https://gastroenterology.acponline.org/archives/2021/10/22/3.htm

NAFLD progression associated with increased mortality risk

Patients with stage F4 nonalcoholic fatty liver disease (NAFLD) have significantly increased risk for liver-related complications, type 2 diabetes, and all-cause mortality compared to those with earlier stages, an observational prospective study found.


A new study offered information about the prognosis for patients with nonalcoholic fatty liver disease (NAFLD).

The prospective study followed 1,773 adults with NAFLD for a median of four years. It found that all-cause mortality increased with increasing fibrosis stage, from 0.32 death per 100 person-years for stage F0 to F2 (no, mild, or moderate fibrosis) to 0.89 and 1.76 deaths per 100 person-years for stage F3 (bridging fibrosis) and stage F4 (cirrhosis), respectively. The incidence of liver-related complications followed a similar pattern, increasing from F0 to F2 versus F3 and F4 as follows: variceal hemorrhage (0.00 vs. 0.06 and 0.70), ascites (0.04 vs. 0.52 and 1.20), encephalopathy (0.02 vs. 0.75 and 2.39), and hepatocellular cancer (0.04 vs. 0.34 and 0.14).

The study also found that stage F4 fibrosis was associated with higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years in stage F0 to F2 fibrosis) and estimated glomerular filtration rate decline of more than 40% (2.98 vs. 0.97 events per 100 person-years in stage F0 to F2). Incidence of cardiac events and nonhepatic cancers did not differ significantly across fibrosis stages. However, after adjustment for age, sex, race, diabetes status, and baseline histologic severity, any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality risk (adjusted hazard ratio, 6.8; 95% CI, 2.2 to 21.3).

The findings could be useful in assessing clinical trials of therapeutic agents for NAFLD, particularly the indication that improvement from F3 to F2 fibrosis may translate to fewer hepatic decompensation events, the study authors said. They observed that the rate of all-cause mortality in the studied NAFLD population was higher than would be expected in the general population based on age (0.57 vs. 0.4 death per 100 person-years). They noted that the study did not find a statistically significant difference in mortality risk between patients with stage F2 fibrosis compared with those with stage F0 or F1 (hazard ratio, 2.3; 95% CI, 0.8 to 7.0), which differed from some previous retrospective studies, according to an accompanying editorial.

The editorial called this “one of the largest observational prospective studies of histologically characterized nonalcoholic fatty liver disease.” Limitations include the fact that 85% of the patients were White. The study and editorial were published by the New England Journal of Medicine on Oct. 21.