Progenitor cell expansion: an important source of hepatocyte regeneration in chronic hepatitis.
OBJECTIVE
Progenitor cell activation with subsequent maturation to hepatocytes and cells of the biliary lineage has been demonstrated in a variety of chronic liver diseases but the kinetics and magnitude of the progenitor cell response has not been adequately studied in detail in chronic hepatitis. We undertook this study to evaluate factors responsible for the progenitor cell/ductular response and further dissect the role of disease grade and stage as determinants of hepatocellular differentiation of bipotential progenitor cells in chronic hepatitis.


METHODS
Cytokeratin 7 (and 19) stained biopsies from patients with chronic hepatitis C (n = 47), hepatitis B (n = 20), and autoimmune hepatitis (n = 20) were studied. Ploidy analysis and proliferation indices were evaluated in a subset of cases.


RESULTS
Ductular reactions were present in the majority of cases (97%), appeared early in disease, and correlated with disease activity, while progenitor cell derived hepatocyes appeared later in disease and their extent correlated with disease stage. Proliferation indices of all cell types correlated with disease activity.


CONCLUSIONS
Progenitor cell derived hepatocytes accrue in chronic hepatitis, possibly related to native hepatocellular dysfunction. However, the fate of these hepatocytes is unclear.
Eleazar
Jennifer A
JA
Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Memeo
Lorenzo
L
Jhang
Jeffrey S
JS
Mansukhani
Mahesh M
MM
Chin
Steven
S
Park
Soo Mi
SM
Lefkowitch
Jay H
JH
Bhagat
Govind
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001652:Bile Ducts / Q000473:pathology; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000378:metabolism; D005260:Female; D019694:Hepatitis B, Chronic / Q000473:pathology / Q000503:physiopathology*; D019698:Hepatitis C, Chronic / Q000473:pathology / Q000503:physiopathology*; D019693:Hepatitis, Autoimmune / Q000473:pathology / Q000503:physiopathology*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration; D008297:Male; D008875:Middle Aged; D016196:S Phase; D013234:Stem Cells / Q000473:pathology*
C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins; D004247:DNA