The impact of progressive familial intrahepatic cholestasis (PFIC): A condition overview and infographic
PFIC refers to a set of rare genetic conditions where the liver struggles to release bile acid needed to digest dietary fats and oils. This bile build-up, known as intrahepatic cholestasis, can harm the liver, potentially leading to liver failure.1
Although PFIC can present itself later in life, it generally manifests and is most aggressive in infants and young children.2
PFIC can be diagnosed in adulthood. In these cases, symptoms tend to have been milder when younger and could mimic other diseases.2,3,4
PFIC1,2 and 3 are the most common subtypes, but up to 12 different subtypes have been identified to date. With advance in genetic testing, more subtypes may be identified in future.1
Understanding the various PFIC subtypes can help inform the most appropriate treatment approach for people living with PFIC.1
PFIC affects male and females equally—1 per 50,000 to 1 per 100,000 births, although exact prevalence is not known.5
PFIC can progress rapidly and cause cirrhosis (long-term scarring) during infancy or may progress relatively slowly with minimal scarring well into adolescence. Few individuals have survived into their twenties without treatment.5,6
Without liver transplant, only approximately 50% of children with PFIC survive to age 10, and almost none survive to 20 years old.7
What happens in the liver?
The liver is an important organ that removes toxins from the blood and helps turn the food we eat into energy. A healthy liver produces bile, a liquid that helps with digestion by breaking down fats and absorbing vitamins. In people with PFIC, abnormal bile secretion leads to bile build-up in the liver, which may cause a number of symptoms and long-term problems.3
For people living with PFIC, certain processes, like the release of bile salts, do not happen as they should. This may cause a number of symptoms and have long-term impact.8
Symptoms
One of the most debilitating symptoms is pruritus (intolerable itching), which may be so severe that it leads to severe skin injury, loss of sleep, irritability, poor attention and impaired school performance.1,6,9 The itching can be so intense for those living with PFIC that they may scratch through their skin. Some may turn to surgery, including liver transplant, for relief.1
Up to 80% of PFIC patients had pruritus graded as severe (associated with abrasions, severe skin injury, bleeding or scarring).1
The most common symptoms include:10,11
- intolerable itching (pruritus)
- yellowing of skin (jaundice)
- failure to thrive (impaired development or growth)
- liver problems (cholestasis)
- diarrhoea
What causes the itch?
When bile doesn’t flow normally, it can reach high levels in the liver and bloodstream, which may lead to pruritus.11 The bile salts irritate the nerves in the peripheral nervous system, causing the intense itching.
Diagnosis and treatment
Diagnosis can be a lengthy process.3 Symptoms such as pruritus, jaundice and failure to thrive create disease suspicion. A paediatrician or general practitioner may recommend seeing a liver specialist, called a hepatologist, to make a diagnosis. Combined biochemical, radiological and histological approaches can confirm a diagnosis of PFIC and the specific subtype.12
Once diagnosed, there are non-surgical and surgical treatment options for consideration. Discussions between parents or carers and specialist hepatologists can help determine the best treatment approach.12
The impact of PFIC on caregivers
A multinational study called PICTURE focused on the health-related quality of life (HRQoL) and work productivity outcomes investigating the impact of PFIC on 22 caregivers looking after children with PFIC.
The study highlighted that although most caregivers reported fulfilment in their caregiving responsibilities, many experienced problems with mental and physical health, finances, and relationships.13
Almost all caregivers in the study reported an impact of caregiving responsibilities on sleep (86%) and on personal relationships (82%). No caregivers reported having formal care support.13
This study shows the prevalent, comprehensive, and meaningful impact that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL, including mental and physical health, productivity, career prospects, sleep, relationships and finances.13
Francesca, caregiver to Eva Luna, claims that her family has not had a full night’s sleep since Eva Luna was born as she is so uncomfortable that she screams and cries all night. Following her diagnosis with PFIC, her parents were desperate to find something to help her.
Looking to the future
The future of PFIC management and treatment will continue to be shaped by a combination of continued scientific advancements, technological innovations, disease awareness education and collaborative efforts among researchers, clinicians, people living with PFIC, and advocacy groups.
Early diagnosis provides an opportunity for healthcare providers to develop personalized treatment and management strategies tailored to the individual’s needs.1 If caught early, getting the right treatment quickly can slow down how quickly the disease worsens and keep the liver working effectively for longer.14
Coping with PFIC can be challenging, and having access to support networks early on can help patients and families navigate the emotional and practical aspects of living with PFIC.
Download IPSEN’s infographic on the impact of PFIC by clicking the link below.
Download IPSEN’s infographic on the impact of PFIC
References
1. Baker A, et al. 2019. Systematic review of progressive familial intrahepatic cholestasis. Clin Resh Hepatol Gastroenterol. 43(1):20-36.
2. Nayagam NS, et al. 2022. Clinical phenotype of adult‐onset liver disease in patients with variants in ABCB4, ABCB11, and ATP8B1. Hepatol Commun. 6(10):2654-2664.
3. A Siddiqi I and Tadi P. 2023. Progressive Familial Intrahepatic Cholestasis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available at: https://www.ncbi.nlm.nih.gov/books/NBK559317/. Accessed April 2024.
4. Bansal, Nalini and Mukul Rastogi. 2017. “An Itchy Experience – PFIC 3 Masquerading as Wilson’s Disease; Learning from Mistakes.” Oncology, Gastroenterology and Hepatology Reports. 6(1):67-71.
5. Davit-Spraul A, et al. 2009. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 4(1):1-12.
6. AbuBotain H and Khounganian R. 2013. Dental management of a patient with progressive familial intrahepatic cholestasis. King Saud University Journal of Dental Sciences. 4(1):37-45.
7. Jones-Hughes T, et al. 2021. Epidemiology and burden of progressive familial intrahepatic cholestasis: a systematic review. Orphanet J Rare Dis. 16(1):255.
8. Chiang JYL. 2013. Bile Acid Metabolism and Signaling. Comprehensive Physiology. 3(3):1191–1212.
9. Langedijk JAGM, et al. 2021. Cholestasis-Associated Pruritus and Its Pruritogens. Frontiers Medicine. 8(639674):1-13.
10. Srivastava A. 2014. Progressive Familial Intrahepatic Cholestasis. J Clin Exp Hepatol. 4(1):25-36.
11. Mehl A, et al. 2016. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children. World J Transplant. 6(2):278-290.
12. Gunaydin M, et al. 2018. Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment. Hepatic Medicine: Evidence and Research. 10(10):95-104.
13. Mighiu C, et al. 2022. Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study. Orphanet J Rare Dis. 17(32):1-12.
14. McKiernan P, et al. 2023. Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis. Journal of Hepatology Report. 6(1):100949.
Disclaimer: Any medical information included in this article is not intended to form medical advice. It must not be used as a tool to help understand or assess potential options around diagnosis and treatment. Patients must consult a doctor to receive medical advice, diagnosis and treatment that is appropriate to their specific and unique circumstances.
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This digital spotlight has been made possible with financial support from IPSEN. IPSEN provided editorial content for this article. All opinions are those of the contributors and there was no transfer of value for participation. RARE Revolution Magazine and IPSEN are not responsible for the content of any external sites linked to or referred to within this article. RARE Revolution Magazine retains all copyright.
Date of preparation: August 2024 – BYL-PFIC-ALL-000063
