Systematic Review of Progressive Familial Intrahepatic Cholestasis

Short Background:

Epidemiology is the study of how often and when diseases occur (prevalence), what the risk factors are, and how to control diseases. Epidemiology of rare diseases is challenging because the total number of patients in a study is often very small. For example getting precise percentages of subtypes of PFIC is difficult: if 10 PFIC patients participate in a study, and 6 out of the ten have PFIC2, then that results in a prevalence of 60%. Just one more PFIC2 patient (7 out of 10) would result in 70%.

Cholestasis is the reduction or complete stoppage of bile flow. Cholestasis within the liver is called intrahepatic cholestasis. Cholestasis does not only occur in PFIC but can also be part of other disorders.


This paper is a review of 20 previous research studies of the epidemiology, history, health-related quality of life of PFIC. Of the 20 papers they found there were 17 on the history and epidemiology of PFIC, and 5 focused on quality of life. Two papers covered both topics.

            Prevalence of  PFIC: The authors wanted to know how often the different PFIC subtypes occur in the general population. One of the previous studies showed a rate of 1 in 18,000 for intrahepatic cholestasis, which includes PFIC but also other diseases. Among children with different liver diseases the percentage that have PFIC seemed to be between 9 and 13%. Looking at how often the different subtypes occur among children with PFIC, 9 previous studies showed that PFIC2 was the most common subtype but the numbers varied quite a bit: across these studies 37-90% of PFIC patients had PFIC2. The numbers for PFIC1 were 10-38%, and for PFIC3 28-38%.

            Symptoms of PFIC: Nine previous studies described the clinical symptoms of the different PFIC subtypes: jaundice, hepatomegaly (enlarged liver), pruritus (itch), pale stools, splenomegaly (enlarged spleen), diarrhea, discolored stools, failure to thrive, vitamin E and vitamin D deficiencies, and for PFIC 1 also pancreatitis. In PFIC1 and 2 patients these symptoms show within the first 3 months of life, while for PFIC3 patients jaundice, hepatomegaly and pruritus may only show after 2-3 years. Itch was often severe (76-80%). Symptoms outside the liver were reported for PFIC1 (diarrhea 61%, pancreatitis 8%, elevated sweat chloride 15%), for PFIC2 (vitamin D deficiency 3-22%, vitamin K deficiency 8%), and for PFIC3 (vitamin D deficiency 6%).

            Severity of PFIC: Progression to severe liver disease was more common and occurred earlier in patients with PFIC2 than in those with PFIC1. The authors also looked at mortality rates reported in previous studies, which varied a lot (0-87%). The high number (87%) is probably the mortality rate when PFIC is not treated. Causes of death include infections, liver failure, and complications related to liver transplant. 

            Quality of Life: Five previous studies looked at quality of life or itch in PFIC patients. Both children themselves and their parents consistently rated quality of life lower than (parents of) healthy children. Three studies reported that itch was the most bothersome symptom.

            Conclusion: The authors of this review conclude that data about prevalence, mortality rates, and health related quality of life are very limited, and studies of the economic burden for a family with a child with PFIC are lacking entirely. They recommend more studies to be done in the future.


PFIC subtypes, prevalence, symptoms, quality of life


Baker et al. Systematic Review of Progressive Familial Intrahepatic Cholestasis. Clinics and Research in Hepatology and Gastroenterology, 43, 20-36. 2019

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