INCREASED CIRCULATING PRODUCTS OF LIPID-PEROXIDATION IN PATIENTS WITHALCOHOLIC LIVER-DISEASE

F-2-isoprostanes (F-2-IP) and 4-hydroxynonenal (4-HNE), peroxidation p roducts of polyunsaturated fatty acids (PUFA), are considered the most reliable indicators of endogenous lipid peroxidation in vivo, To dete rmine to what extent these are also altered in patients with alcoholic liver disease, plasma free and esterified F-2-IP as well as 4-HNE wer e measured by GC/MS in 49 fasting subjects who underwent diagnostic pe rcutaneous needle biopsies of the liver, Compared to patients with mil d steatosis and no fibrosis, free F-2-IP and 4-HNE were strikingly inc reased in individuals with alcoholic hepatitis, There was also a signi ficant but lesser rise of 4-HNE in patients with perivenular fibrosis. An increase of F-2-IP was also found in subjects with transition to, or complete, alcoholic cirrhosis, with a comparable trend for 4-HNE, B y contrast, in patients who were drinking heavily up to 48 hr before a dmission, F-2-IP were not abnormal, but they increased later (p < 0.00 5), Contrasting with plasma free F-2-IP, esterified F-2-IP were not si gnificantly changed with fibrosis, Thus, whereas circulating esterifie d F-2-IP were unchanged in patients with alcoholic liver disease, ther e was an increase in free F-2-IP as well as 4-HNE during recovery from intoxication, The increase was not a result of accompanying hepatitis C but a function of the stage of alcoholic liver injury, possibly ref lecting enhanced lipid peroxidation as well as interference with bilia ry excretion and/or hepatic esterification.