Management of chronic hepatitis B in Africa: is a one-stop assessment of liver disease enough? The MATCH-B study

B型肝炎病毒（HBV）感染是全世界主要的公共卫生问题，约有2.5亿人慢性感染。HBV是导致严重肝病包括肝癌的重要原因，其预后不良。虽然有一种有效的疫苗可以预防HBV传播，但许多人没有接种疫苗，特别是在非洲，并感染了严重的肝脏并发症的风险。世界卫生组织（WHO）最近认识到HBV感染是一个重要的健康威胁，并呼吁在全球范围内扩大B型肝炎的筛查和治疗干预措施，以便到2030年控制HBV相关死亡率并最终消除感染。在HBV感染患者的管理方面取得了重大进展。目前，在许多国家都可以以低成本获得一种高效的治疗方法，并推荐给活动性肝炎的最严重患者。然而，在占HBV流行80%的发展中国家，对抗B型肝炎的干预措施非常有限。在非洲，估计约有8000万人慢性感染HBV。然而，在非洲几乎不存在防治B型肝炎的筛查和治疗干预措施以及研究活动。目前国际上关于管理B型肝炎的建议的复杂性和高成本是在非洲扩大HBV筛查和治疗干预措施的障碍之一。2011年在冈比亚和塞内加尔建立了非洲首个B型肝炎筛查和治疗方案，称为PROLIFICA（非洲预防肝纤维化和癌症）。在冈比亚和塞内加尔卫生部以及当地社区的支持下，该方案非常成功：对近20 000人进行了乙型肝炎病毒检查，对约2 000名感染者进行了临床评估，并对283人进行了抗病毒治疗。PROLIFICA还生成了关于非洲慢性B型肝炎的独特数据，这些数据向世卫组织和当地卫生部通报了西非B型肝炎的负担。这项研究表明，西非绝大多数感染HBV的成年人患有非活动性或轻度肝炎，不需要立即治疗。然而，这些患者是否在中长期内没有肝脏疾病进展，或者他们是否需要定期随访，因为他们可能会发生肝脏并发症，在非洲尚不清楚。此外，HBV抗病毒治疗对控制肝脏并发症是否有效和安全尚未得到证实。在以下研究中，我们建议重新评估先前入组PROLIFICA项目的2，108例患者（未经治疗或治疗）的肝脏疾病。我们将重新邀请之前在冈比亚和塞内加尔参加该计划的每名患者进行全面的肝脏评估。肝病进展的感染受试者将接受治疗。因此，本研究将解决非洲的两个关键未知问题：1/暴露于非洲环境的非活动性或轻度B型肝炎非洲患者的肝病进展率是多少，能否为他们提供有限的监测？2/HBV抗病毒治疗对减少非洲活动性慢性B型肝炎患者的肝脏并发症是否有效和安全？如果我们证明在一个单一时间点诊断为非活动性或轻度B肝炎的患者随着时间的推移没有显著的肝病进展，则可能没有必要对非洲数百万轻度B肝炎患者进行常规的频繁随访。这将节省大量资源，因为非洲的医疗资源严重有限。我们相信，我们的研究也将促进对B型肝炎的认识，其研究结果将最终有助于制定非洲HBV感染管理的简化指南。

Infection with hepatitis B virus (HBV) is a major public health issue worldwide with about 250 million people chronically infected. HBV is an important cause of severe liver disease including liver cancer, which has a poor prognostic. Although an effective vaccine is available to prevent HBV transmission, many people are not vaccinated in particular in Africa and get infected with a risk of serious hepatic complications. The World Health Organization (WHO) has recently recognized HBV infection as an important health threat and has called for scaling up screening and treatment interventions for hepatitis B globally in order to control HBV-related mortality by 2030 and eventually eliminate the infection. Significant progress has been made in the management of HBV-infected patients. A highly effective treatment is now available at low cost in many countries and is recommended to the most severe patients with active hepatitis. However in developing countries, which account for 80% of the HBV epidemic, interventions to fight against hepatitis B are very limited. In Africa about 80 million people are estimated to be chronically infected with HBV. Yet screening and treatment interventions and research activities to fight against hepatitis B are almost inexistent in Africa. The complexity and high cost of the current international recommendations for the management of hepatitis B represent one of the barriers to scale up HBV screening and treatment interventions in Africa. The first screen-and-treat programme for hepatitis B in Africa called PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) has been set up in 2011 in Gambia and Senegal. With the support of the Gambian and Senegalese Ministries of Health and the local communities, the programme has been very successful: almost 20,000 persons have been screened for HBV and about 2,000 infected persons have been offered clinical assessment, and 283 given antiviral treatment. PROLIFICA has also generated unique data on chronic hepatitis B in Africa, which have informed the WHO and the local Ministries of Health on the burden of hepatitis B in West Africa. The study demonstrated that the vast majority of HBV-infected adults in West Africa have inactive or mild hepatitis and do not require immediate treatment. However, whether these patients remain so without liver disease progression in mid- to long-term or do they require regular follow-up as they may develop liver complications is unknown in Africa. In addition whether HBV antiviral therapy is effective and safe to control liver complications has never been demonstrated. Within the following study, we propose to re-assess the liver disease of the 2,108 patients (untreated or treated) previously enrolled in the PROLIFICA programme. We will re-invite each patient previously enrolled in the programme in Gambia and Senegal for a comprehensive liver assessment. Infected subjects with liver disease progression will be given treatment. This study will therefore address two key unknown questions for Africa: 1/ What is the rate of liver disease progression in African patients with inactive or mild hepatitis B exposed to the African environment and can they be offered a limited monitoring? 2/ Is HBV antiviral therapy effective and safe to reduce hepatic liver complications in patients with active chronic hepatitis B in Africa? If we demonstrate that patients diagnosed to have inactive or mild hepatitis B at one single time point have no significant liver disease progression over time, it may be unnecessary to do the conventional frequent follow-up for the millions of patients with mild hepatitis B in Africa. This will save considerable amount of resources since healthcare resources are seriously limited in Africa. We believe that our study will also promote awareness on hepatitis B and its findings will eventually contribute to the development of simplified guidelines for the management of HBV infection in Africa.