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Large-Scale Long-Term Follow-Up Study of Japanese Patients With Non-Alcoholic Fatty Liver Disease for the Onset of Hepatocellular Carcinoma
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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“APRI > 1.5 predicted HCC occurrence in Asian individuals with an ultrasound diagnosis of MASLD, 179”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [179]
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Metadata
- 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
- Published
- 2012-02
- Volume
- 107
- Issue
- 2
- Pages
- 253-261
- ISSN
- 0002-9270 (ISSN-L)
- 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
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Okinaka Memorial Institute for Medical Research
- Topics
- Health Sciences › Medicine › Hepatology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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