Later Stage Fibrosis Linked to Higher Mortality Rate in NAFLD Patients


There was a higher risk of type 2 diabetes in patients with fibrosis stage F4 compared to patients with stage F0 or F2.

Arun J. Sanyal, MD

Arun J. Sanyal, MD

The mortality rate increases as the fibrosis stage increases for patients with non-alcoholic fatty liver disease (NAFLD).

A team, led by Arun J. Sanyal, Virginia Commonwealth University School of Medicine, identified the all-cause mortality rate of patients with NAFLD across the different fibrosis stages.

Currently the prognosis of mortality and hepatic and nonhepatic outcomes are not well defined across the histologic spectrum of NAFLD. The clinical and histologic spectrum can range from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH).

The Study

In the 72-week multicenter, randomized study, the investigators examined 1773 adult patients with NAFLD across the full histologic spectrum of the disease.

The patients were followed for a median of 4 years and the mean age is 52 years.

The investigators sought outcomes of incidences of death from any cause, hepatic decompensation (clinically apparent ascites, overt encephalopathy, or variceal hemorrhage), a Model for End-stage Liver Disease (MELD) score of 15 or higher, hepatocellular cancer, nonhepatic cancer, cardiovascular events, including myocardial infarction, unstable angina, sudden death, revascularization intervention, and hospitalization for heart failure, and cerebrovascular events, including transient ischemic attack and stroke.

Mortality Rates

Overall, the investigators found all-cause mortality increased as fibrosis stage increased (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]).

This trend was also true for the incidence of liver-related complications per 100 person-years, which increased with fibrosis stage as well (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).

For patients with stage F4 fibrosis, in comparison with patients with stage F0 or F2, there was a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) as well as a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years).

Cardiac events and nonhepatic cancers also had similar incidence rates across the different fibrosis stages.

The investigators also adjusted for age, sex, race, diabetes status, and baseline histologic severity and found the incidence of any hepatic decompensation event, including variceal hemorrhage, ascites, or encephalopathy was linked to increased all-cause mortality (aHR, 6.8; 95% CI, 2.2-21.3).

“In this prospective study involving patients with NAFLD, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death,” the authors wrote.

Approximately 14% of patients with stage F0 or F2 fibrosis have progression to stage F3, while 2% have progression to stage F4 over a mean duration of 4.5 years.

The study, “Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease,” was published online by the New England Journal of Medicine.

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