Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management

Background and aims: There remains uncertainty about the natural history of non-alcoholic fatty liver disease (NAFLD). The spectrum of NAFLD includes non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and steatohepatitis (NASH; steatosis with hepatocyte ballooning degeneration±fibrosis). Our aim was to assess the histological severity of NAFLD in a cohort with serial biopsy data, and determine factors predicting progression.

Methods: Patients with two liver biopsies more than a year apart were identified. Clinical and laboratory data were collected from the time of liver biopsy.

Results: 108 patients had serial biopsies (median interval 6.6years, range 1.3-22.6). 81 (75%) patients had NASH and 27 had NAFL. Overall, 45 (42%) patients had fibrosis progression, 43 (40%) had no change in fibrosis, while 20 (18%) had fibrosis regression. Importantly, no significant difference in the proportion exhibiting fibrosis progression was found between those with NAFL or NASH at index biopsy (37% vs. 43%, p=0.65). Progression to NASH was seen in 44% of patients with baseline NAFL. Of 10 patients with NAFL who had fibrosis progression, 3 progressed by 1 stage, 5 by 2 stages and 2 by 3 stages; all had NASH on follow-up biopsy. Of concern, 6 of 27 (22%) patients with baseline NAFL, reached stage 3 fibrosis at follow-up biopsy. Among the patients with NAFL, 80% of those having fibrosis progression were diabetic at the follow-up liver biopsy compared with 25% of non-progressors (p=0.005).

Conclusions: Contrary to current dogma, this study suggests that steatosis can progress to NASH and clinically significant fibrosis.