单磷酸阿糖腺苷治疗慢性乙型肝炎的肝组织学前瞻性研究

目的 观察单磷酸阿糖腺苷治疗慢性乙型肝炎患者肝组织学变化。方法 采用肝组织损伤程度Knodell计分法、免疫组织化学及原位杂交法对11 例中层者肝组织治疗前后的组织学进行比较。结果 治疗结束6个月后11例病人中有8例病人的肝组织学得以改善（肝组织学活指数减少≥2分），其中肝组织小叶内炎症及纤维化程度较治疗前相比明显减轻（P＜0．05）；6例肝组织炎症活动度（G）≥3者治疗后肝组织学活动指数有明显降低（P＜0．05），而G≤2的5例未见显著。免疫组化检测显示，治疗前肝组织中HBeAg阳性的9例病人中，治疗后4例阴转，活化的星状细胞数显著减少（P＝0．018）。原位杂交检测HBV DNA显示，治疗前9例阳性病人中治疗后4例阴转。结论 单磷酸阿糖腺苷治疗慢性乙型肝炎可明显改善其肝组织学的炎症及纤维化程度。

A prospective study of histological changes after AraAMP treatment in patients with chronic hepatitis B infection

OBJECTIVE: To investigate the histological changes in liver biopsy tissue induced by AraAMP therapy for 50 days in patients with chronic hepatitis B infection. METHODS: Eleven patients were enrolled into this prospective study. All the patients had liver biopsy performed within 1 week before starting AraAMP therapy. A second liver biopsy was taken for comparison six months after the end of therapy. Blinded biopsies were scored according to Knodell's histology activity index (HAI), and examined for HBeAg and alpha-smooth muscle actin with immunohistochemistry as well as HBV DNA by using in situ hybridization. RESULTS: Histological improvement of >or=2 points decrease in the necroinflammatory HAI scores was seen in 8 of the 11 (72.7%) of patients after treatment. In these patients histological assessment revealed a significant improvement in intralobular inflammation and fibrosis as compared with pretreatment values(P < 0.05). There was significant difference of HAI changes in 6 cases graded as G3 based on the degree of periportal interface hepatitis and spotty parenchymal injury, but not in 5 cases graded as G2. HBeAg disappeared from liver tissue in 4 of the 9 cases and a significant reduction of activated liver stellate cells was demonstrated in the second biopsy(P = 0.018). Of the nine cases with HBV DNA positive at the first biopsy with in situ hybridization examination, 4 were negative at the second biopsy. CONCLUSION: Significant improvement in intralobular inflammation and fibrosis can be observed in liver tissue from patients with chronic hepatitis B infection treated with AraAMP.