Brunetto M R, Stemler M, Bonino F, Schodel F, Oliveri F, Rizzetto M, Verme G, Will H
Department of Gastroenterology, Molinette Hospital, Torino, Italy.
J Hepatol. 1990 Mar;10(2):258-61. doi: 10.1016/0168-8278(90)90062-v.
In hepatitis B virus carriers who are anti-HBe positive despite ongoing viral replication (HBcAg in liver and HBV-DNA in serum) the natural course of hepatitis is severe and the response to interferon is low. We investigated whether a new hepatitis B virus (HBV) strain could be involved. A translational termination codon at the carboxyterminal end of the pre-C region responsible for the lack of HBeAg secretion was found in 18 of 19 HBV clones isolated from seven pedigreed patients with this clinical syndrome. The same findings were confirmed by direct sequencing. One of these patients underwent a liver transplant and HBV infection of the new liver resulted in high titered viremia and intrahepatic expression of HBcAg, without detectable HBeAg in serum. Another patient was superinfected by hepatitis delta virus (HDV) and developed high titres of total and IgM anti-HD. In spite of this, chronic hepatitis remained unchanged during 7 years of follow-up. These data strongly suggest that a viable precore minus mutant of hepatitis B virus is responsible for the lack of HBeAg in the serum of these patients. The HBV variant may explain the peculiar geographic distribution of anti-HBe positive hepatitis. The variations in the virus genome sequence may cause the more severe form of liver disease and modify the pathogenicity in the case of HDV superinfection.
在乙肝病毒携带者中，尽管病毒仍在复制（肝脏中有乙肝核心抗原，血清中有乙肝病毒DNA），但e抗原阴性者的肝炎自然病程严重，对干扰素的反应较低。我们研究了是否有新的乙肝病毒（HBV）毒株参与其中。从7例患有这种临床综合征的家系患者中分离出的19个HBV克隆中，有18个在负责e抗原分泌缺失的前C区羧基末端发现了一个翻译终止密码子。直接测序证实了相同的发现。其中一名患者接受了肝移植，新肝脏感染HBV导致高滴度病毒血症和肝内乙肝核心抗原表达，血清中未检测到e抗原。另一名患者被丁型肝炎病毒（HDV）重叠感染，总抗HD和IgM抗HD滴度升高。尽管如此，在7年的随访中慢性肝炎仍无变化。这些数据强烈表明，一种可行的乙肝病毒前核心区缺失突变体是这些患者血清中缺乏e抗原的原因。HBV变异体可能解释了e抗原阴性肝炎独特的地理分布。病毒基因组序列的变化可能导致更严重的肝病形式，并在HDV重叠感染的情况下改变致病性。
