Impact of FIB-4 index on hepatocellular carcinoma incidence during nucleos(t)ide analogue therapy in patients with chronic hepatitis B: An analysis using time-dependent receiver operating characteristic.
OBJECTIVE
Nucleos(t)ide analogue (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). However, even during NA therapy, development of HCC has been observed in patients with CHB. Therefore, we clarified the predictive power of clinical factors for HCC incidence using receiver operating characteristic (ROC) analysis that takes time dependence into account.


METHODS
A total of 539 patients with CHB treated with NAs were enrolled. Univariate, multivariate, and time-dependent ROC curves for clinical factors associated with the development of HCC were analyzed.


RESULTS
Eighty-one patients developed HCC during the follow-up period (median duration, 5.9 years). α-fetoprotein (AFP) and FIB-4 index at 24 weeks from the initiation of treatment and sex were significantly associated with HCC incidence according to the log-rank test. Cox proportional hazards models including the covariates of sex, hepatitis B genotype, basal core promoter mutations, AFP at 24 weeks, and FIB-4 index at 24 weeks showed that FIB-4 index >2.65 (HR, 5.03; 95% CI, 3.06-8.26; P < 0.001) and male sex were independently associated with HCC incidence. In addition, time-dependent ROC analysis showed that compared with AFP at 24 weeks, FIB-4 index at 24 weeks had higher predictive power for HCC incidence throughout the follow-up period.


CONCLUSIONS
Elevated FIB-4 index at 24 weeks in patients with CHB receiving NA therapy is a risk factor for developing HCC. The FIB-4 index is an excellent predictor of HCC development.
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
Toshifumi
T
Tada
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
Takashi
T
Kumada
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
Hidenori
H
Toyoda
Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan.
Kunihiko
K
Tsuji
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan.
Atsushi
A
Hiraoka
Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Hiroshima, Japan.
Junko
J
Tanaka
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000627:therapeutic use*; D010757:Phosphorous Acids / Q000627:therapeutic use*; D010976:Platelet Count; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors
C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D000998:Antiviral Agents; D015415:Biomarkers; D063065:Organophosphonates; D010757:Phosphorous Acids; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil
FIB-4 index; hepatitis B; hepatocellular carcinoma; nucleos(t)ide analogue; time-dependent receiver operating characteristic; α-fetoprotein