Depression Is Associated With Non-alcoholic Fatty Liver Disease Among Adults in the United States

Donghee Kim; Eric R. Yoo; Andrew A. Li; Sean P. Tighe; George Cholankeril; Stephen A. Harrison; Aijaz Ahmed


Aliment Pharmacol Ther. 2019;50(5):590-598. 

In This Article

Abstract and Introduction


Background: Currently, the relationship between depression and non-alcoholic fatty liver disease (NAFLD) is not clearly defined.

Aim: To determine whether depression is associated with NAFLD and NAFLD-related advanced fibrosis in a large population sample.

Methods: We performed a cross-sectional analysis using the 2007-2016 National Health and Nutrition Examination Survey database among adults (20 years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ-9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis-4 score.

Results: Of the 10 484 subjects (mean age 47.0 years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6-2.2-fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17-1.87), HSI (OR 1.51 95% CI 1.04-2.19) and FLI (OR 2.01 95% CI 1.65-2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD-related advanced fibrosis.

Conclusions: In a nationally representative sample of US adults, depression was independently associated with NAFLD.


Currently, non-alcoholic fatty liver disease (NAFLD) is recognised as the most prevalent chronic liver disease in the United States (US) and the world.[1,2] Not surprisingly, a recent study showed that NAFLD-related advanced fibrosis is on the rise at an accelerated pace in American adults,[3] which may result in increased overall mortality and cause-specific death.[4,5] Another study based on a national US mortality database reported an increase in mortality rate from NAFLD from an annual rate of 6.1% in 2007-2013 to 11.3% in 2013-2016.[6] These are particularly ominous trends, especially in the absence of approved pharmacologic therapy for NAFLD. There is a clear need to better understand modifiable risk factors for NAFLD and NAFLD-associated advanced fibrosis to reduce the disease burden and associated healthcare costs.

According to the Global Burden of Disease 2015, depression was estimated to be the world's third leading cause of disability.[7] In the US, the estimated 12-month and lifetime prevalence of a major depressive episode were 8.6% and 29.9% respectively.[8] The economic burden of major depressive disorder in the US steadily increased from $173 billion in 2005 to $210 billion in 2010, with comorbidities associated with depression accounting for a substantial portion of costs.[9] Depression has been associated with obesity, metabolic syndrome, diabetes and cardiovascular diseases,[10,11] with increased predisposition for NAFLD. Depression and NAFLD share several risk factors, including but not limited to abdominal obesity, diabetes and chronic systemic inflammation.[12] However, past studies looking at the association between depression and NAFLD have yielded inconsistent results, varying from a strong association[13] to no association.[14,15] Several studies in patients with biopsy-proven NAFLD have linked depression with non-alcoholic steatohepatitis (NASH),[16] hepatocyte ballooning,[17] hepatic steatosis[18] and NAFLD activity score,[18] but these studies had limitations, including small sample size, possible confounders and variation in the definition of depression. Currently, it remains unclear whether depression affects NAFLD via modification of shared risk factors or whether the presence of depression alone has clinical significance on NAFLD and associated advanced fibrosis. Therefore, we aimed to determine the independent associations between depression and NAFLD in the general US population. Furthermore, our study aimed to investigate whether depression is associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors.