1Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115.
2LipoScience, Laboratory Corporation of America Holdings, Raleigh, NC, 27616.
3Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115.
4Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115.
A major challenge in the management of nonalcoholic fatty liver disease (NAFLD) is to identify patients with nonalcoholic steatohepatitis (NASH) and early liver fibrosis. The progression of NAFLD is accompanied by distinctive changes in very low density lipoprotein (VLDL), a lipoprotein particle produced exclusively in the liver. Herein, we sought to determine the characteristics of VLDL profiles associated with NASH and liver fibrosis.
We evaluated VLDL profiles of128 patients from a single center NAFLD registry, and examined VLDL size, total and subclass VLDL concentrations in relation to NAFLD activity score (NAS), steatohepatitis and liver fibrosis as determined by liver biopsy.
A near linear relationship was observed between mean VLDL particle size and NAFLD activity score (NAS). In multivariate models, VLDL particle size was significantly associated with both NAS and NASH, after adjustment for BMI and diabetes. A decrease in small VLDL particle concentration was associated with more advanced liver fibrosis. In receiver operative characteristic analyses, mean VLDL size performed similarly to cytokeratin 18 in predicting NASH, whereas small VLDL particle concentration had similar performance to NAFLD fibrosis score in predicting stage 2 or above liver fibrosis.
The increase in mean VLDL size in NASH and decrease in small VLDL particle concentration in liver fibrosis likely reflect the changes in the number and state of hepatocytes associated with NASH and fibrosis. In addition to its value in risk stratification of cardiovascular diseases, circulating VLDL profile may provide information for the staging of NAFLD disease severity.