For US Health Care Professionals

Long-Term Outlook for PFIC

Current
Therapies

Medical therapy is the first line of treatment in patients with all types of progressive familial intrahepatic cholestasis (PFIC). The objectives are1:

  • Provide relief from pruritus
  • Improve nutritional status
  • Correct vitamin deficiencies
  • Treat complications of advanced liver disease

If medical therapy is ineffective, invasive surgery may be needed to effectively treat the disease.2

Partial External Biliary Diversion (PEBD)

PEBD has been used successfully in some patients with PFIC1 and PFIC2 who do not respond to medical therapy and are as yet not candidates for liver transplant.1 For patients with PFIC, PEBD relieved pruritus in 54%.3 However, PEBD has the disadvantage of a permanent stoma, which can be challenging for children in their daily lives and impact their quality of life.4

Liver Transplant

Beyond biliary diversion procedures, liver transplant is the last surgical option for patients with all types of PFIC. Transplant should be considered for patients with end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC), or those with poor quality of life due to refractory pruritus despite medical treatment and biliary diversion. Liver transplant improved cholestasis and its symptoms in 75% to 100% of patients, irrespective of PFIC subtype, over a short-term follow-up of 3 to 5 years.1

Liver transplant, on the other hand, is associated with complications such as rejection, post-transplant hepatic steatosis and recurrence of disease, and lifelong antirejection medication.5,6

Current Therapies
Treatment Landscape

Treatment Landscape

For patients with progressive familial intrahepatic cholestasis (PFIC), there is a need for more noninvasive treatment options that target the root cause of the cholestasis early in the course of disease.6

The goals of these treatments should be to6:

Reducethe accumulation of bile acids in the liver and bloodstream

Relievecholestatic pruritus

Limitthe progression of liver disease

Improvelong-term prognosis

Promising
Research

A number of alternative, nonsurgical therapies for cholestatic liver diseases are currently under investigation.6

Transplant can often
improve the itch, but we
hope that it will not be
the only option. –Emily K.
Promising Research

PFIC Resources

  • Progressive Familial Intrahepatic Cholestasis Advocacy and Resource Network
ASBT=apical sodium-dependent bile acid transporter; ESLD=end-stage liver disease; HCC=hepatocellular carcinoma; IBAT=ileal bile acid transporter; PEBD=partial external biliary diversion; PFIC=progressive familial intrahepatic cholestasis.
References: 1. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4(1):25-36. doi:10.1016/j.jceh.2013.10.005 2. Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019;43(1):20-36. doi:10.1016/j.clinre.2018.07.010 3. van Wessel DBE, Thompson RJ, Gonzales E, et al. Genotype correlates with the natural history of severe bile salt export pump deficiency. J Hepatol. 2020;73(1):84-93. doi:10.1016/j.jhep.2020.02.007 4. Wassman S, Pfister ED, Kuebler JF, et al. Quality of life in patients with progressive familial intrahepatic cholestasis: no difference between post-liver transplantation and post-partial external biliary diversion. J Pediatr Gastroenterol Nutr. 2018;67(5):643-648. doi:10.1097/MPG.0000000000002118 5. van der Woerd WL, Houwen RH, van de Graaf SF. Current and future therapies for inherited cholestatic liver diseases. World J Gastroenterol. 2017;23(5):763-775. doi:10.3748/wjg.v23.i5.763 6. Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020;40(8):1812-1822. doi:10.1111/liv.14553