Medicine (St Vincent's) - Research Publications
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ItemFive-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy(WILEY, 2017-06)BACKGROUND: Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study. METHODS: A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily. RESULTS: Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma. CONCLUSIONS: Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV.
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ItemManaging HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders(BMJ PUBLISHING GROUP, 2016-02)Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These include the lack of a current cohesive strategy for treatment and follow-up of mothers and their babies; the uncertain risk of postpartum HBV flares; the lack of randomised trial data on the safety and efficacy of antiviral treatment in pregnancy; the lack of head-to-head studies comparing different antivirals in pregnancy; and the lack of epidemiologic information regarding infection across different populations globally. This position paper provides a comprehensive review of the management of women with HBV infection prior to conception, throughout each stage of pregnancy and postpartum, as well as recommendations and clinical approaches for the follow-up of children born to infected mothers, based on available evidence in the literature and recommendations from international experts. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for most of the chronic infection worldwide.
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ItemNo Preview AvailableViral Adaptation to Host Immune Responses Occurs in Chronic Hepatitis B Virus (HBV) Infection, and Adaptation Is Greatest in HBV e Antigen-Negative Disease(AMER SOC MICROBIOLOGY, 2012-01)Hepatitis B virus (HBV)-specific T-cell responses are important in the natural history of HBV infection. The number of known HBV-specific T-cell epitopes is limited, and it is not clear whether viral evolution occurs in chronic HBV infection. We aimed to identify novel HBV T-cell epitopes by examining the relationship between HBV sequence variation and the human leukocyte antigen (HLA) type in a large prospective clinic-based cohort of Asian patients with chronic HBV infection recruited in Australia and China (n = 119). High-resolution 4-digit HLA class I and II typing and full-length HBV sequencing were undertaken for treatment-naïve individuals (52% with genotype B, 48% with genotype C, 63% HBV e antigen [HBeAg] positive). Statistically significant associations between HLA types and HBV sequence variation were identified (n = 49) at 41 sites in the HBV genome. Using prediction programs, we determined scores for binding between peptides containing these polymorphisms and associated HLA types. Among the regions that could be tested, HLA binding was predicted for 14/18 (78%). We identified several HLA-associated polymorphisms involving likely known anchor residues that resulted in altered predicted binding scores. Some HLA-associated polymorphisms fell within known T-cell epitopes with matching HLA restriction. Enhanced viral adaptation (defined as the presence of the relevant HLA and the escaped amino acid) was independently associated with HBeAg-negative disease (P = 0.003). Thus, HBV appears to be under immune pressure in chronic HBV infection, particularly in HBeAg-negative disease.