Determinants and Outcome of Hyperbilirubinemia in Children and Adolescents Receiving Eltrombopag Therapy

Introduction Eltrombopag (ELT) is a thrombopiotin receptor agonist approved for treatment of pediatric immune thrombocytopenia (ITP) and severe aplastic anemia (SAA) with reported hepatobiliary adverse events (AE). We assessed the frequency and clinical determinants of hepatobiliary AE in patients with ITP or SAA receiving ELT therapy. Methods we retrospectively reviewed the records of 61 patients aged from 1 to 18 years receiving ELT; 42 patients with ITP and 19 with SAA. Patients were categorised according to hepatobiliary toxicity into three groups: no toxicity (group A), isolated hyperbilirubinemia (group B), and transaminitis with/without hyperbilirubinemia (group C). Results we observed our patients along the first three courses of treatment. The mean duration of the 1st course in group A, B and C was 8.2, 9.5 and 7 months, respectively. While, the mean duration of the 2nd course in group A, B and C was 2.6, 2.8 and 2.1 months, respectively. Also, the mean duration of the 3rd course in group A, B and C was 5.2, 1.7 and 8.9 months, respectively. Overall, 36% of patients developed hepatobiliary toxicity (24.6% had isolated hyperbilirubinemia while 11.5% had transaminitis with/without hyperbilirubinemia). Most patients (93%) in isolated hyperbilirubinemia group had SAA, in contrast to transminitis group in which 40% out of 54.29% had ITP (p < 0.001). Isolated hyperbilirubinemia occurred at similar doses in ITP and SAA (50-75mg), while transaminitis devleoped in ITP at a lower dose (50- 75 mg) than those with SAA (100-125mg). Ten patients discontinued treatment for toxicity; one with liver cell failure. All patients showed normalization of their liver function tests after discontinuation of treatment. Conclusion hepatobiliary toxicity represents a common occurrence with ELT therapy, and it requires regular follow up of liver function tests.