Oxidant stress in type I autoimmune hepatitis: the link between necroinflammation and fibrogenesis?
Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology characterized by circulating autoantibodies, hyperglobulinaemia and interface hepatitis. The mechanisms of progression from initial autoimmune attack to fibrosis and cirrhosis are unclear but oxidant stress may be involved. Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood and urine in 35 controls and in 33 patients with type-1 AIH; histology was assessed in 18 patients. In AIH, markers of lipid peroxidation were significantly elevated (8-isoprostane in both plasma and urine P < 0.001; plasma malondialdehyde P = 0.017). Total antioxidant capacity in protein-free serum and total glutathione in both whole blood and plasma were significantly reduced (P = 0.007, P = 0.037, P < 0.001, respectively). The antioxidants selenium, vitamin A and vitamin E were significantly decreased (P = 0.007, P < 0.001, P = 0.025, respectively); vitamin C was unchanged. Urinary 8-isoprostane correlated positively with interface hepatitis and necroinflammatory score and with hepatic fibrogenesis (type III procollagen peptide). Interface hepatitis correlated negatively with vitamin A and whole blood total glutathione. Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of AIH and provides a probable mechanism linking hepatic necroinflammation to fibrogenesis and disease progression.
Department of Gastroenterology, The Liver Unit, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
Philip W
PW
Pemberton
Ali
A
Aboutwerat
Alexander
A
Smith
Peter C
PC
Burrows
Raymond F T
RF
McMahon
Thomas W
TW
Warnes
D019693:Hepatitis, Autoimmune / Q000209:etiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D009336:Necrosis; D018384:Oxidative Stress