Severe fibrosis, not NAS, predicted disease-specific mortality in NAFLD

WASHINGTON — Patients with more advanced fibrosis were at greater risk for cardiovascular- and liver-related death, while elevated nonalcoholic fatty liver disease activity score did not have as significant an impact on mortality in a cohort study presented at The Liver Meeting.

Researchers assessed the incidence of all-cause and disease-specific mortality in a cohort of 229 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), with each patient compared with 10 matched controls. Patients underwent follow-up for a mean of 26.4 years, and all had liver biopsy.

Death, including those from cardiovascular disease (CVD; n=41) and extrahepatic malignancy (n=22), occurred in 96 patients with NAFLD during follow-up.

No significant difference in mortality risk was observed among patients with NAFLD compared with controls (HR=1.26; 95% CI, 1-1.6). Risk for cardiovascular-related mortality (HR=1.5; 95% CI, 1.1-2.2), however, and death due to infection (HR=2.7; 95% CI, 1.7.3), cirrhosis (HR=3.2; 95% CI, 1.-9.8) or hepatocellular carcinoma were significantly elevated in this population.

In subgroup analysis of patients with low NAFLD activity score (NAS) and less severe fibrosis (stage 0 to 2), no significant increase in overall mortality or death due to any specific causes was observed. In patients with high NAS and low fibrosis, a significant increase was observed for HCC risk (HR=15.7; 95% CI, 4.1-59.9) and death due to respiratory issues (HR=3.9; 95% CI, 1.2-13), although the investigators said they were unable to control for smoking.

Among patients with more severe fibrosis (stage 3 to 4), significant risk increases for overall mortality (HR=3.7; 95% CI, 2.4-5.7) and death due to HCC (HR=16.9; 95% CI, 1.9-145.6) and CVD (HR=4.6; 95% CI, 2.3-8.3) were observed compared with controls. Risk for death due to infection, cirrhosis and extrahepatic malignancy also were significantly elevated in this subgroup.

“In this cohort, the fibrosis stage was of greater importance than NAS for prediction of overall and disease-specific mortality,” Hannes Hagström, MD, department of gastroenterology and hepatology at the Institution of Medicine, Huddinge, Karolinska Institutet in Stockholm, said. “Often, we use the NAS in pharmacological studies; we focus on a reduction in that instead of fibrosis stage. Maybe we should look more on fibrosis stage as an endpoint in pharmacological studies.”

Disclosure: Hagström reports no relevant financial disclosures.

For more information:

Ekstedt M. LB-5: Late-Breaking Abstract Session: Fibrosis Stage, but not NAS, Is Predictive for Disease-specific Mortality in NAFLD After 33 Years of Follow-up. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.