Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B: A pilot study.
Indian J Med Res
; 144(3): 424-432, 2016 Sep.
Article
em En
| MEDLINE
| ID: mdl-28139541
ABSTRACT
BACKGROUND & OBJECTIVES:
Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients.METHODS:
A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed.RESULTS:
Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations. INTERPRETATION &CONCLUSIONS:
LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
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Hepatite B Crônica
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Farmacorresistência Viral
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Tenofovir
/
Guanina
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Indian J Med Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Índia