CK18 as a Biomarker in NASH Clinical Trials

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in developed countries, and it affects over 25% of the population worldwide. Within the next five years, the more advanced form of this disease, Non-alcoholic steatohepatitis (NASH), is expected to become the leading cause for liver transplants in the US. There are currently no approved pharmacologic therapies for NAFLD or NASH.  Several drug pipelines with diverse mechanisms of action are in clinical development to address this unmet medical need.  While improvement in liver histology confirmed through biopsy is still a required endpoint for regulatory approval, non-invasive biomarkers may be used in early-stage trials to assess treatment effect. Serum Cytokeratin 18 (CK18) levels are reflective of hepatocyte apoptosis and necrosis, which are thought to be important processes involved in the progression of NAFLD. Monitoring serum CK18 levels, therefore, provides mechanistic information on the effect of drug treatment. Furthermore, changes in Serum Cytokeratin 18 Levels have been shown to correlate with changes in liver histology.

The aims of this talk are to:
1. Introduce the audience to the growing epidemic of NAFLD
2. Elucidate challenges in developing therapies for the treatment of NASH
3. Present data that support the value of CK18 as a biomarker for assessing the efficacy of drugs in NASH clinical trials.