Occult hepatitis B virus infection and reactivation in Africans in the context of the human immunodeficiency virus pandemic

就发病率和死亡率而言，乙型肝炎病毒（HBV）感染是非洲最重要的病毒感染之一，造成了巨大的公共卫生问题。乙型肝炎病毒感染可导致急性和慢性感染，但在成年免疫能力者中，只有10%的乙型肝炎病毒感染导致明显的慢性感染，而90%的人显示出缓解的血清学迹象。然而，即使在解决的病例中，HBV也可以以隐性乙型肝炎的形式在肝脏中静默存在，并且可以在患者严重的免疫抑制后重新激活。在欧洲，这主要是免疫抑制治疗的结果，但在艾滋病毒感染的获得性免疫缺陷综合征（艾滋病）患者中也观察到。在非洲，严重的免疫抑制主要是由于艾滋病的出现，因为大多数艾滋病毒感染者没有得到适当的抗病毒药物治疗。在欧洲，由于病例数量有限和高效的艾滋病毒抗病毒治疗（HAART）可用，HBV/HIV合并感染中隐匿性乙型肝炎的出现和再激活是罕见的。然而，在非洲，由于艾滋病毒大流行，乙型肝炎/艾滋病毒合并感染的频率要高上百倍，导致隐性乙型肝炎病例高得多，并且由于艾滋病毒免疫缺陷，乙型肝炎/艾滋病毒感染患者的乙型肝炎病毒再激活风险增加。这通常与HBV突变体的选择有关，偶尔会导致致命的乙型肝炎疾病。由于逃逸突变的出现，选择性HBV再激活突变的传播增加危及HBV诊断、抗病毒治疗和整个HBV疫苗计划。我们的主要目的是阐明HBV/HIV合并感染患者中再激活HBV的性质，这些患者显示出先前的缓解或隐匿性HBV感染的迹象。这些患者中新出现的HBV突变体的特征将有助于了解HBV逃逸突变体在HBV和HIV患病率非常高的人群中的流行病学和致病作用。由于与欧洲伙伴的密切合作，预期实验室基础设施和科学人员培训将得到改善，这将促进非洲对乙型肝炎的管理。

Infection with hepatitis B virus (HBV) is one of the most important viral infections in Africa, in terms of morbidity and mortality, causing massive public health problems. Infection with HBV can result in acute and chronic infections, but only 10% of HBV infections in adult immune competent persons lead to overt chronic infections while 90% showing serological signs of resolution. However, even in resolved cases, HBV can persist silently in the liver in form of occult hepatitis B, and can be reactivated following severe immunosuppression of the patient. In Europe, this is mostly the result of immunosuppressive therapy, but is also observed during acquired immunodeficiency syndrome (AIDS) in HIV-infected patients. In Africa, severe immunosuppression is mostly due to the appearance of AIDS, since most of the HIV-infected persons are not well treated with suitable antivirals. In Europe, the appearance of occult hepatitis B and reactivation in HBV/HIV co-infections is rare, due to the limited number of cases and highly efficient antiviral HIV therapy (HAART) available. However, in Africa, HBV/HIV coinfections are hundred times more frequent due to the HIV pandemic, leading to much higher cases of occult hepatitis B and an increased risk of HBV reactivation in HBV/HIV infected patients due to immunodeficiency by HIV. This is often associated with selection of HBV mutants, occasionally leading to fatal hepatitis B disease. The increased transmission of selected HBV mutants from reactivation endangers HBV diagnosis, antiviral therapy and the whole HBV vaccine program in Africa because of the appearance of escape-mutations. Our major objectives are to elucidate the nature of reactivated HBV in HBV/HIV co-infected patients, showing previous signs of resolved or occult HBV infection. The characterisation of emerging HBV mutants in those patients will help to understand the epidemiological and pathogenic role of HBV escape mutants in a population with very high HBV and HIV prevalence. The anticipated improvement of laboratory infrastructure and training of scientific personnel as a result of the close cooperation with European partners, will facilitate in the management of hepatitis B in Africa.