Hepatocyte cytokeratin 7 expression in chronic allograft rejection.

Dept of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
American Journal of Clinical Pathology (Impact Factor: 2.88). 02/2011; 135(2):238-44. DOI: 10.1309/AJCPNRXCAP92KNOJ
Source: PubMed

ABSTRACT We examined hepatocyte cytokeratin 7 (CK7) expression in chronic allograft rejection (CR), a ductopenic condition in which this has not been systematically evaluated, in 20 patients with the clinicopathologic diagnosis of CR and age-, sex-, and native-disease-matched control subjects. We also studied baseline biopsy specimens from both groups. Three pathologists independently reviewed H&E- and CK7-stained sections, counting interlobular bile ducts (BDs) and portal tracts (PTs), noting the morphologic pattern of injury and scoring hepatocyte CK7 expression (0, none; 1+, rare; 2+, multifocal, predominantly periportal; 3+, extension into the lobule; 4+, diffuse). Mean BD/PT ratios and CK7 scores were calculated. The mean BD/PT ratio (0.58) and CK7 score (1.01) for the "CR, diagnostic" group were significantly different from all other group means (P < .05); no other comparisons were significant (P > .05). A CK7 score of 1 or more was observed in 9 (56%) of 16 CR specimens and in 3 (7%) of 41 remaining specimens. Hepatocyte CK7 expression is frequently noted in CR, and it would appear to reflect ductopenia. CK7 staining may be a useful diagnostic adjunct in evaluation of transplant liver biopsy specimens.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Liver transplantation has been a successful therapy for liver failure. However, a significant number of recipients suffer from graft dysfunction. Considerably, ischemia and reperfusion (I/R) injury is the most important factor leading to organ dysfunction, although the pathogenesis has not been fully described. I/R injury have several established features that are accompanied by and/or linked to bile duct loss or ductopenia, cholestasis, and biliary ductular proliferations in the posttransplant liver biopsy. However, biliary marker levels increase usually only 5-7 days after transplantation. Intermediate filaments are one of the three cytoskeletal proteins that have a major role in liver protection and maintaining both cellular structure and integrity of eukaryotic cells. We reviewed the canine liver transplantation model as I/R injury model to delineate the intermediate filaments of the cytoskeleton that are probably the determinants in changing the phenotype of hepatocytes to cholangiocytes. Remarkably, this interesting feature seems to occur earlier than frank cholestasis. We speculate that I/R liver injury through a phenotypical switch of the hepatocytes may contribute to the poor outcome of the liver graft.
    BioMed Research International 03/2012; 2012:131324. · 2.71 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Matsukuma S, Takeo H, Kono T, Nagata Y & Sato K (2012) Histopathology Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study Aims:  This study has attempted to elucidate the clinicopathological features of aberrant cytokeratin 7 (CK7) expression by centrilobular hepatocytes. Methods and results:  A total of 113 liver biopsy specimens from patients with common non-neoplastic liver diseases, including hepatitis B or C, non-alcoholic steatohepatitis, alcoholic liver disease and other diseases were examined. In 56 specimens (49.6%), CK7-positive centrilobular hepatocytes (CK7 + CHs) were identified and sometimes showed binuclear features. CK7 + CHs were associated with patients' older age (P = 0.004), higher serum levels of aspartate aminotransferase (P = 0.016) and γ-glutamyltransferase (P = 0.006), centrilobular fibrosis (P < 0.001), prominent thickening of hepatocytic plates (P < 0.001) and higher scores of total and periportal CK7-positive hepatocytes (both P < 0.001), but were not correlated with gender, steatosis, serum levels of total bilirubin or alanine aminotransferase. In 55 cases of hepatitis B and hepatitis C only, CK7 + CHs were related to a higher stage of fibrosis (P = 0.006). Conclusion:  CK7 + CHs occur relatively frequently in non-neoplastic liver disease, associated with centrilobular scarring and the presence of CK7-positive periportal hepatocytes, and appear to be a non-specific phenomenon with respect aetiology of underlying disease. CK7 + CHs may represent age-dependent activation of hepatic progenitor cells or a regenerative phenomenon of hepatocytes themselves, both of which might contribute to liver regeneration.
    Histopathology 03/2012; · 3.30 Impact Factor