Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis
Authors: Pageaux Georges-Philippe , Nzinga Clovis Lusivika , Ganne Nathalie , Samuel Didier , Dorival Céline , Zoulim Fabien , Cagnot Carole , Decaens Thomas , Thabut Dominique , Asselah Tarik , Mathurin Philippe , Habersetzer François , Bronowicki Jean-Pierre , Guyader Dominique , Rosa Isabelle , Leroy Vincent , Chazouilleres Olivier , de Ledinghen Victor , Bourliere Marc , Causse Xavier , Cales Paul , Metivier Sophie , Loustaud-Ratti Véronique , Riachi Ghassan , Alric Laurent , Gelu-Simeon Moana , Minello Anne , Gournay Jérôme , Geist Claire , Tran Albert , Abergel Armand , Portal Isabelle , d’Alteroche Louis , Raffi François , Fontaine Hélène , Carrat Fabrice , Pol Stanislas ,   For the French ANRS CO22 Hepather Cohort, Bonnet Delphine , Payssan-Sicart Virginie , Pomes Chloe , Bailly François , Beaudoin Marjolaine , Giboz Dominique , Hartig-Lavie Kerstin , Maynard Marianne , Billaud Eric , Boutoille David , Cavellec Morane , Chevalier Caroline , Hubert Isabelle , Goepfert Pierre , Lannes Adrien , Lunel Françoise , Boursier Jérôme , Boyer Nathalie , Giuily Nathalie , Castelnau Corinne , Scoazec Giovanna , Chibah Aziza , Keser Sylvie , Bonardi Karim , Vallet-Pichard Anaïs , Sogni Philippe , Foucher Juliette , Hiriart Jean-Baptiste , Legendre Amandine , Chermak Faiza , Irlès-Depé Marie , Ahmed Si Nafa Si , Ansaldi Christelle , Amara Nisserine Ben , Oules Valérie , Dunette Jacqueline , Anty Rodolphe , Gelsi Eve , Truchi Régine , Luckina Elena , Messaoudi Nadia , Moussali Joseph , De Dieuleveult Barbara , Goin Héloïse , Labarrière Damien , Potier Pascal , Ahmed Si Nafa Si , Grando-Lemaire Véronique , Nahon Pierre , Brulé Séverine , Monard Rym , Jezequel Caroline , Brener Audrey , Laligant Anne , Rabot Aline , Renard Isabelle , Baumert Thomas F. , Dofföel Michel , Mutter Catherine , Simo-Noumbissie Pauline , Razi Esma , Barraud Hélène , Bensenane Mouni , Nani Abdelbasset , Hassani-Nani Sarah , Bernard Marie-Albertine , Pageaux Georges-Philippe , Bismuth Michael , Caillo Ludovic , Faure Stéphanie , Ripault Marie Pierre , Bureau Christophe , Launay Sarah , Peron Jean Marie , Robic Marie Angèle , Tarallo Léa , Faure Marine , Froissart Bruno , Hilleret Marie-Noelle , Zarski Jean-Pierre , Goria Odile , Grard Victorien , Montialoux Hélène , François Muriel , Ouedraogo Christian , Pauleau Christelle , Varault Anne , Andreani Tony , Angoulevant Bénédicte , Chevance Azeline , Serfaty Lawrence , Antonini Teresa , Coilly Audrey , Vallée Jean-Charles Duclos , Tateo Mariagrazia , Bonny Corinne , Brigitte Chanteranne , Lamblin Géraldine , Muti Léon , Babouri Abdenour , Filipe Virginie , Barrault Camille , Costes Laurent , Hagège Hervé , Merbah Soraya , Carrier Paul , Debette-Gratien Maryline , Jacques Jérémie , Lassailly Guillaume , Artu Florent , Canva Valérie , Dharancy Sébastien , Louvet Alexandre , Latournerie Marianne , Bardou Marc , Mouillot Thomas , Bacq Yannick , Barbereau Didier , Nicolas Charlotte , Chevalier Caroline , Archambeaud Isabelle , Habes Sarah , Amara Nisserine Ben , Botta-Fridlund Danièle , Saillard Eric , Lafrance Marie-Josée , Cagnot Carole , Diallo Alpha , Wadouachi Lena , Petrov-Sanchez Ventzi , Ammour Douae , Ayour Loubna , Benhida Jaouad , Carrat Fabrice , Chau Frederic , Dorival Céline , Gilibert Audrey , Goderel Isabelle , Hadi Warda , Nzinga Clovis Luzivika , Pannetier Grégory , Pinot François , Stahl Odile , Téloulé François 
Published: January 2022

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.