Analysis of full-length hepatitis A virus genome in sera from patients with fulminant and self-limited acute type A hepatitis

Background/Aims: Type a hepatitis still poses a considerable problem worldw ide. Why some patients progress to fulminant type A hepatitis and others do not is still unknown. To examine whether genomic differences of hepatitis A virus (HAV are responsible for the severity of the disease, we analyzed t he whole HAV genomes from patients with fulminant and self-limited acute ty pe A hepatitis. Methods: Sera from three patients with sporadic type A fulminant hepatitis (FR) and three patients with acute hepatitis (AII) were examined for HAV RN A. Full-length nucleotide sequences were determined using long reverse tran scription polymerase chain reaction, 5 ' and 3 ' rapid. amplification of cD NA ends methods, and direct sequencing. The amino acid sequences were deduc ed from the nucleotide sequences. Results: HAV RNA was detected in all six patients examined. From the sequen ce of viral protein 1/2A, all cases were revealed to be genotype IA. By com paring with genotype Ia, wild-type HAV strain GEM, the analysis of whole ge nomes from the six cases showed no specific substitutions between FH and AH . Completely identical nucleotide sequences were observed at 3 ' non-transl ated region (NTR) in all six cases. In 5 ' NTR, less nucleotide substitutio ns were found in FH than in AR, and in the non-structural protein 2B region , a little more amino acid substitutions seemed to be found in FH than in A IP. Conclusions: This study showed that full-length HAV could be analyzed from serum samples. Although there were no unique nucleotide or amino acid subst itutions, possible associations were suggested between the severity of type A hepatitis and the nucleotide substitutions in 5 ' NTR and the amino acid substitutions in 2B. (C) 2001 European Association for the Study of the Li ver. Published by Elsevier Science B.V. All rights reserved.