The cytoskeleton in nonalcoholic steatohepatitis: 100 years old but still youthful

The hepatocellular cytoskeleton consists of three filamentous systems: microfilaments, microtubules and keratins (Ks). While the alterations in microfilaments and microtubules during nonalcoholic steatohepatitis (NASH) are largely unexplored, K8/K18 reorganization into Mallory–Denk bodies (MDBs) represents a NASH hallmark, and serological K18 fragments constitute an established tool to monitor NASH severity. To commemorate the 100th anniversary of the first description of MDBs, this article summarizes the composition and function of the hepatocellular cytoskeleton, as well as the importance of cytoskeletal alterations in NASH. The significance of MDBs in clinical routine is illustrated, as are the findings from MDB mouse models, which shape our current view of MDB pathogenesis. Even after 100 years, the cytoskeleton represents a fascinating but greatly understudied area of NASH biology.