Optimal Long-term Outcome of Chronic Hepatitis B

描述（由申请人提供）：虽然最近在B肝炎（HBV）治疗方面取得了重大进展，但目前对HBV感染管理的了解有限，因为治疗试验最多使用一到两年的治疗，而大多数患者需要更长时间的治疗以获得最佳长期结局。 我们的第一个项目致力于HBeAg阳性慢性B型肝炎患者的最佳长期管理。因此，在项目1中，我们提出了一项在HBeAg阳性慢性肝炎患者中进行的试验，以评估聚乙二醇干扰素联合替诺福韦（TDF）改变自然病程的能力，通过实现以下目标：（项目1a）比较聚乙二醇干扰素和TDF联合治疗与TDF单独治疗的长期疗效和安全性，（项目1 B）确定对联合治疗反应的预测因子，并测量抗病毒治疗的长期获益。 在我们的第二个项目中，我们将研究优化HBV感染患者（包括HCC和终末期肝病）长期结局的方法。这些患者中的大多数将是HBeAg阴性。这些患者处于慢性HBV感染的后期，因此往往年龄较大，纤维化程度较高，这使他们患肝细胞癌（HCC）的风险较高。因此，在项目2中，我们提出了观察性研究来剖析宿主的影响（例如，年龄、性别、种族、肝病分期）和病毒学（基因型，连续HBV DNA水平）特征对HCC风险的影响，通过进行以下目的的研究：（项目2a）比较亚洲和非洲患者的HCC年龄和性别特异性发病率，（项目2b）测量基线患者特征和系列HBV DMA和ALT水平的影响，以开发估计HCC风险的评分并评估抗病毒药物的影响。治疗对发展终末期肝病和HCC的风险。 虽然大多数活动性肝病往往见于年轻的HBeAg阳性肝炎患者，但我们的大多数临床患者是HBeAg阴性的，几乎没有活动性肝病的证据。我们的项目解决了这两个人群中的重要问题。

DESCRIPTION (provided by applicant): Although significant progress has been made recently in hepatitis B (HBV) therapy, the current knowledge in the management of HBV infection is limited because treatment trials have utilized one to two years of therapy at most, whereas most patients require treatment of much longer duration for optimal long term outcome. Our first project addresses optimal long term management of patients with HBeAg-positive chronic hepatitis B. Thus, in Project 1, we propose a trial in patients with HBeAg-positive chronic hepatitis to evaluate the ability of pegylated interferon in combination with tenofovir (TDF) to alter the natural history, by achieving the following aims: (Project 1a) to compare the long term efficacy and safety of combination of pegylated interferon and TDF versus TDF alone and (Project 1 b) to identify predictors of response to the combination therapy and measure the long term benefit of antiviral therapy. In our second project, we will investigate means to optimize the long term outcome in patients with HBV infection including HCC and end stage liver disease. The majority of these patients will be HBeAg-negative. These patients are in a later phase of chronic HBV infection and thus tend to be older and to have more fibrosis, which predispose them to a higher risk of developing hepatocellular carcinoma (HCC). Thus, in Project 2, we propose observational studies to dissect the effect of host (e.g., age, gender, race, stage of liver disease) and virologic (genotype, sequential HBV DMA levels) characteristics on the risk of HCC, by conducting studies with following aims: (Project 2a) to compare the age- and gender-specific incidence of HCC between patients of Asian and African origin and (Project 2b) to measure the effect of baseline patient characteristics and serial HBV DMA and ALT levels to develop a score estimating the risk of HCC and assess the impact of antiviral therapy on the risk of developing end stage liver disease and HCC. While the most active liver disease tends to be seen in young, HBeAg-positive hepatitis patients, the majority of our clinic patients are HBeAg-negative with little evidence of active liver disease. Our project addresses important questions in both of these populations.