Evidence map›Paper›PMID 27206517›Full record

Trial reportHepatology international2016

Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure.

Fabien Zoulim, Jolanta Białkowska-Warzecha, Mircea Mihai Diculescu, Adrian Eugen Goldis, Renate Heyne, Tomasz Mach, Patrick Marcellin, Jörg Petersen, Krzysztof Simon, Soumaya Bendahmane and 3 more

Open access · greenAbstract readClinical TrialMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Hepatology international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. HBV replication inhibitors.Antiviral research · 2020
    Review
  5. Article
  6. Article
  7. Recommendations for the treatment of hepatitis B in 2017.Clinical and experimental hepatology · 2017
    Review
  8. Observational
  9. Review
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 11 institutions in 7 countries.

Fabien ZoulimHepatology Department, Hospices Civils de Lyon, INSERM U1052, INSERM, Lyon University, 151 Cours Albert Thomas, 69424, Lyon Cedex 03, France. fabien.zoulim@inserm.fr.
Jolanta Białkowska-WarzechaDepartment of Infectious and Liver Diseases, Medical University of Lodz, Lodz, Poland.
Mircea Mihai DiculescuCentre of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania.
Adrian Eugen GoldisClinic of Gastroenterology, University of Medicine, Timisoara, Romania.
Renate HeyneLeberzentrum Checkpoint, Berlin, Germany.
Tomasz MachDepartment of Gastroenterology and Hepatology, Jagiellonian University, Krakow, Poland.
Patrick MarcellinHôpital Beaujon, Assistance Publique-Hôpitaux de Paris, University of Paris 7, Paris, France.
Jörg PetersenIFI Institute for Interdisciplinary Medicine, Asklepios Klinik St Georg, Hamburg, Germany.
Krzysztof SimonDivision of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland.
Soumaya BendahmaneBristol-Myers Squibb, Braine-I'Alleud, Belgium.
Isabelle KlauckBristol-Myers Squibb, Paris, France.
Wojciech WasiakinVentiv Health Clinical Poland, Warsaw, Poland.
Harry L A JanssenDepartment of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Asklepios Klinik St. Georg · DEBristol-Myers Squibb (Belgium) · BEBristol-Myers Squibb (France) · FRErasmus MC · NLHôpital Beaujon · FRInserm · FRInstitutul Clinic Fundeni · ROJagiellonian University · PLMedical University of Lodz · PLWest University of Timişoara · ROWroclaw Medical University · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsIn patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen.

methodsIn this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks.

resultsAt baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed.

conclusionsIn NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.

Indexed as

AdultAntiviral AgentsDNA, ViralDrug Administration ScheduleDrug Resistance, ViralDrug Therapy, CombinationFemaleGuanineHepatitis B, ChronicHepatitis B e AntigensHepatitis B virusHumansMaleMiddle AgedTenofovirTreatment OutcomeAntiviral AgentsDNA, ViralentecavirGuanineHepatitis B e AntigensTenofovirAntiviral resistanceMultidrug failurePartial responsePrimary non-responseRescue therapyVirologic breakthrough

Identifiers

PMID27206517
OpenAlexW2403244649

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.