Effects of Additional Risk Factors on the Histopathological Progression of Non-Alcoholic Fatty Liver Disease

Abstract

Purpose: Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of clinical and histological manifestations, ranging from simple steatohepatitis to cirrhosis and end-stage liver disease. NAFLD is strongly associated with hypertension (HTN), type 2 diabetes (DM), and hyperlipidemia (HLD). However, it is unclear whether NAFLD patients with two or more risk factors have advanced forms of liver disease compared to those with one risk factor. Therefore, the purpose of our study was to examine clinical, laboratory, and histological features in biopsy-proven NAFLD patients with two or more risk factors, compared to those with one risk factor, using the nonalcoholic steatohepatitis clinical research network (NASH CRN) scoring system. Methods: A retrospective cohort of patients with biopsy-proven NAFLD were selected from University of Chicago Medical Center (UCMC) pathology database between June 1, 1995 to June 30, 2005. Patients with other chronic liver diseases (Hepatitis B and C, iron over load, drug-induced liver disease, significant alcohol use [>40 g/d in males, >20 g/d in females], and liver transplant) were excluded. Medical records were used to obtain demographic, clinical, and laboratory data. Criteria for HTN, DM, and HLD were based on American Diabetes Association and ATP III. Liver biopsies were scored by a single, blinded pathologist, using the NASH CRN scoring system. Results: Eighteen NAFLD patients had HTN as their only risk factor, 35 had HTN and HLD, and 41 had HTN, DM, and HLD. Data for NAFLD patients with HTN and DM were excluded, due to small sample size (n=6). Relevant demographics and laboratory data are presented in Table 1. NAFLD patients with two and three risk factors had progressively and significantly higher mean NAS compared to NAFLD patients with one risk factor (table 2). In addition, NAFLD patients with three risk factors had significantly higher ballooning and inflammation compared to those with one risk factor (table 2). There were no significant differences in mean fibrosis score. However, there was a trend of higher fibrosis scores in patients with three risk factors, compared to patients with two risk factors.Table 1: Patient demographics and clinical characteristics of NAFLD patients with one, two, and three risk factorsTable 2: Mean histological, NAS, and fibrosis scores for NAFLD patients with one, two, and three risk factorsConclusion: NAFLD patients with two or more risk factors may have progressively worse histopathological features compared to NAFLD patients with one risk factor. There was a trend in advanced fibrosis in patients with three risk factors, compared to two risks factors, although not significant. Clinicians should have a higher index of suspicion for progressive and advanced forms of NAFLD in patents with multiple risk factors. An early liver biopsy should be considered in patients with multiple risk factors. Further well-powered studies are needed to confirm our findings.