Clinical Diversity and Outcomes of Progressive Familial Intrahepatic Cholestasis Diagnosed by Whole Genome Sequencing in Pakistani Children

This study analyzes 116 Pakistani children with Progressive Familial Intrahepatic Cholestasis (PFIC), diagnosed with whole genome sequencing. PFIC3 was the predominant type (44.8%), followed by PFIC2 (24.1%), PFIC1 (16.4%), PFIC4 (12.9%), and PFIC5 (1.7%). Diverging from prior studies, we found a notable absence of pruritus in a quarter of PFIC1 and PFIC3 patients, and in one-third of those with PFIC2 and PFIC4; diarrhea in 6.7% of PFIC4; hearing loss in 13.3% of PFIC4 and some PFIC3; elevated GGT levels in about half the patients with PFIC1, PFIC2, and PFIC4; anemia in 84.2%-89.3% of cases; no liver tumors observed in PFIC patients even into the second decade. Survival analysis revealed a grim 20-year cumulative survival rate of 20%. However, liver transplantation significantly improved survival to 89%, compared to 9% with standard medical treatment. PFIC3 patients showed a less aggressive disease course and better survival. This study, highlighting the genetic and phenotypic diversity within PFIC and the poor outcomes with conventional treatment, underscores the critical need for revising medical management strategies for PFIC patients.