Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver diseases worldwide with an overall prevalence of ~25%. NAFLD contributes to an increased overall mortality by 57%, mainly from liver and cardiovascular causes. Some studies have shown a potentially faster progression of NAFLD and higher fibrosis rates among smokers. Our aim is to investigate the prevalence of NAFLD among smokers, assessing whether it's independently associated with worse liver related outcomes.
Methods: We utilized a large multicenter database (Explorys Inc., Cleveland, OH, USA) of aggregated inpatient and outpatient electronic health records of 26 healthcare systems, total of 360 hospitals and more than 70 million patients across the US. A cohort of patients with a SNOMED-CT diagnosis of “Non-Alcoholic Fatty Liver” between 1999-2021 was identified. A second cohort of patients with active smoking and NAFLD was then identified. We excluded patients age < 18 years, and those with viral hepatitis, hemochromatosis, Wilson’s disease, biliary cirrhosis, alcoholic cirrhosis, cystic fibrosis, alpha-1-antitrypsin deficiency, and autoimmune hepatitis. Statistical Package for Social Sciences was used for analysis, and for all analyses, a 2-sided p-value of < 0.05 was considered statistically significant. Multivariate analysis was performed to adjust for age, gender, ethnicity, cirrhosis, hepatocellular carcinoma, esophageal varices (EV) and metabolic syndrome.
Results: Among the 79,798,670 screened individuals, a total of 3020 patients with NAFLD were identified, with prevalence rate of 4 per 100,000. Among these, 6.2% had NAFLD-related cirrhosis. Baseline characteristics of study population is shown in Table 1. Compared to non-smokers, patients with smoking history were more likely to develop NAFLD (OR 3.90), and related cirrhosis (OR 1.97). Among patients with NAFLD-cirrhosis, smokers were more likely to have EV (OR 4.30). Smoking history had a higher risk association with hepatocellular carcinoma but was not statistically significant Figure 1.
Discussion: This is the largest study to date to evaluate the impact of smoking on NAFLD. Smoking was significantly associated with the development of NAFLD, NAFLD-cirrhosis, and EV compared to those without.
