Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD

Background and AimsLong-term studies of the prognosis of nonalcoholic fatty liver disease (NAFLD) are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.MethodsWe conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to ten reference individuals from the general population (n = 12,529). Major adverse liver outcomes (MALO) were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.ResultsMALO occurred in 111 (8.8%, incidence rate (IR) = 5.9/1,000 person-years (PYs)) patients with NAFLD and 197 (1.6%, IR = 1.0/1,000 PYs) reference individuals during a median follow-up of 13 years. The rate of MALO was higher in patients with NAFLD (HR=6.6; 95%CI=5.2-8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without nonalcoholic steatohepatitis. The twenty-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at ten years).ConclusionsThis study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.