FIB-4 Risk Trajectories Linked to Cirrhosis, HCC Progression in NAFLD

Noninvasive liver fibrosis tests like FIB-4 can help predict risk for cirrhosis and hepatocellular carcinoma in NAFLD.

The noninvasive liver fibrosis test, fibrosis 4 (FIB-4), is strongly associated with cirrhosis and hepatocellular carcinoma (HCC) progression among patients with nonalcoholic fatty liver disease (NAFLD), according to study findings published in the Journal of Hepatology.

Researchers sourced data for the retrospective cohort study from the national Veterans Affairs (VA) Corporate Data Warehouse and VA Central Cancer Registry. Patients (N=202,319) with NAFLD were evaluated for longitudinal changes in FIB-4 scores and the association with progression to cirrhosis or HCC at 3 years.

The study cohort comprised patients with a mean (SD) age of 55.2[12.9] years, 93.9% were men, 69.5% were White, 57.6% were obese, FIB-4 score was 1.20[0.91], and 0.2% were diagnosis with cirrhosis at baseline, respectively.

At the follow-up, FIB-4 scores had increased to 1.45[1.11] and 0.5% were diagnosed with cirrhosis.

At 3 years, there were 433 HCC events and 2161 composite events of cirrhosis or HCC, amounting to an HCC incidence rate (IR) of 0.28 per 1000 person-years (py) and cirrhosis and HCC IR of 1.31 per 1000 py.

Integrating serial measurements of non-invasive tests for fibrosis in the care pathway for patients with NAFLD can help tailor HCC risk prevention.

Using FIB-4 scores to stage patients at baseline and follow-up, most patients who were at low, intermediate, or high risk at baseline remained in low (79.1%), intermediate (61.3%), and high (55.3%) risk groups at follow-up, respectively. Among the low-risk group at baseline, 19.5% progressed to intermediate risk and 1.4% to high risk; among the intermediate risk group at baseline, 22.4% reverted to low risk and 16.2% progressed to high risk; and for the high-risk baseline group, 44.7% reverted to low or intermediate risk.

On the basis of the FIB-4 trajectories, risk for HCC was associated with high-to-high risk (adjusted hazard ratio [aHR], 57.69), intermediate-to-high risk (aHR, 26.52), low-to-high risk (aHR, 11.51), high-to-intermediate or low risk (aHR, 10.35), intermediate-to-intermediate risk (aHR, 7.96), intermediate-to-low risk (aHR, 3.92), and low-to-intermediate risk (aHR, 3.45) compared with low-to-low risk. In addition, diabetes (aHR, 2.65), hypertension (aHR, 1.83), and obesity (aHR, 1.43) were associated with HCC risk.

Similar findings were observed for the cirrhosis or HCC risk analysis with the additional association with Hispanic ethnicity (aHR, 1.36).

These findings may not be generalizable for a more diverse, more female population.

“Integrating serial measurements of noninvasive tests for fibrosis in the care pathway for patients with NAFLD can help tailor risk prevention,” the study authors wrote. “These data also provide valuable information for future cost-effectiveness studies determining which high risk NAFLD subgroups will benefit from frequent monitoring and HCC surveillance.”


Cholankeril G, Kramer JR, Chu J, et al. Longitudinal changes in fibrosis markers are associated with risk of cirrhosis and hepatocellular carcinoma in non-alcoholic fatty liver disease. J Hepatol. Published online November 16, 2022. doi:10.1016/j.jhep.2022.10.035