Keratins: markers and modulators of liver disease

Purpose of review Keratins are a subgroup of intermediate filaments expressed in the epithelia. Keratins emerged as important tissue-protecting genes and keratin variants cause/predispose to development of more than 50 human disorders. Our review focuses on the importance of keratins in context of liver disease. Recent findings K8/K18 variants are found in approximately 4% of white population and predispose to development and adverse outcome of multiple liver diseases. K8/K18 are major constituents of Mallory-Denk bodies, that is inclusions found in alcoholic and nonalcoholic steatohepatitis (NASH) and dysregulated keratin expression, K8 hyperphosphorylation, misfolding and crosslinking via transglutaminase 2 facilitate aggregate formation. Necrosis-generated and apoptosis-generated keratin serum fragments are emerging as important noninvasive markers of multiple liver diseases, particularly NASH. Keratins are established markers of tumor origin and in hepatocellular carcinoma, K19 expression is associated with poor prognosis. Summary Keratins are established tumor markers and are widely used as noninvasive markers of liver injury. In addition, the data that have become available in recent years have greatly advanced our understanding of keratins as modifiers of liver disease development.