Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease

Abstract

Background: The prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.

Methods: We prospectively followed a multicenter patient population that included the full histologic spectrum of NAFLD. The incidences of death and other outcomes were compared across baseline histologic characteristics.

Results: A total of 1773 adults with NAFLD were followed for a median of 4 years. All-cause mortality increased with increasing fibrosis stages (0.32 deaths per 100 person-years for stage F0 to F2 [no, mild, or moderate fibrosis], 0.89 deaths per 100 persons-years for stage F3 [bridging fibrosis], and 1.76 deaths per 100 person-years for stage F4 [cirrhosis]). The incidence of liver-related complications per 100 person-years increased with fibrosis stage (F0 to F2 vs. F3 vs. F4) as follows: variceal hemorrhage (0.00 vs. 0.06 vs. 0.70), ascites (0.04 vs. 0.52 vs. 1.20), encephalopathy (0.02 vs. 0.75 vs. 2.39), and hepatocellular cancer (0.04 vs. 0.34 vs. 0.14). As compared with patients with stage F0 to F2 fibrosis, patients with stage F4 fibrosis also had a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) and a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years). The incidence of cardiac events and nonhepatic cancers were similar across fibrosis stages. After adjustment for age, sex, race, diabetes status, and baseline histologic severity, the incidence of any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality (adjusted hazard ratio, 6.8; 95% confidence interval, 2.2 to 21.3).

Conclusions: In this prospective study involving patients with NAFLD, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; NAFLD DB2 ClinicalTrials.gov number, NCT01030484.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1.. Selection Criteria for Analysis Database.

Patients from the Nonalcoholic Fatty Liver Disease (NAFLD) Database-2 noninterventional registry (DB2) were enrolled along with a subgroup of patients who had previously participated in and completed all study visits for the Farnesoid X Receptor Ligand Obeticholic Acid in Noncirrhotic Nonalcohlic Steatohepatitis (NASH) Treatment (FLINT) trial conducted by the NASH Clinical Research Network. IQR denotes interquartile range.

Figure 2.. Outcomes in NAFLD.

Shown is a Kaplan–Meier time-to-event analysis for patients with early disease (mild fibrosis stage F0 to F2), bridging fibrosis (stage F3), and cirrhosis (stage F4). Data for stages F0 to F2 are combined owing to very few events in the individual stages within this grouping. Numbers shown in parentheses are the number of events within the interval. The number of censored events is the difference between the number at risk at the beginning and at the end of the interval minus the number of events in the interval. Shown are all-cause mortality (Panel A), new-onset clinical decompensation events (variceal bleed, ascites, or encephalopathy) (Panel B), hepatocellular carcinoma (Panel C), and extrahepatic cancer (Panel D). Widths of confidence intervals have not been adjusted for multiplicity and should not be used to infer generalizable effects. Insets show the same data on an enlarged y axis.