Research Article - Current Pediatric Research (2025) Volume 29, Issue 1

Clinical Outcome of Children with Progressive Familial Intrahepatic Cholestasis: A Cohort Study

Nasrin Motazedian¹, Seyed Mohsen Dehghani¹, Alireza Shamsaeefar², Kourosh Kazemi², Ali Ghorbanpour^3*, Mehrab Sayadi⁴, Maryam Ataollahi⁵, Saman Nikeghbalian²

¹Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

²Abu Ali Sina Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran

³Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

⁴Cardiovascular Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran

⁵Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran

Corresponding Author:

Ali Ghorbanpour
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
Phone number: 00989178868682
E-mail: a00.ghp@gmail.com

Received: 02 December, 2024, Manuscript No. AAJCP-24-153912; Editor assigned: 05 December, 2024, Pre QC No. AAJCP-24-153912 (PQ); Reviewed: 19 December, 2024, QC No. AAJCP-24-153912; Revised: 26 December, 2024, Manuscript No. AAJCP-24-153912 (R); Published: 03 January, 2025, DOI:10.35841/0971-9032.29.01.2408-2422.

Abstract

Background: Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare genetic liver disorder characterized by cholestasis and progressive liver damage, often leading to cirrhosis and liver transplantation. Understanding the clinical course and outcomes of PFIC is important for improving management techniques, particularly in resource-limited settings like Iran. This study aimed to assess the clinical outcomes and survival rates of children with PFIC in Iran, emphasizing the importance of early diagnosis and liver transplantation. Methods: This cohort study is part of the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), initiated in 2018. Data were collected on demographic characteristics, clinical features and laboratory findings. Cox regression analysis was employed to identify risk factors for mortality. Results: Out of 100 PFIC cases, 35% of the children died, with younger age at diagnosis and higher Pediatric End-Stage Liver Disease (PELD) scores associated with increased mortality risk. Liver Transplantation (LTx) was performed in 50% of the cohort, with survival rates of 74%, 70% and 66% at 12 months, 24 months and 60 months, respectively, post-transplant. Higher White Blood Cells (WBC), Aspartate Aminotransferase (AST) and direct bilirubin levels were also significant predictors of mortality. Conclusions: Early diagnosis and liver transplantation are important for improving survival in children with PFIC. High PELD scores, WBC, AST and bilirubin levels are associated with increased mortality risk, emphasizing the need for early intervention and regular monitoring

Keywords

Survival, Pediatrics, Progressive Familial Intrahepatic Cholestasis, Cohort study

Abbreviations

Progressive Familial Intrahepatic Cholestasis (PFIC), Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), Pediatric End- Stage Liver Disease (PELD), Liver Transplantation (LTx), White Blood Cell (WBC), Aspartate Aminotransferase (AST), Standard Deviation (SD), Statistical Package for Social Science (SPSS), Red Blood Cell (RBC), Hemoglobin (Hb), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Alkaline phosphatase (ALP), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), International Normalized Ratio (INR), Hazard Ratio (HR), Partial External Biliary Diversion (PEBD), Total Internal Biliary Diversion (TIBD), Live Donor Liver Transplantation (LDLT), Partial Internal Biliary Diversion (PIBD), Model for End-Stage Liver Disease (MELD)

Background

Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare congenital disorder with several subtypes, all of which are autosomal recessive in nature. These subtypes involve various genes, characterized by liver dysfunction and cholestasis and typically progress to liver cirrhosis, necessitating Liver Transplantation (LTx). However, it's essential to recognize that despite transplantation, patients may still experience ongoing complications associated with the disorder [1,2].

PFIC poses a significant burden on affected individuals and their families due to its potentially life-threatening complications. This highly impacts patient?s quality of life and imposes substantial economic and emotional burdens on caregivers as well [3?5].

Given the complexity and variability of PFIC subtypes, there remains a need for more comprehensive studies to improve diagnostic approaches and better treatment options. Further research endeavors are essential not only to better understand the pathophysiology of PFIC, but also to develop targeted therapies that can lessen the symptoms, reduce disease progression and ultimately improve outcomes for affected individuals [6,7].

The exclusive hub for pediatric LTx within Iran can be found in Shiraz. Consequently, children and adolescents suffering from cirrhosis are directed to this facility from all corners of the country for transplant assessments. This unique resource creates an opportunity for researchers to conduct comprehensive studies on cirrhotic conditions in the pediatric population. The establishment of the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) aims to evaluate cirrhotic children, monitor the progression of their illness and observe the effectiveness of various treatments over time. Furthermore, the substantial sample size and consistent patient follow-up procedures offer an ideal environment for conducting longitudinal investigations [8]. The objective of SPLCCS was to conduct a prospective assessment of the natural progression of chronic liver disease in children, identifying factors influencing complications and mortality rates among those referred to the Shiraz Liver Transplant Center. This current report, based on SPLCCS data, delves into the demographic landscape of the PFIC subgroup. By shedding light upon the characteristics of PFIC in Iran, we aimed to contribute to the vast understanding of this rare but debilitating condition and further facilitate targeted approaches to its prevention and management.

Methods

The SPLCCS initiative commenced in September 2018 after obtaining approval from the ethics committee at Shiraz University of Medical Sciences (IR.SUMS.REC.1398.142). Prior to participation, written consent was secured from the parents or legal guardians of the participants. Operating as an open cohort study, enrollment remains ongoing to date.

All children in SPLCCS, who were diagnosed with PFIC since 2018, were eligible to be included in the current prospective cohort study. Then, those who were misdiagnosed and children with insufficient or incomplete medical data were excluded. Patient?s demographic information, parents? information, prenatal and neonatal history including associated congenital malformations and transplantation, in addition to surgical history, post-operation events and complications were taken into consideration. Furthermore, patients? laboratory data, histopathological findings and radiologic findings were collected. However, unreliable evidence was not regarded. Patient?s follow-ups if available were extracted from the Shiraz Pediatric Cirrhosis database (IR.SUMS.REC.1399.530).

Further information on children who underwent liver transplantation, such as the outcome of transplantation was also fetched from Abu-Ali Sina Hospital's HIS system.

The protocol of this study was approved by Shiraz Ethic Committee (IR.SUMS.REC.1403.091).

Statistical methods: Quantitative data were reported as Mean