Shaded areas adjacent to curves indicate 95% CIs. Data are based on 34 423 individuals in NHANES surveys.
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Wong T, Dang K, Ladhani S, Singal AK, Wong RJ. Prevalence of Alcoholic Fatty Liver Disease Among Adults in the United States, 2001-2016. JAMA. 2019;321(17):1723–1725. doi:10.1001/jama.2019.2276
Alcoholic liver disease (ALD), comprising a spectrum of diseases ranging from alcoholic fatty liver disease (AFLD) to advanced ALD (including alcoholic hepatitis, cirrhosis, and cirrhosis complications),1 is a leading cause of mortality in the United States, with nearly 250 000 deaths attributed to ALD in 2010.2,3 Overall US clinical burden of ALD remains unclear, perhaps because of lack of a definitive standard for identifying ALD. This study focused on the specific, more well-defined subset of AFLD to estimate national prevalence among US adults.
We used the 2001-2016 National Health and Nutrition Examination Survey (NHANES) data set, a series of cross-sectional, nationally representative surveys of the noninstitutionalized US population, including in-person interviews and health examinations in mobile examination centers. The NHANES 2001-2016 overall response rate was 70.3% (range, 60.7%-78.3%) for interviews and 67.2% (range, 58.1%-72.7%) for examinations. AFLD was identified based on alcohol use (>28 g/d in women and >42 g/d for men in the past 12 months) and elevated liver enzyme levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >25 U/L [0.42 μkat/L] in women and >35 U/L [0.58 μkat/L] in men), in the absence of elevated total bilirubin level (<3 mg/dL [51.3 μmol/L]) and after excluding hepatitis C and hepatitis B infections.1 Individuals with metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III4 criteria) were excluded given associated increased risks of nonalcoholic fatty liver disease. Hepatic fibrosis was assessed using an AST-to-platelet ratio index ([AST/upper limit of normal for AST]/platelet count) greater than 0.7 (stage ≥2 fibrosis) and Fibrosis-4 score ([age × AST]/[platelet count × ALT½]) greater than 2.67 (stage ≥3 fibrosis), which represent standard definition cutoffs of well-validated tools for assessing hepatic fibrosis.
Multivariable logistic regression with appropriate sample weights was used to derive AFLD prevalence. Linear trends in prevalence were analyzed using orthogonal polynomial contrasts. Interaction terms were included in logistic regression models to assess whether prevalence changes differed by sex, age, and race/ethnicity. Missing data, ranging from less than 1% to 15%, were addressed using multivariable imputation by chained equations, which included relevant demographic and clinical covariates. Two-tailed P < .05 indicated statistical significance (Stata version 14.0 [StataCorp]). The Alameda Health System institutional review board granted exempt status and waiver of informed consent.
Among 34 423 respondents included, 4.3% were identified with AFLD (60.6% men; 63.0% non-Hispanic white; mean age, 40.2 years). From 2001-2002 to 2015-2016, AFLD prevalence remained stable from 4.3% (95% CI, 3.5%-5.0%) to 4.7% (95% CI, 4.2%-5.1%) (P = .69), AFLD with stage 2 or greater fibrosis increased from 0.6% (95% CI, 0.5%-0.8%) to 1.5% (95% CI, 1.3%-1.8%) (P < .001), and AFLD with stage 3 or greater fibrosis increased from 0.1% (95% CI, 0.02%-0.10%) to 0.2% (95% CI, 0.2%-0.4%) (P = .045) (Figure). Changes in prevalence over time did not differ by sex, age, or race/ethnicity, and no significant interactions were observed across all variables (Table).
The prevalence of AFLD among US adults remained stable from 2001 to 2016, affecting 4.7% of adults in 2015-2016. However, the prevalence of AFLD with stage 2 or greater fibrosis and AFLD with stage 3 or greater fibrosis increased significantly, affecting 1.5% and 0.2% of adults, respectively, in 2015-2016. This is a particularly concerning observation given that developing fibrosis is the strongest predictor of progression to cirrhosis, liver cancer, and death.5 While studies evaluating national ALD prevalence are lacking, existing studies have demonstrated increasing burden of ALD in population subsets. For example, among patients with end-stage liver disease, ALD became the leading indication for US liver transplants in 2016,6 and a 2018 US population-based study demonstrated increasing cirrhosis death rates largely driven by alcoholic cirrhosis, particularly among individuals aged 25 to 34 years.3
Limitations include the challenges in accurately identifying AFLD using observational data, which may have been affected by misclassification. Noninvasive serologic markers of fibrosis used in this study are well validated, but not specifically for AFLD. The increasing prevalence of US adults with AFLD with stage 2 or greater fibrosis and AFLD with stage 3 or greater fibrosis is concerning and emphasizes the need for greater awareness of unhealthy alcohol use and need for early prevention and intervention efforts.
Accepted for Publication: February 19, 2019.
Corresponding Author: Robert J. Wong, MD, MS, Division of Gastroenterology and Hepatology, Alameda Health System–Highland Hospital, 1411 E 31st St, Highland Care Pavilion Fifth Floor, Oakland, CA 94602 (Rowong@alamedahealthsystem.org).
Author Contributions: Dr R. J. Wong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr T. Wong and Ms Dang were co–first authors.
Concept and design: T. Wong, Ladhani, R. J. Wong.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: T. Wong, Dang, Singal, R. J. Wong.
Critical revision of the manuscript for important intellectual content: T. Wong, Dang, Ladhani, R. J. Wong.
Statistical analysis: T. Wong, Dang, R. J. Wong.
Administrative, technical, or material support: T. Wong, Dang.
Supervision: T. Wong, Dang, Singal, R. J. Wong.
Conflict of Interest Disclosures: Dr R. J. Wong reported serving on an advisory board for Gilead; serving on speakers bureaus for Gilead, Salix, and Bayer; and receiving research grants form Gilead and AbbVie. No other disclosures were reported.
Funding/Support: Dr R. J. Wong is supported by an American Association for the Study of Liver Diseases (AASLD) Foundation Clinical and Translational Research Award in Liver Diseases.
Role of the Funder/Sponsor: The AASLD Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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