Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao
Clin Mol Hepatol 2025;31(3):796-809. Published online January 6, 2025
Background/Aims There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies.
Methods Patients with various CLDs were included from medical centers in Taiwan. The SAFE score, consisting of age, body mass index, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC. The predictability of the SAFE score for HCC was analyzed using the sub-distribution hazard model with adjustments for competing risks.
Results Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC. The SAFE score classifies 1-, 3-, and 5-year HCC risk regardless of CLD etiologies. High (≥100) and intermediate (0–100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores. Combining two lower risk tiers (SAFE<100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR] 7.54; 95% confidence interval (CI) 5.38–10.60). A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR 11.10; 95% CI 3.97–31.30) and MASLD (aSHR 4.23; 95% CI 1.43–12.50). A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction.
Conclusions The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.
Citations
Citations to this article as recorded by
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Can SAFE score be utilized as a universal hepatocellular carcinoma prediction score?: Editorial on “High Steatosis-Associated Fibrosis Estimator scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction-associated Michael Kwan-Lung Ko, Loey Lung-Yi Mak Clinical and Molecular Hepatology.2026; 32(1): 371. CrossRef
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Predictors of Discordance Between Controlled Attenuation Parameter and Magnetic Resonance-Proton Density Fat Fraction in Hepatic Steatosis Dong Yun Kim, Hyung-Jin Rhee, Beom Kyung Kim Clinical and Translational Gastroenterology.2026; 17(7): e01042. CrossRef
Risk of HCC in Elderly Patients With MASLD: Proposal of an Effective Surveillance Strategy Young Eun Chon, Kyung‐Do Han, Ju Dong Yang, Ju‐Yeong Park, Hyun‐Seok Kim, Hyung Woong Lee, Tae Seop Lim, Beom Kyung Kim Journal of Gastroenterology and Hepatology.2026;[Epub] CrossRef
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