Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study

Cas J. Isfordink*, Thijs J.W. van de Laar, Sjoerd P.H. Rebers, Els Wessels, Richard Molenkamp, Marjolein Knoester, Bert C. Baak, Cees Van Nieuwkoop, Bart van Hoek, Sylvia Brakenhoff, Hans Blokzijl, Joop E. Arends, Marc van der Valk, Janke Schinkel, HepNed Study Group

*Corresponding author for this work

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Abstract

Background. The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which
harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we
aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands.
Methods. We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV
genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end
point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions
(RAS) evaluation.
Results. We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients
were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with
available SVR-12 data. Only 73% (8/11) genotype 3–infected patients achieved SVR-12, the majority being genotype 3b patients with
63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS.
Conclusions. The DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However,
the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside
earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.
Original languageEnglish
Article numberofab006
Number of pages10
JournalOpen Forum Infectious Diseases
Volume8
Issue number2
DOIs
Publication statusPublished - 1 Feb 2021

Bibliographical note

Acknowledgments:
The authors would like to thank all the physicians who contributed to data collection. These are: Dr. Pieter Honkoop, Albert Schweitzer Ziekenhuis. Dr. Sunje Abraham, Alrijne zorgroep. Dr. Karen Steenhuisen—van Erp, Bernhoven. Dr. Svend Rietdijk, BovenIJ. Dr. Ton Dofferhoff, Canisius-Wilhelmina Ziekenhuis. Dr. Pieter Friederich, Catharina Ziekenhuis. Dr. Frank ter Borg, Deventer Ziekenhuis. Dr. Xander Vos, Dr. Johannes Schmidt-Böhmer, Dr. Joost Vermeulen Dijklander Ziekenhuis. Dr. Hanna Telleman, Dr. Ulrike Schlüter, Dr. Judith Branger, Flevoziekenhuis. Dr. Robert Roomer, Fransiscus Gasthuis & Vlietland. Dr. Paul Groeneveld, Dr. Jolanda Lammers, Isala. Dr. Henk-Marijn de Jonge, Jeroen Bosch Ziekenhuis. Dr. Eric de Goede, Laurentius Ziekenhuis. Dr. Jan den Hollander, Maasstad Ziekenhuis. Dr. Philip Friederich, Meander MC. Dr. Kamilla Lettinga, Dr. Jan Veenstra, Dr. Willem Blok, Dr. Guido van den Berk, Marijke Spelbrink, Onze Lieve Vrouwe Gasthuis. Dr. Nicole van Gerven, Rode Kruis Ziekenhuis. Dr. Tim Schreuder Treant zorggroep. Dr. Khalida Soufidi, Zuyderland MC.

HepNed study group. Dr. Sophie Willemse, Robin Erken, Dr. Marije Bomers, Dr. Dewkoemar Ramsoekh, Amsterdam UMC. Dr. Rob de Knegt, Prof. Dr. Rob de Man, Dr. Bart Rijnders, Erasmus MC. Dr. Hanneke van Soest, Haaglanden MC. Dr. Ger Koek, Dr. Dirk Posthouwer, Ozgür Koc, Maastricht UMC. Prof. Dr. David Burger, Marleen van Dijk, Prof. Dr. Joost Drenth, Daan von den Hoff, Radboud UMC. Dr. Johannes Brouwer, Reinier de Graaf Gasthuis. Dr. Greet Boland, Dr. Karel van Erpecum, UMC Utrecht.

Funding Information:
C.I. has received research funding from Gilead. B.B. has received fees for advisory boards for AbbVie, Gilead, and Norgine and received research grants from Gilead and MSD. B.v.H. participated in advisory boards of WillPharma and received research grants from Zambon Pharma, Astellas, and Chiesi Pharma. S.B. has received research funding from Gilead. H.B. has participated in advisory boards for Gilead. J.A. has participated in advisory boards for Gilead, MSD, Janssen, and AbbVie. M.v.d.V. has participated in advisory boards (fees paid to institution) for AbbVie, Gilead, Johnson & Johnson, MSD, and ViiV and has received independent research grants from AbbVie, Johnson & Johnson, Gilead, and MSD. J.S. has participated in advisory boards for Gilead and received research grants from Gilead and AbbVie. All other authors declare no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Publisher Copyright:
© 2021 The Author(s).

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