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Cited by 280Liver Disease Diagnosis and TreatmentHepatocellular Carcinoma Treatment and PrognosisLiver physiology and pathology

Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma

Kawamura, Yusuke, Arase, Yasuji, Ikeda, Kenji, Seko, Yuya, Imai, Norihiro, Hosaka, Tetsuya, Kobayashi, Masahiro, Saitoh, Satoshi +8 more·2012·American Journal of Gastroenterology
DOI 10.1038/ajg.2011.327
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Abstract

OBJECTIVES: 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.

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Authors
Kawamura, Y., Arase, Y., Ikeda, K., Seko, Y., Imai, N., Hosaka, T., Kobayashi, M., Saitoh, S., Sezaki, H., Akuta, N., Suzuki, F., Suzuki, Y., Ohmoto, Y., Amakawa, K., Tsuji, H., & Kumada, H.
Affiliations
Toranomon Hospital (JP)
Corresponding author
Kawamura, Yusuke
ORCID
Venue
American Journal of Gastroenterology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-02
Volume
107
Issue
2
Pages
253-261
ISSN
0002-9270 (ISSN-L)
DOI
10.1038/ajg.2011.327
OpenAlex
W2064890337
Cited by
280
References
53
Citations by year
2026: 8 · 2025: 10 · 2024: 21 · 2023: 14 · 2022: 29 · 2021: 28 · 2020: 24 · 2019: 23 · 2018: 28 · 2017: 13 · 2016: 19 · 2015: 24 · 2014: 16 · 2013: 18 · 2012: 4
FWCI
9.07
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • The American Journal of Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Okinaka Memorial Institute for Medical Research
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
non-alcoholic fatty liver disease, hepatocellular carcinoma, HCC incidence, HCC risk factors, liver fibrosis, APRI, BARD score, noninvasive fibrosis prediction, aspartate aminotransferase, platelet count, diabetes mellitus, Japanese patients, nonalcoholic steatohepatitis, long-term follow-up
MeSH terms
Adult, Aged, Aged, 80 and over, Aspartate Aminotransferases, Fatty Liver, Female, Follow-Up Studies, Carcinoma, Hepatocellular, Humans, Japan, Liver, Liver Neoplasms, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Risk Factors, Cohort Studies, Incidence, Asian People

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