Cryptogenic cirrhosis: what are we missing?

Cryptogenic cirrhosis remains a common clinical condition although recent advances have allowed for a better understanding of underlying conditions and associations. The evolving terminology applied to this condition has resulted in some confusion and persistent variation among pathologists and clinicians. Typical patients are middle aged with only minor liver enzyme abnormalities. Presentations range from incidentally discovered cirrhosis to complications of advanced portal hypertension and hepatocellular cancer. Clinicopathologic analysis of these patients indicates that the leading causes include previously unrecognized nonalcoholic steatohepatitis, silent autoimmune hepatitis, non-B, non-C viral hepatitis, and occult past ethanol exposure. In this article, we review these associations as well as a proposed classification system for cryptogenic cirrhosis and other lesser known genetic and syndromic associations that warrant consideration when evaluating these individuals.