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Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs

Pierre Nahon 1, 2, * Richard Layese 3 Valérie Bourcier 2 Carole Cagnot 4 Patrick Marcellin 5 Dominique Guyader 6 Stanislas Pol 7, 8, 9 Dominique Larrey 10, 11 Victor de Ledinghen 12 Denis Ouzan 13 Fabien Zoulim 14 Dominique Roulot 15 Albert Tran 16 Jean-Pierre Bronowicki 17 Jean-Pierre Zarski 18, 19 Ghassan Riachi 20 Paul Calès 21 Jean-Marie Péron 22, 23 Laurent Alric 24, 22 Marc Bourlière 25 Philippe Mathurin 26 Jean-Frédéric Blanc 27, 12 Armand Abergel 28, 29, 30 Lawrence Serfaty 31 Ariane Mallat 32, 33, 34 Jean-Didier Grangé 35 Pierre Attali 36 Yannick Bacq 37 Claire Wartelle 38 Thong Dao 39 Dominique Thabut 40 Christophe Pilette 41 Christine Silvain 42 Christos Christidis 43 Eric Nguyen-Khac 44 Brigitte Bernard-Chabert 45 David Zucman 46 Vincent Di Martino 47 Angela Sutton 2 Françoise Roudot-Thoraval 48 Etienne Audureau 48, 3 
* Auteur correspondant
Abstract : Background & aims - Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). Methods - Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. Results - Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73). Conclusions - Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.
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Soumis le : vendredi 29 mai 2020 - 09:35:58
Dernière modification le : mardi 27 septembre 2022 - 04:21:58

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Pierre Nahon, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, et al.. Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs. Gastroenterology, Elsevier, 2018, 155 (5), pp.1436-1450.e6. ⟨10.1053/j.gastro.2018.07.015⟩. ⟨hal-02648450⟩



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