Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis.
The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver-related death in patients of hepatitis C virus (HCV) genotype 1b (HCV-1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV-infected patients, who had not received antiviral therapy, were included in a follow-up study to determine predictive factors of hepatocarcinogenesis and survival for liver-related death. The cumulative hepatocarcinogenesis rates in HCV-1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV-1b of Arg70 (arginine at aa 70) and HCV-2a/2b. The cumulative survival rates for liver-related death in HCV-1b of Gln70(His70) were significantly lower than those in HCV-1b of Arg70 and HCV-2a/2b. Multivariate analysis identified gender (male), age (≥ 60 years), albumin (<3.9 g/dL), platelet count (<15.0 × 10(4) /mm(3) ), aspartate aminotransferase (≥ 67 IU/L), and HCV subgroup (HCV-1b of Gln70(His70)) as determinants of both hepatocarcinogenesis and survival rates for liver-related death. In HCV-1b patients, the cumulative change rates from Arg70 to Gln70(His70) by direct sequencing were significantly higher than those from Gln70(His70) to Arg70. In patients of Arg70 at the initial visit, the cumulative change rates from Arg70 to Gln70(His70) in IL28B rs8099917 non-TT genotype were significantly higher than those in the TT genotype.


CONCLUSIONS
Substitution of aa 70 in the core region of HCV-1b is an important predictor of hepatocarcinogenesis and survival for liver-related death in HCV patients who had not received antiviral therapy. The IL28B genotype might partly affect changes over time of dominant amino acid in core aa 70 of HCV-1b.
Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan. akuta-gi@umin.ac.jp
Norio
N
Akuta
Fumitaka
F
Suzuki
Yuya
Y
Seko
Yusuke
Y
Kawamura
Hitomi
H
Sezaki
Yoshiyuki
Y
Suzuki
Tetsuya
T
Hosaka
Masahiro
M
Kobayashi
Tasuku
T
Hara
Mariko
M
Kobayashi
Satoshi
S
Saitoh
Yasuji
Y
Arase
Kenji
K
Ikeda
Hiromitsu
H
Kumada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D015996:Survival Rate; D014758:Viral Core Proteins / Q000378:metabolism*; D055815:Young Adult; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda