Cirrhosis-Flagging Tool Stands Out for Steatotic Liver Disease in Primary Care

For patients with steatotic liver disease (SLD), one risk calculator showed promise for predicting cirrhosis in the primary care setting, but a good tool for hepatocellular carcinoma (HCC) remained elusive.

Among nine risk scores evaluated for the prediction of cirrhosis or HCC within 10 years, the SAFE (steatosis-associated fibrosis estimator) score had the largest net benefit for detecting 10-year cirrhosis risk, with a score of 29.5 corresponding to a 10-year cirrhosis risk of 2.5% and yielding a net benefit of 0.019, or 1.9 additional individuals who develop cirrhosis per 100 individuals classified as at-risk patients.

“These findings suggest that the SAFE score can be used to counsel patients with SLD and to inform decision-making regarding repeat assessments for cirrhosis,” reported Catherine Mezzacappa, MD, PhD, MPH, of the Yale School of Medicine in New Haven, Connecticut, and colleagues, in JAMA Internal Medicine.

SLD is a leading risk factor for advanced liver disease, and early stages can be treated in primary care as many cases do not lead to cirrhosis or HCC. The concern is that as cirrhosis is often clinically silent, many individuals at risk of advanced liver disease may go undetected, whereas others with more benign SLD may undergo unnecessary secondary testing, Mezzacappa’s group explained.

The present study supports the development of a SLD screening and management pathway in the primary care setting.

“Ongoing advances in SLD-related NITs [noninvasive tests] provide an opportunity for primary care to consider improved screening pathways,” observed Melinda Wang, MD, MHS, of the University of California, San Francisco, in an accompanying editorial.

“[G]uidance for SLD screening and management in the primary care setting is currently in its nascent stages,” Wang noted. “Compared with hypertension and chronic kidney disease, which have mature screening, risk-assessment, management, and specialty referral pathways as authored by respective national societies, SLD pathways are relatively new.”

The American Association for the Study of Liver Diseases currently recommends that primary care practitioners repeatedly screen patients with metabolic risk factors or incidentally identified steatosis with the Fibrosis-4 Index (FIB-4), a low-cost composite of age plus routine blood tests.

However, the FIB-4 is not very sensitive or specific, the authors suggested. “As a result, many individuals at risk of advanced liver disease may go undetected and many others with more benign SLD may undergo unnecessary secondary testing,” they wrote.

The SAFE calculator includes seven measures: age, BMI, diabetes status, aspartate aminotransferase, alanine aminotransferase, globulins, and platelets.

Mezzacappa and colleagues reported that the SAFE score also demonstrated the largest net benefit with respect to decision-making around HCC screening, albeit one that was still modest. A SAFE score of 43.8 corresponded to a 10-year HCC risk of 0.25%, which yielded a net benefit of 0.0016, meaning 1.6 true positives for HCC within 10 years per every 1,000 individuals.

“Put differently, 625 individuals classified as at-risk would have to undergo routine HCC screening to achieve a net benefit of one additional case of HCC identified within 10 years,” the authors said. “Thus, existing risk scores do not adequately predict HCC to inform HCC screening for persons with noncirrhotic SLD.”

Study authors had tested the nine risk scores, all deemed feasible for use in primary care, in a cohort of 853,131 veterans with imaging-confirmed noncirrhotic steatotic liver disease (without viral hepatitis or primary liver disease). The study covered SAFE, the FIB-4, as well as seven other risk scores.

For their analysis, Mezzacappa and colleagues used data from the national U.S. Veterans Affairs health system encompassing adults with imaging-confirmed SLD without viral hepatitis or primary liver disease from 2008 and 2020.

The study included mostly men (92.7%). The median age was 61 years, median BMI was 31.3, and just under one in three participants had diabetes. Most individuals reported low-risk alcohol consumption.

Of the total study population, 3.96% developed cirrhosis and 0.35% developed HCC within 10 years. Median duration of follow-up was 8.5 years.

The authors acknowledged the study had several limitations. “Six risk scores were not included due to data availability,” they noted. “Risk scores were calculated for individuals with nonmissing laboratory data elements, and patients lacking these data may differ from those with complete data.”