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. 2022 Jan 27;22(1):94.
doi: 10.1186/s12879-022-07076-0.

Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Georges-Philippe Pageaux  1 , Clovis Lusivika Nzinga  2 , Nathalie Ganne  3   4 , Didier Samuel  5   6   7 , Céline Dorival  2 , Fabien Zoulim  8 , Carole Cagnot  9 , Thomas Decaens  10   11   12 , Dominique Thabut  13 , Tarik Asselah  14 , Philippe Mathurin  15 , François Habersetzer  16 , Jean-Pierre Bronowicki  17 , Dominique Guyader  18   19 , Isabelle Rosa  20 , Vincent Leroy  21 , Olivier Chazouilleres  22 , Victor de Ledinghen  23 , Marc Bourliere  24 , Xavier Causse  25 , Paul Cales  26   27 , Sophie Metivier  28 , Véronique Loustaud-Ratti  29 , Ghassan Riachi  30 , Laurent Alric  31 , Moana Gelu-Simeon  32   33 , Anne Minello  34 , Jérôme Gournay  35 , Claire Geist  36 , Albert Tran  37 , Armand Abergel  38   39 , Isabelle Portal  40 , Louis d'Alteroche  41 , François Raffi  42 , Hélène Fontaine  43 , Fabrice Carrat  2   44 , Stanislas Pol  44   45   46 ; French ANRS CO22 Hepather Cohort
Collaborators, Affiliations

Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Georges-Philippe Pageaux et al. BMC Infect Dis. .

Abstract

Background: In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort.

Methods: We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits.

Results: 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7-51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24-0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08-0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15-0.54, p < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17-0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06-0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05-0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29-0.93, p = 0.03).

Conclusion: Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis.

Trial registration: ClinicalTrials.gov registry number: NCT01953458.

Keywords: Decompensated cirrhosis; Direst-acting antiviral agents; Hepatitis C virus; Hepatocellular carcinoma; Survival; Sustained virological response.

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Conflict of interest statement

Prof. Pageaux received lecturing fees from Gilead, Abbvie, outside the submitted work. Dr Lusivika Nzinga has nothing to disclose. Prof. Ganne reports grants from Echosens, personal fees and non-financial support from Gilead Sciences, personal fees and non-financial support from Abbvie, non-financial support from MSD, personal fees and non-financial support from Bayer, outside the submitted work. Prof. Samuel reports other from Astellas, BMS, Gilead, LFB, MSD, Novartis, Roche, Biotest, Abbvie, Intercept, outside the submitted work. Dr Dorival has nothing to disclose. Prof. Zoulim reports personal fees from Abbvie, Gilead, during the conduct of the study. C. Cagnot has nothing to disclose. Prof. Decaens reports personal fees from Bayer, MSD, Abbvie, Gilead Sciences, outside the submitted work. Prof. Thabut reports personal fees from MSD, Abbvie, Gilead Sciences, outside the submitted work. Prof. Asselah reports grants from ANRS-INSERM, personal fees from ABBVIE, GILEAD, JANSSEN, MSD, outside the submitted work. Prof. Mathurin reports personal fees from MSD, Abbvie, Gilead Sciences, outside the submitted work. Prof. Habersetzer reports personal and travel fees from Abbvie and Gilead, during the conduct of the study. Prof. Bronowicki reports personal fees from Abbvie, Gilead, MSD, BMS, JANSSEN outside the submitted work. Prof. Guyader reports personal fees and non-financial support from Gilead sciences, MSD, and Abbbvie, grants, personal fees and non-financial support from Janssen, during the conduct of the study. Dr Rosa has nothing to disclose. Prof. Leroy reports grants, personal fees and non-financial support from Abbvie, grants, personal fees and non-financial support from BMS, grants, personal fees and non-financial support from Gilead, personal fees and non-financial support from MSD, personal fees from echosens, outside the submitted work. Prof. Chazouillères reports personal fees from Abbvie, Gilead Sciences, Intercept, Pliant Therapeutics, outside the submitted work. Prof. De Lédinghen has received consulting and/or lecturing fees from Gilead, AbbVie, Echosens, Intercept Pharma, SuperSonic Imagine, Indivior, Spimaco, Pfizer, Bristol Myers Squibb, Myr-Pharma. Dr Bourlière reports grants and personal fees from AbbVie, grants and personal fees from Gilead, personal fees from MSD, personal fees from Janssen, personal fees from Boehringher Ingelheim, personal fees from intercept, personal fees from BMS, outside the submitted work. Dr Causse reports personal fees from AbbVie, Gilead, Intercept, Janssen, MSD, during the conduct of the study, outside the submitted work. Prof. Cales has nothing to disclose. Dr Metivier has nothing to disclose. Prof. Loustaud-Ratti is a Clinical Investigator/Speaker for AbbVie, Gilead Sciences, Merck Sharp & Dohme. Dr Riachi reports personal fees from MSD, Abbvie, Gilead Sciences, outside the submitted work. Dr Alric reports personal fees from MSD, Abbvie, Gilead Sciences, outside the submitted work. Dr Gelu-Simeon reports invitations for medical meeting from Gilead, Abbvie. Pr. Minello reports personal fees from for Gilead, Abbvie, Intercept, during the conduct of the study, outside the submitted work. Dr Gournay reports personal fees from Gilead, MSD, Abbvie, during the conduct of the study; personal fees from Intercept, outside the submitted work. Dr Geist has nothing to disclose. Prof. Tran has nothing to disclose. Dr Abergel reports personal fees from AbbVie, Gilead Sciences, Merck Sharp & Dohme, Intercept, during the conduct of the study, outside the submitted work. Dr Portal reports personal fees from MSD, Abbvie, Gilead Sciences, outside the submitted work. Dr D’Alteroche reports invitations for medical meeting from Gilead, Abbvie, BMS, MSD and Janssen outside this work. Prof. Raffi reports personal fees from for Gilead, ViiV, Abbvie, MSD, Janssen during the conduct of the study, outside the submitted work. G. Haour has nothing to disclose. Dr. Fontaine reports personal fees and invitations for medical meeting from Gilead, Abbvie, BMS, MSD, Janssen, MSD outside this work. Prof. Carrat reports grants from INSERM-ANRS, during the conduct of the study; personal fees from Imaxio, outside the submitted work. Prof. Pol received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, Biotest, Shinogi, ViiV, MSD and Abbvie, and grants from Bristol-Myers Squibb, Gilead and MSD.

Figures

Fig. 1
Fig. 1
a Survival using inverse probability of treatment weighting (IPTW)-based analysis of hepatocellular carcinoma for all patients under study. b Survival using inverse probability of treatment weighting (IPTW)-based analysis of all-cause mortality for all patients under study. c Survival using inverse probability of treatment weighting (IPTW)-based analysis of liver transplantation for all patients under study
Fig. 2
Fig. 2
Inverse probability of treatment weighting (IPTW)-adjusted cumulative incidence functions of hepatocellular carcinoma, all-cause mortality, and liver transplantation in all patients under study. HCC hepatocellular carcinoma, DAA direct-acting antiviral, IPW inverse probability of treatment weighting
See this image and copyright information in PMC

References

    1. Beste LA, Leipertz SL, Green PK, et al. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001–2013. Gastroenterology. 2015;149:1471–148.e5. doi: 10.1053/j.gastro.2015.07.056. - DOI - PubMed
    1. Kim WR, Smith JM, Skeans MA, et al. OPTN/SRTR 2012 annual data report: liver. Am J Transplant. 2014;14:69–96. doi: 10.1111/ajt.12581. - DOI - PubMed
    1. Charlton M, Everson GT, Flamms SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149:649–659. doi: 10.1053/j.gastro.2015.05.010. - DOI - PubMed
    1. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618–2628. doi: 10.1056/NEJMoa1512614. - DOI - PubMed
    1. Foster GR, Irving WL, Cheung MCM, et al. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol. 2016;64:1224–1231. doi: 10.1016/j.jhep.2016.01.029. - DOI - PubMed

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