Co-Morbidities as a Predictor for Progression of Non-Alcoholic Fatty Liver Disease

Abstract

Introduction: Greater than 64 million people in the US have Non-alcoholic fatty liver disease (NAFLD), constituting an economic burden of more than $100 billion annually in healthcare costs. Though metabolic syndrome is a major risk factor, there remains uncertainty about the natural history of disease and the interplay of major comorbidities. A better understanding of the progression from NAFLD to nonalcoholic steatohepatitis (NASH) and cirrhosis has major implications for healthcare cost, screening recommendations, evaluation and treatment. Methods: Retrospective review of outpatients between 2008 and 2016 using ICD-9 and ICD-10 codes. Over 500 patients with NAFLD were identified. Those without liver biopsy or incomplete data were excluded. Biopsies were categorized based on the NAFLD activity score (NAS) which is the unweighted sum of the grade of steatosis, lobular inflammation and hepatocellular ballooning. NAS score of 0-2 was classified as non-NASH, 3-4 as borderline steatohepatitis and 5-8 as NASH. Patients with cirrhosis were excluded as NAS is not an accurate representation of severity of liver disease in this population and cirrhotics tend to have low NAS. Chi-square was used for categorical values and analysis of variance (ANOVA) was used for numerical values. Results: 114 patients were available for review. 60.5% were female, mean age (SD): 54 (12), and 82.4% Caucasian. There was no statistical difference in age, gender, BMI or ethnicity among the three groups. Final analysis revealed a distribution of non-NASH, borderline steatohepatitis and NASH in 8 (70%), 59 (51.7%) and 47 (41.2%), respectively. Polycystic ovarian syndrome (PCOS) and Coronary Artery Disease (CAD) were seen in 4.4% and 1.8% of the population. NAFLD patients with CAD, gallstone disease, obstructive sleep apnea (OSA) and PCOS were more likely to have borderline steatohepatitis or NASH (p < 0.05). Conclusion: Our data suggests that gallstone disease, CAD, OSA, and PCOS, all diseases related to obesity, may have implications in predicting risk for progression of NAFLD to NASH. Evolving our understanding of NAFLD will help mitigate disease progression to fibrosis and cirrhosis, and to target patients at higher risk for developing NASH. NAFLD is a major cause of chronic liver disease worldwide, and its clinical and economic burden will continue to grow with parallel increases in rates of obesity and metabolic syndrome. Further evaluation with a larger dataset, at multiple institutions, is warranted to validate our results.