title: De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.
abstract: Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P < 0.001), sdLDL-C to low-density lipoprotein cholesterol ratio (32.6 ± 11.6 versus 24.6 ± 10.2; P < 0.01), small-dense low-density lipoprotein particle concentration (sdLDL-P; 770 ± 440 versus 486 ± 402 nmol/L; P < 0.01), very low density lipoprotein particle concentration (VLDL-P; 7.90 ± 7.91 versus 3.86 ± 3.18 nmol/L; P < 0.01), and very low density lipoprotein size (VLDL-size; 51.9 ± 6.4 versus 48.7 ± 6.3 nm; P = 0.06). LTRs with hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P < 0.01) but similar fasting glucose and hemoglobin A1c. Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors.
authors.affiliation: Departments of Pathology.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Ravi
authors.initials: R
authors.lastname: Chhatrala
authors.affiliation: Department of Internal Medicine, University of Texas Medical School, Houston, TX.
authors.forename: M Bilal
authors.initials: MB
authors.lastname: Siddiqui
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Driscoll
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Transplant Surgery, Virginia Commonwealth University, Richmond, VA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Bhati
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Carol
authors.initials: C
authors.lastname: Sargeant
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.affiliation: Departments of Pathology.
authors.forename: Melissa
authors.initials: M
authors.lastname: Contos
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Scott
authors.initials: S
authors.lastname: Matherly
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: Puneet
authors.initials: P
authors.lastname: Puri
authors.affiliation: Gastroenterology, Hepatology, and Nutrition.
authors.forename: M Shadab
authors.initials: MS
authors.lastname: Siddiqui
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D015992:Body Mass Index; D008078:Cholesterol, LDL / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D066027:Transplant Recipients; D014768:Virginia / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D008074:Lipoproteins