S3256 Hyperbilirubinemia in Chronis Hepatitis C Patients Treated With Protease Inhibitors

Abstract

INTRODUCTION: Sofosbuvir/velpatasvir/voxilaprevir (SVV) and Glecaprevir/pibrentasvir (GP) are direct acting antiviral (DAA) agents used for chronic hepatitis C virus (HCV) infection. Both are pan-genotypic and used for treatment-experienced patients without cirrhosis or with compensated cirrhosis. Additionally, GP is approved in treatment-naïve patients. Hyperbilirubinemia has emerged as a potential adverse effect for these two medications due to significantly elevated NS3/4A protease inhibitor concentration. We aim to assess the incidence of hyperbilirubinemia in patients treated with these medications. METHODS: This is a retrospective study at a single tertiary care center. Patients who were treated with either SVV or GP between August 2017, and February 2020, were included. Patients who lost to follow-up were excluded. Laboratory exams were performed on a monthly basis. The population was analyzed based on treatment received: SVV +/- Ribavirin (RBV) and GP groups. Abnormal total bilirubin (Tbili) was defined as >1.2 mg/dL. Analyzed data included demographics, therapy history, achievement of sustained virologic response (SVR), hyperbilirubinemia incidence during the treatment period, timing and peak of T.bili, and all-cause mortality rate. RESULTS: Of the 229 charts reviewed, 196 met the inclusion criteria. Age ranged from 19 to 89 years old with a mean of 61, and 63% were males. 164 patients received GP, whereas 32 received SVV +/- RBV. Genotype 1 was the most prevalent. 25% of the population had compensated cirrhosis, and 4 patients underwent liver transplant. The incidence of hyperbilirubinemia was 12.8%, with a mean duration between therapy initiation and peak Tbili of 40 days. The highest Tbili measured was 6 mg/dL. 8.6% of patients had a peak Tbili >1.5 mg/dL, 3% had a peak Tbili >2 mg/dL, and only 1.5% had a peak Tbili >3 mg/dL. None of the patients had to stop therapy due to hyperbilirubinemia. The all-cause mortality rate was 2%, and causes were unrelated to hyperbilirubinemia or liver disease. There was no statistically significant difference in mean Tbili at treatment initiation or at peak between patients who received SVV +/- RBV and those who received GP, P = 0.227 and P = 0.129, respectively. CONCLUSION: Hyperbilirubinemia is a common side effect of DAAs containing NS3/4A protease inhibitors. Although it may not be clinically significant, clinicians should be mindful of potential hyperbilirubinemia and closely monitor chronic HCV patients treated with these agents with follow-up labs.