Autoimmune Hepatitis in a Patient with Pulmonary Arterial Hypertension Treated with Endothelin Receptor Antagonists

Abstract

A 48-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension (PAH) and administered PAH-specific therapies, including bosentan. Four years after the initiation of treatment with bosentan, liver dysfunction appeared, and ambrisentan was substituted for bosentan. One-and-a half years later, a second episode of liver dysfunction occurred. The pathological findings of a liver biopsy specimen were not definitive, although drug-induced hepatotoxicity caused by ambrisentan was considered. However, the patient's liver dysfunction did not improve even after the discontinuation of ambrisentan. Finally, we diagnosed her with autoimmune hepatitis (AIH). Providing careful observation with a suspicion of AIH is important when treating PAH patients with autoantibodies.

Bosentan Inducing Autoimmune Hepatitis in a Patient with Idiopathic Pulmonary Arterial Hypertension

“…In the adult population, a case was described by Naito et al [6], in which a 48-year-old woman was receiving bosentan for a period of four years when she presented drug-related hepatotoxicity. Bosentan was replaced by ambrisentan, another ERA but, after a year and a half, a second episode of hepatic dysfunction occurred, with no improvement after discontinuation of medication, leading the team to further investigation with a subsequent diagnosis of AIH.…”

Effect of treatment with epoprostenol and endothelin receptor antagonists on the development of thyrotoxicosis in patients with pulmonary arterial hypertension

“…However, other than autoimmune thyroid disease no other autoimmune diseases were detected in the patients with PAH in the present study. Only a few reports have described the comorbidity of IPAH or HPAH with autoimmune diseases other than autoimmune thyroid disease: two IPAH patients developed polyglandular autoimmune syndromes [26,27] and one IPAH patient developed autoimmune hepatitis [28] after the start of PAH treatment. The reason for the low incidence of IPAH or HPAH complicated with autoimmune diseases other than autoimmune thyroid disease is unclear.…”