W1848 Keratin Variants Associate with Primary Biliary Cirrhosis

940 Loss of Keratin 19 Predisposes to the Development of Cholestatic Liver Disease

“…This is consistent with a recent study showing that K19 expression in HCC was associated with increased tumor size and bad prognosis [52, 54,191]. Furthermore, our finding might be relevant to the pathogenesis of biliary diseases such as PBC since K19 variants, K19 G17S, was identified in patients with advanced PBC [57].With regard to our findings, it is tempting to speculate that diminished regenerative ability in K19 deficient ductal cells may contribute to the development of ductopenia that is seen in advanced PBC. To support this hypothesis, OV-6 positive ductular structures were observed in patients with PBC, thereby demonstrating that LPC proliferation really takes place in these subjects [192].…”

“…Recently, K19 G17S variant was found in patients with cholestatic liver disease termed as primary biliary cirrhosis [57] whereas K19 expression within hepatocellular carcinoma was described to constitute a "stemness"-related marker that is associated with poor prognosis.…”

“…For example, in mice, a dominant negative mutation in K18 accelerated thiacetamide (TAA)-induced liver fibrosis but had no impact on CCl 4 -induced liver scaring [149]. In humans, presence of K8/K18 variants has been shown to predispose to development of advanced liver fibrosis in patients with chronic hepatitis C and to development of advanced disease in PBC [57,200], whereas the same exonic K8/K18 variants did not influence the fibrogenic process in patients with hemochromatosis [201]. Another report supporting our data comes from Scholten et al, who performed lineage tracing and did not find any transdifferentiation of K19 positive cholangiocytes into extracellular matrix producing cells [202].…”