Beyond pruritus in Alagille syndrome: potential effects of maralixibat on fibrosis and portal hypertension–insights from two case studies

TL;DR

Maralixibat treatment in two Alagille syndrome patients improved pruritus and showed potential benefits on liver fibrosis and portal hypertension.

Contribution

Demonstrates maralixibat's potential to improve fibrosis and portal hypertension in Alagille syndrome beyond pruritus relief.

Findings

Maralixibat led to fibrosis regression from cirrhosis to stage F2 in a newborn with Alagille syndrome.

Treatment improved portal hypertension, liver stiffness, and splenomegaly in both patients.

Pruritus resolved completely in one patient and significantly improved in another.

Abstract

Alagille syndrome (ALGS) is a genetic disorder primarily affecting the liver, often leading to cholestasis and pruritus. Ileal Bile Acid Transporter inhibitors (IBATi), such as maralixibat, have shown promise in controlling pruritus and potentially modifying disease progression.

We report two patients with ALGS treated with maralixibat. Case 1 involved a 10-days-old newborn presenting with cholestasis, jaundice, and acholic stools. Genetic testing confirmed a pathogenic JAG1 mutation. Despite preserved liver function, the patient was evaluated for liver transplantation (LT) due to severe pruritus and portal hypertension. Maralixibat initiation led to marked improvement in pruritus, serum bile acids, bilirubin, and cholesterol. Liver biopsies performed 13 months apart demonstrated fibrosis regression from cirrhosis to stage F2. Elastography showed decreased liver stiffness, reduced splenomegaly, and improved platelet counts. Liver enzymes transiently increased, but treatment continued without dose adjustment. Case 2 involved a 15-years-old female with moderate portal hypertension and mild pruritus. After 24 months of maralixibat, pruritus resolved completely, serum bile acids decreased, liver stiffness and splenomegaly improved, and platelet counts increased. Liver enzymes remained mildly elevated without requiring treatment modification. These findings suggest maralixibat may improve portal hypertension and hepatic injury, even in patients with less severe biochemical abnormalities.

In ALGS, maralixibat treatment improved pruritus, lowered serum bile acids, and suggested potential benefits on fibrosis and portal hypertension, indicating a possible role beyond symptomatic relief.

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