摘要
目的 了解不明原因慢性肝病中隐匿性乙型肝炎所占比例 ,隐匿性乙型肝炎的发病机制及临床、病理特点。方法 给予 2 0例不明原因慢性肝病患者肝穿刺病理检查 ,应用免疫组织化学方法检测肝组织内的乙型肝炎病毒表面抗原 (HBsAg)、核心抗原 (HBcAg) ,丙型肝炎病毒NS3、NS4抗原。采用荧光定量PCR方法对血清HBVDNA进行定量 ,用套式PCR方法扩增HBVS基因 ,对PCR产物进行直接测序 ,比较S基因的核苷酸和推导出的氨基酸序列的差异。结果 5例患者经肝脏病理检查表现为慢性炎症 ,3例在肝组织内HBsAg、HBcAg同时阳性 ,2例仅HBcAg阳性。S基因的氨基酸序列分析显示 ,1例患者S基因的 74位密码子发生终止变异 ,另 1例在HBsAg的“a”决定簇内有 2个氨基酸发生变异 (T13 1N ,M 13 3S) ,其他 3例患者HBsAg的“a”决定簇内未发现变异。 结论 在我国隐匿性乙型肝炎是不明原因肝病的主要原因之一 ,低水平的血清HBVDNA可以引起慢性肝炎。部分隐匿性乙型肝炎HBsAg阴性的原因是S基因变异引起的 ,而有些患者则可能因为血清HBsAg水平过低 ,导致HBsAg检测阴性。
Objective To investigate the incidence of occult hepatitis B among chronic liver diseases of unknown etiology, the mechanisms and histopathologic characteristics of occult HBV infection. Methods 20 patients with chronic liver diseases of unknown etiology were enrolled in this study. Liver histology was analyzed and immunohistochemistry staining for HBV antigens (HBsAg and HBcAg) and HCV antigen (NS3 and NS4) was performed on liver biopsies. HBV DNA levels were quantified by real time fluorescence PCR assay, the S gene was amplified by a nested PCR and the purified PCR products were directly sequenced. The nucleotides and predicted amino acid sequences of S gene were analyzed. Results Liver biopsies from these patients showed chronic hepatitis in 5 cases, non alcoholic steatohepatitis in 15 cases. Of the 5 patients with chronic hepatitis, three were positive for both HBsAg and HBcAg, two for HBcAg only. Analysis of amino acid sequences of S gene showed that a stop codon at position 74 occurred in one patient, 2 amino acid changed (T131N, M133S) in the HBV “a” determinant in another patient, and the rest of patients had no mutation in the HBV “a” determinant.Conclusion Occult HBV infections may account for a high proportion of chronic liver diseases of “unknown” etiology. Low serum level of HBV DNA may cause disease progression. Loss of HBsAg in a portion of occult hepatitis B patients was associated with mutations in HBsAg “a” determinant. It is possible that extremely low serum HBsAg levels may result in negative HBsAg by the routine commercial assays in those patients without mutation of HBsAg “a” determinant.
出处
《肝脏》
2002年第4期229-232,共4页
Chinese Hepatology
