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Carine Richou1,7 12
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Eléonore Brumpt1,8 Besançon, Besançon, France
Aurélie Fillion9 *
Corresponding author. Address: Pr Solange Bresson-Hadni, National
Brigitte Bartholomot10 Reference Center for Echinococcosis, Parasitology-Mycology
Oleg Blagosklonov1,11 Laboratory, Jean Minjoz University Hospital 25030 Besançon cedex,
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Frédéric Grenouillet1,3,12 E-mail address: sbresson@chu-besancon.fr (S. Bresson-Hadni)

EASL recommendations on treatment of hepatitis C: Final update of

the series – Some issues
To the Editor: guidance on hepatitis C published in 2019.3 Actually in the
We read with great interest the final update of the EASL rec- discussion about simplified, genotyping/subtyping-free, pan-
ommendations on the treatment of hepatitis C, which is one of genotypic (S-Gf-P) anti-HCV treatment, 8-week glecaprevir/
the most important guidelines in the world.1 Having read the pibrentasvir was recommended in any setting where genotype
guidelines, we wanted to raise the following points: and subtype determination is not available, not affordable and/or
For the treatment-naïve patients infected with genotype 3 would limit access to therapy, based on the determination of the
with compensated (Child-Pugh A) cirrhosis (naïve GT-3 CC), the presence or absence of cirrhosis by a non-invasive method.1
recommendations mentioned that they should be treated with Since confirming the presence/absence of cirrhosis is
the fixed-dose combination of glecaprevir and pibrentasvir mandatory in pretreatment evaluation for direct-acting antivi-
(glecaprevir/pibrentasvir) for 12 weeks, the fixed-dose combi- rals (DAAs), 8-week glecaprevir/pibrentasvir can be recom-
nation of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir) mended for treatment-naïve GT-3 CC patients. Notably, protease
with weight-based ribavirin (1,000 or 1,200 mg in patients <75 inhibitor-containing regimens are contraindicated not only in
kg or >−75 kg, respectively) for 12 weeks, or the fixed-dose patients with currently decompensated (Child-Pugh B or C)
combination of sofosbuvir, velpatasvir and voxilaprevir for 12 cirrhosis but also in patients with compensated (Child-Pugh A)
weeks. For these naïve GT-3 CC patients, 8-week glecaprevir/ cirrhosis with previous episodes of decompensation.1 Thus, it is
pibrentasvir therapy is effective2 and has been approved by the very important to carefully identify the history of
U.S. FDA (September 2019) and European Commission (March decompensation in patients with compensated cirrhosis who
2020), as well as being recommended by the AASLD-IDSA are due to be treated with S-Gf-P regimens of glecaprevir/
pibrentasvir. On the other hand, S-Gf-P regimens of 12-week
sofosbuvir/velpatasvir are recommended for treatment-naïve
Keywords: Hepatitis C virus; Chronic hepatitis C; Direct acting antivirals.
Received 13 October 2020; accepted 17 October 2020; available online 19 November 2020
and -experienced patients without cirrhosis or with
https://doi.org/10.1016/j.jhep.2020.10.013 compensated (Child-Pugh A) cirrhosis.1 However, sofosbuvir/

Journal of Hepatology 2021 vol. 74 j 469–490 473

Letters to the Editor

velpatasvir with weight-based ribavirin for 12 weeks has less Supplementary data
favorable efficacy in genotype 3b patients (reported previously4), Supplementary data to this article can be found online at https://
as mentioned in the present EASL recommendations1 and the doi.org/10.1016/j.jhep.2020.10.013.
Taiwan consensus statement on the management of hepatitis
C, 2020.5 As such, we believe that the recommendation for a S- References
Gf-P regimen of sofosbuvir/velpatasvir need to be limited to [1] EASL recommendations on treatment of hepatitis C: final update of the
treatment-naïve GT-3 patients without cirrhosis. series. J Hepatol 2020;73(5):1170–1218.
[2] Brown RS Jr, Buti M, Rodrigues L, Chulanov V, Chuang WL, Aguilar H, et al.
Sofosbuvir-containing regimens can be used in patients with
Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with
renal diseases, including those with an eGFR < −30 mL/min and chronic HCV genotypes 1-6 and compensated cirrhosis: the EXPEDITION-8
those with end-stage renal disease on hemodialysis, based on trial. J Hepatol 2020;72:441–449.
previous guidance,1,6 with no need for dose adjustments of [3] Ghany MG, Morgan TR, AASLD-IDSA Hepatitis C Guidance Panel. Hepatitis
DAAs.1,7 Thus, these patients are considered eligible for S-Gf-P C guidance 2019 update: American Association for the Study of Liver
Diseases-Infectious Diseases Society of America recommendations for
regimens. Under the circumstances, evaluation of renal testing, managing, and treating hepatitis C virus infection. Hepatology
function does not seem necessary if applying S-Gf-P anti-HCV 2020;71:686–721.
treatments. [4] Wei L, Lim SG, Xie Q, Van KN, Piratvisuth T, Huang Y, et al. Sofosbuvir-
Lastly, we believe that it may be inadequate to omit the tests velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a
single-arm, open-label, phase 3 trial. Lancet Gastroenterol Hepatol
for sustained virologic response (SVR) even with the very high
SVR12 rates expected with these regimens, as determining [5] Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, et al. Taiwan
treatment response is crucial for the further management of pa- consensus statement on the management of hepatitis C: part (I) general
tients, particularly for those with advance fibrosis or cirrhosis.1,3,6 population. J Formos Med Assoc 2020;119:1019–1040.
[6] AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 up-
date: AASLD-IDSA recommendations for testing, managing, and
Financial support treating hepatitis C virus infection. Clin Infect Dis 2018;67:1477–
The authors received no financial support to produce this [7] Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, et al. 2020 Taiwan
manuscript. consensus statement on the management of hepatitis C: Part (II) special
populations. J Formos Med Assoc 2020;119:1135–1157.

Conflict of interest Chia-Yen Dai1,2,3

CY Dai: Consultant of Gilead, Abbvie; Speaker of Gilead, Abbvie Wan-Long Chuang1,2
and Merck. WL Chuang: Speaker of Gilead and Abbvie. ML Yu: Ming-Lung Yu1,2,3,*
Research support (grant) from Gilead and Abbott; Consultant of Hepatobiliary Division, Department of Internal Medicine, Kaohsiung
Gilead, Abbvie and Merck; Speaker of Gilead, Abbvie and Merck. Medical University Hospital, Kaohsiung Medical University,
Please refer to the accompanying ICMJE disclosure forms for Kaohsiung, Taiwan
further details. Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung
Medical University, Kaohsiung, Taiwan
Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical
Authors’ contributions University, Kaohsiung, Taiwan
Chia-Yen Dai and Ming-Lung Yu conceived of the presented idea. *
Corresponding author. Address: Department of Internal Medicine,
Chia-Yen Dai and Ming-Lung Yu wrote the manuscript in Kaohsiung Medical University Hospital, 100, Shi-Tzyou 1st Road,
consultation with Wan-Long Chuang. All authors discussed the Kaohsiung 807, Taiwan.
results and contributed to the final manuscript. E-mail address: fish6069@gmail.com (M.-L. Yu)

Reply to: “EASL recommendations on treatment of hepatitis C: Final

update of the series – some issues”
The EASL Panel read with interest the Letter to the Editor by Dai Regarding glecaprevir/pibrentasvir treatment duration in
et al. reporting their opinions on the final update of the EASL patients infected with genotype 3 with compensated cirrhosis:
Recommendations on Treatment of Hepatitis C, published in the “A small number of patients infected with HCV genotype 3a with
November 2020 issue of Journal of Hepatology.1 The compensated (Child-Pugh A) cirrhosis have been included in
Recommendations contain the responses to their comments, as clinical trials with the fixed-dose combination of glecaprevir and
well as the scientific evidence that supports them, as follows. pibrentasvir [.]. In the phase III EXPEDITION-8 trial, the efficacy
of an 8-week treatment regimen in treatment-naïve patients
with genotype 3a and cirrhosis is supported by the inclusion of
Received 20 October 2020; accepted 20 October 2020; available online 20 November 2020 only 63 patients, with 1 post-treatment relapse. In a real-world
https://doi.org/10.1016/j.jhep.2020.10.025 study including 11,101 adults treated with glecaprevir/

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