Serum binding activity for human albumin polymers in acute and chronic virus hepatitis

We considered the serum binding activity for human albumin polymerized with glutaraldehyde in 346 serum samples of 205 subjects with acute and chronic type A, B and non-A, non-B virus hepatitis. We showed that the binding activity for pHSA in the control groups did not have a titer higher than 2(-6). All sera from patients with HAV and HBV acute infection showed a high binding titer that returned to below the threshold in the former after the peak of hepatocytolysis, and in the latter after the seroconversion of HBsAg to anti-HBs. In the subjects who became HBsAg chronic carriers after the acute episode of HBV infection, the pHSA binding activity showed a decrement of the titer in relation to the seroconversion of HBeAg to anti-HBe. Furthermore, 92% of HBsAg chronic carriers who were HBeAg positive had a high titer of pHSA binding, while only 14.3% of the anti-HBe positives showed a high titer. Acute and chronic hepatitis non-A, non-B virus showed a pHSA binding titer similar to that of the control group. The results indicate that the non-A, non-B virus does not seem to be correlated to pHSA or related factors.     

Delta infection and hepatitis B virus replication in Danish patients with fulminant hepatitis B

The presence of hepatitis B virus and delta agent markers was investigated in 41 patients referred during the years 1970-1985 with fulminant hepatitis classified as type B or non-A non-B and compared to findings in patients with uncomplicated hepatitis B and chronic hepatitis B infection. 13 patients had no markers of hepatitis B and delta infection and were classified as non-A non-B hepatitis. The remaining 28 patients were all HBsAg and IgM anti-HBc positive and 14 (50%) had evidence of delta infection. In contrast, only 13/71 patients (18%) with acute benign hepatitis B had evidence of delta coinfection (p less than 0.005). This corresponds to an odds ratio of 4.5 for development of fulminant hepatitis among patients with hepatitis B and delta coinfection. In 100 chronic HBsAg carriers 29% were positive for delta markers. 12 of the delta infected patients with fulminant hepatitis were positive for total antibody to the delta antigen, and 2 were delta antigen positive. Three were HBeAg positive/anti-HBe negative. None had hepatitis B virus DNA. Among the 14 patients without delta infection, hepatitis B virus DNA was found in 2/4 HBeAg positive/anti-HBe negative patients and in 1/8 patients negative for both markers. The present data indicate that a high proportion of Danish patients with fulminant hepatitis B have hepatitis B and delta agent coinfection. Further, the findings suggest that hepatitis B and delta coinfection may be associated with an increased risk of development of fulminant hepatitis as compared to that of hepatitis B alone.     

Long-term follow-up of 60 patients with chronic hepatitis B. II. Hepatitis B virus DNA in serum correlated to the hepatitis Be-system and presence of delta superinfection

Forty-six patients with liver biopsy-documented chronic hepatitis B were followed for a mean period of 44 months. A total of 200 serum samples from these patients was analyzed for the presence of hepatitis B virus DNA (HBV-DNA). The results were correlated to the HBeAg/anti-HBe status and to the presence of anti-delta as a marker for delta superinfection. In the initial serum samples HBV-DNA was detected in the vast majority of the patients independent of the HBeAg/anti-HBe results and whether the patients were superinfected by delta agent or not. During the complete follow-up period, HBV-DNA was detected in 88% of those patients who were positive for HBeAg, irrespective of the presence or absence of a simultaneous delta infection. When anti-HBe positive, 79% of the patients with anti-delta had detectable HBV-DNA in their sera, while only 43% of those negative for anti-delta were positive for HBV-DNA. The results indicate a high prevalence of virus release into the blood of patients with chronic hepatitis B, especially among patients positive for HBeAg and among those anti-HBe positive patients who have a delta superinfection.     

The role of delta superinfection in acute exacerbations of chronic type B hepatitis

Serum specimens collected from patients with chronic type B hepatitis during their acute exacerbations were studied with radioimmunoassay for serological markers of delta (delta) agent infection. Serum delta antigen was negative in all 56 hepatitis B e antigen (HBeAg)-positive and 25 anti-HBe-positive acute exacerbations. Two (3.6%) HBeAg-positive and five (20%) anti-HBe-positive acute exacerbations were found to be positive for both IgG anti-delta and IgM anti-delta. The incidence in anti-HBe-positive patients was significantly higher than in HBeAg-positive patients. These results indicated that some of the acute exacerbations, particularly in anti-HBe-positive phase, could be attributed to delta-superinfection. However, acute exacerbations preceding HBeAg/anti-HBe seroconversion were not associated with delta-superinfection.     

Acute exacerbation in patients with liver cirrhosis: a clinicopathological study.

The incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis B surface antigen (HBsAg) positive and 71 HBsAg negative patients. During an 11-year period and a mean follow-up duration of 26.8 months, 148 acute exacerbation occurred in 107 HBsAg positive patients and 32 episodes occurred in 18 HBsAg negative patients. The calculated annual incidence was 11.5%. The clinical, laboratory and histologic features were similar to those in patients with chronic hepatitis. Confluent hepatic necrosis and alphafetoprotein elevation over 100 ng/ml occurred frequently, particularly in HBeAg positive patients. In general, acute exacerbations in HBsAg negative patients were less severe than their HBsAg positive counterparts. Of the exacerbations in HBsAg positive patients, 54.8% of the HBeAg positive ones and 38.6% of the HBeAg negative ones were attributable to hepatitis B virus reactivation, while 4.8% and 7.9%, respectively, were due to hepatitis delta virus superinfection. The others might be the results of hepatitis non-A, non-B virus superinfection or increased piecemeal necrosis. The immediate outcome of acute exacerbations in cirrhotic patients was usually good, although 13.8% developed hepatic decompensation and 4.4% died. Further follow-up study is required to evaluate the long-term effect of the frequent occurrence of bridging hepatic necrosis, high elevation of alphafetoprotein and hepatic decompensation during acute exacerbation in cirrhotic patients.     

Acute exacerbation in patients with liver cirrhosis: a clinicopathological study

ABSTRACT— The incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis B surface antigen (HBsAg) positive and 71 HBsAg negative patients. During an 11-year period and a mean follow-up duration of 26.8 months, 148 acute exacerbation occurred in 107 HBsAg positive patients and 32 episodes occurred in 18 HBsAg negative patients. The calculated annual incidence was 11.5%. The clinical, laboratory and histologic features were similar to those in patients with chronic hepatitis. Confluent hepatic necrosis and alphafetoprotein elevation over 100 ng/ml occurred frequently, particularly in HBeAg positive patients. In general, acute exacerbations in HBsAg negative patients were less severe than their HBsAg positive counterparts. Of the exacerbations in HBsAg positive patients, 54.8% of the HBeAg positive ones and 38.6% of the HBeAg negative ones were attributable to hepatitis B virus reactivation, while 4.8% and 7.9%, respectively, were due to hepatitis delta virus superinfection. The others might be the results of hepatitis non-A, non-B virus superinfection or increased piecemeal necrosis. The immediate outcome of acute exacerbations in cirrhotic patients was usually good, although 13.8% developed hepatic decompensation and 4.4% died. Further follow-up study is required to evaluate the long-term effect of the frequent occurrence of bridging hepatic necrosis, high elevation of alphafetoprotein and hepatic decompensation during acute exacerbation in cirrhotic patients.     

Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B

Seventy consecutive HBsAg- and HBeAg-positive patients with biopsy-proven chronic hepatitis were followed prospectively with serial determinations of SGPT levels and hepatitis B virus serum markers including HBsAg, HBeAg, anti-HBe and hepatitis B virus DNA. During a period of 1 to 11 years (mean +/- S.D.: 5.0 +/- 2.3 years), 28 patients remained persistently HBeAg positive, most with continuing biochemical and histologic activity, while 41 cases seroconverted to anti-HBe. One patient became HBeAg and anti-HBe negative. After seroconversion, 87.8% of the cases showed sustained normalization of SGPT, and clearance of hepatitis B virus DNA from serum and histologic improvement was documented in 79% of the cases who had a control liver biopsy, while 15.8% developed cirrhosis. In two patients (4.9%), the disease remained active despite seroconversion, and both cases had evidence of continuing hepatitis B virus replication. Finally, reactivation of liver damage and of hepatitis B virus replication was observed in three additional patients (7.3%) who had transiently normalized SGPT after seroconversion. All 70 patients were analyzed for hepatitis delta virus markers, and only two persistently HBeAg-positive cases were found positive for antibody to hepatitis delta virus in serum, one also having hepatitis delta antigen in the liver. These findings indicate that, in chronic hepatitis type B, termination of virus replication is associated in most patients with biochemical and histologic regression of inflammatory activity. After anti-HBe seroconversion has occurred, virus replication and liver disease may persist or reactivate in a small proportion of patients thus giving origin to the well-recognized group of anti-HBe positive, hepatitis B virus DNA-positive chronic hepatitis type B.     

Search for hepatitis B virus DNA in sera from patients with acute type B or non-A, non-B hepatitis

One hundred and three single sera from adults hospitalized with acute type B (78) or non-A, non-B (25) hepatitis were tested for the presence of hepatitis B virus DNA (HBV DNA). All sera from patients with type B hepatitis were IgM anti-HBc-positive. These patients were classified as benign (47) or fulminant (31) hepatitis. The 25 acute non-A, non-B patients were also classified as benign (21) or fulminant (4) hepatitis and were negative for serologic markers of past HBV infection. Serum HBV DNA was detected with similar frequency in benign (38.5%) and fulminant (FH, 34.6%) HBsAg-positive cases. HBV DNA was not detected in either the 26 acute HBsAg-negative hepatitis B cases who were positive for anti-HBc and anti-HBs or the 25 acute non-A, non-B hepatitis cases. The absence of HBV DNA in 43.8% of benign hepatitis B patients who were positive for HBsAg and HBeAg could possibly be attributed to either low level replication of HBV that was not detectable by the [32P]HBV DNA probe or to a period of delayed clearance of free HBeAg following cessation of HBV replication. Emergence of anti-HBs in the presence of HBsAg did not always correspond to clearance of HBV in fulminant type B cases. However, in acute type B hepatitis, irrespectively of severity, disappearance of HBsAg and appearance of anti-HBs was accompanied by reduction of HBV replication to undetectable levels.     

Delta infection in asymptomatic carriers of hepatitis B surface antigen: low prevalence of delta activity and effective suppression of hepatitis B virus replication

We examined the prevalence of serum anti-delta antibody among 769 intravenous drug abusers in Taiwan. delta infection was found extremely common in the HBsAg-positive carriers with drug abuse, because 128 (85%) of 151 carriers were positive for anti-delta. However, most of antibody titers were low (less than 1:5,000). By molecular hybridization, delta RNA genomes were detectable in only five (4%) of 128 asymptomatic carriers positive for anti-delta. The results suggested that most of them had previous, instead of ongoing, delta infection. We also studied the serum markers reflecting hepatitis B virus replication in these carriers and a control group. Hepatitis B e antigen was positive in only 12 (10%) of 115 anti-delta positive carriers in contrast to 22 (23%) of 95 age- and sex-matched HBsAg-positive, anti-delta negative volunteers donating blood (p less than 0.025). Furthermore, in contrast to the close association between HBeAg and hepatitis B virus DNA generally present in HBsAg carriers (concordance in this series: 79%), among the 12 HBeAg-positive subjects of the delta infected group, only two, or 17%, had serum hepatitis B virus DNA (p less than 0.003). Such suppressing effects did not require a simultaneous presence of the delta agent, as shown by the lack of delta RNA genomes in the serum by sensitive assay. We conclude that although delta superinfection is common in the asymptomatic HBsAg carriers with intravenous drug abuse in the nonendemic area of Taiwan, continuous delta activities are uncommon in them. In addition, the previous delta infection probably exerts effective suppression on the hepatitis B virus replication in these HBsAg carriers.     

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.     

Fulminant viral hepatitis: Indian experience

Thirty-six patients with fulminant viral hepatitis were studied. Enzyme immunoassay was used to detect the presence of HBsAg, IgM anti-HBc, and IgM anti-HAV. Non-A, non-B virus was the most common aetiological agent (61.1%) followed by hepatitis B virus (HBV; 30.6%) and hepatitis A virus (8.3%). Presence of IgM anti-HBc confirmed the diagnosis of HBV infection in three cases who were negative for HBsAg. Similarly, in one case who was positive for HBsAg, absence of IgM anti-HBc suggested superinfection with some other agent. Survival was significantly higher (P less than 0.01) in the hepatitis A virus (HAV) group (66.6%) compared with non-A, non-B (31.2%) and HBV groups (27.3%). Fever at the onset of illness was seen in all patients with HAV, 54.5% of patients with HBV and 38.88% of patients with non-A, non-B infection (P less than 0.01). The median time interval between the first symptom and the onset of encephalopathy was 16, 13 and 8 days in HAV, HBV and non-A, non-B groups, respectively, but this difference was statistically not significant (P greater than 0.05).     

Demonstration of hepatitis B virus DNA by polymerase chain reaction in the serum and the liver after spontaneous or therapeutically induced HBeAg to anti-HBe or HBsAg to anti-HBs seroconversion in patients with chronic hepatitis B.

The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion. Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient. Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HBsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested. Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion.     

Double infections with hepatitis A and B viruses

Ten (2.8%) asymptomatic carriers of HBsAg and four (1.1%) patients with acute hepatitis B virus (HBV) infection were detected among 356 adults with acute viral hepatitis A (HAV) consecutively admitted to the Athens Hospital for Infectious Diseases from May 1981 to March 1984. These patients did not differ in clinical, epidemiologic (except in age), biochemical or serologic characteristics from patients acutely infected with HAV alone. Transient suppression of the HBV replication and disappearance of the HBV DNA accompanied by seroconversion from HBeAg positive to anti-HBe positive were detected in one and two carriers respectively. The titer of non-class-specific anti-HBc was low (less than or equal to 10(-2)) in all cases. These data suggest that superinfection of HBsAg carriers with HAV does not cause more severe disease or influence adversely the course of chronic hepatitis B disease. However, accurate diagnosis of double infections is necessary for prognosis of the liver disease and appropriate management of the patient's environment. This is quite important in areas with a high prevalence of HBV infections, like Greece, where double infections are relatively common.     

Why most patients with hepatitis delta virus infection are seronegative for hepatitis B e antigen. A prospective controlled study

A prospective age/sex matched control and follow-up study was conducted to explore the reason(s) for the association of hepatitis delta virus (HDV) infection with hepatitis B e antigen (HBeAg) negative hepatitis B surface antigen (HBsAg) carrier state. Over a 3-year period, a total of 110 patients (104 males and six females) with acute HDV superinfection were documented in our unit. Twenty-four (21.8%) of them were HBeAg positive at the onset of acute HDV infection. In the control study, 110 age- and sex-matched asymptomatic HBsAg carriers with normal serum transaminase, as well as 110 age- and sex-matched patients with chronic type B hepatitis were randomly selected from the computer files of the same 3-year period of entry. The prevalence of serum HBeAg in patients with HDV infection was similar to that of asymptomatic HBsAg carriers (20.9%), but significantly lower than that of the patients with chronic type B hepatitis (72.7%). In a follow-up study of 16 HBeAg-positive patients with HDV infection, eight (50%) cleared HBeAg and three (18.8%) seroconverted to anti-HBe within 3 months. The HBeAg clearance rate was significantly higher than for chronic type B hepatitis and asymptomatic carriers (p less than 0.01). The results suggest that the low prevalence of serum HBeAg in HDV infection simply reflects the HBeAg/anti-HBe status of the asymptomatic HBsAg carriers in the population under study. Also in some patients HDV superinfection may itself suppress HBV and thus clear HBeAg.     

Reverse seroconversion of hepatitis B virus infectious status after allogeneic bone marrow transplantation from a carrier donor.

A 35-year-old man with acute promyelocytic leukemia received an allogeneic bone marrow transplant (BMT) in second complete remission. The donor was his 18-year-old brother, a chronic hepatitis B virus (HBV) carrier with detectable serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus DNA (HBV DNA). Before BMT, the recipient was immune to HBV, with serum antibody to HBsAg (anti-HBs), antibody to HBeAg (anti-HBe) and normal liver function. Examination of the recipient serum drawn 2 months after BMT revealed reverse seroconversion from anti-HBs/anti-HBe to HBsAg/HBeAg, which remained positive thereafter. Upon reducing cyclosporin 6 months after BMT, acute hepatitis occurred with HBV DNA in serum as evidence of active HBV replication; the patient then developed chronic hepatitis which progressed to cirrhosis and hepatic decompensation within 8 months. Transfusion of HBV DNA/HBeAg-positive bone marrow is thus harmful even when the recipient has anti-HBs prior to BMT.     

Early upsurge in anti-HBs titer possibly caused by the immunomodulative, not by the mutagenetic effect of interferon and ribavirin

A patient with chronic hepatitis B and C undergoing treatment with interferon and ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs) titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg) during the early treatment phase. Simultaneously, elevation of alanine aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV) DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion occurred. The anti-HBs titer gradually returned to the pretreatment level after cessation of ribavirin treatment and HBV-DNA became undetectable. We found no nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti-HBs titer. The appearance of anti-HBs was considered to be a break in immune tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might have caused this unexpected early immune response to HBsAg that preceded seroconversion to anti-HBe.     

Serologic markers with fulminant hepatitis in persons positive for hepatitis B surface antigen. A worldwide epidemiologic and clinical survey

Of 377 cases of fulminant hepatitis in persons positive for hepatitis B surface antigen (HBsAg) in Greece, Italy, the United States, the United Kingdom, the Central African Republic, Taiwan, Egypt, and India, only 52% could be attributed to infection with hepatitis B virus, which was defined as the presence of the IgM antibody to the hepatitis B core antigen (IgM anti-HBc) and the absence of serum markers of infection by extraneous viruses. Thirty percent of cases were caused by coinfection with hepatitis B virus and hepatitis delta virus or by infection with hepatitis delta virus superimposed on carriers of chronic HBsAg. In 18.5% of the patients, the absence of IgM anti-HBc indicated that they were not known to carry HBsAg, but no obvious superimposed factor of hepatitis could be identified. The cause of fulminant hepatitis is complex, and major risk factors are a pre-existing HBsAg state and hepatitis delta virus infection. Superinfection of HBsAg carriers by non-A, non-B viruses seems to be the cause in a consistent proportion of cases.     

慢性乙型肝炎肝病急性加重的原因探讨

目的 为了弄清慢性乙型肝炎病程中肝病急性加重的原因。方法 用酶联免疫吸附试验检测慢性乙型肝炎病程中肝病急性加重时甲、丙、丁或戊型肝炎病毒的重叠感染以及HBeAg和抗-HBe的血清学状态。结果 在83例慢性乙型肝炎的92次肝病急性加重中,甲、丙、丁或戊型肝炎病毒重叠感染分别为3.3％(3/92)、5.4％(5/92)、3.3％(3/92)和5.4％(5/92),共为17.4％(16/92);使用肝损害药物为1.1％(1/92);HBeAg至抗-HBe的自发血清转换为9.8％(9/92);HBeAg至抗-HBe的不稳定自发血清转换状态为12.0％(12/92);保持HBeAg至抗-HBe血清学状态不变为59.8％(55/92)。重叠其它嗜肝病毒感染、HBeAg至抗-HBe的不稳定自发血清转换以及保持HBeAg和抗-HBe的状态不变均可出现致死性肝衰竭。结论 重叠其它嗜肝病毒感染、使用肝损害药物和HBeAg至抗-HBe的自发血清转换与慢性乙型肝炎病程中40％左右的肝病急性加重有关,大约60％的肝病急性加重与HBeAg和抗-HBe血清学状态无关。促使致死性肝衰竭发生的原因更为复杂。     

Hemagglutination and immunofluorescence studies on polymerized human serum albumin binding activity in chronic hepatitis B virus infection

The binding activity of polymerized human serum albumin was determined in 202 HBsAg carriers. The presence of polymerized human serum albumin receptor sites was tested by hemagglutination and differentiated from antihuman albumin antibodies by immunofluorescence, isolation of IgG and IgM fractions and testing of HBsAg anti-HBs immune complexes. A granular pattern with anti-HBs was specific for polymerized human serum albumin receptor sites as demonstrated with purified HBsAg. In addition, a linear pattern with fluoresceinated antihuman immunoglobulins might suggest the presence of antihuman albumin antibodies (which was generally due to an IgG antibody). However, a granular pattern with fluoresceinated antihuman immunoglobulins may indicate the presence of HBsAg anti-HBs immune complexes. A weak linear pattern was also observed simultaneously in these cases, probably due to IgM antihuman albumin antibodies or an antipolymerized human serum albumin receptor site antibody. Of 202 HBsAg-positive patients, 71 showed polymerized human serum albumin receptor sites activity. The highest percentage of polymerized human serum albumin receptor sites was found among patients showing HBeAg and hepatitis B virus DNA polymerase positivity (96%), followed by HBeAg positivity and hepatitis B virus DNA polymerase negativity (48%), and anti-HBe positivity and hepatitis B virus DNA polymerase negativity (17%). In addition, a significant correlation between polymerized human serum albumin titers and hepatitis B virus DNA polymerase was found (r = 0.573, p less than 0.01). However, at similar HBeAg titer, patients who were positive for hepatitis B virus DNA polymerase had a higher polymerized human serum albumin receptor sites titer than those who were negative for hepatitis B virus DNA polymerase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fulminant hepatitis in infants in Taiwan: Strong association with hepatitis B e antigen-negative but antibody-positive maternal hepatitis B surface antigen carriage

This study examined the virologic profiles and pathologic features in 10 infants with fulminant hepatitis and aged 2–7 months. Nine male infants were related to hepatitis B virus infection: as evidenced by positive anti-HBc IgM (4 cases); positive serum HBsAg, and/or liver HBcAg (4 cases); or born to an HBsAg carrier mother (1 case). Only one female infant had presumed non-A non-B fulminant hepatitis, but none had hepatitis A. The mothers of eight infants with HBV-ralated fulminant hepatitis were all positive for serum HBsAg, and most (5/6) were negative for HBeAg but positive for anti-HBe. These findings suggest that infants born to HBsAg carrier mothers, particularly those who are negative for HBeAg, may contract fulminant hepatitis B in infancy in Taiwan. Six infants studied had massive hepatic necrosis and all died, whereas four had submassive or bridging hepatic necrosis and all survived, suggesting a close correlation between the extent of liver necrosis and the patient's outcome. None of the infants had hepatocyte HBsAg, although four had cytoplasmic HBcAg. Anti-HBc IgM was commonly detected (4/6), in sharp contrast to the constant negativity in infants who had contracted an asymptomatic HBV infection. These findings suggest that cytoplasmic HBcAg and anti-HBc IgM may be related to the occurrence of severe liver disease.