Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 Sep;98(39):e17343.
doi: 10.1097/MD.0000000000017343.

A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis

Jae Hyun Yoon  1 , Sun Min Kim  1 , Gaeun Kang  2 , Hee Joon Kim  3 , Chung Hwan Jun  1 , Sung Kyu Choi  1
Affiliations
Case Reports

A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis

Jae Hyun Yoon et al. Medicine (Baltimore). 2019 Sep.

Abstract

Rationale: Glecaprevir/pibrentasvir, a pan-genotypic and ribavirin-free direct acting antiviral agent regimen, has shown significant efficacy and very few serious complications. However, as the drug metabolizes in the liver, it is not recommended in patients with decompensated liver cirrhosis. Herein, we report the case of a patient with compensated liver cirrhosis who developed severe jaundice after glecaprevir/pibrentasvir medication.

Patient concerns: A 77-year-old man diagnosed with chronic hepatitis C-related compensated liver cirrhosis visited hospital due to severe jaundice after 12 weeks of glecaprevir/pibrentasvir medication.

Diagnoses: On the laboratory work-up, the total/direct bilirubin level was markedly elevated to 21.56/11.68 from 1.81 mg/dL; the alanine aminotransferase and aspartate aminotransferase levels were within the normal range. We checked the plasma drug concentration level of glecaprevir, and 18,500 ng/mL was detected, which was more than 15 times higher than the drug concentration level verified in normal healthy adults.

Interventions: Glecaprevir/pibrentasvir was abruptly stopped and after 6 days, the drug concentration level decreased to 35 ng/mL and the serum total/direct bilirubin decreased to 7.49/4.06 mg/dL.

Outcomes: Three months after drug cessation, the serum total bilirubin level normalized to 1.21 mg/dL and HCV RNA was not detected.

Lessons: We report what is likely the first known case of severe jaundice after medication with glecaprevir/pibrentasvir in a patient with compensated liver cirrhosis. Clinicians should bear potential hyperbilirubinemia in mind when treating chronic hepatitis C with this regimen and should monitor the patient closely during follow-up laboratory exams, especially in elderly cirrhotic patients.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Course of plasma glecaprevir concentration and total bilirubin level.
Figure 2
Figure 2
Sequential action of intestinal and hepatic P450 enzymes on orally ingested drugs. CPR = NADPH-cytochrome P450 reductase,[15] P-gp = P-glycoprotein.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kanda T. Interferon-free treatment for HCV-infected patients with decompensated cirrhosis. Hepatol Int 2017;11:38–44. - PubMed
    1. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol 2018;69:461–511. - PubMed
    1. Kosloski MP, Wang H, Pugatch D, et al. Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment. Eur J Clin Pharmacol 2019;75:217–26. - PubMed
    1. A SPECIAL MEETING REVIEW EDITION: Highlights in Hepatitis C Virus From the 2017 AASLD Liver Meeting: A Review of Selected Presentations From the 2017 AASLD Liver Meeting ∗ October 20-24, 2017 ∗ Washington, DCSpecial Reporting on:∗ Efficacy, Safety, and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis∗ Hepatitis C Virus Reinfection and Injecting Risk Behavior Following Elbasvir/Grazoprevir Treatment in Participants on Opiate Agonist Therapy: Co-STAR Part B∗ Efficacy and Safety of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Treatment-Naive Patients With Chronic HCV Genotype 3: An Integrated Phase 2/3 Analysis∗ SOF/VEL/VOX for 12 Weeks in NS5A-Inhibitor-Experienced HCV-Infected Patients: Results of the Deferred Treatment Group in the Phase 3 POLARIS-1 Study∗ Adherence to Pangenotypic Glecaprevir/Pibrentasvir Treatment and SVR12 in HCV-Infected Patients: An Integrated Analysis of the Phase 2/3 Clinical Trial Program∗ The C-BREEZE 1 and 2 Studies: Efficacy and Safety of Ruzasvir Plus Uprifosbuvir for 12 Weeks in Adults With Chronic Hepatitis C Virus Genotype 1, 2, 3, 4, or 6 Infection100% SVR With 8 Weeks of Ledipasvir/Sofosbuvir in HIV-Infected Men With Acute HCV Infection: Results From the SWIFT-C Trial (Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1-Infected Individuals)PLUS Meeting Abstract SummariesWith Expert Commentary by:Fred Poordad, MDChief, HepatologyUniversity Transplant CenterClinical Professor of MedicineThe University of Texas Health, San AntonioSan Antonio, Texas. Gastroenterology & hepatology. 2017; 13(12 Suppl 5):1-24. PubMed PMID: 29950953; PubMed Central PMCID: PMC6015237. - PMC - PubMed
    1. AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis 2018;67:1477–92. - PMC - PubMed

Publication types

MeSH terms