The SAFE score, a proposed risk assessment tool, shows promise in predicting cirrhosis development in patients with steatotic liver disease and could improve screening decisions. While the score demonstrated modest benefits for cirrhosis surveillance, current risk scores remain limited for identifying hepatocellular carcinoma in patients without existing cirrhosis.
- The SAFE score (steatosis-associated fibrosis estimator) achieved the greatest net benefit in predicting 10-year cirrhosis risk compared to eight other risk scores tested.
- Among 853,131 patients with imaging-confirmed steatotic liver disease, 3.96% developed cirrhosis and 0.35% developed HCC within 10 years.
- A SAFE score of 29.5 identified patients with a 2.5% 10-year cirrhosis risk, adding 1.9 additional true cirrhosis cases per 100 at-risk patients.
- Current risk scores show minimal utility for HCC screening in patients with noncirrhotic steatotic liver disease, highlighting a critical gap in surveillance strategies.
- Risk-based approaches to liver disease surveillance require prospective clinical studies before routine implementation in medical practice.
A proposed risk score could inform decisions to repeat screening for cirrhosis in patients with imaging-confirmed steatotic liver disease (SLD), suggest findings published September 21 in JAMA Internal Medicine.
While more work needs to be done before regular use, the steatosis-associated fibrosis estimator (SAFE) score showed “modest benefit” to inform surveillance strategies for cirrhosis, wrote a team led by Catherine Mezzacappa, MD, PhD, from the Yale School of Medicine in New Haven, CT.
“None of the risk scores assessed can readily inform the decision to initiate [hepatocellular carcinoma] screening for persons with noncirrhotic SLD,” the Mezzacappa team wrote.
About one in three cases of hepatocellular carcinoma (HCC) in people with SLD develops with no preexisting cirrhosis. The researchers pointed out there is a lack of HCC screening for people with noncirrhotic SLD.
Despite low HCC incidence in this population, the high prevalence of SLD has drawn interest toward HCC risk stratification. And while several HCC risk scores have been proposed, their respective performances haven’t been directly compared to each other, the researchers noted.
To bridge the gap, the researchers compared the performance and utility of nine risk scores to predict incident cirrhosis and HCC side by side in a national sample of adults with imaging-confirmed SLD. SLD was confirmed via MRI, ultrasound, or CT.
They included the following clinical risk scores: albumin-bilirubin (ALBI); age-male-albumin-bilirubin-platelet (aMAP); the aspartate aminotransferase-to-platelet ratio (APRI), body mass index (BMI), age, alanine aminotransferase-to-aspartate aminotransferase ratio, and diabetes (BARD); fibrosis-4 (FIB-4) index; nonalcoholic fatty liver disease fibrosis (NFS); SAFE; and two additional scores.
Additionally, the team included HCC risk scores from research teams led by Tate et al, Hung et al, and Sinn et al.
The study included 853,131 patients with a median age of 61 years. The patients had a median BMI of 31.3 and 275,898 (32.3%) had diabetes. And 33,794 (3.96%) developed cirrhosis while 2,978 (0.35%) developed HCC within 10 years.
The FIB-4, APRI, and SAFE scores achieved the greatest discrimination of cirrhosis risk. The SAFE, Tate, and FIB-4 scores showed the greatest discrimination of HCC risk.
However, the SAFE score achieved the greatest net benefit in predicting cirrhosis. A score of 29.5 corresponded to a 10-year cirrhosis risk of 2.5% and yielded a net benefit of 0.019, or 1.9 additional individuals who develop cirrhosis per 100 individuals classified as at-risk patients.
And at a 0.25%10-year risk of HCC, the SAFE score had a net benefit of 0.0016, meaning 1.6 additional true positives per 1,000 individuals.
Despite the results, the study authors noted that these HCC clinical risk scores show “minimal utility” to inform HCC screening decisions for patients with noncirrhotic SLD. The scores performed poorly for stratifying HCC risk compared to prior research, they wrote.
The authors added that results highlight the importance of assessing test performance at “relevant thresholds for clinical practice.” The SAFE score, however, provided a more favorable balance of true- and false-positive results in the study.
“Risk-based approaches to surveillance for advanced liver disease require prospective study,” the authors wrote.
Read the full study here.
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&dpr=2&fit=crop&h=167&q=70&w=250)