Potential Complications of Hyperbilirubinemia on Therapy With Glecaprevir and Pibrentasvir for Therapy of Hepatitis C in Complex Real World Patients

Abstract

Introduction Treatment of Hepatitis C (HCV) in the cirrhotic and renal insufficiency population is complex. Here we present 2 patients: one with HCV genotype 1b cirrhosis and another with HCV genotype 3 in a transplanted liver with unusual complications on therapy with glecaprevir/pibrentasvir. Case 1 A 64 year-old female presented with history of alcohol abuse and treatment naïve HCV genotype 1b with compensated cirrhosis and chronic kidney disease (CKD) stage 3. Glecaprevir/pibrentasvir was approved for 12 weeks. Baseline bilirubin of 1.1 rose by two weeks on therapy to 6.1. Labs were monitored over time but given persistent elevation and recent alcohol use therapy was held. Labs 1 week following glecaprevir/pibrentasvir cessation showed rapid improvement of bilirubin to 1.9. In total, this patient received a total of three weeks of treatment and did have sustained viral response at 8 weeks after treatment. Case 2 A 33 year-old female with dual kidney-liver transplant with recurrent CKD stage 3B, mitral valve and aortic valve replacement and pacemaker presents with treatment naïve genotype 3 HCV without known recurrence of cirrhosis on imaging. Patient was started on glecaprevir/pibrentasvir for planned 12 week course. Patient was admitted to the hospital with acute jaundice leading to fluid overload and acute tubular necrosis requiring dialysis. Prior to glecaprevir/pibrentasvir therapy bilirubin was 1.4. After 2 weeks on treatment bilirubin rose to 7.6 with fluid overload and renal failure. After glecaprevir/pibrentasvir was held bilirubin improved to 4.6 within one week. Discussion Glecaprevir/pibrentasvir is approved for treatment of HCV with compensated cirrhosis including patients with severe renal impairment (CKD Stage 4 and 5). Our study highlights potential risks when treating patients with compensated cirrhosis and renal insufficiency. Glecaprevir/pibrentasvir is not indicated for patients with decompensated cirrhosis and has been reported to cause hyperbilirubinemia in a small number of patients in clinical studies. Given these two cases, it remains prudent to be wary of hyperbilirubinemia as a side effect and potential for cirrhotic decompensation with renal failure during treatment of complex liver patients.