Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma.
OBJECTIVE
The aim of this study was to determine the incidence and risk factors of hepatocellular carcinoma (HCC), and to elucidate the utility of two non-invasive predictive procedures for liver fibrosis: the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the BARD score (which includes the following three variables: body mass index, AST/alanine aminotransferase ratio, and diabetes) in the prediction of HCC in a large population of Japanese patients with non-alcoholic fatty liver disease (NAFLD).


METHODS
This was a retrospective cohort study conducted at a public hospital. Study subjects included 6,508 patients with NAFLD diagnosed by ultrasonography. The median follow-up period was 5.6 years. The primary end point was the onset of HCC. Evaluation was performed using Kaplan-Meier methodology and Cox's proportional hazards analysis.


RESULTS
In all, 16 (0.25%) new cases with HCC were diagnosed during the study. The cumulative rates of NAFLD-related HCC were 0.02% at year 4, 0.19% at year 8, and 0.51% at year 12. The annual rate of new HCC was 0.043%. Multivariate analysis identified serum AST level ≥40 IU/L (hazard ratio (HR): 8.20; 95% confidence interval (95% CI): 2.56-26.26; P<0.001), platelet count <150 × 10(3)/μl (HR: 7.19; 95% CI: 2.26-23.26; P=0.001), age ≥60 years (HR: 4.27; 95% CI: 1.30-14.01; P=0.017), and diabetes (HR: 3.21; 95% CI: 1.09-9.50; P=0.035) as independent risk factors for HCC. With regard to the APRI, 184 patients (2.83%) were considered to have significant fibrosis (equivalent to non-alcoholic steatohepatitis (NASH) stage 3-4). The cumulative rate of HCC was significantly higher in this group (HR: 25.03; 95% CI: 9.02-69.52; P<0.001). In contrast, regarding the BARD score, 3,841 (59%) patients were considered to have advanced fibrosis (NASH stage 3-4). However, no significant associations between the BARD score and the incidence of HCC were observed (HR: 1.16; 95% CI: 0.40-3.37; P=0.780).


CONCLUSIONS
This retrospective study indicates that the annual incidence rate of HCC among Japanese NAFLD patients is low. Elderly NAFLD patients with diabetes, elevated serum AST, and especially thrombocytopenia (suggested to be associated with advanced liver fibrosis) should be monitored carefully during follow-up that includes using the APRI to ensure early diagnosis and treatment of HCC.
Department of Hepatology, Toranomon Hospital, Tokyo, Japan. k-yusuke@toranomon.gr.jp
Yusuke
Y
Kawamura
Yasuji
Y
Arase
Kenji
K
Ikeda
Yuya
Y
Seko
Norihiro
N
Imai
Tetsuya
T
Hosaka
Masahiro
M
Kobayashi
Satoshi
S
Saitoh
Hitomi
H
Sezaki
Norio
N
Akuta
Fumitaka
F
Suzuki
Yoshiyuki
Y
Suzuki
Yuki
Y
Ohmoto
Kazuhisa
K
Amakawa
Hiroshi
H
Tsuji
Hiromitsu
H
Kumada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D015331:Cohort Studies; D005234:Fatty Liver / Q000150:complications / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors
D001219:Aspartate Aminotransferases