WILD-TYPE AND E-ANTIGEN-MINUS HEPATITIS-B VIRUSES AND COURSE OF CHRONIC HEPATITIS
WILD-TYPE AND E-ANTIGEN-MINUS HEPATITIS-B VIRUSES AND COURSE OF CHRONIC HEPATITIS
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DOI：
10.1073/pnas.88.10.4186
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
BONINO, F
中科院分区：
文献类型：
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作者：
BRUNETTO, MR;GIARIN, MM;BONINO, F
我们采用寡核苷酸杂交试验，研究了106例慢性B型肝炎B表面抗原阳性患者中野生型B病毒（HBV）和由于前C区终止密码子导致翻译缺陷而不能分泌B e抗原（HBeAg）的HBV突变体的临床意义。 在42例HBeAg阳性患者中，31例（73.8%）检测到野生型HBV，而10例（23.8%）存在混合病毒群。 在两组患者中未观察到肝病严重程度和结局的显著差异。 然而，在野生型HBV携带者中HBeAg阴性HBV的出现与肝脏疾病的恶化相关，并且随后在50%的病例中血清中存在抗HBeAg抗体（抗-HBe）。 在64例抗-HBe阳性患者中有61例（95.3%），HBeAg阴性HBV是主要病毒：42例（65.6%）患者中检测到HBeAg阴性HBV，而19例（29.7%）患者中同时存在野生型和HBeAg阴性HBV。 HBeAg阴性的HBV与以肝细胞坏死为特征的肝炎病程相关，肝细胞坏死的发作与无症状的HBV携带期相间隔（P < 0.01）。 这些数据支持HBV基因异质性显著影响慢性B型肝炎病程和转归的假设。 分泌HBeAg的野生型HBV诱导免疫耐受并引起慢性感染。 HBeAg阴性的HBV在没有野生型HBV的辅助功能的情况下可能无法诱导慢性感染，但它似乎更具致病性。 一旦慢性感染建立，HBeAg阴性的HBV变异体可能占优势并取代野生型病毒。
Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of 42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P < 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wild-type HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus.