Evidence map›Paper›PMID 40581807›Full record

ArticleThe Journal of antimicrobial chemotherapy2025

Development of a ribavirin dosing regimen in transplant recipients with chronic hepatitis E virus infection: a population pharmacokinetic and -dynamic model.

Midas B Mulder, Martijn van Noort, Robert A de Man, Nassim Kamar, Joep de Bruijne, Marjolein Knoester, Hans Blokzijl, Thomas Vanwolleghem, Laurence Roosens, Jacques Izopet and 7 more

Abstract readMulticenter Study
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Midas B MulderDepartment of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID 0000-0002-0925-3771
Martijn van NoortLAP&P Consultants BV, Leiden, The Netherlands.
Robert A de ManErasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID 0000-0002-1932-7412
Nassim KamarDepartment of Nephrology and Organs Transplantation, CHU Rangueil, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Université Paul Sabatier, Toulouse, France.
Joep de BruijneDepartment of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Marjolein KnoesterDepartment of Clinical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID 0000-0002-4129-5234
Hans BlokzijlDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID 0000-0003-4240-7506
Thomas VanwolleghemDepartment of Gastroenterology and Hepatology, University Hospital of Antwerp, Edegem, Belgium.
Laurence RoosensLaboratory for TDM and Toxicology, Antwerp University Hospital, Edegem, Belgium.
Jacques IzopetDepartment of Virology, CHU Purpan, INSERM U1043, IFR-BMT, University Paul Sabatier, Toulouse, France.
Peggy GandiaDepartment of Toxicology, CHU Purpan, INSERM U1043, IFR-BMT, University Paul Sabatier, Toulouse, France.
Annemiek A van der EijkDepartment of Virology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID 0000-0002-8918-5536
Herold J MetselaarErasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Maurice J AhsmanLAP&P Consultants BV, Leiden, The Netherlands.ORCID 0000-0002-6084-2571
Tamara J van SteegLAP&P Consultants BV, Leiden, The Netherlands.ORCID 0000-0003-1387-1369
Dennis A HesselinkErasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID 0000-0003-1871-1962
Brenda C M de WinterDepartment of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID 0000-0002-4452-8443

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe optimal ribavirin dosing regimen for the treatment of chronic hepatitis E virus (HEV) infection in solid organ transplant (SOT) is unknown. We modelled ribavirin plasma concentrations versus virologic response and haemoglobin concentrations. PATIENTS AND

methodsData were collected in a retrospective, multicentre study of adult SOT recipients with chronic HEV infection treated with ribavirin between September 2009 and November 2019. Population pharmacokinetic and pharmacodynamic analyses were conducted using nonlinear mixed-effects modelling. Simulations were performed to select the most suitable RBV dosing regimen considering efficacy and safety.

resultsIn total, 107 chronically HEV-infected SOT recipients with 305 ribavirin plasma levels, 592 viral load and 443 haemoglobin concentrations were included. Sustained virologic response was achieved in 68.2% of the subjects. Owing to a low IC50, the decline in viral load was independent of ribavirin concentration and dose, whereas haemoglobin decreased with increasing ribavirin concentration and dose. A model-supported ribavirin dose for 180 days of 600 mg/day and kidney function (eGFR) ≥ 60 mL/min/1.73 m2, 400 mg/day and eGFR 30-59 mL/min/1.73 m2 and 200 mg/day and eGFR ≤30 mL/min/1.73 m2 showed good efficacy and low toxicity.

conclusionsThis study constitutes a valuable first step in determining the optimal ribavirin treatment regimen for chronic HEV infections in SOT recipients. Our model suggests a lower dose of ribavirin and longer treatment duration compared to the suggested dosing regimen in the EASL Clinical Practice Guidelines on HEV infection. Implementing our dosing regimen in clinical practice will allow for lower toxicity rates, improved tolerability and equal efficacy in chronically HEV-infected SOT recipients. CLINICAL TRIAL NUMBER: MEC-2018-1326.

Indexed as

Antiviral AgentsHepatitis, ChronicHepatitis ERibavirinTransplant RecipientsAdultAgedFemaleHemoglobinsHepatitis E virusHumansMaleMiddle AgedRetrospective StudiesSustained Virologic ResponseViral LoadAntiviral AgentsHemoglobinsRibavirin

Identifiers

PMID40581807
PMCPMC12313452

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.