Keratin 7 expression in hepatic cholestatic diseases

Abstract

We evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

Prominent Pseudoacini in Focal Nodular Hyperplasia

“…16 CK7 is a marker of cholangiocytes but has also been used to highlight cholestatic hepatocytes. 24,25 Studies have demonstrated that CK7 positive hepatocytes with or without pseudoacinar morphology in central areas of the FNH, suggesting chronic cholestasis is likely a common feature of FNH. 5,12,13,16,26 It is thought that the capacity of hepatocytes in FNH to take up bile acids from the blood and to secrete bile persists, but the lack of draining bile ducts and hepatocytic senescence may lead to increasing cholestasis, ductular reaction, and even pseudoacini formation.…”

Colonocyte keratin 7 is expressed de novo in inflammatory bowel diseases and associated with pathological changes and drug-resistance

“…Keratins and other intermediate filaments are cytoprotective proteins and reportedly upregulated in various stress and regenerative conditions, which may explain the here described K7 neo-expression in the colonic epithelium of IBD patients 8 , 32 . Simple epithelial keratins including K7 have been shown to be upregulated or neo-expressed in patients and in mouse disease models, for example in kidney epithelial cells during renal injury 33 , in β-cells after diabetes induction 34 , and in hepatocytes of patients with cholestatic diseases 35 . Similarly, in mouse models of colonic stress and inflammation, simple epithelial keratins were upregulated, including K7 which was increased in a model of chronic colitis and in aging mice 19 .…”

Update on Hepatobiliary Plasticity

“…Many histopathological examinations have reported the expression of the BEC marker KRT7 in hepatocytes during cholangiopathies. [36][37][38][39][40][41][42] In cases of Alagille syndrome as well as biliary atresia, the number of IHBCs co-expressing the BEC markers KRT7 or HNF6 and the hepatocyte markers LKM-1, BSEP, or HNF4a is significantly increased. 43 In both primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the appearance of IHBCs increases with the stage of fibrotic damage to the tissue.…”