核苷（酸）类似物联合干扰素治疗HBeAg阳性慢性乙型肝炎120周的疗效随访

A retrospective follow-up study of prolonged nucleos（t）ide analogue and interferon combination therapy in HBeAg-positive chronic hepatitis B patients

目的观察核苷（酸）类似物联合干扰素延长疗程至96周治疗HBeAg阳性慢性乙型肝炎，随访24周的疗效。方法135例HBeAg阳性慢性乙型肝炎患者，90例接受核苷（酸）类似物联合干扰素治疗（联合治疗组），45例接受单一核苷（酸）类似物治疗（对照组）。分别在治疗12、24、48、72、96周及随访24周时进行生物化学、病毒学、血清学评估。应答疗效比较采用爿。检验。结果135例患者纳入分析。联合治疗组90例完成96周疗程后，17例（占18．9％）患者发生HBsAg血清学转换，37例（占41．1％）患者发生HBeAg血清学转换；对照组无患者发生HBsAg血清学转换，15例（占33．3％）患者发生HBeAg血清学转换，联合治疗组HBsAg血清学转换明显高于对照组，x2=8．08，P〈0．01，差异有统计学意义。两组患者HBeAg血清学转换差异无统计学意义。出现HBsAg血清转换〈30岁为64．7％（11／17），30～40岁为9．7％（6／62），〉40岁11例中无一例出现HBsAg血清转换，〈30岁患者HBsAg血清转换率明显高于其他年龄组，X2值分别是12．62和4．24，P值均〈0．05，差异有统计学意义。结论核苷（酸）类似物联合干扰素延长疗程治疗HBeAg阳性慢性乙型肝炎能提高HBsAg血清学转换，年龄〈30岁者出现HBsAg血清学转换比例最高。

Objective To investigate the efficacy of a 96-week course of nucleos（t）ide analogue and interferon （IFN） combination therapy for achieving seroconversion at 24 weeks after completion in patients with chronic hepatitis B （CHB）. Methods One-hundred-and-thirty-five CHB patients with positivity for hepatitis B e antigen （HBeAg） were recruited for study between January 2005 and December 2008. All patients were given a 96-week course of nucleos（t）ide analogue （lamivudine or adefovir dipivoxil） alone （monotherapy controls, n = 45） or in combination with IFN or Pegylated-IFN-alpha-2a （Peg-IFNα-2α） （n = 90）. At treatment weeks 12, 24, 48, 72, and 96, and at 24 weeks after treatment completion, serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. The biochemical response was indicated by normalization of the alanine aminotransferase （ALT） level. The virologic response was indicated by a reduction in the hepatitis B virus （HBV） DNA level to 〈 1000 copies/ml. The serological response was indicated by seroconversion of either HBeAg or hepatitis B surface antigen （HBsAg）. Statistical analysis was performed with the Chi-squared test. Results Among the patients treated with nucleos（t）ide analogue and IFN combination therapy, 41.1% （37/90） achieved HBeAg seroconversion and 18.9% （17/90） achieved HBsAg seroconversion at the end of treatment. However, significantly less of the patients treated with nucleos（t）ide analogue monotherapy achieved HBeAg seroconversion and none achieved HBsAg seroconversion by end of treatment （33.3% and 0%, respectively; X2 = 8.08, P 〈 0.01 vs. the combination therapy group）. Age stratification of the 17 HBsAg-seroconverted patients treated with combination therapy indicated that the HBsAg seroconversion rate was significantly higher in patients 〈 30-years-old than those 30 and older （X2= 12.62 and 4.24, respectively, P 〈 0.05）. At post- treatment week 24, the 17 HBsAg-seroconverted patients treated with combination therapy showed HBsAg titers of 〈 250 IU/ml; moreover, 11.8% （2/17） of these patients remained HBeAg-positive and 17.6% （3/17） showed abnormal ALT levels and elevated HBV DNA. Conclusion Prolonged nucleos（t）ide analogue plus IFN combination therapy can significantly improve the rate of HBsAg seroconversion in HBeAg-positive CHB patients, and this treatment regimen is especially efficacious in patients under the age of 30.