干扰素治疗慢性乙型肝炎的肝组织学及血清学前瞻性研究

A prospective study on histological and serological changes after interferon alpha-2b treatment in patients with chronic hepatitis B infection

目的 观察干扰素α－ ２ｂ治疗 １８周后的慢性乙型肝炎患者肝组织学及血清 ＨＢＶ ＤＮＡ等变化。方法采用肝组织损伤程度Ｋｎｏｄｅｌｌ计分法、免疫组织化学及血清ＨＢＶ ＤＮＡ定量检测对２２例患者治疗前后进行比较。结果治疗结束时肝组织学中坏死及炎症程度与治疗前相比明显减轻（Ｐ＜０．０１）；５５％（１２／２２）患者肝组织学活动指数得以改善，其中门静脉炎症及纤维化程度无明显改善（Ｐ＞０．０５）。免疫组织化学检测显示治疗后肝组织中 ＨＢｅＡｇ阴转率为 ５３．８％（７／１３），活化的星状细胞数显著减少（ Ｐ＝ ０．０００４）。血清 ＨＢＶ ＤＮＡ水平较治疗前明显下降（Ｐ＜ ０．０１）。治疗结束 ＨＢｅＡｇ阴转率为 ４２．９％（６／１４）。 ＨＢｅＡｇ阳性与 ＨＢｅＡｇ阴性患者相比，其肝组织学损伤程度的改善及血清ＨＢＶ ＤＮＡ的下降无明显区别。结论干扰素α－２ｂ治疗慢性乙型肝炎可明显降低血清ＨＢＶ ＤＮＡ的水平，并改善其肝组织学的炎症及坏死程度。

Objective To investigate the histological changes in liver biopsies and HBV DNA changes in sera induced by 18 weeks of interferon alpha-2b therapy in patients with chronic hepatitis B infection. Methods Twenty-two patients were enrolled into this prospective study. All patients had a liver biopsy within 1 week before starting interferon therapy. Interferon alpha-2b was given at a dose of 3MU thrice a week for 18 weeks. A second liver biopsy was taken for comparison at the end of week 18. Blinded biopsies were scored according to Knodell's histology activity index (HAI), and examined for HBsAg, HBeAg, HBcAg and a - SMA by immunohistochemistry. The serum samples corresponding with liver biopsies were collected and HBV DNA, e-antigen were measured. Results Histological assessment revealed a significant improvement in intralobular inflammation and periportal necrosis after treatment(P<0.01). Fifty-five percent (12/22) patients had a reduction of hepatic necroinflammatory HAI score at the end of 18 weeks of interferon alpha-2b therapy compared to pretreatment values, but periportal inflammation and fibrosis failed to show improvement. HBeAg disappeared from liver tissues in 7 from 13 cases(53.8% )and a significant reduction of activated liver stellate cells was demonstrated in biopsies performed after suspending the interferon treatment(P=0.000 4 ). Serum HBV DNA levels decreased significantly after treatment (P<0.01). The clearance rate of HBeAg was 42.9% after treatment. There was no significant difference between HBeAg positive and negative patients either in liver histological improvements or declining level of serum HBV DNA. Conclusions Interferon alpha-2b may decrease the level of serum HBV DNA in the patients with chronic hepatitis B infection, and improve their necroinflammation in liver tissues.