S1411 Gender Disparities in Extrahepatic Manifestations Among NAFLD Patients

Introduction: Non-alcoholic fatty liver disease (NAFLD) has been an emerging concern in recent years due to increasing incidence which reached 25% of the general population. Although recent publications shed light on gender differences in this patient population, we still face many limitations in elucidating them. NALFD can cause significant morbidity as it progresses to nonalcoholic steatohepatitis (NASH), which increases the risk of cirrhosis and liver failure. Gaining a deeper understanding of these disparities will aid in developing targeted prevention strategies and personalized therapeutic interventions for NAFLD. In this study, we aim to elucidate extrahepatic differences between males and females who were diagnosed with NAFLD. Methods: We conducted a retrospective cohort study using the TrinNetX, a multi-institutional database. The study included all adult patients aged 18 years or older diagnosed with NAFLD using International Classification of Diseases-10th Edition (ICD-10) codes. The study population was divided into 2 groups based on gender. Data on extrahepatic manifestations were gathered. We excluded patients with alcoholic liver disease, drug induced liver injury, autoimmune hepatitis, viral hepatitis, and cirrhosis. We employed 1:1 propensity score matching for age, race, tobacco use, obesity, diabetes, and alcohol abuse. Results: Before matching, we identified 526,493 females and 425,799 males with NAFLD. After appropriate matching, 402,454 patients were included in each arm. The presence of the following was lower in females when compared with male patients with NAFLD: chronic kidney disease (CKD) (OR 0.71), obstructive sleep apnea (OSA) (OR 0.68), Esophageal cancer (OR 0.24), Gastric cancer (OR 0.52), Colon cancer (OR 0.79), HCC (OR 0.74), Myocardial infarction (MI) (OR 0.60), and Heart failure (HF) (OR 0.71). Contrarily, the following were found to be more prevalent in female patients with NAFLD when compared with males: COPD (OR 1.04), general anxiety disorder (GAD) (OR 1.92), Depression (OR 1.95), Hypothyroidism (OR 2.86), Osteoporosis (OR 5.16) and Sarcopenia (OR 1.13). No significant gender differences were noted in psoriasis and pancreatic cancer among patients with NAFLD. Conclusion: Patients with NAFLD show significant difference in prevalence of extrahepatic manifestations with regards to gender. Clinicians must be aware of the gender disparities among NAFLD patients and appropriate screening should be applied. Future studies are needed to understand the mechanisms underlying these differences (Figure 1, Table 1).Figure 1.: Gender disparities of extra-hepatic manifestations in Females vs Males patients with NAFLD. Odds ratio represents odds of Females with NAFLD compared to odds of Males with NAFLD. Abbreviations: OR: odds ratio, CI: confidence interval, CKD: chronic kidney disease, OSA: obstructive sleep apnea, COPD: chronic obstructive pulmonary disease, GAD: general anxiety disorder, HCC: Hepatocelluliar carcinoma, MI: myocardial infarction, HF: heart failure. Table 1. - Comparison of Demographic Parameters between Male vs Female patients with NAFLD before propensity score matching Demographics Before propensity score matching Female with NAFLD (526,493) Male with NAFLD (423,433) P value Age 51.8 +/- 15.7 50.7 +/- 15.9 < 0.001 White 321,574 266,006 < 0.001 Black 54,020 33,411 < 0.001 Comorbidities Tobacco use 16,687 (3.2%) 15,784 (3.7%) < 0.001 Alcohol abuse 12,227 (2.3%) 24,476 (5.8%) < 0.001 BMI 30-39 57,483 (11.0%) 40,947 (9.7%) < 0.001 BMI >40 48,669 (9.3%) 20,742 (4.9%) < 0.001 HTN 212,710 (40.7%) 173,324 (40.9%) < 0.001 HLD 184,360 (35.2%) 153,802 (36.3%) < 0.001 NAFLD: Non-alcoholic fatty liver disease; HTN; Hypertension; HLD: Hyperlipidemia.