Idiopathic cholestasis in adults: Genetics as another lens for liver pathologists.

Abstract

Chronic liver disease (CLD) is a significant global health problem, responsible for approximately two million deaths annually. Despite extensive diagnostic evaluations, a proportion of patients with CLD remain undiagnosed, making the study and quantification of these cases challenging. Genetic testing has emerged as a critical diagnostic tool, identifying monogenic causes in a substantial portion of undiagnosed cases. In addition, nearly 50 % of known genetic liver diseases were identified in the past 20 years, underscoring the rapid expansion of genetic knowledge. Notably, recent data demonstrates that genetic testing provides diagnoses in up to nearly half of adult patients with idiopathic cholestasis. Furthermore, wide application of genetic testing in adult populations is revealing that genetic cholestatic liver diseases primarily thought to be of pediatric presentation are now often recognized in adulthood. As genomic medicine continues to evolve rapidly in the context of cholestatic liver disease, pathologists must stay informed about genetic diseases and their implications for liver biopsy interpretation. Interdisciplinary efforts merging hepatologists, clinical geneticists and pathologists' expertise, such as Hepatology Genome Rounds, are envisioned to become standard practice, enhancing disease understanding and patient care.