Abstract 5062A: Non-alcoholic fatty liver disease and increased risk of mortality in NHANES III: Results after 27 years follow-up
Authors: Alvarez Christian S. , Graubard Barry I. , Thistle Jake E. , Petrick Jessica L. , McGlynn Katherine A. 
Published: August 2019

Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the US. It encompasses a range of conditions from hepatic steatosis to cirrhosis and liver cancer. Prior studies of the association between NAFLD and mortality have been limited by fairly short follow-up times, proxy measures of NAFLD and relatively few outcome events. Thus, the current study examined the association of NAFLD with all-cause and cause-specific mortality in the Third National Health and Nutrition Examination Survey (NHANES III) conducted in 1988-1994, with mortality follow-up through 2015.
Methods: The analysis included 12605 individuals aged 20-74 years who underwent a hepatic/gallbladder ultrasound examination in NHANES III. NAFLD was defined as mild to severe hepatic steatosis detected by ultrasound in the absence of high alcohol consumption. Individuals were followed up for mortality by linkage to the National Death Index. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cause-specific mortality by NAFLD status as well as by a fibrosis score after adjustment for age, gender, race/ethnicity, education, physical activity, smoking, moderate alcohol consumption and body mass index.
Results: The prevalence of NAFLD in the study was 33% and a total of 3,843 deaths occurred. More than 50% of the deaths were due to either cardiovascular disease (CVD) (34.2%) or cancer (18.7%). In addition, there were 83 (2.2%) deaths related to liver disease, including liver cancer. The risks of all-cause and cause-specific mortality were higher among persons with NAFLD than among persons without NAFLD: all-cause mortality [HR:1.22, 95%CI:1.10,1.36]; CVD [HR:1.12, 95%CI:0.96,1.31]; cancer [HR:1.34, 95%CI:1.04,1.72]; liver disease [HR:3.03, 95%CI:1.58,5.82]; kidney disease [HR:2.22, 95%CI:1.09,4.51]; diabetes [HR:2.55, 95%CI:1.48,4.39]. The risks of mortality from all-causes [HR:1.52, 95%CI:1.11,2.07], and from liver disease [HR:6.08, 95%CI:1.79,20.66] were markedly higher among persons with NAFLD with elevated liver enzymes than among persons without NAFLD. Among persons with NAFLD, a higher liver fibrosis score was significantly associated with increased risks of all-cause and liver disease mortality compared to those with lower fibrosis score: [HR:1.59, 95%CI:1.09,2.31] and [HR:17.08, 95%CI:4.08,71.56], respectively.
Conclusions: Persons with NAFLD had an increased risk of all-cause and certain types of cause-specific mortality, independent of sociodemographic and lifestyle risk factors after 27 years of follow-up. Elevated liver enzymes as well as a higher fibrosis score among persons with NAFLD further increased the risk of all-cause and liver disease mortality. Persons with NAFLD should be closely monitored to prevent disease progression and reduce the risk of mortality in the US population.
Citation Format: Christian S. Alvarez, Barry I. Graubard, Jake E. Thistle, Jessica L. Petrick, Katherine A. McGlynn. Non-alcoholic fatty liver disease and increased risk of mortality in NHANES III: Results after 27 years follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5062A.