FIGURE 2.

Framework for considering and incorporating genetic testing into the evaluation and management of patients with liver disease. Hepatologists may consider obtaining the PNPLA3 p.I148M genotype for individuals with MASLD to assess their risk for progression to advanced liver disease. In cases of unexplained liver disease despite a thorough workup, genomic analysis is recommended as the next step, and referral to a hepatologist with expertise in human genetics or a clinical geneticist may be beneficial. *If there is strong suspicion for a specific group of genetic liver diseases (eg, cholestasis, iron overload, cystic liver/kidney disease, etc.), TGS for a relevant gene panel may be considered. Otherwise, unbiased WES should be considered. For patients diagnosed with HCA, referral to molecular genetic pathology for liver tumor molecular profiling is advised to guide further management. Abbreviations: HCA, hepatocellular adenoma; MASLD, metabolic dysfunction–associated steatotic liver disease; TGS, targeted gene sequencing; WES, whole-exome sequencing.