Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals.
OBJECTIVE
Predictive factors for hepatocarcinogenesis following eradication of hepatitis C virus (HCV) RNA by antiviral therapy with direct-acting antivirals are unknown. Especially the impact of treatment with or without interferon on hepatocarcinogenesis is not clear.


METHODS
A total of 958 patients with HCV genotype 1-related chronic liver disease and a sustained virological response defined as negative HCV RNA 24 weeks after cessation of antiviral therapy with direct-acting antivirals (triple therapy of NS3/4A protease inhibitor/peginterferon/ribavirin or all-oral combination therapy with NS3/4A protease inhibitor plus NS5A inhibitor) were included in a retrospective study. None of the patients had hepatocellular carcinoma before and during antiviral therapy.


RESULTS
In all, 14 patients developed hepatocellular carcinoma during follow-up, and the development rate per 1,000 person-years was 7.35. The cumulative hepatocarcinogenesis rates were 4.2 and 4.2% at the end of 5 and 7 years, respectively. Multivariate analysis identified fibrosis 4 (FIB4) index (≥2.7) and body mass index (≥23.0) as determinants of hepatocarcinogenesis, but they did not identify the treatment regimen. In patients with a FIB4 index ≥2.7, the hepatocarcinogenesis rates with the interferon regimen were not different from those for the regimen without interferon, regardless of gender.


CONCLUSIONS
Liver fibrosis and body mass index, but not treatment regimen, are important predictors of hepatocarcinogenesis following eradication of HCV RNA by direct-acting antivirals.
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Norio
N
Akuta
Masahiro
M
Kobayashi
Fumitaka
F
Suzuki
Hitomi
H
Sezaki
Shunichiro
S
Fujiyama
Yusuke
Y
Kawamura
Tetsuya
T
Hosaka
Mariko
M
Kobayashi
Satoshi
S
Saitoh
Yoshiyuki
Y
Suzuki
Yasuji
Y
Arase
Kenji
K
Ikeda
Hiromitsu
H
Kumada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D002219:Carbamates; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000821:virology; D002471:Cell Transformation, Neoplastic; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007370:Interferon Type I / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000473:pathology* / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D013449:Sulfonamides / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007370:Interferon Type I; D007546:Isoquinolines; D009842:Oligopeptides; D011759:Pyrrolidines; D012367:RNA, Viral; D013449:Sulfonamides; D012254:Ribavirin; C486464:telaprevir; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir