Livmarli helps ease stubborn itching in Alagille syndrome after surgery
Case report shows relief in two girls before and after biliary diversion reversal
Livmarli (maralixibat) safely eased severe, treatment-resistant itching in two girls with Alagille syndrome who previously underwent surgical biliary diversion (SBD), a procedure that redirects the flow of bile when it builds up in the body, a study showed.
Livmarli was used either as an add-on to the surgery, allowing the diversion to be reversed while still keeping itching controlled, or as a treatment started after the reversal.
“These findings expand the therapeutic scope of [Livmarli] beyond patients who have not undergone SBD or SBD reversal,” the researchers wrote.
The study, “Treatment of intractable pruritus with maralixibat in patients with Alagille syndrome before and after reversal of biliary diversion,” was published in JPGN Reports by a team of researchers in the U.S.
What drives itching and bile-flow problems in Alagille syndrome
Alagille syndrome is caused by genetic mutations, most often in the JAG1 gene, that lead to too few bile ducts inside the liver. This slows or blocks bile flow, a problem known as cholestasis, causing bile to build up in the liver and bloodstream.
Itching, or pruritus, is one of the most common symptoms and can disrupt sleep, comfort, and daily activities. Treatment may involve medications or surgical interventions, such as SBD, which is used when itching does not respond to standard care.
SBD creates a new pathway for bile to leave the body, either by connecting the gallbladder or bile duct to the small intestine or by diverting bile through an external opening.
However, “even after a technically successful SBD, pruritus may not be alleviated in some patients,” the researchers wrote, and the procedure is associated with “cosmetic and psychosocial concerns (e.g., stigma, lifestyle limitations)” that are common reasons for SBD reversal.
Livmarli is an oral therapy approved to reduce itching in Alagille patients, as young as 3 months in the U.S. and 2 months in the European Union. It works by blocking bile recycling from the intestines back to the liver, helping more bile exit the body in stool and reducing its buildup.
Case details show how Livmarli was used before and after diversion surgery
Here, U.S. researchers reported on two girls with Alagille syndrome who were treated with Livmarli either before or after SBD.
Both girls were diagnosed with Alagille in early infancy, at 3 months and 2.5 months, with diagnoses confirmed through liver biopsy. Genetic testing showed mutations in the JAG1 gene — one already identified as disease-causing in the first girl, and another likely disease-causing mutation, called c.685T>C, in the second girl.
Both had persistent jaundice (yellowing of the skin and eyes due to bile buildup in the blood) from early infancy. Itching began at 6 months in the first girl and 12 months in the second.
Both girls tried several medications for itching, with little benefit, and eventually underwent SBD due to treatment-resistant itching — at 11 months for the first girl and 21 months for the second.
The surgery eased itching for several years in both girls. However, the first girl still had mild itching and required occasional medication.
At age 5, the first girl started Livmarli at a dose of 380 mcg/kg once daily. The therapy was well tolerated and eased itching. One year later, her SBD was reversed, leading to increased itching. The dose of Livmarli was increased to 380 mcg/kg twice daily, which effectively reduced symptoms.
Second case shows relief after surgery reversal and worsening symptoms
The second girl requested SBD reversal at age 15. Soon afterward, she developed treatment-resistant itching along with sleep loss and self-mutilation behaviors. She began Livmarli at 190 mcg/kg once daily for seven days, then increased to 380 mcg/kg once daily, which significantly reduced her itching.
After about 1.5 months, her dose was further increased to 380 mcg/kg twice daily, which led to continued improvement in itching, sleep, and overall quality of life over roughly three years of follow-up.
There were no clinically meaningful changes in liver enzyme or bilirubin levels. Blood bile-acid levels, a key component of bile, decreased compared with baseline before starting Livmarli.
“Treatment with [Livmarli] can improve outcomes in patients with [Alagille] who have SBD refractory [itching], and in patients who have had a reversal of their SBD and experience refractory [itching],” the researchers wrote.
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