Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (H
CC). Progressive accumulation of mutations and genomic instability in chron
ic viral hepatitis might flag an increased risk of HCC development. Genomic
instability at dinucleotide microsatellite loci in chromosomes 2, 13, and
17 and at 2 mononucleotide repeat loci was examined in liver tissues from 4
1 patients, including 30 without HCC (18 patients with chronic hepatitis an
d 12 with cirrhosis) and 11 with HCC. Genomic instability was detected in 5
1% of the 41 cases. Allelic imbalance at informative dinucleotide loci occu
rred in 37% of the cases. In 14 cases (34%), allelic imbalance was detected
in chronic hepatitis or cirrhosis without HCC. Allelic imbalance at the ch
romosome 13 locus was detected in 50% of the cases of chronic hepatitis C.
Allelic imbalance at the TP53 chromosome locus and/or at the chromosome 13
locus was significantly more frequent than alterations at the chromosome 2
locus (P = .026). Low-level microsatellite instability was found in 20% of
all cases examined and high-level microsatellite instability in 3 patients
(7.5%), including 2 cases of chronic hepatitis and 1 case of cirrhosis. Our
results show that allelic imbalance occurs frequently in hepatitis-related
HCC as well as in chronic hepatitis in patients without HCC. Allelic imbal
ance at the D13S170 chromosome 13 locus (13q31.2) occurs frequently in chro
nic hepatitis, suggesting that genomic alterations affecting the long arm o
f chromosome 13 might be used to monitor the natural progression of chronic
hepatitis-associated liver carcinogenesis. HUM PATROL 32:698-703. Copyrigh
t (C) 2001 by W.B. Saunders Company.