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- Klinische proef NCT01063036
Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment
25 november 2014 bijgewerkt door: Bristol-Myers Squibb
A Study of the Safety and Efficacy of Entecavir Plus Tenofovir in Adults With Chronic Hepatitis B Virus Infection With Previous Nucleoside/Nucleotide Treatment Failure
The purpose of this study is to show that the combination of entecavir and tenofovir, is effective and well tolerated in chronic hepatitis B patients who have failed previous treatment.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Studietype
Ingrijpend
Inschrijving (Werkelijk)
144
Fase
- Fase 3
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Berlin, Duitsland, 13353
- Local Institution
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Berlin, Duitsland, 10969
- Local Institution
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Hamburg, Duitsland, 20246
- Local Institution
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Hamburg, Duitsland, 20099
- Local Institution
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Hannover, Duitsland, 30625
- Local Institution
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Heindelberg, Duitsland, 69120
- Local Institution
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Munchen, Duitsland, 81675
- Local Institution
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Tubingen, Duitsland, 72076
- Local Institution
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Clichy, Frankrijk, 92110
- Local Institution
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Lyons Cedex 04, Frankrijk, 69317
- Local Institution
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Orleans Cedex 2, Frankrijk, 45067
- Local Institution
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Strasbourg, Frankrijk, 67000
- Local Institution
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Bagno A Ripoli (Fi), Italië, 50012
- Local Institution
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Bari, Italië, 70124
- Local Institution
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Foggia, Italië, 71100
- Local Institution
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Milano, Italië, 20122
- Local Institution
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Amsterdam, Nederland, 1105 AZ
- Local Institution
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Arnhem, Nederland, 6815 AD
- Local Institution
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Rotterdam, Nederland, 3015 CE
- Local Institution
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Kielce, Polen, 25-317
- Local Institution
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Krakow, Polen, 31-531
- Local Institution
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Lodz, Polen, 91-347
- Local Institution
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Wroclaw, Polen, 50-349
- Local Institution
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Bucuresti, Roemenië, 021105
- Local Institution
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Burcuresti, Roemenië, 022328
- Local Institution
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Timisoara, Roemenië, 300 002
- Local Institution
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Barcelona, Spanje, 08025
- Local Institution
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Valencia, Spanje, 46014
- Local Institution
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Subjects with chronic hepatitis B virus (HBV) infection; either hepatitis B-e antigen(HBeAg)-negative or HBeAg-positive
- Subjects must have a treatment failure to their current nucleoside/ nucleotide treatment regimen
- Prior entecavir and/or tenofovir monotherapy is allowed
- Subjects must have compensated liver function
Exclusion Criteria:
- Women who are pregnant or breastfeeding
- Evidence of decompensated cirrhosis
- Co-infection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
- Moderate or severe renal impairment
- Recent history of pancreatitis
- Therapy with interferon, thymosin alpha or other immuno-stimulators within 24 weeks of being assigned to study drug into this study
- Prior entecavir/tenofovir combination therapy
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Entecavir + Tenofovir
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Tablets, Oral, 1 mg, once daily, 96 weeks
Andere namen:
Tablets, Oral, 300 mg, once daily, 96 weeks
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Percentage of Participants With a Virologic Response at Week 48 - Treated Population
Tijdsspanne: Week 48
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Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL.
Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory.
The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
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Week 48
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population
Tijdsspanne: Week 24, Week 96
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Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL.
Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay.
The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
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Week 24, Week 96
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Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
Tijdsspanne: Baseline to Weeks 12, 24, 48, 96
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HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay.
The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Baseline was Day 1, prior to study drug administration.
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Baseline to Weeks 12, 24, 48, 96
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Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
Tijdsspanne: Weeks 24, 48, 96
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HBV DNA less than (<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96.
Percentage was calculated as number of participants with HBV DNA < LLD at Weeks 24, 48, 96 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
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Weeks 24, 48, 96
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Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
Tijdsspanne: Baseline to Weeks 24, 48, and 96
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Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline.
Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples.
Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline.
Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
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Baseline to Weeks 24, 48, and 96
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Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
Tijdsspanne: Baseline, Weeks 24, 48, and 96
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HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline.
Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples.
Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline.
Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, and 96
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
Tijdsspanne: Baseline, Weeks 24, 48, 96
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Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline.
The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized).
Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg).
Treated participants (HBsAg-positive at baseline) were evaluated using NC=F.
Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, 96
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
Tijdsspanne: Baseline, Weeks 24, 48, and 96
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HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline.
Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline.
Positive result for HBsAg was one of the inclusion criteria.
Treated participants (HBsAg positive at baseline) were evaluated using NC=F.
The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma [potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized].
Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, and 96
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Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population
Tijdsspanne: Day 1 to last dose of study drug plus 5 days; up to Week 96
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
On-treatment = on Day 1 through last dose of study therapy + 5 days.
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Day 1 to last dose of study drug plus 5 days; up to Week 96
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Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population
Tijdsspanne: Baseline to Weeks 48, 96
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Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough.
Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S).
Primary non-response was defined as < 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy.
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Baseline to Weeks 48, 96
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Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Tijdsspanne: Day 1 to last dose of study drug plus 5 days; up to Week 96
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Selected criteria presented in each category.
Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (>);greater than, equal to (>=); less than (<).
Creatinine data presented below were confirmed, ie, at least 2 consecutive values.
On-treatment = after Day 1 through last dose of study therapy + 5 days.
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Day 1 to last dose of study drug plus 5 days; up to Week 96
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Nuttige links
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 mei 2010
Primaire voltooiing (Werkelijk)
1 november 2012
Studie voltooiing (Werkelijk)
1 februari 2014
Studieregistratiedata
Eerst ingediend
3 februari 2010
Eerst ingediend dat voldeed aan de QC-criteria
4 februari 2010
Eerst geplaatst (Schatting)
5 februari 2010
Updates van studierecords
Laatste update geplaatst (Schatting)
15 december 2014
Laatste update ingediend die voldeed aan QC-criteria
25 november 2014
Laatst geverifieerd
1 november 2014
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het spijsverteringsstelsel
- RNA-virusinfecties
- Virusziekten
- Infecties
- Door bloed overgedragen infecties
- Overdraagbare ziekten
- Lever Ziekten
- Hepatitis, viraal, menselijk
- Hepadnaviridae-infecties
- DNA-virusinfecties
- Enterovirusinfecties
- Picornaviridae-infecties
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, chronisch
- Hepatitis, chronisch
- Moleculaire mechanismen van farmacologische werking
- Anti-infectieuze middelen
- Antivirale middelen
- Reverse Transcriptase-remmers
- Nucleïnezuursyntheseremmers
- Enzymremmers
- Anti-hiv-middelen
- Antiretrovirale middelen
- Tenofovir
- Entecavir
Andere studie-ID-nummers
- AI463-203
- 2009-015705-40 (EudraCT-nummer)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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Mahidol UniversityOnbekendChronische hepatitis B, HBsAg, hepatitis B-vaccinThailand
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University Hospital, Strasbourg, FranceWerving
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French National Agency for Research on AIDS and...Gilead Sciences; PharmassetBeëindigdHBe-negatieve chronische hepatitis B | Hepatitis B-virale infectieFrankrijk
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ShuGuang HospitalShanghai Zhongshan Hospital; Ruijin Hospital; Shanghai Public Health Clinical Center en andere medewerkersOnbekend
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Beijing Friendship HospitalPeking University; Peking University First Hospital; Peking University People's... en andere medewerkersVoltooid
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Peking UniversityOnbekend
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Taipei Veterans General Hospital, TaiwanBristol-Myers SquibbVoltooidHepatitis B | Non Hodgkin-lymfoomTaiwan
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National Taiwan University HospitalOnbekendHBV/HCV-co-infectieTaiwan
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Guangxi Medical UniversityVoltooid
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Sun Yat-sen UniversityOnbekendColorectale neoplasmataChina