Initial load of hepatitis B virus (HBV), its changing profile, and precore/core promoter mutations correlate with the severity and outcome of acute HBV infection.

BACKGROUND: The pathogenesis of the fulminant or severe form of acute hepatitis B virus (HBV) infection remains unclear, although both host- and virus-specific factors are considered to have a great impact on the c course. We aimed to define possible viral factors implicated in the severe form of acute HBV infection. METHODS: We investigated viral factors in 42 patients with acute HBV infection: 11 had fulminant hepatitis (FH); 9 had a severe form of acute hepatitis (SAH), defined as having a prothrombin activity of less than 40% without encephalopathy; and 22 had acute self-limited hepatitis (AH). RESULTS: Although there was no significant difference in serum HBV DNA levels on admission among the three groups, the level decreased more rapidly in patients with SAH or FH than in those with AH. In patients with SAH or FH, the HBV load on admission was higher in patients who died than in those who recovered (7.0 +/- 1.6 vs 5.6 +/- 1.0 log copies/ml; P=0.0293). In univariate analysis, seronegativity for hepatitis B envelope antigen (HBeAg) and mutations in both the precore (G1896A and/or G1899A) and core promoter (T1753A/C and/or T1754C/G and/or A1762T/G1764A) were associated with FH (odds ratio [OR], 5.60; P=0.0269 and OR, 52.0; P=0.0006; respectively). In multivariate logistic regression analysis, only the presence of precore/core promoter mutations was associated with FH (OR, 42.8; P=0.0020). CONCLUSIONS: The rapid decrease in viral load in the early phase of acute HBV infection was associated with the severity of the disease. A high viral load on admission and the presence of both precore and core promoter mutations in patients with severe coagulopathy closely correlated with mortality.

A male patient with severe acute hepatitis who was domestically infected with a genotype H hepatitis B virus in Iwate, Japan.

Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load of 1.0 x 10(9) copies/ml, elevated levels of total bilirubin (7.0 mg/dl) and alanine aminotransferase (3606 IU/l), and reduced prothrombin activity of 39.0%. The HB-JAIW05 isolate obtained in the present study was composed of 3215 nucleotides and had the highest similarity of 99.7% with the reported genotype H HBV isolate recovered from a Japanese blood donor. The HB-JAIW05 isolate had neither precore (A1896) nor core promoter (T1762/A1764) mutations. However, upon comparison with the consensus sequence of ten reported HBV isolates of the same genotype, the HB-JAIW05 isolate had 17 nucleotide substitutions including five missense mutations in the P gene, which may be related to vigorous replication of HBV in this case. He had no history of traveling abroad, but had had extramarital sexual contact with two Japanese women living in Iwate, Japan, 2 weeks and 2 months before the disease onset, respectively. Our results suggest that rare HBV genotypes such as H may be spreading in Japan via sexual contact. Further molecular epidemiological studies on HBV to clarify the exact changing profiles of de novo HBV infection in Japan in relation to genotype and genomic variability are warranted.

Epidemiological and clinical study of sporadic acute hepatitis E caused by indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A.

BACKGROUND: We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan. METHODS: We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20-72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E. RESULTS: Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island ( P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 +/- 10.6 vs 45.9 +/- 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher ( P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period. CONCLUSIONS: Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E.

Pretreatment hepatitis C virus dynamics for predicting virological response to interferon-alpha2b monotherapy in patients with chronic hepatitis C virus infection.

One hundred and forty-one patients with chronic hepatitis C virus (HCV) infection treated with 6 MIU of interferon (IFN)-alpha2b for 24 weeks were studied to compare pretreatment viral dynamics during 1 month before the initiation of treatment (DeltaHCV) with other predictive factors. The patients were classified into three groups according to DeltaHCV: the Increase group (DeltaHCV >0.20log copies/ml/month), the Stable group (-0.20

Influence of load of hepatitis A virus on disease severity and its relationship with clinical manifestations in patients with hepatitis A.

BACKGROUND AND AIM: The purpose of the present study was to investigate the influence of viral load on disease severity and analyze the possible relationship of the load of hepatitis A virus (HAV) with disease severity and laboratory findings. METHODS: Fifty-eight patients diagnosed with acute hepatitis A were used in the current study, of whom 12 patients progressed to severe acute hepatitis (s-AH) defined on the basis of a prothrombin time (PT) of <40% and 46 patients were diagnosed as having mild acute hepatitis (m-AH). The load of HAV was measured with real-time polymerase chain reaction. RESULTS: Peak viral load showed a significant correlation with alanine aminotransferase (ALT) (r = 0.363, P = 0.0048) and PT levels (r = -0.330, P = 0.0110). In terms of disease severity, there was a significant correlation with ALT (r = 0.462, P = 0.0012) and PT levels (r = 0.400, P = 0.0059) in the m-AH group, but not in the s-AH group. A significant positive correlation of peak viral load with the C-reactive protein level (r = 0.270, P = 0.0400) and a significant negative correlation of peak viral load with the platelet count (r = -0.313, P = 0.0015) was also found. CONCLUSIONS: The load of HAV was closely correlated with liver damage and disease severity in m-AH, but not in s-AH. The load of HAV was also closely associated with the increase in C-reactive protein level and enhancement of thrombocytopenia.