Association between postprandial LDL conjugated dienes and the severity of liver fibrosis in NASH
Authors: Giovanni Musso, Maurizio Cassader, Roberto Gambino, Marilena Durazzo, Gianfranco Pagano
Journal: Hepatology (2006)

To the Editor: We read with interest the report by Targher on the association of liver histology with early atherosclerosis in NAFLD, independently of insulin resistance and metabolic syndrome, suggesting atherosclerosis and hepatic injury share common molecular mediators in these patients. Postprandial lipemia has been linked to the magnitude of hepatic fat storage in NASH.2-4 The postprandial phase is regarded as atherogenic in diabetes and recent experimental evidence suggests postprandial LDL may be even more atherogenic that the same lipoprotein in fasting conditions,5 an effect possibly mediated by postprandial lipid peroxidation. The magnitude of postprandial Tg, FFA and LDL conjugated dienes (measured by capillary electrophoresis as markers of lipid peroxidation) responses on a 10-hour oral fat load test was correlated to dietary habits, serum adipokines (adiponectin, TNF-α, leptin and resistin) and liver histology in 24 non-obese non-diabetic patients with biopsy-proven NASH and in 24 healthy controls matched for age (39 ± 2 vs. 37 ± 2 yr), sex (M/F: 20/4 vs. 21/3), BMI (25.2 ± 0.4 vs. 25.2 ± 0.6 kg/m2) waist circumference (91 ± 2 vs. 87± 2 cm) and smoking habits (7 vs. 5 smokers). Steatosis was mild in 8, moderate in 9 and severe in 7 patients; necroinflammation was grade 1 in 7 patients, grade 2 in 9 and grade 3 in 8; fibrosis was stage 0 in 6, 1 in 5, 2 in 5 and 3 in 8 patients. NASH group was insulin resistant (ISI index from OGTT: 4.25± 0.53 vs. 7.71± 0.79) and displayed the metabolic syndrome (ATP III criteria7) in 6 subjects versus 0 controls. Dietary vitamin C (40 ± 10 vs. 70 ± 10 μg/kcal; P = .006) and E (total tocopherols: 2 ± 1 vs. 4 ± 1 μg/kcal, P = .0001) intake and serum adiponectin (5031± 570 vs. 10850 ± 710 ng/mL; P = .00001), but not the other cytokines, were lower in NASH. Postprandial plasma Tg and FFA responses were higher in NASH group than in controls, as previously reported.4 Postprandial LDL conjugated diene response was higher in patients with NASH (IAUC LDL conjugated dienes : 5.7± 1.1 vs. 0.2 ± 0.1 uA 234 nm/uA 200 nm x 100 x hr; P = .0005; Fig 1). Postprandial LDL conjugated dienes. Data are represented as mean ± SEM. Diamonds indicate P < .005 vs. controls. On multiple regression analysis, IAUC-FFA (β = .50; P = .011) and vitamin C intake (β =−0.42; P = .043) independently predicted IAUC-LDL conjugated dienes. Adiponectin (β = −0.55; P = .011) and IAUC-FFA(β = 0.51; P = .031) predicted hepatic steatosis. On logistic regression analysis, adiponectin (OR 6.8; CI 2.5-12.0; P = .003) and IAUC-LDL conjugated dienes (OR 4.4; CI 1.6-18.1; P = .021) predicted stage 3 fibrosis, independently of age, BMI, ISI index and metabolic syndrome. An enhanced postprandial LDL lipid peroxidation, along with a failing protective action of adiponectin, may thus be key in hepatic oxidative injury in NASH, by binding scavenger receptors CD36 of stellate cells and triggering fibrogenesis.8-10 Therapeutically, postprandial lipoprotein lipid peroxidation could be a major target for those drugs, such as statins and PPAR-α agonists, directly modulating lipid handling and oxidative stress during this phase of metabolism. Dietary intake of antioxidant vitamins should also be encouraged in NASH. Giovanni Musso M.D.*, Maurizio Cassader M.D.*, Roberto Gambino M.D.*, Marilena Durazzo M.D.*, Gianfranco Pagano M.D.*, * Department of Internal Medicine, University of Turin, Turin, Italy.