Keratin 18 phosphorylation as a progression marker of chronic hepatitis B

Background: The intermediate filament proteins keratins 18 (K18) and 8 (K8) polymerize to form the cytoskeletal network in the mature hepatocytes. It has been shown that the phosphorylation of K18 at two serine residues, 33 and 52, correlates with the progression of hepatitis C, but little is known of chronic hepatitis B (CHB). In this study, we examined K18 phosphorylation in relation to CHB. Results: Site-specific phosphorylation of K18 was determined in livers of twelve healthy donors, and non-cirrhosis (n = 40) and cirrhosis (n = 21) patients. On average, progressively higher level of Ser52 phosphorylation was observed in non-cirrhotic and cirrhotic livers, while elevated Ser33 phosphorylation was detected in both livers but no significant difference. Progressive increase of Ser33 and Ser52 phosphorylation correlated with the elevation of both histological lesions and enzymatic activities of alanine aminotransferase in non-cirrhotic livers. In the hepatocytes of an inactive HBV carrier, strong signals of Ser33 phosphorylation were co-localized with viral infection, while only basal level of Ser52 phosphorylation was detected in infected cells. Conclusion: Assuming all obtained data, our data suggest that K18 phosphorylation is a progression marker for CHB.