Orphanet Journal of Rare Diseases | Therapeutic Study of MYO5B Gene Mutations in Progressive Familial Intrahepatic Cholestasis

This study systematically evaluates the efficacy of odevixibat in children with MYO5B-deficiency-associated PFIC for the first time, demonstrating the drug's ability to effectively reduce serum bile acid and bilirubin levels while alleviating pruritus and sleep disturbances, providing a novel viable treatment option for this rare disease.

 

Literature Overview
This article titled 'Odevixibat therapy in progressive familial intrahepatic cholestasis with MYO5B variants: a retrospective case series', published in Orphanet Journal of Rare Diseases (2025) 20(1), reviews clinical data from five MYO5B-deficient PFIC children treated with odevixibat. Findings indicate good tolerability and sustained clinical benefits, supporting its application as a therapeutic option.

Background Knowledge
Progressive familial intrahepatic cholestasis (PFIC) represents a group of rare autosomal recessive liver diseases characterized by bile acid transport dysfunction and intrahepatic cholestasis. MYO5B encodes myosin 5B, where mutations cause mislocalization of bile salt export pump (BSEP), impair bile secretion, and induce cholestasis with severe pruritus. Although MYO5B mutations were initially linked to microvillus inclusion disease (MVID), recent studies confirm isolated hepatic manifestations presenting as low-GGT cholestasis, hypercholanemia, and intractable pruritus. Current management includes UDCA, rifampin, biliary diversion, or liver transplantation. Odevixibat, a potent selective IBAT inhibitor, reduces enterohepatic bile acid circulation and has proven efficacy in PFIC1/2. This study expands evidence for odevixibat application in MYO5B-related PFIC, providing foundation for future clinical research.

 

 

Research Methods and Experiments
This retrospective case series enrolled five MYO5B-deficient PFIC children from four European countries (Germany, France, Italy, UK). All received odevixibat treatment between March 2021 and July 2022 (initial dose: 37.2–120 µg/kg.day) with follow-up durations of 22–39 months. Data included bile acid, bilirubin, ALT, pruritus scores, and sleep status before/after treatment, with documentation of treatment interruptions, dose modifications, and adverse events.

Key Conclusions and Perspectives

• Four of five children showed significant pruritus improvement within three months post-treatment, with complete resolution in three cases; total bilirubin and serum bile acid levels normalized within six months.
• One patient experienced symptom recurrence after treatment interruption with diminished response upon restarting, highlighting the importance of continuous medication.
• Dose adjustments were required in some patients, with treatment response correlating positively to dosage, supporting individualized therapeutic strategies.
• Despite adherence challenges in two patients, overall tolerability was good with no new/worsened gastrointestinal symptoms.
• This study confirms odevixibat's efficacy in MYO5B-related PFIC and provides data foundation for future real-world studies and patient registries.

Research Significance and Prospects
This work provides preliminary clinical evidence supporting odevixibat's therapeutic value for MYO5B-associated PFIC, particularly in managing refractory pruritus and hepatic function. Future research should employ larger cohorts with standardized follow-up to confirm efficacy, investigate combination therapy mechanisms, and establish long-term safety profiles.

 

 

Conclusion
In summary, this retrospective study demonstrates odevixibat's favorable clinical efficacy and safety profile in MYO5B-deficient PFIC children, with significant reductions in serum bile acid and bilirubin levels, alongside effective pruritus and sleep disturbance management. While treatment interruptions and adherence issues in some patients affected outcomes, most maintained stable symptom relief throughout therapy. These findings encourage further real-world validation studies to confirm broader clinical applicability and explore potential combination treatment strategies.

 

Bertrand Roquelaure, Marco Sciveres, Tassos Grammatikopoulos, Fatine Elaraki, and Emmanuel Gonzales. Odevixibat therapy in progressive familial intrahepatic cholestasis with MYO5B variants: a retrospective case series. Orphanet Journal of Rare Diseases.