Michalak T I, Pasquinelli C, Guilhot S, Chisari F V
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
J Clin Invest. 1994 Jan;93(1):230-9. doi: 10.1172/JCI116950.
Contrary to current opinion, the disappearance of hepatitis B surface antigen (HBsAg) from the serum, the development of anti-HBs antibodies, and normalization of liver function may not reflect complete virological recovery from acute hepatitis B virus (HBV) infection. By using the polymerase chain reaction (PCR), in the current study we demonstrate long-term persistence of HBV DNA in the serum and peripheral blood mononuclear cells (PBMC) of four patients for up to 70 mo after complete clinical, biochemical, and serological recovery from acute viral hepatitis. Serum HBV DNA reactivity co-sedimented with HBsAg in sucrose gradients, and it displayed the size and density characteristics of naked core particles and intact HBV virions, presumably contained within circulating immune complexes in these anti-HBs antibody-positive sera. HBV DNA was also present in PBMC in late convalescent samples from all four patients, and HBV RNA was detected in late convalescent phase PBMC in two of these patients. These results suggest that HBV DNA, and possibly HBV virions, can be present in the serum, and that the viral genome can persist in a transcriptionally active form in PBMC for > 5 yr after complete clinical and serological recovery from acute viral hepatitis.
与当前观点相反,血清中乙肝表面抗原(HBsAg)消失、抗-HBs抗体产生以及肝功能恢复正常,可能并不反映急性乙型肝炎病毒(HBV)感染后病毒学的完全恢复。在本研究中,我们采用聚合酶链反应(PCR)证明,4例患者在急性病毒性肝炎临床、生化及血清学完全恢复后长达70个月,血清及外周血单个核细胞(PBMC)中持续存在HBV DNA。在蔗糖梯度中,血清HBV DNA反应性与HBsAg共沉降,其大小和密度特征显示为裸露核心颗粒及完整HBV病毒体,推测存在于这些抗-HBs抗体阳性血清中的循环免疫复合物内。所有4例患者恢复期晚期样本的PBMC中均存在HBV DNA,其中2例患者恢复期晚期PBMC中检测到HBV RNA。这些结果表明,急性病毒性肝炎临床及血清学完全恢复后,血清中可存在HBV DNA,甚至可能存在HBV病毒体;病毒基因组可在PBMC中以转录活性形式持续存在5年以上。