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中国人慢性乙型肝炎HBsAg抗原血清学清除：病毒学、组织学和临床方面的认识
很少有研究探讨中国人慢性乙型肝炎患者HBsAg的血清学清除问题。我们全面的研究了92位（平均随访时间126个月）发生HBsAg血清学清除患者的生化学、病毒学、组织学和临床方面的资料。年龄、性别和随访时间相匹配的92位HBsAg阳性作为对照组。研究对肝脏生化学、血清乙型肝炎病毒DNA水平和临床并发症进行监测。对16位病人进行了肝内总的和cccHBV－DNA水平的定量检测，有30位患者进行HBV－DNA分型。发生HBsAg血清学清除的平均年龄是48.8岁（±13.81岁），发生HBsAg血清学清除者其ALT水平明显改善（p<0.0001），且B型乙肝患者发生HBsAg血清学清除的几率高于较C型乙肝患者（p＝0.014）；发生HBsAg血清学清除者中98％的患者HBV-DNA检测阴性，37％的患者肝内HBV-DNA滴度降到较低滴度，主要以cccHBV-DNA的形式存在（71％～100％）。所有14位进行肝活检的患者肝组织学基本接近正常肝脏。肝癌的发生率在发生HBsAg血清学清除者与未清除者相比没有明显差异（p＝0.016）。
结论：发生HBsAg血清学清除的患者具有令人鼓舞的生化学、病毒学和组织学指数改善。肝内HBV-DNA水平降低一个非常低且主要以cccHBV-DNA的形式存在。然而，肝细胞肝癌的进展仍在继续，特别是在哪些老年肝硬化且发生HBsAg血清学清除者中。
Man-Fung Yuen,1 Danny Ka-Ho Wong,1 Erwin Sablon,2 Eric Tse,3 Irene Oi-Lin Ng,4 He-Jun Yuan,1 Chung-Wah Siu,1
Tamara J. Sander,5 Eric J. Bourne,6 Jeff G. Hall,5 Lynn D. Condreay,6 and Ching-Lung Lai1
Few studies have examined Chinese patients with chronic hepatitis B who exhibit hepatitis B surface antigen (HBsAg) seroclearance. We comprehensively studied the biochemical, virological, histological, and clinical aspects of 92 patients with HBsAg seroclearance (median follow-up, 126 months). Ninety-two HBsAg-positive controls matched for age, sex, and duration of follow- up were also recruited. Liver biochemistry, serum hepatitis B virus (HBV) DNA levels, and development of clinical complications were monitored. Intrahepatic total and covalently closed circular (ccc) HBV DNA were measured quantitatively in 16 patients. HBV genotype was determined in 30 patients. The mean age at HBsAg seroclearance was 48.8 (_13.81) years. There was a signi.cant improvement in serum alanine aminotransferase levels after HBsAg seroclearance (p<0.0001). Patients with genotype B had a higher chance of HBsAg seroclearance than those with genotype C (P _ .014). Ninety-eight percent of patients had undetectable serum HBV DNA. Thirty-seven percent of patients had low titer of intrahepatic HBV DNA, mainly in the form of cccDNA (71%-100%). All 14 patients with liver biopsies had near normal histology. There was no difference in the risk of development of hepatocellular carcinoma (HCC) between patients with and without HBsAg seroclearance. However, the mean age of HBsAg seroclearance was signi.cantly older in patients with HCC than in patients without HCC (P _ .016). In conclusion, patients with HBsAg seroclearance had favorable biochemical, virological, and histological parameters. Intrahepatic HBV DNA level was low and predominantly in the form of cccDNA. However, HCC could still develop, particularly in patients with cirrhosis who had HBsAg seroclearance at an older age. (HEPATOLOGY 2004;39:1694–1701.)
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发表于 2005-1-13 02:56
