Clinical significance of two forms of IgM antibody to hepatitis delta virus

Separation of 7-8 S and 19 S forms of serum IgM antibodies to the hepatitis delta virus by rate-zonal centrifugation was carried out on serum from 24 patients with hepatitis delta virus infection: 4 patients with acute, self-limited hepatitis; 5 patients with hepatitis delta virus superinfection progressing to chronicity; and 15 patients with chronic hepatitis delta virus. The high molecular weight IgM form (19 S) was predominantly detected in acute hepatitis delta virus cases, whereas the low molecular weight (7 S) form was found in chronic hepatitis delta virus cases. The serological profile of these two forms of IgM antibody to hepatitis delta virus was investigated in serial samples from five patients with acute hepatitis delta virus superinfection that evolved to chronic hepatitis delta virus. We found that, in the acute stage of the disease, the 19 S form was predominant, whereas 6 mo later a predominance of 7-8 S IgM was observed. These results suggest that IgM antibody to hepatitis delta virus antibody forms are different in acute and chronic hepatitis delta virus infection and that their detection only helps in differentiating an acute infection from a chronic infection but not a hepatitis delta virus-hepatitis B virus-HBV coinfection from hepatitis delta virus superinfection in the acute stage of the disease.     

A retrospective study of the role of delta agent infection in children with HBsAg-positive chronic hepatitis

The prevalence of intrahepatic delta antigen and/or anti-delta antibody was retrospectively investigated in 102 children with chronic HBsAg-positive hepatitis who were seen consecutively in three medical institutions between 1974 and 1982. Delta infection markers were found in 13 patients (12.7%) who exhibited high serum titers of anti-delta antibody; intrahepatic delta antigen was detected in ten. Eleven of the 13 children had severe progressive liver disease associated in all but one with absence of hepatitis B virus replication as evaluated by analysis of serum hepatitis B virus DNA. The factors which seem to increase the risk of delta infection in children who are hepatitis B virus carriers are geographic origin, a history of exposure to blood derivatives and age. A further 37 of 102 children had chronic active hepatitis (20 patients) or cirrhosis (17 patients) without evidence of delta infection. These results indicate that delta infection occurs in children with chronic hepatitis. This possibility should be considered in investigation of children with HBsAg-positive chronic liver disease. Although the delta agent is an important cause of progressive liver disease in children who are chronic HBsAg carriers, severe liver injury and especially cirrhosis can occur without evidence of delta infection.     

Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients.

One hundred liver biopsies from 100 patients with clinical presumptive diagnosis of hepatitis were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBSAg) and hepatitis B core antigen (HBcAg). Of the 60 HBsAg-positive livers, 51 were diagnosed as chronic hepatitis on histological grounds, 6 as acute hepatitis, and 3 as "near-normal liver." From the 60 tissue-positive cases, 3 subjects were HBsAg seronegative. HBcAg was detected in 44 livers, all of which also had HBcAg in the localized in the cytoplasm and the membranes of the hepatocytes, and HBcAg in the nuclei and in 4 cases also in the cytoplasm. Predominant HBsAg expression in the cytoplasm was observed in near-normal liver, chronic persistent hepatitis, and cirrhosis with little activity. This correlated with the amount of ground glass hepatocytes in the biopsies. HBcAg and membrane-localized HBsAg were minimal in those conditions. HBcAg was most prevalent in patients with chronic aggressive hepatitis and active cirrhosis treated with immunosuppressive drugs, whereas the amounts of HBsAg and HBcAg in nontreated patients of those two groups and in acute hepatitis with signs of transition to chronicity were almost equal. HBsAg expression in liver cell membranes was most prominent in active forms of chronic hepatitis (chronic aggressive hepatitis and in active cirrhosis) and in acute hepatitis with signs of transition to chronicity. This observation correlated in the presence of HBcAg in the biopsies of those patients. In acute hepatitis both HBsAg and HBcAg were detected rarely and no membrane expression of HBsAg was observed. The over-all results show a significant relationship between the different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis and further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis B.     

Long-term follow-up of anti-HBe-positive chronic active hepatitis B

Twenty-eight patients with chronic active hepatitis without cirrhosis who were positive for hepatitis B surface antigen and antibody to hepatitis B e antigen were followed for 1 to 15 years (mean 6.6 years) and underwent follow-up biopsy. At presentation, 12 of the 28 patients (43%) had hepatitis B virus DNA in serum, 10 (36%) had serologic evidence of hepatitis delta virus infection and 6 (21%) had no serologic markers of either hepatitis B virus replication or hepatitis delta virus infection. During follow-up, 15 (54%) patients developed active cirrhosis, including eight patients with hepatitis delta virus infection and five with hepatitis B virus DNA in serum. In seven (47%) of the 15 patients, cirrhosis developed within the first 2 years; all seven patients had bridging necrosis in the first liver biopsy, and five of these were infected with hepatitis delta virus. The remaining 13 (46%) patients did not develop cirrhosis during follow-up and showed either unchanged features of chronic active hepatitis (seven cases) or histologic improvement to chronic persistent hepatitis (five cases) or to normal liver (one case). In conclusion, the prognosis of anti-HBe-positive patients with chronic hepatitis B is poor, as 54% of the cases developed cirrhosis during a mean histologic follow-up period of 4.5 years, mainly in association with hepatitis delta virus infection or continuing hepatitis B virus replication.     

Monomeric (7S) immunoglobulin M antibodies to hepatitis delta virus in hepatitis type D

The pattern of the immunoglobulin M antibody to the hepatitis delta virus distinguishes acute from chronic hepatitis D. Expression of the immunoglobulin M antibody to the hepatitis delta virus is relatively weak and short-lived in self-limited hepatitis but strong and persistent in chronic forms. To study the nature of the immunoglobulin M antibody to the hepatitis delta virus in acute hepatitis D and in chronic hepatitis D, antibody-positive sera were submitted to rate zonal centrifugation to separate monomeric 7S from pentameric 19S immunoglobulin M antibodies. Sera were from 6 patients with acute self-limited hepatitis, 4 patients with chronic hepatitis D, and 6 patients with hepatitis D progressing to chronicity. The immunoglobulin M reactivity was measured by a specific immunoassay based on capture of mu-chains by anti-mu linked on a solid phase. Only 19S antibody was found in acute hepatitis D. In contrast, all patients with chronic hepatitis D circulated 7S antibody in addition to the 19S antibody. In patients with progressive hepatitis D, both the 7S and 19S antibody variants were present at the onset of the disease. The difference in the antibody response between acute hepatitis D and chronic hepatitis D is not only temporal and quantitative but also qualitative. The expression of 7S antibody seems to be an immunologic event specific for chronic hepatitis D.     

A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required?

BackgroundHepatitis delta virus infection occurs as acute coinfection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma.Case reportWe report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis.ConclusionsIn patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.     

Natural course of patients with chronic type B hepatitis following acute hepatitis delta virus superinfection

A 6-96-month prospective follow-up study on the natural course of chronic type B hepatitis after contracting acute hepatitis delta virus (HDV) superinfection was conducted in 30 patients with clear-cut onset of acute HDV superinfection (HDV group). Thirty patients with acute exacerbation without evidence of HDV infection, and well matched in terms of age, sex and hepatitis B e antigen/antibody status, served as the control group. The clinical and biochemical presentations tended to be more severe in the HDV group. More patients in the HDV group had persistent abnormal liver biochemical tests (69% vs 47%) and progressed to chronic active hepatitis (46% vs 20%) or cirrhosis (9.4%/year vs 5.2%/year), but the differences were not significant statistically. The results suggest that HDV superinfection induces slow progression of liver disease. However, in the early stage, the impact of HDV superinfection is not particularly different from that of the acute exacerbation unrelated to HDV in patients with chronic type B hepatitis.     

Intrahepatic markers of hepatitis delta virus infection: a study by in situ hybridization

The intrahepatic distribution of hepatitis delta virus RNA was studied by in situ hybridization in 33 formalin-fixed, paraffin-embedded biopsies from 17 chronic hepatitis B virus carriers superinfected with hepatitis delta virus. The findings were correlated with the expression of the hepatitis delta antigen, the duration of the hepatitis delta virus infection and the eosinophilic degeneration of the hepatocytes. Intranuclear hepatitis delta virus RNA and antigen were found in 28 specimens, whereas the remaining five were negative for both markers. Hepatitis delta virus RNA and antigen were mostly found within the same cell. In 20 specimens, however, a variable number of hepatocytes showed the presence of hepatitis delta virus RNA alone. The percentage of these over the total number of infected cells was higher in the specimens taken within 1 year from the acute delta hepatitis, whereas their absence was invariably associated with a long-established hepatitis delta virus infection. Interestingly, the vast majority of hepatocytes undergoing eosinophilic degeneration, a change significantly associated with hepatitis delta virus infection, did not show the presence of either hepatitis delta virus RNA or the viral antigen, suggesting a lack of association, at the cellular level, between viral replication and cytopathological change. The specificity of the detection of hepatitis delta virus RNA was confirmed by negative findings in nine specimens from seven chronic hepatitis B virus carriers without evidence of past or current hepatitis delta virus infection. The loss in sensitivity due to the formalin fixation was estimated to be 50% of that obtained in frozen biopsies, as determined by counting autoradiographic grains over infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between apoptasis, tumour necrosis factor, cell proliferation in chronic cholestasis

BACKGROUND: Target of the immune response in chronic autoimmune cholestasis, is the bile duct epithelium. Lymphocytic infiltration and apoptosis have both been suggested to mediate the destruction of hepatocytes and biliary epithelium in primary biliary cirrhosis. AIMS: To further address this issue in two cholestatic liver diseases characterized by an autoimmune pathogenesis and, furthermore, evaluate the relationship between apoptosis and both tumour necrosis factor alpha and cell proliferation. METHODS: Liver tissue specimens from 16 patients with primary biliary cirrhosis, 15 with primary sclerosing cholangitis, and 16 with chronic hepatitis C (controls) were evaluated. DNA-fragmentation of apoptotic cells was ascertained by the TdT-mediated deoxyuridine triphosphate nick-end labelling method. Tumour necrosis factor alpha expression and cell proliferation (Ki-67 antigen) were assayed by immunohistochemistry. RESULTS: Hepatocytes with DNA fragmentation were observed in 75% of patients with primary biliary cirrhosis, in 66.6% with primary sclerosing cholangitis, and in 43.7% with chronic hepatitis C. Biliocytes showed apoptosis in only 3 cases of primary biliary cirrhosis. Biliocytes showed a strong cytoplasmic expression in 4 cases (1 primary biliary cirrhosis, 2 primary sclerosing cholangitis and 1 chronic hepatitis C). A few intralobular and portal inflammatory mononuclear cells expressing tumour necrosis factor alpha were observed in 62.5% of patients with primary biliary cirrhosis, 46.1% with primary sclerosing cholangitis, and 56.2% with hepatitis C virus chronic hepatitis. The amount of intraportal mononuclear cells expressing Ki-67 antigen was significantly higher in primary biliary cirrhosis specimens than in primary sclerosing cholangitis (p<0.001) or hepatitis C virus-related chronic hepatitis (p<0.03). No correlation was found within the 3 groups of patients between the Ki-67 histological score and the severity of liver disease. Moreover, no relationship was found between TdT-mediated deoxyuridine triphosphate nick-end labelling and either tumour necrosis factor alpha or Ki-67 staining. CONCLUSIONS: Apoptosis is a phenomenon which frequently involves hepatocytes in chronic autoimmune cholestasis. This process is apparently parallel, but unrelated to cell proliferation. Cell proliferation mainly involves mononuclear cells in portal tracts of primary biliary cirrhosis specimens. The finding of tumour necrosis factor alpha expression in biliocytes deserves further study to establish whether this cytokine is involved in triggering bile duct lesions.     

Deficiency of antibody formation to HBsAg in the pathogenesis of chronic hepatitis and cirrhosis?

Sera of 832 healthy persons and patients suffering from chronic inflammatory liver disease were investigated by radioimmunoassay for HBsAg and anti-HBs. Diagnosis in patients was secured by biopsy. The persons were divided into: 1. Healthy persons: n = 478 blood donors, hospital especially exposed to HBV, patients with healed hepatitis; 2. Patients: n = 354 acute hepatitis, chronic persistent and aggressive hepatitis, post-hepatitic, cryptogenic and alcoholic cirrhosis. The results demonstrate considerable accumulation of HBsAg in chronic liver disease (72% in CAH, 66% in posthepatic liver cirrhosis) whereas anti-HBs was more frequently observed in healthy persons (38% in hospital staff, 49% in healed hepatitis). Furthermore, HBsAg and anti-HBs were frequently observed simultaneously in chronic hepatitis and cirrhosis (23% in CAH). A strong shift in the relation of antigen to antibody to the disadvantage of antibody in the examined collectives of chronic hepatitis and cirrhosis is evident. Chronic inflammatory HBsAg positive liver disease should therefore be regarded as chronic virus infection. We suppose an absolute or relative deficiency of antibody to HBsAg is probably an important factor for the development of chronicity of hepatitis B.     

Correlation of serum delta RNA with clinical course of acute hepatitis delta virus superinfection in Taiwan: a longitudinal study

Twenty of 22 hepatitis delta virus (HDV)-superinfected chronic hepatitis B carriers who had detectable HDV RNA at the acute stage progressed to chronicity, while only 6 of 16 patients without HDV RNA did so (P less than .005). The poor outcome of patients with persistently positive or fluctuating HDV RNA has been indicated by the following findings: 24 of 38 patients suffered from prolonged hepatic inflammation complicated by three to eight episodes of exacerbations; among them, 5 developed cirrhosis and 2 died in a follow-up period of 4 years. For most patients, the replication of HBV was suppressed at acute stage; only 3 of the 38 cases had detectable HBV DNA in sera. While reactivation of HBV was found in another 8 patients in the follow-up period, for 5 it was in the presence of serum HDV RNA and 2 developed cirrhosis. Therefore, serial assays of serum HDV RNA and HBV DNA appeared to be of value in monitoring the clinical course and outcome of acute HDV superinfection and in the study of the long-term interactions between these two viruses.     

Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment

To assess the characteristics of chronic hepatitis in hepatitis B surface antigen (HBsAg) carriers with intrahepatic delta antigen, the hepatic histologic findings of 137 patients were reviewed; 101 patients were followed for 2 to 6 years. The predominant liver disease was chronic active hepatitis in 93 patients or cirrhosis in 32; minor forms of chronic persistent or lobular hepatitis were seen in 12 patients. Eight of the 26 patients with an initial diagnosis of cirrhosis died during the follow-up period. Cirrhosis developed in 31 of 75 patients (41%) without nodular regeneration seen in the first biopsy specimen; 5 of these patients died. Treatment with prednisone or azathioprine did not induce histologic amelioration of delta hepatitis or prevent cirrhosis. Chronic HBsAg hepatitis with intrahepatic expression of the delta antigen is an active, progressive disease unresponsive to conventional immunosuppressive treatment.     

Pathology of livers infected with “silent” hepatitis B virus mutant

We have discovered that non-A, non-B, non-C, non-D, non-E (so-called type F) acute and chronic hepatitis is caused by a hepatitis B virus (HBV) variant with mutations in the X open reading frame. This silent HBV mutant does not induce immunoserological markers. In the present investigation we attempted to elucidate the putative mechanism of hepatocellular necrosis and expression patterns of hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) in biopsied liver tissue. The subjects consisted of 14 patients with acute hepatitis, 11 with chronic hepatitis and eight with liver cirrhosis, all of whom had been previously diagnosed as having so-called hepatitis F. Nine of the 14, 10 of the 11 and all eight, respectively, of the above patients exhibited significant positive immunostaining for HBsAg within their hepatocellular cytoplasm, diffusely or focally. HBcAg stained in a few hepatocellular nuclei in 24.2% of the patients. Histological features were characterized by necroinflammation, indicating immune-mediated hepatocellular necrosis. Despite the serological-marker negativity, the results of immunostaining for HBsAg and HBcAg support replication and expression of HBV DNA, though weak.     

The long-term prognosis of non-transfusion-associated non-A, non-B hepatitis. A clinical, epidemiological, and histological investigation

In a prospective study of the natural course of acute hepatitis, 157 of 1020 patients with biopsy-verified acute hepatitis could be classified as having hepatitis type non-A, non-B. We here report on the long-term prognosis for these 157 patients. The main type of exposure was drug addiction (40%), whereas 40% had no known hepatitis exposure. Only two patients had received blood products (blood transfusion and factor VIII). Follow-up liver biopsy (mean histological follow-up, 22 months) in 94 of the 157 patients showed chronic liver disease in 15-that is, cirrhosis in 6, suspicion of cirrhosis in 2, chronic aggressive hepatitis in 5, and chronic persistent hepatitis in 2. There was a striking predominance of elderly women with no known hepatitis exposure and with a high frequency of autoantibodies in serum among the patients with progression to chronicity, whereas chronic non-A, non-B hepatitis in drug addicts or after blood transfusions seems to be a limited problem. A comparison of histological features in the initial biopsies from patients with progression to chronicity or complete resolution showed piecemeal necrosis and abnormal bile duct epithelium to be of prognostic value.     

Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis

One hundred and thirty-five patients who developed non-A, non-B post-transfusion hepatitis mostly after cardiac surgery, were followed for a mean (±S.D.) of 90±41 months (range: 13–180) to evaluate clinical and histological outcome.Thirty-one cases resolved within 12 months, while 104 (77%) progressed to chronicity. Twenty-one of 65 (32%) biopsied patients developed cirrhosis at the end of the follow-up, and one further progressed to hepatocellular carcinoma. One patient had a complete histological remission (1%). The remaining cases had chronic active (37%), chronic persistent (27%) or chronic lobular hepatitis (3%). About half of the cases with cirrhosis developed portal hypertension, and three of these died due to esophageal varices hemorrhage, one due to liver failure, and one due to hepatocellular carcinoma. Out of 26 patients with the initial histologic diagnosis of chronic hepatitis that were rebiopsied during follow-up, 13 (50%) progressed to cirrhosis. These patients were significantly older than patients who did not develop cirrhosis (mean age 57 and 45 years respectively; p<0.01).During acute hepatitis anti-HCV was positive in all but one of the 114 patients tested. Percentages were similar for patients who recovered (95%) and those who developed chronic hepatitis (100%). However, during follow-up, 71% of the 1st generation and 21% of the 2nd generation ELISA test patients with acute resolved hepatitis became anti-HCV negative, while the same figures in chronic cases were only 8.5% (p<0.0001) and 1.4% (p=0.012). This suggests a correlation between anti-HCV antibody activity, hepatitis C virus replication, and the development of chronic liver disease.     

A follow-up study of an outbreak of non-A, non-B hepatitis in a plasmapheresis unit

A cluster of acute non-A, non-B hepatitis comprising 12 blood donors was diagnosed in a plasmapheresis unit. Nine cases were followed-up for 2-5.5 years and seven out of them progressed to chronicity, as judged by biochemical abnormalities. In six, liver biopsy was performed 1 year after the acute disease revealing chronic active hepatitis in two, chronic persistent hepatitis in two, chronic lobular hepatitis in one and normal liver in one. Repeated biopsies showed progression to cirrhosis in one case of chronic active hepatitis, and resolution of the disease in another one, while in the remaining patients liver morphology remained unchanged. Circumstantial epidemiologic evidence suggests a single agent being the cause of the outbreak, which resulted in a broad spectrum of liver disease.     

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

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.     

Prognostic significance of piecemeal necrosis in acute viral hepatitis

ABSTRACT— The predictive value of piecemeal necrosis (PMN) in acute hepatitis was investigated in 62 patients (39 hepatitis B virus infection, 9 hepatitis A virus infection and 14 possible hepatitis NANB virus infection). The 62 initial biopsies were blindly recoded and classified into three groups: 1. Acute hepatitis with signs of possible transition to chronicity (AHTC) (n = 35)(i.e. a picture of acute hepatitis associated with PMN). 2. AHTC-borderline group (BL) (n = 15) (i.e. a picture of acute hepatitis with minimal PMN). 3. Uncomplicated acute hepatitis (AH) (n = 12) (i.e. a picture of acute hepatitis without PMN). Follow-up of the patients revealed an evolution to chronicity in a very high percentage of the AHTC-cases of hepatitis B (95%) and NANB (89%) etiology. Also 67% of the BL-cases of hepatitis B etiology developed chronic liver disease. In hepatitis B the immunohistochemical pattern of HBsAg is of additional help. In hepatitis A, PMN is often present (5/9) but no evolution to chronicity was observed. This study shows that PMN in acute hepatitis appears to be a useful prognostic feature for chronicity in hepatitis B and NANB.     

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.