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Review A systematic review of T-cell epitopes in hepatitis B virus: identification, genotypic variation and relevance to antiviral therapeutics. 2008
Desmond CP, Bartholomeusz A, Gaudieri S, Revill PA, Lewin SR. · Department of Gastroenterology, Alfred Hospital, Melbourne, Australia. · Antivir Ther. · Pubmed #18505168 No free full text.
Abstract: BACKGROUND: The immune response to hepatitis B virus (HBV) is important for both viral control and disease pathogenesis. A detailed understanding of the HBV-specific T-cell responses may potentially lead to novel therapeutic strategies for HBV. METHODS: All English language journal articles (including articles in press) up to October 2007 were retrieved using searches of MEDLINE, EMBASE and the Cochrane Controlled Trial Registry. An extensive database of HBV sequences (SeqHepB) and GenBank were used to assess the degree of sequence variation in each epitope. The new standardized nomenclature for HBV amino acid position number was applied to all previously defined epitopes. RESULTS: Forty-four HBV-specific human leukocyte antigen (HLA) class I restricted and 32 HBV-specific HLA class II restricted epitopes have been defined and have been identified in all HBV genes. The majority of HLA class I restricted epitopes have been defined in HLA-A2-positive individuals in the setting of acute HBV infection. There is significant sequence variation of these epitopes within and between HBV genotypes. Newer HBV immunotherapeutics appear promising but are still in early phases of development. CONCLUSIONS: Identification of HBV-specific epitopes in non-HLA-A2-positive individuals and recognition of genotypic variation across epitopes are important for the future development of novel immunotherapeutic strategies for the management of chronic HBV infection.
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Article Sustained virological response rates and durability of the response to interferon-based therapies in hepatitis C patients treated in the clinical setting. 2006
Desmond CP, Roberts SK, Dudley F, Mitchell J, Day C, Nguyen S, Pianko S. · Department of Gastroenterology, The Alfred Hospital, Melbourne, Vic., Australia. · J Viral Hepat. · Pubmed #16637861 No free full text.
Abstract: International controlled trials have demonstrated increasing sustained virological response (SVR) rates to interferon-based therapies in hepatitis-C-treated patients. Response rates of 6-20% in the era of interferon monotherapy are compared with 42-82% with pegylated interferon plus ribavirin. The virological durability of the SVR is unknown and the optimal follow-up for these patients is unclear. The aim of our study was to determine SVR rates and the durability of the response to interferon-based therapies in the clinical setting. From our database of 1540 hepatitis C patients, 344 treatment courses of at least 12 weeks duration were identified, including interferon monotherapy (175 patients), interferon plus ribavirin (96 patients) and peginterferon plus ribavirin (73 patients). Interferon monotherapy was associated with an SVR rate of 5% in 103 genotype 1 patients and 25% in 72 genotype 2/3 patients. Response rates were higher (P < 0.001) with interferon plus ribavirin-41% in 34 genotype 1 patients and 73% in 62 genotype 2/3 patients-and with peginterferon plus ribavirin-47% in 47 genotype 1 patients and 79% in 26 genotype 2/3 patients. Of 147 patients with an SVR, 146 (>99%) remained hepatitis C virus PCR negative during a mean 2.3 years (range 0.3-10.3) of follow-up. In conclusion, with advances in therapies, we are achieving higher response rates in hepatitis C patients treated in the clinical setting. We can now expect an SVR in over half of the treated patients. Importantly, the response is durable and medium and long-term follow-up of these patients are of low yield and largely unnecessary.
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