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Dosing ribavirin in hepatitis E-infected solid organ transplant recipients.
Pharmacol Res. 2018 04; 130:308-315.PR

Abstract

Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsible for a chronic hepatitis that can lead to cirrhosis in immunocompromized patients, i.e. solid-organ- and stem-cell-transplant-patients, human immunodeficiency virus-infected patients, and patients receiving chemotherapy or immunotherapy. HEV has also been associated with extra-hepatic manifestations such as neurologic disorders (Guillain-Barré Syndrome and neuralgic amyotrophy) and kidney disease. In patients with chronic hepatitis, reduction of immunosuppression, when possible, is the first therapeutic option. In the remaining patients, ribavirin therapy has been shown to very efficient for treating HEV infection leading to a sustained virological response in nearly 80-85% of patients. However, the mechanism of action of ribavirin in this setting is still unknown, as is the impact of HEV RNA polymerase mutations. There are unmet needs with regard to the treatment of chronic HEV with ribavirin. These include the optimal dosing and duration of treatment, and the potential beneficial effects of therapeutic drug monitoring on the virological response and the incidence of side effects. In the present review, we will provide an overview of HEV epidemiology, its mode of transmission and clinical manifestations, as well as its treatment by ribavirin with a focus on the drug's pharmacokinetics and dosing.

Authors+Show Affiliations

Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, The Netherlands.Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands; Rotterdam Transplant Group, Division of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, Toulouse, France.Department of Internal Medicine, Division of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, Toulouse, France. Electronic address: kamar.n@chu-toulouse.fr.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

29499270

Citation

De Winter, Brenda C M., et al. "Dosing Ribavirin in Hepatitis E-infected Solid Organ Transplant Recipients." Pharmacological Research, vol. 130, 2018, pp. 308-315.
De Winter BCM, Hesselink DA, Kamar N. Dosing ribavirin in hepatitis E-infected solid organ transplant recipients. Pharmacol Res. 2018;130:308-315.
De Winter, B. C. M., Hesselink, D. A., & Kamar, N. (2018). Dosing ribavirin in hepatitis E-infected solid organ transplant recipients. Pharmacological Research, 130, 308-315. https://doi.org/10.1016/j.phrs.2018.02.030
De Winter BCM, Hesselink DA, Kamar N. Dosing Ribavirin in Hepatitis E-infected Solid Organ Transplant Recipients. Pharmacol Res. 2018;130:308-315. PubMed PMID: 29499270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dosing ribavirin in hepatitis E-infected solid organ transplant recipients. AU - De Winter,Brenda C M, AU - Hesselink,Dennis A, AU - Kamar,Nassim, Y1 - 2018/02/27/ PY - 2017/11/23/received PY - 2018/02/06/revised PY - 2018/02/26/accepted PY - 2018/3/3/pubmed PY - 2019/1/19/medline PY - 2018/3/3/entrez KW - Cirrhosis KW - Hepatitis E KW - Immunosuppression KW - Liver injury KW - Organ transplantation KW - Ribavirin SP - 308 EP - 315 JF - Pharmacological research JO - Pharmacol Res VL - 130 N2 - Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsible for a chronic hepatitis that can lead to cirrhosis in immunocompromized patients, i.e. solid-organ- and stem-cell-transplant-patients, human immunodeficiency virus-infected patients, and patients receiving chemotherapy or immunotherapy. HEV has also been associated with extra-hepatic manifestations such as neurologic disorders (Guillain-Barré Syndrome and neuralgic amyotrophy) and kidney disease. In patients with chronic hepatitis, reduction of immunosuppression, when possible, is the first therapeutic option. In the remaining patients, ribavirin therapy has been shown to very efficient for treating HEV infection leading to a sustained virological response in nearly 80-85% of patients. However, the mechanism of action of ribavirin in this setting is still unknown, as is the impact of HEV RNA polymerase mutations. There are unmet needs with regard to the treatment of chronic HEV with ribavirin. These include the optimal dosing and duration of treatment, and the potential beneficial effects of therapeutic drug monitoring on the virological response and the incidence of side effects. In the present review, we will provide an overview of HEV epidemiology, its mode of transmission and clinical manifestations, as well as its treatment by ribavirin with a focus on the drug's pharmacokinetics and dosing. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/29499270/Dosing_ribavirin_in_hepatitis_E_infected_solid_organ_transplant_recipients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(17)31510-4 DB - PRIME DP - Unbound Medicine ER -