Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study

Abstract

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.

Aberrant Centrizonal Features in Chronic Hepatic Venous Outflow Obstruction

“…23 Centrilobular CK7 + hepatocytes were reported to correlate with periportal ductular reaction in that study, which the authors interpret as indirect support for their association with periportal hepatic progenitor cells and therefore possible derivation from centrizonal or migrating progenitors. 23 In the current study, however, we did not find an association between CK7 + centrilobular hepatocytes and periportal ductular reaction in chronic venous outflow obstruction. Given the distance of centrilobular CK7 + hepatocytes and associated ductules from the known periportal hepatic progenitor cell niche and the lack of identified perivenular progenitor cells, we favor these features to represent a metaplastic process and/or dedifferentiation of centrilobular hepatocytes with possible acquisition of progenitor cell-like phenotypes.…”

“…In addition to arteriolar ingrowth and microvessel formation, central zones in both steatohepatitis 10,12,23 and chronic venous outflow obstruction demonstrate ductular reaction and/or CK7 + intermediate-phenotype hepatocytes, suggesting an association between these features and centrilobular hypoxia. Indeed, centrizonal ductular reactions (so-called "type 2B") are thought to develop secondary to tissue hypoxia in conditions of impaired venous outflow and in centrinodular locations of focal nodular lesions.…”

“…The histogenesis of associated centrizonal CK7 + hepatocytes is also unclear, as these cells may represent partially differentiated descendants of bipotential progenitor cells or partially dedifferentiated, metaplastic hepatocytes. 23,24 It is noteworthy that, in addition to chronic venous outflow obstruction and steatohepatitis, centrilobular CK7 + hepatocytes have recently also been identified in various other chronic liver diseases, including autoimmune hepatitis, primary biliary cirrhosis, and hepatitis B and C infection. 23 Centrilobular CK7 + hepatocytes were reported to correlate with periportal ductular reaction in that study, which the authors interpret as indirect support for their association with periportal hepatic progenitor cells and therefore possible derivation from centrizonal or migrating progenitors.…”

“…23,24 It is noteworthy that, in addition to chronic venous outflow obstruction and steatohepatitis, centrilobular CK7 + hepatocytes have recently also been identified in various other chronic liver diseases, including autoimmune hepatitis, primary biliary cirrhosis, and hepatitis B and C infection. 23 Centrilobular CK7 + hepatocytes were reported to correlate with periportal ductular reaction in that study, which the authors interpret as indirect support for their association with periportal hepatic progenitor cells and therefore possible derivation from centrizonal or migrating progenitors. 23 In the current study, however, we did not find an association between CK7 + centrilobular hepatocytes and periportal ductular reaction in chronic venous outflow obstruction.…”

Liver Pathology in Infantile Mitochondrial DNA Depletion Syndrome

“…The aberrant expression under reactive conditions suggests a reversion to the pluripotent hepatic progenitor cell. This aberrant hepatocyte CK7 expression has been documented in a variety of disorders affecting the liver, including extrahepatic biliary obstruction, infection, progressive familial intrahepatic cholestasis, inborn errors of bile acid synthesis, bile duct paucity, chronic liver graft rejection, and primary biliary cirrhosis [20][21][22]. In this study, aberrant CK7 expression in hepatocytes was noted in the livers of patient 1 at 2 months (autopsy), patient 2 at 2 months and 9 months (autopsy), and patient 3 at 2 months.…”