Amino acid substitutions in the hepatitis C Virus core region and lipid metabolism are associated with hepatocarcinogenesis in nonresponders to interferon plus ribavirin combination therapy.
BACKGROUND
Substitution of amino acid 70 and/or 91 in the core region of hepatitis C virus (HCV) genotype 1b (HCV-1b) is an important predictor of hepatocellular carcinoma (HCC), but its impact on HCC in nonresponders to interferon (IFN) and ribavirin (RIB) combination therapy is not clear.


METHODS
A total of 292 patients with HCV-1b-related chronic liver disease who did not achieve a sustained virological response to 24-48 weeks of IFN+RIB combination therapy were included in a follow-up study to investigate the risk factors for HCC.


RESULTS
Sixteen patients developed HCC during the follow-up. The cumulative HCC rates were 5.0, 13.1 and 16.9% at the end of 3, 5 and 7 years, respectively. Multivariate analysis identified substitution of core amino acid 70 (Gln70/His70; hazard ratio 4.64, p = 0.018) and low serum levels of high-density lipoprotein cholesterol (<50 mg/dl; hazard ratio 9.35, p = 0.041) as determinants of HCC. Gender, stage of fibrosis and interleukin-28B showed no such relationship.


CONCLUSIONS
Amino acid substitution in the core region of HCV-1b and low serum levels of high-density lipoprotein cholesterol are significant and independent predictors of HCC in nonresponders to IFN+RIB combination therapy. These results emphasize the importance of viral and lipid metabolic factors in the development of HCC after combination therapy.
Department of Hepatology, Toranomon Hospital, Tokyo 105-0001, Japan. yseko523@toranomon.gr.jp
Yuya
Y
Seko
Norio
N
Akuta
Fumitaka
F
Suzuki
Yusuke
Y
Kawamura
Hitomi
H
Sezaki
Yoshiyuki
Y
Suzuki
Tetsuya
T
Hosaka
Masahiro
M
Kobayashi
Mariko
M
Kobayashi
Satoshi
S
Saitoh
Yasuji
Y
Arase
Kenji
K
Ikeda
Hiromitsu
H
Kumada
D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D008076:Cholesterol, HDL / Q000097:blood*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load
D000998:Antiviral Agents; D008076:Cholesterol, HDL; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012254:Ribavirin; D007372:Interferons