Abstract

BackgroundNonalcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD) relative to the general population. We sought to evaluate whether differences in lipoprotein subfractions in obese patients with and without NASH contributes to this difference in CVD risk.FindingsIon mobility analysis was performed on 78 individuals with obesity undergoing weight loss surgery. All individuals had standard of care liver biopsies performed during surgery. Patients with NASH had significantly smaller peak LDL diameter (P = 0.02, 219.0 Å vs. 222.6 Å), and levels of IDL2 (P = 0.01, 104. nmol/L vs. 133.4 nmol/L) and HDL2b (P = 0.05, 676.7 nmol/L vs. 880.1 nmol/L) compared to those without NASH. NASH patients had significantly higher LDL-IVb levels than those without NASH (P = 0.02, 49.0 nmol/L vs. 37.1 nmol/L).The inverse association of LDL peak diameter with NASH remained significant after adjustment for diabetes (P = 0.02). HDL2b levels were inversely correlated with hepatocyte ballooning and NASH and these remained significant after adjustment for diabetes (P = 0.0017 and P = 0.007, respectively). IDL2 levels were inversely correlated with NASH, hepatocyte ballooning and fibrosis stage but these were not significant after adjustment for diabetes.ConclusionsThe lipoprotein subfraction profile in subjects with NASH is characterized by small peak LDL diameter, reduced HDL2b levels and elevated LDL-IVb levels. These changes may contribute to the increased CVD seen in patients with NASH.

Highlights

  • Cardiovascular disease (CVD) is prevalent in individuals with nonalcoholic fatty liver disease (NAFLD)

  • The lipoprotein subfraction profile in subjects with Nonalcoholic steatohepatitis (NASH) is characterized by small peak low density lipoprotein (LDL) diameter, reduced HDL2b levels and elevated LDL-IVb levels

  • Diabetes mellitus and hyperlipidemia were more prevalent in NASH patients than in non-NASH patients (P = 0.03, 50.0% vs. 25% and P = 0.02, 54.1% vs. 26.9%, respectively)

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Summary

Introduction

Cardiovascular disease (CVD) is prevalent in individuals with nonalcoholic fatty liver disease (NAFLD). Individuals with histologically defined nonalcoholic steatohepatitis (NASH) have been shown to have an increased CVD mortality when compared to the general population [4,5]. Individuals with both radiographic NAFLD and histologically defined NASH are at increased risk for CVD and CVD-related mortality. We hypothesized that IM would reveal important differences in the lipoprotein subfraction profiles of individuals with obesity with and without NASH that may contribute to the increased CVD seen in NASH. Nonalcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD) relative to the general population. We sought to evaluate whether differences in lipoprotein subfractions in obese patients with and without NASH contributes to this difference in CVD risk

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