New study finds that half of all young children with PFIC will need a liver transplant before age 10.
Progressive familial intrahepatic cholestasis (PFIC) is a rare disorder that primarily occurs in children and often leads to progressive liver disease, resulting ultimately in liver failure. Due to how rare the disorder is—estimated to affect between 1 in 50,000 and 1 in 100,000 births—researchers are determined to learn more about it in order to inform the development of more targeted treatments for those who have it.
Now, a recent study conducted by an international study group called the NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) Consortium report that by the age of 10, about half of the patients with 2 different types of PFIC have already received a liver transplant.
"PFIC1 and PFIC2 are very rare conditions and, because of this, very little is known about their natural history, the impact of different genetic mutations on phenotype, and the overall effectiveness of the treatment options available," Daan van Wessel, BSc of the University Medical Center Groningen in The Netherlands said in a recent statement. He presented the findings recently at the 51st Annual Congress of the European Society for Paediatric Gastroenterology Hepatology and Nutrition.
PFIC1 and PFIC2 are caused by inherited genetic mutations that result in impaired bile flow through the liver (cholestasis). As a result, bile accumulates and liver damage progresses, which increases end-stage liver disease and death probability. While ursodeoxycholic acid (UDCA) treatment or surgical biliary diversion techniques can benefit pediatric PFIC patients, a large number of them will need a liver transplant in their youth.
For their study, published by the Journal of Hepatology, the researchers performed a retrospective analysis which included data from 42 children with PFIC1 and 184 children with PFIC2. In the PFIC1 group, participating children attended their first specialist center at a median age of 6 months (range: 0 months to 201 months); 33% of these had been previously administered UDCA treatment. In the PFIC2 group, participating children attended their first specialist center at a median age of 9 months (range: 0 months to 195 months); 47% had been previously administered UDCA.
The researchers found that 27% of children with PFIC1 and 36% of children with PFIC2 had already received a liver transplant by age 5. The percentages of children with PFIC1 and PFIC2 who received a liver transplant were even higher by age 10: 49% and 52%, respectively.
The study also highlighted the benefits of surgical biliary diversion in pediatric PFIC patients as the procedure can diminish the amount of bile that enters the liver. While the procedure did not appear to decrease the need for liver transplantation in PFIC1 children, it did result in a 63% increase in the percentage of children who were able to survive with their own livers compared with those who did not undergo the procedure.
“This study has demonstrated for the first time that surgical biliary diversion is a highly effective treatment option for children with mild or moderate PFIC2 mutations,” Dr Wessel said. “Present data on PFIC1 are still inconclusive, but we expect to assess the value of surgical biliary diversion for PFIC1 shortly, based on the ongoing collection of patients' data. The current data also provide strong support for the recent development of oral drugs that accomplish similar effects as surgical biliary diversion.”
With the information yielded by the study, Dr Wessel professed the hope that it can be used by health care providers to educate their patients and their parents regarding potential prognosis. Furthermore, with this insight providers may be able to be better equipped to choose stronger treatment options.
The NAPPED Consortium, which is comprised of 28 specialist centers worldwide, aims to better define the natural course of PFIC, the outcomes of different treatment options, and identify biomarkers that could help target treatment more effectively.
“The current data provide strong support for the recent development of oral drugs that accomplish similar effects as surgical bilary diversion,” Dr Wessel concluded.