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接受干扰素治疗的 HBeAg 阳性患者中肝 HBsAg 表达的临床意义和演变。

Clinical significance and evolution of hepatic HBsAg expression in HBeAg-positive patients receiving interferon therapy.

机构信息

Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei, 10002, Taiwan.

出版信息

J Gastroenterol. 2014 Feb;49(2):356-62. doi: 10.1007/s00535-013-0840-z. Epub 2013 Jun 5.

Abstract

BACKGROUND

Serum hepatitis B surface antigen (HBsAg) level is important in the management of chronic hepatitis B (CHB). However, it is unclear whether serum HBsAg reflects its expression in liver and the hepatic HBsAg evolution following interferon therapy.

METHODS

Forty-five HBeAg-positive CHB patients receiving interferon-based therapy within a randomized, controlled, multicenter study during 1998-1999 were included. The hepatic HBsAg expressions were categorized into cytoplasmic, inclusion, marginal and negative patterns by immunohistochemical staining. The HBsAg-positive hepatocytes were quantified by image-based cytometry and correlated to HBV serological and virological profiles for clinical implications. The evolution of hepatic HBsAg levels was analyzed among 22 patients with paired liver biopsies before and after interferon therapy, sequentially.

RESULTS

There was a positive correlation between pretreatment serum HBsAg and hepatic HBsAg levels (r = 0.67, P < 0.0001). The hepatic HBsAg expression pattern significantly evolved from cytoplasmic/inclusion pattern to marginal/negative pattern after interferon treatment. The serum HBV-DNA, HBsAg and hepatic HBsAg levels all decreased significantly after interferon therapy. Among 36 % patients with HBeAg loss after therapy, pretreatment hepatic HBsAg levels were significantly lower compared with those without HBeAg loss. After multivariate analysis, low pretreatment hepatic HBsAg levels rather than serum HBsAg titers were associated with a higher rate of HBeAg loss (OR: 4.97, 95 % CI: 1.12-22.00, P = 0.035).

CONCLUSIONS

The serum HBsAg level positively reflects the HBsAg level in liver which evolves significantly after interferon therapy. A lower hepatic HBsAg level is associated with HBeAg loss after interferon treatment. Hepatic HBsAg may have clinical significance in CHB patients receiving interferon treatment.

摘要

背景

血清乙型肝炎表面抗原(HBsAg)水平在慢性乙型肝炎(CHB)的管理中很重要。然而,尚不清楚血清 HBsAg 是否反映了其在肝脏中的表达,以及干扰素治疗后肝内 HBsAg 的演变。

方法

纳入 1998 年至 1999 年期间在一项随机、对照、多中心研究中接受基于干扰素治疗的 45 例 HBeAg 阳性 CHB 患者。通过免疫组织化学染色将肝内 HBsAg 表达分为细胞质、包涵体、边缘和阴性模式。通过基于图像的细胞计数定量 HBsAg 阳性肝细胞,并将其与 HBV 血清学和病毒学特征相关联以探讨临床意义。分析 22 例患者治疗前后配对肝活检的肝内 HBsAg 水平演变。

结果

治疗前血清 HBsAg 与肝内 HBsAg 水平呈正相关(r=0.67,P<0.0001)。干扰素治疗后肝内 HBsAg 表达模式从细胞质/包涵体模式显著演变为边缘/阴性模式。治疗后血清 HBV-DNA、HBsAg 和肝内 HBsAg 水平均显著下降。治疗后 HBeAg 丢失的患者中有 36%,其治疗前肝内 HBsAg 水平明显低于未丢失 HBeAg 的患者。多因素分析显示,治疗前低肝内 HBsAg 水平而不是血清 HBsAg 滴度与 HBeAg 丢失率较高相关(OR:4.97,95%CI:1.12-22.00,P=0.035)。

结论

血清 HBsAg 水平与肝内 HBsAg 水平呈正相关,干扰素治疗后肝内 HBsAg 水平显著变化。较低的肝内 HBsAg 水平与干扰素治疗后 HBeAg 丢失相关。肝内 HBsAg 可能在接受干扰素治疗的 CHB 患者中有临床意义。

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