Keratin 18, Apoptosis, and Liver Disease in Children

Keratins, a major component of epithelial cell intermediate filaments, provide structural support to the cell and are important for the maintenance of structural integrity. Beyond its role of structural integrity in hepatocytes, keratin 18 (K18) is a known marker of apoptosis and has been proposed as an indicator of progression in chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common cause of chronic liver disease in children and adolescents in the United States and throughout the world and comprises a wide spectrum of disease ranging from simple steatosis (fatty liver) to nonalcoholic steatohepatitis (NASH) and cirrhosis. While simple steatosis is typically benign in nature, NASH is a more serious condition that may progress to end-stage liver disease and liver failure. Currently, liver biopsy is considered the most reliable method of assessing the histological severity of disease and differentiating between simple steatosis and NASH. Because biopsy is invasive in nature, expensive, and subject to sampling error and/or variability in interpretation, it is not suitable as a screening test. Therefore, it is necessary to examine known mechanisms associated with the progression of liver disease, such as hepatocellular apoptosis, and identify potential biomarkers that could be used as a diagnostic tool in NASH. This review will focus on the role of apoptosis in pediatric liver disease and how K18, an early marker of apoptosis, can be utilized as a noninvasive biomarker to diagnose NASH.