Genetic Testing in Liver Diseases: Clinical Applications

Human genetics has been a central tool for elucidating the molecular basis of disease. Completion of the sequencing of the human genome, coupled with technological advances, has markedly reduced sequencing costs while enhancing the scale, accuracy, and interpretability of genomic data. These developments have accelerated the translation of genomic testing into clinical medicine. Although genomic medicine has traditionally been widely adopted in pediatrics, neurology, and oncology, its application in adult hepatology is rapidly expanding. This review synthesizes the growing body of evidence supporting the use of genetic testing in the diagnosis and management of adults across a broad spectrum of liver diseases, including cholestatic disorders, unexplained hepatic steatosis, cryptogenic cirrhosis, idiopathic portal hypertension, and acute liver failure. We underscore high yield learning points and actionable clinical insights for real-world practice and highlight the critical role of specialized centers with expertise in genomic hepatology, including multidisciplinary Hepatology Genome Rounds. Lastly, we present our perspective on the current state and near future of a liver-centric, integrative genomic ecosystem and its anticipated impact on the training and practice of clinical hepatology.