Association between severity of type A hepatitis and nucleotide variations in the 5' non-translated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions.
BACKGROUND
Type A hepatitis is still a considerable problem in both underdeveloped and developed countries. Why some patients progress to fulminant type A hepatitis and others do not is unclear.


OBJECTIVE
To determine if nucleotide differences in the genome of hepatitis A virus (HAV) are responsible for the range of clinical severities, we analysed the 5' non-translated region (5'NTR) of the HAV genome, which has an internal ribosomal entry site and is important for cap independent translation of the viral message.


METHODS
Serum samples from 84 Japanese patients with sporadic type A hepatitis from five distant regions of Japan, comprising 12 patients with fulminant hepatitis (FH), 13 with severe acute hepatitis (AHs), and 59 with acute hepatitis (AH), were examined for HAV RNA. The fragment between nucleotides 75 and 638 of the 5'NTR was amplified by reverse transcription-polymerase chain reaction, and the nucleotide sequence was determined by direct sequencing.


RESULTS
Comparison of sequences of the 5'NTR revealed relatively fewer nucleotide substitutions in FH and AHs patients compared with the considerable sequence variations found in strains of AH. This tendency was most prominent between nucleotides 200 and 500. Strains from FH and AHs cases had fewer nucleotide substitutions (p<0.001) in this region.


CONCLUSIONS
Nucleotide variations in the central portion of the 5'NTR of HAV may influence the severity of type A hepatitis.
Fujiwara
K
K
First Department of Internal Medicine, Chiba University School of Medicine, Chiba, Chiba 260-8670, Japan.
Yokosuka
O
O
Ehata
T
T
Saisho
H
H
Saotome
N
N
Suzuki
K
K
Okita
K
K
Kiyosawa
K
K
Omata
M
M
D020121:5' Untranslated Regions; D000208:Acute Disease; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D006506:Hepatitis A / Q000821:virology*; D017957:Hepatitis A Virus, Human / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D020121:5' Untranslated Regions; D018076:DNA, Complementary; D004279:DNA, Viral; D012367:RNA, Viral