Case study supports safety, efficacy of liver transplant for PFIC3
Pharmacological treatments for the condition often predict poor prognosis
A 3-year-old boy with progressive familial intrahepatic cholestasis type 3 (PFIC3) was safety and effectively treated with a liver transplant from his mother after failing to respond to standard therapeutic regimens, a case study reports.
“Given the rapid progression associated with PFIC-3, pharmacological treatments often predict a poor prognosis,” the researchers wrote, adding that “liver transplantation should be promptly considered and prepared for.
”The case report, “Parental liver transplantation for treating progressive familial intrahepatic cholestasis: A rare case report,” was published as a letter to the editor in the Asian Journal of Surgery.
Progressive familial intrahepatic cholestasis in an umbrella term for rare genetic liver diseases marked by problems producing and/or secreting bile by liver cells. Bile is a digestive fluid made in the liver that flows out to the intestines through a series of bile ducts.
As a result, patients develop intrahepatic cholestasis — slowed or stalled bile flow in the bile ducts inside the liver — and bile builds up, causing damage that can lead to liver failure. Common symptoms include dark urine, itching, and jaundice, that is, yellowing of the skin and whites of the eyes.
PFIC3 is caused specifically by mutations in the ABCB4 gene that lead to the deficient production of a working MDR3 protein, which is involved in transporting compounds that neutralize bile components to prevent damage to bile duct cells.
Treatment with ursodeoxycholic acid (UDCA), sold as Urso and Actigall, is a mainstay first-line therapy for PFIC and other forms of cholestasis.
Confirming a PFIC3 diagnosis
“Liver transplantation is usually the last resort when pharmacological treatment fails to control progression,” the researchers wrote.
Now, researchers in China described the case of a 3-year-old boy diagnosed with PFIC3 who was successfully treated with a liver transplant one year after his diagnosis.
The boy showed signs of liver damage, the main symptoms being jaundice and dark urine. He received standard of care treatments, but his condition worsened.
After the common causes of cholestasis were ruled out, genetic tests showed two mutations in the ABCB4 gene: c.202G>A, which was considered likely disease-causing, and c.3838T>C, whose effect on the resulting MDR3 protein was deemed uncertain. The findings, along with the boy’s clinical profile, confirmed a PFIC3 diagnosis.
Blood work showed abnormally high levels of bilirubin and liver enzymes, all markers of liver damage. Liver ultrasound and CT scans showed liver lesions and increased liver stiffness, and a liver biopsy revealed mild chronic inflammation and bile duct changes.
The boy had a piggyback liver transplant with liver tissue donated from his mother. In this type of surgery, the recipient’s hepatic inferior vena cava, a major vessel that carries blood from the liver into the heart, is preserved, ensuring better outcomes.
Post-surgery scans showed no signs of liver lesions or blood vessel obstruction. The boy was treated daily with medications to prevent the transplant from being rejected, to protect the liver, and ease symptoms.
While liver damage markers increased after surgery, they returned to normal the third day after the transplant. A CT scan showed no abnormalities and he was discharged.
This case report highlights how a PFIC3 diagnosis should be considered when “other common causes for cholestasis have been ruled out,” and that comprehensive genetic testing should be performed as soon as possible, the researchers wrote.
“In the case discussed, the transplanted [liver] quickly became functional, leading to positive clinical outcomes,” they wrote.
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