Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue The Lancet Gastroenterology & Hepatology Année : 2017

Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial

1 Hôpital Saint-Joseph [Marseille]
2 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
3 Hôpital Jean Verdier [AP-HP]
4 CHU Saint-Antoine [AP-HP]
5 Service d'hépatologie
6 CHU Pitié-Salpêtrière [AP-HP]
7 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
8 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
9 Centre Hospitalier du Pays d'Aix
10 CHRO - Centre Hospitalier Régional d'Orléans
11 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
12 CHU Nancy - Centre Hospitalier Universitaire de Nancy
13 SESSTIM - U912 INSERM - Aix Marseille Univ - IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
14 ORS PACA - Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille]
15 Hôpital Charles Nicolle [Rouen]
16 CHI Créteil
17 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
18 Service de maladies infectieuses et tropicales [Saint-Louis]
19 CHU Trousseau [Tours]
20 CHU Nice - Centre Hospitalier Universitaire de Nice
21 CHU Tenon [AP-HP]
22 Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL]
23 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
24 Service d'hépatologie médicale [CHU Cochin]
25 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
26 ANRS France Recherche Nord & sud Sida-hiv hépatites
27 IMRB - Institut Mondor de Recherche Biomédicale
28 INSERM - Institut National de la Santé et de la Recherche Médicale
Nathalie Ganne-Carrie
  • Fonction : Auteur
  • PersonId : 849827
Lawrence Serfaty
Isabelle Rosa
  • Fonction : Auteur

Résumé

BACKGROUND: Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. METHODS: In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum alpha fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (\textless or \textgreater/=2.25 log10 IU/mL) to allocate patients (1:1) to receive a 48 week course of subcutaneous injections of 180 mug per week of pegylated interferon alfa-2a in addition to the nucleos(t)ide analogue regimen or to continue to receive nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by intention-to-treat analysis. This trial is closed and registered with ClinicalTrials.gov, number NCT01172392. FINDINGS: Between Jan 20, 2011, and July 18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We excluded two patients from the pegylated interferon plus nucleos(t)ide analogues group from analyses because of withdrawal of consent (one patient) or violation of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in seven (7.8%) of 90 patients in the pegylated interferon plus nucleos(t)ide analogues group versus three (3.2%) of 93 in the nucleos(t)ide analogues-alone group (difference 4.6% [95% CI -2.6 to 12.5]; p=0.15). 85 (94%) of 90 patients started pegylated interferon, three (4%) of whom had a dose reduction and 17 (20%) had an early discontinuation of pegylated interferon (seven [41%] for serious adverse events). Grade 3 and 4 adverse events were more frequent in the pegylated interferon plus nucleos(t)ide analogues group (26 [29%] grade 3 adverse events; 19 [21%] grade 4 adverse events) than in the nucleos(t)ide analogues-alone group (three [3%] grade 3; six [6%] grade 4). INTERPRETATION: Addition of a 48 week course of pegylated interferon to nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B with undetectable HBV DNA for a least 1 year was poorly tolerated and did not result in a significant increase of HBsAg clearance. FUNDING: Institut national de la sante et de la recherche medicale-Agence nationale de recherches sur le sida et les hepatites virales (France Recherche Nord&sud Sida-vih Hepatites)
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hal-01795715 , version 1 (31-08-2022)

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Marc Bourliere, Pascaline Rabiega, Nathalie Ganne-Carrie, Lawrence Serfaty, Patrick Marcellin, et al.. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial. The Lancet Gastroenterology & Hepatology, 2017, 2, pp.177-188. ⟨10.1016/S2468-1253(16)30189-3⟩. ⟨hal-01795715⟩
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