Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver...

There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF).

We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater.

Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log₁₀ FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52-0.59). The rate of increase in NFS and log₁₀ FIB-4 was significantly higher in patients with than without CSF (both P < .001). Predicted NFS increased by 0.17 and 0.06 units per year in subjects with and without CSF, respectively. Predicted log₁₀ FIB-4 score increased by 0.032 and 0.0003 units per year in subjects with and without CSF, respectively.

Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF.