Non-invasive monitoring of oxidant stress in alcoholic liver disease.
OBJECTIVE
In alcoholic liver disease (ALD), progression from initial steatosis, through hepatitis to cirrhosis is well described, resulting in 20,000 deaths in the UK annually. However, pathological mechanisms are not well understood and drug trials have led to conflicting results. It has been established that alcohol consumption increases hepatic free radical production and oxidant stress has been implicated in the disease process.


METHODS
Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis, inflammation and liver function were measured in blood and urine from 24 patients with established alcoholic cirrhosis and in 49 age- and sex-matched controls.


RESULTS
In the ALD group, lipid peroxidation markers 8-isoprostane and malondialdehyde were significantly increased (p<0.001), as was the ratio of oxidized to reduced glutathione (p=0.027). The antioxidants selenium, glutathione (whole blood and plasma) and vitamins A, C and E were all significantly decreased (p<0.001); median plasma glutathione levels were only 19% of control levels. Type III procollagen peptide (PIIINP), a serum marker of hepatic fibrogenesis, and C-reactive protein (CRP) were both increased (p<0.001). Urinary 8-isoprostane correlated positively with PIIINP, CRP and markers of cholestasis (alkaline phosphatase and bilirubin) and negatively with glutathione (whole blood), vitamins A and E and albumin.


CONCLUSIONS
Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of alcoholic cirrhosis, providing a mechanism by which alcohol intake may be linked to hepatic inflammation and fibrosis. Non-invasive markers could prove valuable in monitoring response to treatment during clinical trials.
Pemberton
Philip W
PW
The Liver Unit, Manchester Royal Infirmary, Manchester, UK.
Smith
Alexander
A
Warnes
Thomas W
TW
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011379:Prognosis; D012720:Severity of Illness Index
D000975:Antioxidants; D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; C075750:8-epi-prostaglandin F2alpha; D002097:C-Reactive Protein; D015237:Dinoprost