Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in many countries. There remains considerable uncertainty about natural history and prognosis. Few studies, totalling <400 patients, have examined the evolution of steatosis/steatohepatitis and fibrosis of NAFLD in patients with paired biopsies. In general it is thought that fibrosis progression in patients with “NAFL” (steatosis +/- mild inflammation) is uncommon, whereas non-alcoholic steatohepatitis (NASH; steatosis + hepatocyte ballooning and inflammation) more frequently progresses. Our aim was to assess the histological severity of NAFLD in a cohort with serial liver biopsy data and to determine clinical factors that predict fibrosis progression.

Methods Patients with 2 liver biopsies >1 year apart were identified from the Newcastle Hospitals NAFLD clinic. Clinical and laboratory data were collected from the time of liver biopsy.

Results 108 patients (mean age 48 ± 12 years; 66% male; 48% diabetic) were identified with ≥2 liver biopsies (median interval 6.6 years, range 1.3–22.6). 81 (75%) patients had NASH and 27 patients with NAFL. Overall 45 (42%) patients had progression of fibrosis, 43 (40%) had no change in fibrosis, while 20 (18%) had fibrosis regression. The mean rate of fibrosis was 0.08 ± 0.25 stages/year overall, increasing to 0.29 ± 0.24 stages/year in progressors. Importantly, no significant difference in the proportion exhibiting fibrosis progression was found between those with NAFL or NASH at index biopsy (10/27 (37%) vs. 36/83 (43%) p = 0.65). 12/27 (44%) with NAFL at baseline progressed to NASH at follow-up biopsy, whereas 6/75 (8%) with NASH regressed to NAFL. Weight change was a significant factor associated with inter-biopsy change in disease activity measured by NAFLD activity score (r_s,=0.23 p = 0.026). 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 the follow-up biopsy. Of concern, 6 of 27 (22%) patients with baseline NAFL had reached stage 3 fibrosis at the follow up biopsy, but none were cirrhotic. Among the patients with NAFL, 80% of those who had fibrosis progression were diabetic at the time of follow-up liver biopsy compared with 25% of non-progressors (p = 0.005). The FIB-4 score was the only significant baseline factor that predicted fibrosis progression (OR 2.1 [95% CI: 1.1–3.9], p = 0.02). However, the AUROC was only 0.63 (p = 0.04).

Conclusion Contrary to current dogma, this study suggests that NAFL is not entirely benign and has the potential to progress to NASH and clinically significant fibrosis, particularly if patients develop diabetes.

Disclosure of Interest None Declared.