Progressive Familial Intrahepatic Cholestasis, type 2, (PFIC2) is due to decrease (or absent) function of the bile salt export pump (BSEP) encoded by ABCB11 has been treated mainly in a symptomatic manner with medicines like ursodeoxycholic acid and sometimes biliary diversion. PFIC2 has been associated with increased risk for hepatocellular carcinoma (HCC).
A recent study (E Gonzales, et al. Hepatology 2015; 62: 558-66) indicates that newer therapies targeting the specific mutation may be effective.
In this study, treatment with oral 4-phenylbutyrate (4-PB) in four patients improved pruritus, serum bile acid concentrations, and liver function tests. 4-PB is considered a chaperone drug and may partially correct mistrafficking.
The associated editorial (pg 349-50) notes that 4-PB has an unpleasant taste and requires ingestion of a large number of pills. In addition, patients with complete loss of BSEP, 4-PB will not be effective. Finally, even in patients with a clinical response, it is unclear if this will lower the risk of HCC.
A second study (S Varma et al. Hepatology 2015; 62: 198-206) retrospectively studied 22 children with PFIC2. “Children with late-onset presentation, lower ALT, and intracellular BSEP expression are likely to respond, at least transiently, to nontransplant treatment.” Nontransplant treatment in this cohort included ursodeoxycholic acid in 19 (10 mg/kg thrice daily) and partial biliary diversion in 3. Higher ALT values were considered to be >165 IU/L. Another point in this study: response to treatment can be slow and take many months.
My take: These studies provide useful information about which patients with PFIC2 respond medically and introduce a new therapy, 4-PB.
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