Yu Shu-Li, Guo Chao-Ying
Hospital of Infectious of Jinan, Jinan 250021, China.
Zhonghua Gan Zang Bing Za Zhi. 2013 Apr;21(4):267-70. doi: 10.3760/cma.j.issn.1007-3418.2013.04.007.
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).
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-IFNa-2a) (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 less than 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.
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 less than 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 less than 30-years-old than those 30 and older (x2= 12.62 and 4.24, respectively, P less than 0.05). At post-treatment week 24, the 17 HBsAg-seroconverted patients treated with combination therapy showed HBsAg titers of less than 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.
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.
探讨核苷（酸）类似物与干扰素（IFN）联合治疗96周方案在慢性乙型肝炎（CHB）患者治疗结束后24周实现血清学转换的疗效。
2005年1月至2008年12月招募了135例乙肝e抗原（HBeAg）阳性的CHB患者进行研究。所有患者接受96周的核苷（酸）类似物（拉米夫定或阿德福韦酯）单药治疗（单药治疗对照组，n = 45）或与IFN或聚乙二醇化干扰素-α-2a（Peg-IFNa-2a）联合治疗（n = 90）。在治疗第12、24、48、72和96周以及治疗结束后24周，采集所有患者的血清样本，评估治疗的生化、病毒学和血清学反应。生化反应以丙氨酸氨基转移酶（ALT）水平正常化表示。病毒学反应以乙肝病毒（HBV）DNA水平降至低于1000拷贝/ml表示。血清学反应以HBeAg或乙肝表面抗原（HBsAg）血清学转换表示。采用卡方检验进行统计分析。
在接受核苷（酸）类似物与IFN联合治疗的患者中，41.1%（37/90）在治疗结束时实现了HBeAg血清学转换，18.9%（17/90）实现了HBsAg血清学转换。然而，接受核苷（酸）类似物单药治疗的患者中，实现HBeAg血清学转换的患者明显较少，治疗结束时无一例实现HBsAg血清学转换（分别为33.3%和0%；x2 = 8.08，与联合治疗组相比P < 0.01）。对接受联合治疗的17例HBsAg血清学转换患者进行年龄分层显示，年龄小于30岁的患者HBsAg血清学转换率显著高于30岁及以上患者（分别为x2 = 12.62和4.24，P < 0.05）。在治疗后第24周，接受联合治疗的17例HBsAg血清学转换患者的HBsAg滴度低于250 IU/ml；此外，这些患者中有11.8%（2/17）的HBeAg仍为阳性，17.6%（3/17）的ALT水平异常且HBV DNA升高。
延长核苷（酸）类似物加IFN联合治疗可显著提高HBeAg阳性CHB患者的HBsAg血清学转换率，且该治疗方案在30岁以下患者中尤其有效。
