Feld Jordan J, Heathcote E Jenny
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland, USA.
Semin Liver Dis. 2006 May;26(2):116-29. doi: 10.1055/s-2006-939750.
The natural history of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is very heterogeneous. Age at acquisition is a major factor in determining the natural history of chronic infection. The vigor of the host immune response to the virus, viral factors (genotype, core promoter mutations, and duration of viral replication) as well as exogenous factors (alcohol, immune suppression) all influence the severity of disease. The goal of antiviral therapy is HBeAg seroconversion, and preferably HB surface Ag seroconversion as this latter end-point is associated with sustained immune control and the halting of disease progression. Although peginterferon is now considered as the first line of therapy for HBeAg-positive chronic hepatitis B, in most cases there are circumstances where nucleos(t)ide analogues are indicated (e.g., decompensated liver disease) for those requiring cancer chemotherapy/other immunosuppressive agents and for those with contraindications to interferon. The major challenge for the clinician using these agents is the emergence of antiviral drug resistance. Long-term immune control of viral replication is key to improving patient outcome.
乙肝e抗原（HBeAg）阳性慢性乙型肝炎的自然史具有很大的异质性。感染时的年龄是决定慢性感染自然史的主要因素。宿主对病毒的免疫反应强度、病毒因素（基因型、核心启动子突变和病毒复制持续时间）以及外源性因素（酒精、免疫抑制）都会影响疾病的严重程度。抗病毒治疗的目标是实现HBeAg血清学转换，最好是实现乙肝表面抗原（HBsAg）血清学转换，因为后一个终点与持续的免疫控制和疾病进展的停止相关。尽管聚乙二醇干扰素现在被认为是HBeAg阳性慢性乙型肝炎的一线治疗药物，但在大多数情况下，对于那些需要进行癌症化疗/其他免疫抑制剂治疗的患者以及那些有干扰素禁忌证的患者，在某些情况下（如失代偿性肝病）仍需使用核苷（酸）类似物。临床医生使用这些药物面临的主要挑战是抗病毒药物耐药性的出现。对病毒复制进行长期免疫控制是改善患者预后的关键。
