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Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis
E Jacquemin1, D Hermans, A Myara
1Department of Pediatrics (Hepatology Unit) and INSERM U.347, Hôpital de Bicêtre, Cedex, France.
Insights
Ursodeoxycholic acid (UDCA) shows promise in treating progressive familial intrahepatic cholestasis (PFIC), a severe childhood liver disease. This therapy improved liver function and clinical symptoms in a significant number of pediatric patients.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Genetic Liver Diseases
Background:
- Progressive familial intrahepatic cholestasis (PFIC) is a severe, inherited childhood liver disorder with no current effective medical treatments.
- PFIC is classified into subtypes based on serum gamma-glutamyl transpeptidase (GGT) levels.
- Current management options for PFIC are limited, often leading to poor outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in treating pediatric patients with PFIC.
- To assess the impact of UDCA on liver function tests, clinical symptoms, and liver histology in different PFIC subtypes.
- To determine if UDCA can alter the disease progression and potentially reduce the need for liver transplantation.
Main Methods:
- A cohort of 39 pediatric patients with PFIC received oral UDCA (20-30 mg/kg/day) for 2-4 years.
- Patients were divided into two groups: Group 1 (normal GGT, n=26) and Group 2 (high GGT, n=13).
- Liver function tests, clinical symptoms (hepatosplenomegaly, pruritus), and liver histology were monitored throughout the study.
Main Results:
- In Group 1, liver tests normalized in 11, improved in 5, and stabilized/worsened in 10 patients.
- In Group 2, liver tests normalized in 6, improved in 4, and stabilized/worsened in 3 patients.
- Clinical improvements, including reduced hepatosplenomegaly and pruritus, were observed in patients with normalized liver tests. Histological analysis showed decreased fibrosis in some patients after treatment.
Conclusions:
- UDCA appears to be an effective therapeutic option for a significant proportion of children with PFIC, improving liver function and clinical status.
- The study suggests UDCA should be considered in the initial management of PFIC to potentially avoid liver transplantation.
- Re-initiation of UDCA therapy after temporary cessation led to normalization of liver tests in some patients, indicating a potential benefit of sustained treatment.
Abstract:
Progressive familial intrahepatic cholestasis (PFIC) is a lethal inherited childhood cholestasis of hepatocellular origin. Different subtypes of PFIC have been described according to serum gamma-glutamyl transpeptidase (GGT) activity. There is currently no effective medical therapy available for children with PFIC. We report on 39 patients with PFIC who received ursodeoxycholic acid (UDCA) orally (20-30 mg/kg b.w./day) for a period of 2 to 4 years. Group 1 (n = 26) consisted of children with normal GGT activity, and group 2 (n = 13) of children with high GGT activity. Within group 1, liver tests normalized in 11 children, improved in 5, and stabilized or worsened in 10. Within group 2, liver tests normalized in six children, improved in four, and stabilized or worsened in three. Improvement of parameters was associated with an enrichment of the circulating pool of bile acids with UDCA. Hepatosplenomegaly and pruritus disappeared or diminished in children in whom liver tests normalized. In nine of these children, liver tests worsened and normalized again after stopping and restarting UDCA. Liver histology assessed in four children after normalization of liver tests and 2 years of treatment showed a decrease in fibrosis. We conclude that UDCA should be considered in the initial therapeutic management of children with PFIC, because it appears effective in resolving or improving the liver function and the clinical status of a fair proportion of children. Chronic UDCA therapy might thus avoid the need for liver transplantation in some children with PFIC.