Optimal Long-term Outcome of Chronic Hepatitis B

慢性乙型肝炎的最佳长期结果

• 批准号: 8139765
• 负责人: W. Ray KIM
• 金额: $ 41.68万
• 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/8139765
• 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（由申请人提供）：尽管最近在丙型肝炎（HBV）疗法中取得了重大进展，但目前在HBV感染管理方面的知识有限，因为治疗试验最多可以使用一到两年的治疗，而大多数患者则需要更长的持续时间来实现最佳长期结局。 我们的第一个项目介绍了HBEAG阳性慢性肝炎患者的最佳长期管理。因此，在项目1中，我们建议在HBEAG阳性慢性肝炎患者中进行一项试验，以评估与Tenofovir（TDF（TDF）相结合的pe节制干扰素的能力，以实现以下范围的范围，以对1A的安全进行验证：单独使用的干扰素和TDF与TDF和（项目1 B）确定对组合疗法的反应预测指标，并衡量抗病毒疗法的长期益处。 在我们的第二个项目中，我们将调查用于优化HBV感染患者（包括HCC和末期肝病）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HBV感染的后期，因此倾向于年龄较大并具有更多的纤维化，这使他们容易患肝细胞癌（HCC）的风险更高。因此，在项目2中，我们提出了观察性研究，以阐明宿主（例如年龄，性别，种族，肝病的年龄，种族，肝病阶段）和病毒学性（基因型，顺序HBV DMA水平）对HCC风险的影响，通过进行以下目的进行研究：（项目2A）以下目的进行研究：（项目2A）的基础（项目2A），以比较HCC的患者（与HCC的生存相比），而不是针对HCC的患者，而不是HCC的患者，而不是HCC的患者，而不是hcc的生命力。患者特征和串行HBV DMA和ALT水平以发展分数，以估计HCC的风险，并评估抗病毒疗法对发展终末期肝病和HCC风险的影响。 虽然在HBEAG阳性肝炎患者的年轻肝病患者中往往会出现最活跃的肝病，但我们大多数临床患者都是HBEAG阴性，几乎没有活性肝病的证据。我们的项目在这两个人群中都解决了重要问题。