All-Cause and Liver-Related Mortality Tied to Fibrosis Stage in NAFLD, NASH

Microscopic photo of a professionally prepared slide demonstrating macrovesicular steatosis of the liver (fatty liver disease), hepatic steatosis, metabolic syndrome. Can be ssociated with nonalcoholic fatty liver disease (NAFLD) or Alcoholic Liver Disease (ALD). H&E stain.
Estimates are provided for all-cause and liver-related mortality in nonalcoholic fatty liver disease (NAFLD) in various fibrosis stages.

Risk for liver-related and all-cause mortality increases significantly with liver fibrosis stage, according to results from a study published in Clinical Gastroenterology and Hepatology.

Investigators at the National University of Singapore searched publication databases through November of 2021 for studies of mortality outcomes in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Nonclinically significant fibrosis was defined as stages 0 and 1, nonadvanced fibrosis as stages 0 to 2, early fibrosis as stages 1 and 2, clinically significant fibrosis as stages of 2 or more, and advanced fibrosis as stages of 3 or more.

A total of 14 articles comprising 17,301 patients met the inclusion criteria. Patients were mean aged 50.5 (95% CI, 49.1-51.8) years and 52.1% were men.

All-cause mortality was evaluated in 6069 patients. In nonadvanced fibrosis, the 1-, 3-, 5-, 8-, and 10-year mortality rates were .1%, 1.9%, 3.3%, 6.0%, and 7.7%; for clinically significant fibrosis the rates were .3%, 8.4%, 14.0%, 23.7%, and 29.3%; for advanced fibrosis the rates were .3%, 8.8%, 14.9%, 25.5%, and 32.2%; and in cirrhosis were .3%, 13.0%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with fibrosis stage 0, mortality risk was significantly higher among patients with stages 2 (hazard ratio [HR], 1.46; 95% CI, 1.08-1.98; P =.01), 3 (HR, 1.96; 95% CI, 1.41-2.72; P <.01), and 4 (HR, 3.66; 95% CI, 2.65-5.05; P <.01) fibrosis, the researchers noted.

No significant associations with age, BMI, smoking status, hypertension, or diabetes were observed.

In a sensitivity analysis of patients with NASH (n=853), mortality risk was significantly higher among patients with fibrosis stage 4 compared with stage 3 (HR, 5.08; 95% CI, 2.70-9.55; P <.01).

Liver-related mortality was evaluated in 3421 patients. Compared with stage 0, liver-related mortality was increased among patients with stages 2 (HR, 4.07; 95% CI, 1.44-11.5; P <.01), 3 (HR, 7.59; 95% CI, 2.80-20.5; P <.01), and 4 (HR, 15.1; 95% CI, 5.27-43.4; P <.01) fibrosis.

The major limitation of this analysis was the small sample size for the liver-related mortality outcome.

This study found that in patients with NAFLD and NASH, risk for all-cause and liver-related mortality increased with fibrosis stage, highlighting the need for developing cirrhosis-preventing therapeutic agents.


Ng CH, Lim WH, Lim GEH, et al. Mortality outcomes by fibrosis stage in non-alcoholic fatty liver disease. A systematic review and meta-analysis. Clin Gastroenterol Hepatol. Published online May 2, 2022. doi:10.1016/j.cgh.2022.04.014