Evaluation of loss of heterozygosity before and after interferon therapy in patients with hepatitis C virus infection who developed hepatocellular carcinoma during follow up.
OBJECTIVE
The aim of the present study was to determine whether evaluating the status of loss of heterozygosity (LOH) before interferon (IFN) therapy is predictive for development of hepatocellular carcinoma (HCC) in chronic hepatitis and liver cirrhosis patients.


METHODS
Eighteen patients with hepatitis C virus were studied, nine of whom developed HCC (HCC group) after IFN therapy and nine whom did not (non-HCC group). Samples before IFN therapy from both groups (pre-IFN-N and pre-IFN-H samples from the non-HCC and HCC groups, respectively) were analyzed for LOH using 12 microsatellite markers. To evaluate the LOH incidence in different steps in HCC patients, paired samples of cancerous tissue (CT) and adjacent non-CT (ANCT) obtained from the HCC group were also analyzed.


RESULTS
Frequency of LOH in the pre-IFN-H samples was significantly higher than that in the pre-IFN-N samples regardless of the response to IFN therapy. Interestingly, in the HCC group, there is no significant difference in the frequency of LOH among the pre-IFN-H, ANCT and CT samples.


CONCLUSIONS
The present results suggest the theory that genetic instability, such as LOH, had already accumulated at stages before the development of HCC. The authors propose that the status of LOH in chronic hepatitis and liver cirrhosis patients before IFN therapy could be a potential predictor for the development of HCC.
Suzuki
Seiji
S
Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Kondo
Yutaka
Y
Hirashima
Noboru
N
Kato
Hideaki
H
Sugauchi
Fuminaka
F
Tanaka
Yasuhito
Y
Orito
Etsuro
E
Yang
Ying
Y
Shen
Yu
Y
Sakakibara
Kenji
K
Ueda
Ryuzo
R
Mizokami
Masashi
M
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D007372:Interferons