title: Severity of nonalcoholic fatty liver disease and progression to cirrhosis are associated with atherogenic lipoprotein profile.
abstract: OBJECTIVE
  Nonalcoholic fatty liver disease (NAFLD) is associated independently with increased cardiovascular mortality. Although NAFLD is associated with dyslipidemia, it is not clear whether recently identified markers of cardiovascular risk indicate liver disease progression in patients with histologically confirmed NAFLD. We evaluated an extensive panel of serum markers of cardiovascular risk in nondiabetic patients with histologically proven NAFLD.
  
  
  METHODS
  We performed a case-control study in which we compared serum levels of laboratory markers of cardiovascular risk among 81 nondiabetic subjects with histologically confirmed NAFLD vs lean (N = 81) and obese (N = 81) individuals without NAFLD (based on liver fat score, controls). For ex vivo studies, liver tissues were obtained from subjects undergoing elective cholecystectomy or from a tissue repository.
  
  
  RESULTS
  Subjects with NAFLD had increased serum levels of insulin, triglycerides, and apolipoprotein B; increased size and concentration of very large density lipoprotein particles; increased concentrations of low-density lipoprotein (LDL) particles and small dense LDL (sdLDL) cholesterol, and an increased percentage of sdLDL, compared with controls. Although nonalcoholic steatohepatitis was associated with a worse profile of serum atherogenic markers than NAFLD, these differences did not reach statistical significance. Despite hyperinsulinemia, triglyceride and apolipoprotein B levels, concentrations of LDL particles and LDL cholesterol, and sdLDL-related parameters decreased significantly in patients with cirrhosis. Ex vivo studies showed that patients with NAFLD had increased sensitivity of hepatic triglyceride levels and cholesterol synthesis to insulin, and that sensitivity increased the development of cirrhosis.
  
  
  CONCLUSIONS
  Atherogenic dyslipidemia is related to increased insulin-induced hepatic lipid synthesis in patients with NAFLD. Reduced dyslipidemia in patients with cirrhosis is associated with increased insulin resistance and possibly failed lipid synthesis.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia. Electronic address: mssiddiqui@mcvh-vcu.edu.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Siddiqui
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Division of Surgical Pathology, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Sherry
authors.initials: S
authors.lastname: Boyett
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Carol
authors.initials: C
authors.lastname: Sargeant
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Stravitz
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Puneet
authors.initials: P
authors.lastname: Puri
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Scott
authors.initials: S
authors.lastname: Matherly
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.affiliation: Division of Surgical Pathology, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Contos
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis / Q000150:complications / Q000473:pathology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000473:pathology*
chemical_list: D015415:Biomarkers; D008074:Lipoproteins
keywords: Heart Disease; Metabolic Syndrome; NASH; Obesity; Steatosis