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.

Publication Title

Journal of Clinical and Experimental Hepatology