Progressive familial intrahepatic cholestasis in children: clinical features, diagnosis, and management

Abstract

Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare genetically determined liver disorder characterized by impaired bile secretion at the hepatocellular level and progressive cholestasis. The disease typically manifests in early childhood and leads to pruritus, jaundice, malabsorption, and growth retardation. Without timely treatment, it progresses to biliary cirrhosis, liver failure, and the need for liver transplantation.

Aim - to evaluate the clinical, biochemical, and psychophysical manifestations of PFIC in children, as well as the effectiveness of different treatment approaches.

Materials and methods. Seven children with PFIC (2019-2024) were observed and underwent comprehensive clinical, biochemical, and instrumental evaluation. Physical development was assessed using body mass index (BMI) and developmental quotient (DQ), while psycho-emotional status was evaluated using a modified Hamilton Anxiety Rating Scale. Pruritus intensity was assessed using the Visual Analog Scale (VAS). Treatment included conservative therapy, ileal bile acid transporter inhibitors (IBAT inhibitors), and surgical biliary diversion.

Results. All patients with PFIC1 and PFIC2 presented with jaundice and pruritus (VAS 6-10), whereas patients with PFIC3 had jaundice in 50% of cases and milder pruritus (VAS 5-7). Biochemical parameters indicated pronounced cholestasis. BMI and DQ demonstrated impaired physical and psychomotor development, particularly in PFIC2 cases. Conservative therapy improved biochemical parameters in 3 of 5 patients. IBAT inhibitors resulted in significant reduction of pruritus and improvement in quality of life in 2 children. Surgical intervention with subsequent liver transplantation restored liver function and resolved pruritus in 2 patients.

Conclusions. Genetic testing is the gold standard for the diagnosis of PFIC. Management of this condition should be performed in specialized multidisciplinary centers using pathogenetically targeted approaches, including IBAT inhibitors, ursodeoxycholic acid, surgical interventions, and liver transplantation in severe cases. Early diagnosis and comprehensive therapy can slow disease progression, improve quality of life, and delay the need for transplantation.

The study was conducted in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution. Informed parental consent was obtained for participation in the study.

The author declares no conflict of interest.