Genetic analysis of hepatitis A virus protein 2C in sera from patients with fulminant and self-limited hepatitis A.

BACKGROUND/AIMS: To examine whether genetic differences in hepatitis A virus (HAV) are responsible for the range of clinical severities, we analyzed the HAV 2C genome, whose mutations have previously been shown to be important for enhanced replication in cell culture systems and to be related to virulence in simians.

METHODOLOGY: Serum samples from 45 Japanese patients with sporadic hepatitis A, comprising 9 patients with fulminant hepatitis (FH), 10 with severe acute hepatitis (AHs), and 26 with self-limited acute hepatitis (AH), were examined for HAV RNA.

RESULTS

Compared with the sequence of wild-type HAV strain HM-175, the nucleotide sequences of 2C had homology of 89.0 +/- 0.6% in FH, 88.6 +/- 0.9% in AHs, and 89.0 +/- 1.6% in AH. Differences were not statistically significant among the three groups. Deduced amino acid sequences had homology of 97.6 +/- 0.4% in FH, 96.5 +/- 1.9% in AHs, and 96.8 +/- 1.7% in AH. The difference between FH and AH was statistically significant (p < 0.05), although there were no specific nucleotide or amino acid substitutions.

CONCLUSIONS

Fulminant hepatitis patients had fewer amino acid substitutions in 2C, indicating the association between severity of hepatitis A and amino acid variations in 2C of HAV.