Subject(s)
Bronchial Fistula/etiology , Esophageal Fistula/etiology , Esophageal Neoplasms/complications , Airway Obstruction/etiology , Barium Sulfate , Bronchial Fistula/diagnosis , Bronchial Fistula/therapy , Contrast Media , Cough/etiology , Deglutition Disorders/etiology , Esophageal Fistula/diagnosis , Esophageal Fistula/therapy , Esophageal Neoplasms/drug therapy , Esophagoscopy , Humans , Male , Middle Aged , Stents , Treatment OutcomeABSTRACT
Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P<0.001; plasma malondialdehyde (MDA), P=0.007] compared to age- and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P=0.013) and serum selenium and vitamin A were also lower (both P<0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of early-stage PBC.
Subject(s)
Dinoprost/analogs & derivatives , Liver Cirrhosis, Biliary/metabolism , Oxidative Stress , Antioxidants/analysis , Ascorbic Acid/blood , Biomarkers/blood , Biomarkers/urine , Cholestasis/pathology , F2-Isoprostanes/blood , F2-Isoprostanes/urine , Glutathione/blood , Humans , Lipid Peroxidation , Liver/pathology , Liver Cirrhosis, Biliary/blood , Liver Cirrhosis, Biliary/urine , Malondialdehyde/blood , Oxidants/blood , Oxidants/urine , Selenium/blood , Vitamin A/blood , Vitamin E/bloodABSTRACT
BACKGROUND/AIMS: Chronic hepatitis C infection is a major world-wide problem, frequently progressing to cirrhosis, liver failure or hepatoma. The pathological mechanisms of disease progression are unclear but oxidant stress may play a role. METHODS: Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood or urine from 42 chronic hepatitis C patients. Fibrosis was graded histologically in a subgroup of 33 patients. RESULTS: The lipid peroxidation marker 8-isoprostane and the ratio of oxidized to reduced glutathione were significantly elevated (P<0.001, P=0.006). The antioxidants glutathione, selenium and vitamins A, C and E were significantly decreased (all P<0.001) compared to age and sex matched controls. Abnormal values were more marked in cirrhotics, but significant changes were also observed in the non-cirrhotic group. The fibrosis score correlated positively with urinary 8-isoprostane and type III procollagen peptide and negatively with vitamin A. CONCLUSIONS: Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of hepatitis C infection. Although more severe in the cirrhotic group, there was clear evidence of oxidant stress in non-cirrhotic patients. Antioxidant therapy may therefore have a role in slowing disease progression to cirrhosis.
