Optimal Long-term Outcome of Chronic Hepatitis B

慢性乙型肝炎的最佳长期结果

• 批准号: 8545808
• 负责人: LEWIS R ROBERTS
• 金额: --
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545808
• 关键词: Address; African; Age; Antiviral Agents; Antiviral Therapy; Asians; Characteristics; Chronic Hepatitis; Chronic Hepatitis B; Clinic; Combined Modality Therapy; DNA; Data; Fibrosis; Gender; Genotype; Hepatitis; Hepatitis B; Hepatitis B Virus; Hepatitis B e Antigens; Incidence; Infection; Interferons; Knowledge; Link; Liver diseases; Measures; Natural History; Observational Study; Outcome; Pacific Islands; Patients; Phase; Population; Primary carcinoma of the liver cells; Race; Recommendation; Risk; Risk Estimate; Safety; Staging; System; Tenofovir; Woman; high risk; men; response; treatment trial

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.

描述(申请人提供)：尽管最近在乙肝(乙肝)治疗方面取得了重大进展，但目前对乙肝病毒感染管理的知识有限，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的治疗时间才能获得最佳的长期结果。 我们的第一个项目致力于HBeAg阳性慢性乙肝患者的最佳长期治疗。因此，在项目1中，我们提议对HBeAg阳性慢性肝炎患者进行一项试验，以评估聚乙二醇化干扰素联合替诺福韦(TDF)改变自然病史的能力，从而实现以下目标：(项目1a)比较聚乙二醇化干扰素和替诺福韦(TDF)联合治疗与单独使用TDF的长期有效性和安全性，以及(项目1b)确定联合治疗反应的预测因素，并衡量抗病毒治疗的长期益处。 在我们的第二个项目中，我们将研究优化包括肝细胞癌和终末期肝病在内的乙肝感染患者的长期结局的方法。这些患者中的大多数将是HBeAg阴性。这些患者处于慢性乙肝感染的后期，因此往往年龄较大，有更多的纤维化，这使他们患肝细胞癌(HCC)的风险更高。因此，在项目2中，我们建议进行观察性研究，以剖析宿主(例如，年龄、性别、种族、肝病分期)和病毒学特征(基因、顺序HBVDMA水平)对肝癌风险的影响，进行以下目的的研究：(项目2a)比较亚洲和非洲起源的患者之间特定年龄和性别的肝癌发病率；(项目2b)测量基线患者特征和系列HBVDMA和ALT水平的影响，以制定评估肝癌风险的评分，并评估抗病毒治疗对发展为终末期肝病和肝癌的风险的影响。 虽然最活跃的肝病往往见于年轻的、HBeAg阳性的肝炎患者，但我们的大多数临床患者都是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群体中的重要问题。