Non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in Western countries, affecting a staggering 20-25% of the adults. Nearly one-third of patients with NAFLD develop progressive steatohepatitis (non-fibrotic steatohepatitis (NASH)) and fibrosis, which can lead to cirrhosis, decompensated liver disease and death. It has been suggested that among patients with NAFLD, advanced liver fibrosis, rather than inflammatory NASH, is the most important histological predictor of survival. Accordingly, current guidelines recommend that patients with NAFLD undergo risk stratification according to the presence or absence of significant fibrosis on the liver biopsy. However, there are no robust, population-level data to support this recommendation. Therefore, the authors have performed a nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD between 1966 until 2017. This resulted in 10 568 subjects. Over a median of 14.2 years, 4,338 of these NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 per year). Significant excess mortality risk was observed with simple steatosis (8.3/1000 per year), non-fibrotic NASH (13.4/1000 per year), non-cirrhotic fibrosis (18.4/1000 per year) and cirrhosis (53.6/1000 per year). The excess mortality associated with NAFLD was primarily from extrahepatic cancer, followed by cirrhosis, cardiovascular disease and finally hepatocellular carcinoma.

This study shows clearly that all NAFLD histological stages are associated with significantly increased mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.