 11 sera a minor peak was also present in 19S fractions. The low molecular weight of the predominant IgM anti-HBc was confirmed by gel filtration. In competition experiments, the binding of 7-8S antibody to an anti-IgM-coated solid phase was blocked more effectively by purified IgM than by purified IgG. These findings indicate that hepatitis B carriers with chronic active hepatitis have predominantly 7-8S IgM anti-HBc and represent a novel demonstration of naturally occurring 7-8S IgM with defined antiviral specificity.     

IgM anti-HBc in anti-HBe positive chronic type B hepatitis with acute exacerbations

IgM anti-HBc was measured by radioimmunoassay in serially collected serum samples during 20 acute exacerbations which developed in 14 patients with anti-HBe positive chronic type B hepatitis. IgM anti-HBc became positive in 12 of the 14 (86%) patients and in 18 of the 20 (90%) exacerbations, and elevation of IgM anti-HBc which was believed to be significant was also observed in the remaining two patients. In most of the patients who also had determinations of serum hepatitis B virus DNA, the hepatitis B virus DNA became positive. These results suggest that ALT elevation in anti-HBe positive chronic type B hepatitis is associated with active replication of hepatitis B virus. It is considered to be useful to measure IgM anti-HBc for the purpose of identifying the causes of ALT elevation in anti-HBe positive chronic type B hepatitis.     

Studies of HBV replication during acute hepatitis followed by recovery and acute hepatitis progressing to chronic disease

The serologic and viral profiles of 24 patients who presented with acute hepatitis B virus (HBV) infection were studied. Although in rare cases, HBV-DNA was detectable before hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), in the majority the viral proteins appeared first. In acute hepatitis followed by recovery, as IgM anti-HBc (hepatitis B core antigen) titres rose, the level of HBV replication fell and serum transaminases became elevated. In patients progressing to chronic HBV infection, IgM anti-HBc titres rose early, viral replication was initially low but continued to rise as the serum transaminase levels became elevated. 7S IgM anti-HBc, although present in the phase of established chronic HBV infection, was not found in the early phase of the chronic infection. Thus this antibody appears to be a consequence of, rather than a causative factor in, chronic HBV infection.     

Prevalence and significance of anti-HBc IgM (radioimmunoassay) in acute and chronic hepatitis B and in blood donors

Anti-HBc IgM was determined by a modified radioimmunoassay (RIA) in 35 patients with acute hepatitis B, 35 patients with chronic hepatitis B (7 with chronic persistent, and 28 with chronic active hepatitis), 157 HBsAg positive blood donors, and in 143 HBsAg negative but anti-HBc positive donors. The results of the RIA test were compared with those obtained by an ELISA technique. In chronic hepatitis, anti-HBc IgM was correlated with the occurrence of HBeAg, anti-HBe, Dane particles in the serum, HBsAg, and HBcAg in liver tissue and with biochemical and histological degrees of hepatic inflammatory activity. In acute self-limited hepatitis B, anti-HBc IgM (RIA and ELISA) was initially positive in all 35 patients. Twelve months after the acute illness, 94% of the patients were negative for anti-HBc IgM in the RIA test with only one patient showing a persistence of up to 18 months, whereas in the ELISA test anti-HBc IgM persisted in 17% of the patients over 2 years. In chronic hepatitis, the occurrence of anti-HBc IgM (RIA) showed a strong relation with the inflammatory activity, the anti-HBc IgM positive patients revealing a significantly more severe liver disease than did anti-HBc IgM negative patients. Anti-HBc IgM (RIA), however, did not correlate with the occurrence of HBeAg and Dane particles in the serum and HBcAg in liver tissue of patients with chronic hepatitis. Of the 157 HBsAg positive blood donors, anti-HBc IgM (RIA) could be demonstrated in 10 (6%), but in none of the 143 HBsAg negative, but anti-HBc positive donors, as compared to 43 (27%) and 9 (6%), respectively, in the ELISA test. Comparing the two test methods, the RIA exhibits higher specificity than did the ELISA due to a better blocking of nonspecific reactions, but possibly somewhat lower sensitivity. In this form, however, the RIA test is a more useful tool in the diagnosis of the different forms of hepatitis B virus infection and in determining the severity of chronic hepatitis B.     

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。     

Higher cut-off index value of immunoglobulin M antibody to hepatitis B core antigen in Taiwanese patients with hepatitis B

BACKGROUND: The cut-off index value of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc; AxSYM CORE-M, Abbott) for diagnosing acute hepatitis B is 1.2. A high false-positive rate of IgM anti-HBc was observed in acute flare-ups of chronic hepatitis B in Taiwanese patients. Thus the purpose of the present paper was to study the optimal index value of IgM anti-HBc in Taiwanese subjects. METHODS: The peak index values of 42 IgM anti-HBc-positive patients were collected. There were 20 acute hepatitis B patients and 22 patients with chronic hepatitis B with acute flare. The biochemical, virological, and serological data were obtained. RESULTS: There were significant differences in mean age (36 vs 47 years, P = 0.01), serum alanine aminotransferase level (2042 U/L vs 1193 U/L, P = 0.02) and peak index value of IgM anti-HBc (2.9 vs 1.5, P < 0.01) between patients with acute hepatitis B and those with acute flare of chronic hepatitis B. Eleven (50%) of 22 patients with chronic hepatitis B with acute flare had index value of >1.2. The optimal cut-off index value to differentiate acute hepatitis B from chronic hepatitis B with acute flare was 2.4-2.5, with a sensitivity of 90% and specificity of 90%. CONCLUSIONS: The cut-off index value of IgM anti-HBc to differentiate acute hepatitis B from chronic hepatitis B with acute flare among Taiwanese patients should be set at 2.4-2.5 instead of 0.8-1.2.     

Clinical significance of low molecular weight (7-8S) immunoglobulin M antibody to hepatitis B core antigen in chronic hepatitis B virus infections

Separation of 7-8S and 19S forms of serum immunoglobulin M (IgM) hepatitis B core antibody (anti-HBc) by rate-zonal centrifugation was carried out on serum from 80 American chronic carriers of hepatitis B surface antigen (HBsAg), all of whom were positive for IgM anti-HBc and had elevated levels of serum alanine aminotransferase (mean 164 IU/L). Seventy-three of the 80 sera showed a predominance of one or the other form of IgM anti-HBc. Fifty-four (68%) had predominantly 7-8S IgM anti-HBc, and 19 (24%) had predominantly 19S IgM anti-HBc. Sex, age, length of HBsAg-carrier state, mean alanine aminotransferase, mean total IgM anti-HBc level, presence of hepatitis B e antigen, and liver histology were similar in both groups. 19S IgM anti-HBc was detected in 11 (41%) of 27 male homosexuals compared with only 8 (17%) of 46 heterosexual patients (p = 0.03). Despite this apparent association, an explanation for the variable presence of 19S and 7-8S IgM anti-HBc predominance in chronic hepatitis B remains lacking.     

Immunoglobulin M antibody to hepatitis B core antigen in patients with chronic type B hepatitis

Serum samples from 130 persons who were seropositive for hepatitis B surface antigen and who had various forms of accompanying liver disease were tested for immunoglobulin M (IgM) antibody to hepatitis B core antigen. In 99% of patients with hepatitis B antigen-positive chronic type B hepatitis, IgM antibody to hepatitis B core antigen was present. This antibody was not present in "healthy" hepatitis B surface antigen carriers and was detectable in only 30% of patients with delta hepatitis. Testing of serial sera from 38 patients with chronic type B hepatitis revealed that IgM antibody to hepatitis B core antigen persisted in patients who had evidence of persistent hepatitis B virus replication but ultimately disappeared in those patients who exhibited a sustained loss of serum markers of viral replication (hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity). These findings suggest that the presence of IgM antibody to hepatitis B core antigen in chronic hepatitis B surface antigen carriers indicates an active immune response to persistent viral replication.     

Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers

Delta antigen is currently thought to reflect superinfection of the liver with a defective RNA virus (delta agent), requiring helper function from hepatitis B virus for its replication. To assess the influence of delta agent on hepatitis B virus replication in patients persistently infected with both viruses and showing chronic liver disease, we measured serum and liver hepatitis B virus DNA in HBsAg-positive chronic liver disease patients who were either positive or negative for delta antigen in the liver. Hepatitis B virus DNA was assayed in the serum of 21 patients with delta antigen-positive/HBsAg-positive chronic liver disease and in 21 patients with delta antigen-negative/HBsAg-positive chronic liver disease matched for HBeAg/anti-HBe status and underlying liver histology. HBcAg and delta antigen in liver was determined by immunofluorescence or immunoperoxidase staining. In delta antigen-positive/HBsAg-positive chronic liver disease, serum hepatitis B virus DNA was detected transiently in 4 of 21 cases (19%) and was present in these patients at low levels (trace to 2+). In contrast, 9 of 21 (43%) delta antigen-negative/HBsAg-positive chronic liver disease patients were serum hepatitis B virus DNA positive, and five of these had high serum hepatitis B virus DNA levels (3+ to 4+). Serum HBsAg and anti-HBc titers were significantly lower in delta antigen-positive cases and correlated with reduced amount of HBcAg in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection

OBJECTIVES: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, the clinical relevance of low viremia levels remains unclear. We evaluated the clinical significance of a single baseline serum HBV DNA measurement by a quantitative polymerase chain reaction (PCR) assay in this setting. METHODS: In total, 196 patients with HBeAg-negative chronic HBV infection (62 inactive carriers, 134 with chronic hepatitis B) were studied. ALT activity was normal at baseline in 25/134 HBeAg-negative chronic hepatitis B patients (18.7%), whereas it remained normal throughout follow-up in all inactive carriers. RESULTS: HBV DNA was <30,000 copies/ml in 14 (10.5%) and <100,000 copies/ml in 17 (12.9%) HBeAg-negative chronic hepatitis B patients, whereas it was <30,000 copies/ml in all inactive carriers (undetectable in 14). In particular, HBV DNA levels were <100,000 copies/ml in eight (32%) and <30,000 copies/ml in five (20%) of the 25 patients with HBeAg-negative chronic hepatitis B and normal baseline ALT values. HBV DNA levels with a cut-off at 30,000 or 100,000 copies/ml could correctly classify 92.9% or 91.3% of patients with HBeAg-negative chronic HBV infection, whereas ALT or IgM anti-HBc (IgM class antibody to HBV core antigen) index > 0.200 could correctly classify only 87.2% and 82.1% of patients, respectively. A combined HBV DNA and IgM anti-HBc index performed better by correctly classifying 94.4% of cases. CONCLUSIONS: Serum HBV DNA levels evaluated by sensitive quantitative PCR assays can be used for differentiation between HBeAg-negative chronic hepatitis B and inactive hepatitis B surface antigen carrier state, but the cut-off level should be set at approximately 30,000 copies/ml and certainly lower than the recently suggested level of 100,000 copies/ml.     

Chronic evolution of acute hepatitis B: the significance of simultaneous infections with hepatitis C and D. Copenhagen Hepatitis Acuta Programme

Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg)-positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti-HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers.     

Reactivation of hepatitis B virus in anti-HBe-positive chronic active type B hepatitis: molecular and immunohistochemical studies

The causes of acute clinical exacerbations, and the role of reactivation of hepatitis B virus (HBV) in 16 non-cirrhotic patients with chronic active type B hepatitis (CAH-B) negative for serum hepatitis B e antigen (HBeAg) but positive for anti-HBE, were studied by molecular hybridization and immunohistochemical methods. IgM antibody to hepatitis A virus (anti-HAV IgM) and antibody to delta agent (anti-delta) were negative in all. HBeAg reappeared transiently in only two patients. Serum hepatitis B virus (HBV) DNA levels increased during acute exacerbations in 14 patients (88%), and decreased after the episode. Cytoplasmic hepatitis B core antigen (HBcAg) expression was found in 9 out of 13 patients (69%) during acute exacerbation. By Southern blot hybridization, 5 of 6 (83%) liver tissues obtained during clinical exacerbations had free replicative forms of HBV DNA. In 20 control patients with no exacerbation, serum HBV DNA, HBcAg expression in hepatocytes and free replicative forms of HBV DNA were positive in 15% (3/20), 10% (2/20) and 25% (2/8), respectively--figures significantly lower than those of the group studied. We conclude that acute exacerbations sometimes seen in patients with anti-HBe-positive CAH-B in Taiwan are caused mainly by reactivation of HBV.     

Differentiation of acute and chronic hepatitis B in IgM antiHBc positive patients

AIM: To identify the factors that differentiate acute hepatitis B(AHB) from chronic hepatitis B with acute exacerbation(CHB-AE).METHODS: From 2004 to 2013, a total of 82 patients(male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen(Ig M antiHBc) were retrospectively enrolled and divided into two groups; AHB(n = 53) and CHB-AE(n = 29). The AHB group was defined as patients without a history of hepatitis B virus(HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff(S/CO) ratio of Ig M anti-HBc were compared to determine the differential diagnostic factors.RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of Ig M anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of Ig M anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of Ig M anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log10 IU/m L, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of Ig M anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of Ig M anti-HBc and HBV DNA levels were not significantly different(0.933 vs 0.844, P = 0.105). When combining Ig M anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone(P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively.CONCLUSION: The combination of the S/CO ratio of Ig M anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive Ig M anti-HBc.     

Significance of IgM antibody to hepatitis B core antigen in a Greek population with chronic hepatitis B virus infection

IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to persistent infection with hepatitis B virus (HBV). We studied 186 Greek HBsAg carriers for IgM anti-HBc and attempted to correlate it with other HBV and hepatitis delta virus (HDV) markers. Overall, IgM anti-HBc was detected more frequently than HBV DNA in this population (50% vs 34, p less than 0.001); this was also true for the 149 of the 186 HBsAg carriers with antibody to hepatitis B e antigen (anti-HBe) (48% vs 22%, p less than 0.001). The opposite was found in the carriers positive for hepatitis B e antigen (HBeAg): HBV DNA was observed in 93% and IgM anti-HBc in 64% of the cases (p less than 0.05). The detection of these markers was independent of sex. Serum alanine aminotransferase (ALT) levels were significantly more elevated in patients with positive tests for IgM anti-HBc and HBV DNA than in patients positive only for HBV DNA (p less than 0.001) irrespective of their HBeAg or anti-HBe status. Moreover, the detection of elevated ALT was independent of the intensity of the HBV DNA hybridization signal. Antibodies to hepatitis delta antigen (HDAg) were only found in 4 (2.4%) of 167 patients tested.     

Impaired antibody synthesis in patients with chronic hepatitis B infection

In vitro synthesis of the anti-HBc, anti-HBs and polyclonal IgG and IgM classes of antibodies were determined from supernatants of peripheral blood mono-nuclear cells cultured in the presence of pokeweed mitogen. Thirty-seven patients with chronic hepatitis B and 10 healthy control subjects whose sera were positive for anti-HBs formed the study group. Twenty-four of 37 patients showed histologic evidence of chronic active hepatitis B while the remaining 13 patients had chronic persistent hepatitis B. Lymphocytes from chronic persistent hepatitis B, chronic active hepatitis B and healthy controls secreted similar levels of IgM. However, IgG synthesis was markedly impaired (p less than 0.002) in the chronic persistent hepatitis B group as compared with healthy controls or chronic active hepatitis B patients. In vitro anti-HBc production and serum anti-HBc titers correlated directly with hepatocellular inflammation and inversely with serum hepatitis B virus DNA. Anti-HBc synthesis was significantly higher in chronic active hepatitis B patients who exhibited a more pronounced hepatocellular damage when compared to chronic persistent hepatitis B patients who had little or no liver cell injury.     

Hepatitis B virus (HBV) markers and HBV-DNA in serum and liver tissue of patients with acute exacerbation of chronic type B hepatitis

We analysed the serum samples and the liver biopsies of six consecutive chronic HBsAg/anti-HBe carriers admitted to hospital because of an episode of acute hepatitis. The six patients became positive for IgM anti-HBc and negative for HBeAg, hepatitis Delta virus (HDV) markers, IgM anti-hepatitis A virus (HAV), anti-cytomegalovirus (CMV) and anti-Epstein-Barr virus (EBV). Two patients showed positivity for hepatitis B virus (HBV)-DNA in serum obtained on admission, with no positivity in the subsequent weeks; the results of the other four patients were always negative for seric HBV-DNA. The Southern-blot analysis of the DNA extracted from the liver tissue of four subjects showed the presence of HBV-DNA in the form of replicative intermediates; focal positivity of HBcAg was detected in the liver of only one. The liver biopsies of the last two patients were negative for HBV-DNA and for HBcAg. The analysis of HBV-DNA in the liver extracts and the demonstration of an increase of the IgM anti-HBc titre at the time of the abrupt elevation of the aminotransferase levels seem to be the most useful tools in revealing HBV activation as a cause of acute hepatitis in chronic HBsAg carriers, overall when the phase of viremia is transient.     

Rapid progression of chronic active type B hepatitis in a patient with hypogammaglobulinemia.

Rapid progression of acute type B hepatitis to chronic active liver disease and cirrhosis in a young male with hypogammaglobulinemia is described. Absent circulating IgA, significantly low IgG, and normal IgM levels were detected during the acute phase of illness. Enumeration of peripheral lymphocytes revealed a decreased number of T cells and normal numbers of B cells. In vitro pokeweed stimulation of Ig synthesis correlated with the in vivo circulating levels of the three immunoglobulins. Cell-mediated immune responses were normal except for lymphocyte stimulation to hepatitis B surface antigen. It was concluded that the defective synthesis of IgG and IgA antibodies to hepatitis B surface antigen contributed to the accelerated progression to chronic active type B hepatitis in this person.