Substitution of amino acid 70 in the hepatitis C virus core region of genotype 1b is an important predictor of elevated alpha-fetoprotein in patients without hepatocellular carcinoma.
Previous studies identified amino acid (aa) substitutions of the hepatitis C virus core region of genotype 1b (HCV-1b core region) and elevated serum alpha-fetoprotein (AFP) levels as predictors of poor virologic response to pegylated interferon (PEG-IFN) plus ribavirin (RBV), and also as risk factors for hepatocarcinogenesis. The present study evaluated the impact of aa substitutions of HCV-1b core region on AFP, as a surrogate marker of hepatocarcinogenesis, on AFP levels in 569 Japanese patients with HCV-1b but without HCC, and investigated the predictive factors of elevated AFP (> or =11 microg/L). High AFP levels were detected in 27.4% of the patients. The rate of hepatocarcinogenesis in a group of 109 patients who received IFN monotherapy and followed-up for 15 years, was significantly higher in patients with abnormal than normal AFP. Multivariate analysis of 569 patients identified fibrosis stage (F3,4), aspartate aminotransferase (> or =76 IU/L), substitution of aa 70 (glutamine or histidine), and platelet count (<15.0 x 10(4)/microl) as significant determinants of elevated AFP. In 49 patients with abnormal AFP levels and substitutions at aa 70 who were treated with PEG-IFN + RBV, the rate of normalization of AFP was significantly lower in non-virological responders (28.6%) than in transient (71.4%) and sustained (100%) virological responders. The results indicated that substitution of aa 70 of HCV-1b core region is an important predictor of elevated AFP in non-HCC patients, and that eradication of the mutant virus normalizes AFP. The results highlight the importance of eradication of mutant type virus of aa 70 for reducing the risk of hepatocarcinogenesis.
Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
Norio
N
Akuta
Fumitaka
F
Suzuki
Yusuke
Y
Kawamura
Hiromi
H
Yatsuji
Hitomi
H
Sezaki
Yoshiyuki
Y
Suzuki
Tetsuya
T
Hosaka
Masahiro
M
Kobayashi
Mariko
M
Kobayashi
Yasuji
Y
Arase
Kenji
K
Ikeda
Hiromitsu
H
Kumada
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000821:virology; D018936:Hepatitis C Antigens / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D014758:Viral Core Proteins / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000378:metabolism*
D000998:Antiviral Agents; D018936:Hepatitis C Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D000509:alpha-Fetoproteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b