Cryptogenic cirrhosis

Abstract

Cryptogenic cirrhosis (CC) is defined as the development of cirrhosis in the absence of a clear etiology of liver dysfunction. Over time, definitions of various forms of liver disease have been refined and improved so that the incidence of CC is in decline. With the advent of hepatitis C testing and better definitions of alcohol related liver disease these etiologies of cirrhosis have decreased their impact on the diagnosis of CC. Autoimmune hepatitis and non-alcoholic fatty liver disease (NAFLD), both of which can lose their characteristic histologic features with advancement to cirrhosis, have taken over as the primary explanations for developing CC, but even now as definitions and recognition of NAFLD improve these numbers are waning. Since CC is a diagnosis of exclusion, prospective investigations are challenging and thus study methodology has a large impact on how relevant data are interpreted. Herein we focus on how the diagnosis of CC is made, the liver diseases that have contributed most to this diagnosis over time, and how study design affects the results and interpretation of prior investigations.