Cytokeratin 7 staining of hepatocytes predicts progression to more severe fibrosis in alcohol-fed baboons.
OBJECTIVE
Not all alcoholic patients develop severe liver disease with fibrosis progressing to cirrhosis. It is of practical importance to determine whether some markers can predict progression of liver fibrosis.


METHODS
We used a baboon model that mimics human alcoholic liver disease. Cytokeratin 7 and 19 expression and fat deposition were investigated in serial liver biopsies of 18 animals undergoing prolonged alcohol administration (range 2-17 years) and in four controls. Fibrosis was graded histologically and was also assessed quantitatively by image analysis.


RESULTS
Ten animals did not show a progression of liver disease even after 17 years of alcohol administration, but eight animals fed alcohol exhibited a progression of liver disease from no fibrosis or perivenular fibrosis to septal fibrosis or cirrhosis within 7 years. In normal liver, cytokeratin 7 and cytokeratin 19 immunostaining is restricted to bile duct cells. Hepatocellular cytokeratin 7 was observed only in those animals which progressed to more severe stages of fibrosis and it anticipated this progression by 4.2 years on average.


CONCLUSIONS
In alcohol-fed baboons, cytokeratin 7 staining of hepatocytes (but not cytokeratin 19, nor fat deposition) predicts with a high degree of sensitivity and specificity progression to more severe liver disease.
Ren
Chaoling
C
Alcohol Research Center, Veterans Affairs Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468, USA.
Paronetto
Fiorenzo
F
Mak
Ki M
KM
Leo
Maria A
MA
Lieber
Charles S
CS
D000818:Animals; D001652:Bile Ducts / Q000378:metabolism; D018450:Disease Progression; D022781:Hepatocytes / Q000378:metabolism*; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism* / Q000473:pathology*; D010215:Papio; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013194:Staining and Labeling; D013997:Time Factors; D014018:Tissue Distribution
C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins