Natural History of Non-Alcoholic Fatty Liver Disease: A Study With Paired Liver Biopsies.

BACKGROUND

Although there is unequivocal evidence for progression of nonalcoholic steatohepatitis (NASH) to cirrhosis, there is uncertainty with regard to the progression to nonalcoholic fatty liver (NAFL) and NASH.

AIMS

We investigated the rate of progression to NASH and advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and assessed the factors associated with such progression.

METHODS

Histological assessment was performed in 36 patients with NAFLD with paired liver biopsies (≥1 year apart; median, 3.8 years; range, 1-10.33 years). NASH Clinical Research Network (NASH CRN) criteria were used to assess NAFLD Activity Score (NAS).

RESULTS

At baseline, 26 (72%) patients had NAFL and 10 (28%) patients had NASH. At follow-up, 27% NAFL progressed to NASH (NAS score ≥5), and 50% of patients with NASH no longer met the criteria of NASH. Fibrosis progressed in 15 (42%), regressed in 9 (25%), and remained stable in 12 (33%) patients overall. Thirty-five percent of patients with NAFL had fibrosis progression. The incidence of type 2 diabetes mellitus (T2DM) was higher in patients with NASH versus NAFL (40% vs. 27%). Both at the time of baseline and follow-up, liver biopsies, composite models of noninvasive scores such as Fibrosis-4 (FIB-4) score and NAFLD fibrosis score, and ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) were all significantly higher in progressors than in nonprogressors.

CONCLUSIONS

NAFLD is a dynamic liver disease with varying degrees of progression and regression. T2DM was strongly associated with fibrosis progression. Noninvasive fibrosis scores such as AST/ALT ratio, FIB-4 score, and NAFLD fibrosis score can identify those at risk of fibrosis progression.