NASH group was insulin resistant (ISI index from OGTT: 4.25ฯฎ 0.53 vs. 7.71ฯฎ 0.79) and displayed the metabolic syndrome (ATP III criteria 7 ) in 6 subjects versus 0 controls. Dietary vitamin C (40 ฯฎ 10 vs. 70 ฯฎ 10 g/kcal; P ฯญ .006) and E (total tocopherols: 2 ฯฎ 1 vs. 4 ฯฎ 1 g/kcal, P ฯญ .0001) intake and serum adiponectin (5031ฯฎ 570 vs. 10850 ฯฎ 710 ng/mL; P ฯญ .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 : 5.7ฯฎ 1.1 vs. 0.2 ฯฎ 0.1 uA 234 nm/uA 200 nm x 100 x hr; P ฯญ .0005; Fig ).
On multiple regression analysis, IAUC-FFA (โค ฯญ .50; P ฯญ .011) and vitamin C intake (โค ฯญฯช0.42; P ฯญ .043) independently predicted IAUC-LDL conjugated dienes. Adiponectin (โค ฯญ ฯช0.55; P ฯญ .011) and IAUC-FFA(โค ฯญ 0.51; P ฯญ .031) predicted hepatic steatosis.
On logistic regression analysis, adiponectin (OR 6.8; CI 2.5-12.0; P ฯญ .003) and IAUC-LDL conjugated dienes (OR 4.4; CI 1.6-18.1; P ฯญ .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][9][10] Therapeutically, postprandial lipoprotein lipid peroxidation could be a major target for those drugs, such as statins and PPAR-โฃ agonists, directly modulating lipid handling and oxidative stress during this phase of metabolism. Dietary intake of antioxidant vitamins should also be encouraged in NASH.