Glebe Dieter
World J Gastroenterol. 2007 Jan 7;13(1):8-13. doi: 10.3748/wjg.v13.i1.8.
More than 30 years after the discovery of human hepatitis B virus (HBV) this virus remains to be one of the major global health problems. In infected adolescents or adults, 5%-10% will lead to a chronic carrier state, whereas in infected neonates up to 90% develop chronicity. It is estimated that about 370 million people are chronic carriers of HBV worldwide. In many regions of the world, chronic HBV infection is still the major cause of liver cirrhosis and hepatocellular carcinoma. During the last 30 years, many steps of the viral life cycle have been unravelled, mainly due to cloning, sequencing and expression of the genomic DNA extracted from HBV virions. This has lead to the development of a safe and efficient vaccine and sensitive tests for HBV surface protein (HBsAg) allowing reliable diagnosis and screening of blood products. More recently, a growing number of reverse transcriptase inhibitors have been developed. However, together with these improvements new deficiencies in prevention and cure of HBV infections are becoming apparent. Although HBV is a DNA virus, it is highly variable under immunity or drug induced selection pressure, resulting in vaccine-related escape mutants and drug resistance. To overcome these challenging problems new antivirals and optimised vaccines have to be developed.
人类乙型肝炎病毒(HBV)被发现30多年后,该病毒仍是全球主要的健康问题之一。在受感染的青少年或成年人中,5%-10%会发展为慢性携带状态,而在受感染的新生儿中,高达90%会发展为慢性感染。据估计,全球约有3.7亿人是HBV慢性携带者。在世界许多地区,慢性HBV感染仍然是肝硬化和肝细胞癌的主要原因。在过去30年里,病毒生命周期的许多步骤已被阐明,这主要归功于从HBV病毒粒子中提取的基因组DNA的克隆、测序和表达。这促成了一种安全有效的疫苗的研发以及针对HBV表面蛋白(HBsAg)的灵敏检测方法的出现,从而能够对血液制品进行可靠的诊断和筛查。最近,越来越多的逆转录酶抑制剂被研发出来。然而,随着这些进展,HBV感染预防和治疗方面新的不足之处也日益明显。尽管HBV是一种DNA病毒,但在免疫或药物诱导的选择压力下它具有高度变异性,会产生与疫苗相关的逃逸突变体和耐药性。为克服这些具有挑战性的问题,必须研发新的抗病毒药物和优化的疫苗。