Scotto J, Hadchouel M, Hery C, Alvarez F, Yvart J, Tiollais P, Bernard O, Brechot C
Gut. 1983 Jul;24(7):618-24. doi: 10.1136/gut.24.7.618.
Molecular hybridisation using cloned hepatitis B virus DNA (HBV DNA) was applied to liver and serum samples from 46 children (39 with liver diseases and seven controls) for detection of HBV DNA sequences, free and integrated into the liver cell genome. HBV DNA integration was observed in 10 children. The young age of some of these cases indicates that such integration can occur early in liver disease and is not related to the duration of viral infection. Thirteen children exhibited serological evidence of active viral multiplication. All but one had free HBV DNA in liver tissue and integrated HBV DNA sequences were found in four cases. Integrated HBV DNA sequences alone were also detected in three children with neither HBV-antigens nor HBV DNA in serum. One had inactive cirrhosis, and the two others, chronic active hepatitis. Consequently DNA hybridisation may be useful for diagnosis, in the absence of serological signs of HBV infection; its specificity was enhanced in the present investigation by negative results in six children with autoimmune chronic active hepatitis. Taken together, the above results imply that HBV-DNA integration can occur in both active and inactive liver disease. Integrated HBV DNA was also observed in the liver of three children with fatal hepatic failure who presented with antibodies to HBsAg and/or to hepatitis B core antigen in the serum. This finding raises the question of the relationship between the host immune factors and the state of HBV DNA.
采用克隆的乙型肝炎病毒DNA(HBV DNA)进行分子杂交,对46名儿童(39名患有肝脏疾病,7名作为对照)的肝脏和血清样本进行检测,以发现游离的以及整合到肝细胞基因组中的HBV DNA序列。在10名儿童中观察到HBV DNA整合。其中一些病例年龄较小,这表明这种整合可在肝脏疾病早期发生,且与病毒感染持续时间无关。13名儿童表现出病毒活跃增殖的血清学证据。除1名儿童外,其余所有儿童的肝组织中均有游离的HBV DNA,4例发现有整合的HBV DNA序列。在3名血清中既无HBV抗原也无HBV DNA的儿童中也检测到了单独的整合HBV DNA序列。1名患有静止期肝硬化,另外2名患有慢性活动性肝炎。因此,在没有HBV感染血清学迹象的情况下,DNA杂交可能有助于诊断;在本研究中,6名自身免疫性慢性活动性肝炎儿童的阴性结果提高了其特异性。综上所述,上述结果表明HBV - DNA整合可发生在活动性和静止性肝脏疾病中。在3名死于肝衰竭且血清中出现抗HBsAg和/或抗乙型肝炎核心抗原抗体的儿童肝脏中也观察到了整合的HBV DNA。这一发现提出了宿主免疫因素与HBV DNA状态之间关系的问题。