Hepatology Genome Rounds: An interdisciplinary approach to integrate genomic data into clinical practice

Advancing diagnosis and management of liver disease in adults through exome sequencing

“…As exome and genome sequencing becomes more frequently used by clinicians in the evaluation of undiagnosed patients, 10 our knowledge of liver disease taxonomy will refine and expand, 9 , 55 , 56 in part through reverse phenotyping by genetics. Specifically, it will enable the stratification of adult liver disease into categories informed by genotype with direct implications in emergent personalized genetic-based therapeutic approaches and clinical trial design.…”

“… 5 , 6 , 7 , 8 Addressing this unmet need represents a significant opportunity to advance patient care. 9 , 10 …”

Genetics of liver disease in adults

“… “Take-to-clinic message [2]”: Genomic analysis should be considered in adults with unexplained liver disease despite a comprehensive workup, especially if they also have any of the following features: 40 years of age or younger, multisystemic disease, congenital malformations, positive family history, or being offspring of a consanguineous union (Table 1 , Figure 2 ). 100 , 102 This approach has been successful in uncovering a variety of known genetic liver diseases, some of them primarily described in pediatric patients and not traditionally included in the differential diagnosis in adults. …”

“…Whether related to common or rare diseases, these findings offer valuable insights into our understanding of disease pathogenesis, with some of these observations being ready for translation to the clinic (Table 1 ). 102 Continued innovations, such as the release of the first human pangenome reference, are likely to enhance our understanding of ancestry-specific genetic factors and their impact on disease. 144 Furthermore, studies incorporating large population databases, such as the UK Biobank and the more diverse US-based All of Us cohort, will continue to facilitate advances in precision medicine.…”

“…Accordingly, some institutions have already begun to establish these forums (eg, Hepatology Genome Rounds). 102 This provides a crucial step forward in accelerating the translation of new knowledge generated through research endeavors toward our goals of precision medicine and excellent patient care in hepatology.…”