IBAT inhibitors may improve post-liver transplant pruritus

“There’s a lot to still be known and learn about the use of these medications, and some exciting future directions would be larger studies that can further confirm that safety and efficacy,” said study presenter Mary Chandran, (University of North Carolina Health, Chapel Hill, USA).

Such studies could also evaluate the optimal dosing and duration post-transplant, alongside long-term outcomes, the impact on quality of life, and combination strategies with other anti-pruritic agents.

Chandran began by noting that severe and persistent pruritus can occur after liver transplantation. “Fortunately, this does only affect a small minority of our patients,” she said, but it can complicate their post-transplant course, and may be “quite difficult to manage, with significant impacts on quality of life.”

She added that pruritus after liver transplantation is often linked to biliary complications, cholestatic graft dysfunction or recurrent or de novo cholestatic or biliary disease, and that standard antipruritic therapy, such as bile acid sequestrants, rifampin, naltrexone, and sertraline, are “often ineffective and poorly tolerated.”

IBAT inhibitors have been approved for use in cholestatic pruritus due to Alagille syndrome and progressive familial intrahepatic cholestasis, while benefits have also been seen in primary biliary cholangitis and other cholestatic liver diseases.

“So given the mechanism of these medications, their efficacy in other cholestatic diseases and their generally well-tolerated side effect profile,” Chandran said, “IBAT inhibition is an attractive option for our liver transplant recipients that have refractory pruritus.”

She added, however, that “there is a clear knowledge gap to date: there is no published data or trials evaluating the use of IBAT inhibitors in this unique patient population.”

To address that gap, Chandran described the use and outcomes of IBAT inhibitors in three adult liver transplant recipients with treatment-refractory pruritus.

The first case was a 56-year-old male living donor liver transplant recipient who had persistent pruritus from 6 weeks after their transplant related to recurrent biliary strictures that required repeat endoscopic retrograde cholangiopancreatography (ECRP) and stenting.

The pruritus was refractory to standard treatments, so the patient was started on daily odevixibat 9 months after their liver transplant, at a dose of 40 mg/kg. They experienced significant improvements with the drug, with the pruritus well controlled, and they were able to reduce their use of cholestyramine to as needed.

The patient experienced diarrhea soon after starting odevixibat but that resolved without intervention, and there was a transient recurrence of pruritus during an episode of acute rejection/biliary complications, which was successfully treated with steroids.

The second patient was a 49-year-old female living donor liver transplant recipient who had persistent pruritus from 3 weeks after their operation associated with a bile leak and, again, a biliary stricture that required ECRP and stenting.

Following failure of standard pruritus treatments, the patient was started on daily odevixibat 40 mg/kg at 10 months following their transplant but was latterly switched to daily maralixibat 30 mg due to the requirements of her insurance coverage. Chandran said she experienced “near complete resolution” of her pruritus, and although diarrhea occurred, it was consistent with her baseline chronic symptoms and did not worsen.

Finally, the third patient was a 31-year-old female deceased donor liver transplant recipient who developed pruritus during pregnancy 27 years following their surgery, which continued after giving birth. Again, her symptoms were refractory to standard treatments, and she was started on daily maralixibat 29 years after receiving her transplant, at a dose of 28.5 mg.

The patient had an improvement in her pruritus, with itching reduced to 1 or 2 days per week, and a significant improvement in her quality of life. She has even been able to stop taking ursodiol. While she experienced transient elevations in liver function tests, there were no rejection episodes.

In all three patients, tacrolimus levels were stable.

Chandran acknowledged that the study is limited by it being from a single center and having only a small number of cases. Patient monitoring and follow-up times were also variable, and adjustments to concurrent anti-pruritic medications were not fully assessed or standardized.