SIG Greatest Hits: TLM 2025-Cholestatic & Autoimmune Liver Disease SIG: Stump the Hepatologist

Video Transcription

Video Summary

This video features two complex hepatology cases discussed by expert hepatologists and transplant fellows, exploring challenging liver disease diagnoses and management.<br /><br />The first case involves a 69-year-old male with lifelong intermittent cholestasis, severe itching, and a history of dermatomyositis. Despite multiple normal liver biopsies and imaging, genetic testing eventually identified compound heterozygous ATP8B1 mutations associated with PFIC1, a progressive familial intrahepatic cholestasis variant. The panel highlighted that PFIC1 manifests heterogeneously from childhood to adulthood, blurring classical distinctions like BRIC versus PFIC. Elevated GGT and fibrosis assessment via MR elastography and biopsy revealed mild fibrosis. Treatment with an ileal bile acid transporter (IBAT) inhibitor produced significant clinical and biochemical improvement, emphasizing the role of genetics and novel therapies in adult cholestatic liver disease.<br /><br />The second case describes a 16-year-old female with elevated liver enzymes, initially diagnosed with autoimmune hepatitis overlap syndrome based on biopsy and treated with steroids and immunosuppression, complicated by side effects and fluctuating labs. Subsequent findings of bile duct paucity and genetic testing revealing a heterozygous ABCB4 (PFIC3) mutation led to reconsideration of diagnosis. She experienced a difficult clinical course with poor medication adherence, but later improvement without therapy. IBAT inhibitors were considered for symptom control. The panel discussed the importance of early genetic testing to avoid misdiagnosis and overtreatment, the variable phenotypes of genetic cholestasis, and the limited data on treatments in adult or atypical presentations.<br /><br />Key takeaways include the heterogeneous presentations of genetic cholestatic diseases, the utility of genetic testing in unexplained adult and pediatric cholestasis, the evolving understanding of genotype-phenotype correlations, and the promise of IBAT inhibitors for symptom relief and disease control. The discussions highlight the complexity of diagnosis, the need for multidisciplinary evaluation, and cautious interpretation of biomarkers and histology in chronic cholestasis.

Asset Subtitle

The Stump the Hepatologist session demonstrates the “art” behind the science of working through a differential diagnosis. Through live interactions with case presenters, hepatology experts work through interesting and challenging cases, voicing their thought process as the case unfolds. Participants witness how experts in the field, using their knowledge base, break down and narrow their differential diagnosis to solve the case. Following determination of the final diagnosis, each case presenter provides a brief synopsis of relevant literature.

Keywords

hepatology

cholestasis

PFIC1

PFIC3

ATP8B1 mutations

ABCB4 mutation

IBAT inhibitors

genetic testing

liver disease management