SAFE Score May Help Guide Repeat Cirrhosis Screening in Steatotic Liver Disease: Study
USA: A cohort study has found that the SAFE score may help clinicians counsel patients with steatotic liver disease (SLD) and guide decisions on when to repeat cirrhosis assessments. In contrast, existing hepatocellular carcinoma (HCC) risk scores showed limited utility for guiding HCC screening in patients with noncirrhotic SLD.
The findings were published in JAMA Internal Medicine by Catherine Mezzacappa, Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and colleagues. The researchers evaluated whether established clinical risk scores could help identify patients with noncirrhotic SLD who are at increased risk of developing cirrhosis or HCC.
The retrospective cohort study used data from the US Veterans Affairs health system and included adults with imaging-confirmed SLD diagnosed between 2008 and 2020. Patients with viral hepatitis or other primary liver diseases were excluded. Nine clinical risk scores were calculated at the time hepatic steatosis was first identified, including ALBI, aMAP, APRI, BARD, FIB-4, NFS, and SAFE, along with two additional scores.
The study followed patients until development of cirrhosis or HCC, death, or the end of available follow-up. The analysis included 853,131 individuals, with a median age of 61 years. Most participants were men, and nearly one-third had diabetes. Within 10 years, 33,794 patients (3.96%) developed cirrhosis, while 2,978 (0.35%) developed HCC.
Key findings:
- FIB-4, APRI and SAFE showed the strongest ability to distinguish patients according to their future risk of cirrhosis.
- SAFE, Tate and FIB-4 demonstrated the greatest discrimination for HCC risk.
- SAFE provided the highest net benefit for identifying individuals at risk of developing cirrhosis.
- A SAFE score of 29.5 corresponded to a 2.5% estimated 10-year cirrhosis risk and provided a net benefit of 0.019, equivalent to identifying 1.9 additional individuals who developed cirrhosis per 100 people classified as at risk.
- For HCC, the SAFE score provided only a small net benefit at a 0.25% 10-year risk threshold, corresponding to 1.6 additional true-positive cases per 1,000 individuals.
The researchers concluded that the SAFE score could support discussions with patients with SLD and help clinicians determine when repeat assessment for cirrhosis may be appropriate. However, the evaluated clinical risk scores offered limited benefit for deciding whether to initiate HCC surveillance among patients who had SLD without established cirrhosis.
The study highlights the difference between predicting disease progression and using risk scores to guide cancer surveillance. While several scores showed reasonable discrimination for future cirrhosis or HCC, their clinical usefulness depends on whether they meaningfully improve decisions about patient management. The findings suggest that, among the evaluated tools, SAFE may have greater practical value for cirrhosis risk assessment than for determining HCC screening in noncirrhotic SLD.
Reference:
Mezzacappa C, Tate JP, Torgersen J, Skanderson M, Taddei TH, Justice AC. Steatotic Liver Disease Risk Scores to Predict Cirrhosis and Hepatocellular Carcinoma. JAMA Intern Med. Published online September 21, 2026. doi:10.1001/jamainternmed.2026.4110
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