Is alanine aminotransferase level a surrogate biomarker of hepatic apoptosis in nonalcoholic fatty liver disease?
OBJECTIVE
To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters.


METHODS
24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-kappaB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured.


RESULTS
The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT.


CONCLUSIONS
Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.
Canbakan
Billur
B
Cerrahpasa Medical Faculty of Istanbul University, Department of Gastroenterology, Fatih, 34303 Istanbul, Turkey. canbakbil@gmail.com
Senturk
Hakan
H
Canbakan
Mustafa
M
Toptas
Tayfur
T
Tabak
Omur
O
Balci
Huriye
H
Olgac
Vakur
V
Ozbay
Gulsen
G
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000473:pathology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D016328:NF-kappa B; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione