What is the treatment for PFIC-7 (Progressive Familial Intrahepatic Cholestasis type 7)?

Treatment for Progressive Familial Intrahepatic Cholestasis Type 7 (PFIC-7)

For PFIC-7, treatment should follow the general management principles for rare genetic cholestatic disorders, including IBAT inhibitors for pruritus, ursodeoxycholic acid for cholestasis, and liver transplantation for end-stage disease. 1

Understanding PFIC-7

PFIC-7 is one of the newer identified subtypes of Progressive Familial Intrahepatic Cholestasis, a group of autosomal recessive disorders characterized by impaired bile formation and excretion. While the 2024 EASL guidelines mention PFIC-7 in their classification table, it is associated with mutations in the SEMA7A gene 1.

Treatment Algorithm for PFIC-7

First-line Medical Management:

1. IBAT Inhibitors

   • Should be offered as first-line therapy for cholestatic pruritus
   • Medications include maralixibat and odevixibat
   • These interrupt the enterohepatic circulation of bile acids by inhibiting bile acid reabsorption in the terminal ileum 1

2. Ursodeoxycholic Acid (UDCA)

   • Recommended for patients with at least one missense variant
   • Mechanism: Changes bile acid composition from hydrophobic to more hydrophilic
   • Reduces toxic bile acids and increases bile production 1

3. Supportive Care

   • Nutritional support with adequate calories
   • Supplementation of fat-soluble vitamins (A, D, E, K)
   • Medium-chain triglyceride supplementation

Second-line Interventions:

1. Interruption of Enterohepatic Circulation
   • Medical interruption: IBAT inhibitors should be considered first for pruritus management 1
   • Surgical interruption: Partial external biliary diversion (PEBD) or ileal exclusion (IE) should be considered in patients with responsive genotypes to prolong native liver survival 1

End-stage Management:

1. Liver Transplantation
   • Indicated when patients develop progressive liver fibrosis, cirrhosis, or end-stage liver disease
   • Should be considered when medical and surgical interventions fail 1

Special Considerations

• Monitoring: Regular follow-up with laboratory analysis and non-invasive screening for fibrosis every 6 months 1
• Imaging: Liver ultrasound and/or MRI with MRCP recommended at least yearly 1
• Hepatocellular Carcinoma (HCC) Screening: Screening intervals should be based on genotype - every 3-6 months for missense mutations and every 3 months for biallelic protein-truncating mutations 1

Treatment Response Assessment

• Monitor liver biochemistry (ALT, AST, bilirubin, GGT)
• Assess pruritus severity using validated scales
• Evaluate growth parameters in children
• Perform periodic liver imaging to assess disease progression

Emerging Therapies

Gene therapy is being explored as a potential future treatment option for PFIC disorders, which could potentially address the underlying genetic defect rather than just managing symptoms 2.

Important Caveats

• PFIC-7 is an ultra-rare disorder with limited specific treatment data, so management follows principles established for other PFIC types
• Treatment response may vary based on the specific genetic mutation
• Liver transplantation remains the definitive treatment for progressive disease despite medical management
• Post-transplant complications may include disease recurrence and need for immunosuppression
• The efficacy of UDCA may be variable depending on the specific genetic variant 1

While PFIC-7 is a recently identified subtype with limited specific data, following the established treatment protocols for genetic cholestatic disorders provides the best approach to managing these patients and improving their quality of life and survival.