占国清，李　芳，李儒贵，刘　翔，谭华炳

干扰素α-1b联合恩替卡韦治疗高病毒载量慢性乙型肝炎疗效评价

占国清，李芳，李儒贵，刘翔，谭华炳

目的探讨干扰素α-1b联合恩替卡韦（ETV）治疗高病毒载量慢性乙型肝炎（CHB）患者的临床疗效。方法92例高病毒载量（血清HBV DNA≥1×107IU/ml）CHB患者被分为观察组48例和对照组44例。对照组采用干扰素α-1b治疗，观察组采用干扰素α-1b联合ETV治疗，疗程48 w。比较两组治疗后第12、24、48 w血清丙氨酸氨基转移酶（ALT）复常率、HBV DNA不可检出率、HBeAg阴转率和HBeAg转换率。采用ELISA法检测血清乙型肝炎病毒标记物；使用自动生化分析仪检测肝功能指标；采用荧光定量PCR法检测HBV DNA。结果在治疗第24 w和48 w时，观察组血清ALT复常率分别为68.8%和91.7%，显著高于对照组的34.1%和63.6%（P<0.01）；在治疗第12 w、24 w和48 w时，观察组血清HBV DNA不可检测率分别为45.8%、72.9%和87.5%，显著高于对照组的11.4%、31.8%和47.7%（P<0.01）；在治疗第48 w时，观察组HBeAg阴转率和HBeAg转换率分别为67.6%和62.2%，显著高于对照组的42.9%和37.1%（P<0.05）。结论干扰素α-1b联合ETV治疗血清高病毒载量的CHB患者疗效优于单用干扰素α-1b。

慢性乙型肝炎；干扰素α-1b；恩替卡韦；高病毒载量；疗效

Hubei University of Medicine，Shiyan 442000，Hubei Province，China

【Abstract】ObjectiveTo investigate the clinical efficacy of interferon alfa-1b combined with entecavir（ETV）in treatment of patients with chronic hepatitis B（CHB）and high serum viral loads.Methods92 patients with CHB and high serum viral load（HBV DNA≥1×107IU/ml）were divided into observation group（n=48）and control group（n=44）.Patients in the control group were treated with interferon alfa-1b，and patients in the observation group were treated with interferon alfa-1b combined with ETV.The treatment course in two groups lasted for 48 weeks.The recovery rates of serum alanine aminotransferase（ALT），rates of serum HBV DNA loss，negative rates of HBeAg and the conversion rates of HBeAg to anti-HBe were compared at 12，24 and 48 weeks. Serum HBV markers and HBV DNA levels were routinely detected.ResultsThe recovery rates of serum ALT at week 24 and 48 in observation group were 68.8%and 91.7%，respectively，significantly higher than those in the control group（34.1%and 63.6%，P<0.01）;The negative rates of serum HBV DNA at week 12，24 and 48 in the observation group were 45.8%，72.9%and 87.5%，respectively，which were significantly higher than those in the control group（11.4%，31.8%and 47.7%，P<0.01）；The negative rate of HBeAg and the conversion rate of serum HBeAg at the end of week 48 in the observation group were 67.6%and 62.2%，significantly higher than those in the control group（42.9%and 37.1%，P<0.05）.ConclusionEfficacy of interferon alfa-1b combined with ETV in treatment of patients with CHB and high serum viral load is superior to IFN alfa-1b monotherapy.

【Key words】Chronic hepatitis B；Interferon alfa-1b；Entecavir；Serum viral loads；Therapeutic efficacy

血清乙型肝炎病毒（Hepatitis B virus，HBV）DNA载量高是慢性乙型肝炎（Chronic hepatitis B，CHB）患者进展为肝硬化或肝癌的危险因素[1]。研究表明，HBV活跃复制的CHB患者5年内有15%～20%发展为肝硬化，在乙型肝炎肝硬化患者中肝癌年发生率为3%～6%[1，2]。因此，CHB的治疗目标是持续抑制或有效清除HBV，缓解肝脏炎性损伤，预防肝纤维化、肝功能失代偿和肝细胞癌的发生，提高患者的生命质量和改善其预后[3]。核苷（酸）类似物（Nucleotide analogue，NAs）可以直接抑制HBV复制，但治疗后HBeAg血清转换率低，出现血清学转换者停药后免疫应答不持久，长期治疗大部分患者仍难以达到可靠的停药终点，且易发生病毒变异，产生较多的耐药风险[4，5]。干扰素（Interferon-α，INF-α）抗病毒治疗具有疗程短、停药后复发率低、持续应答率较高等优点，多数文献报道其治疗达到HBeAg血清学转换的几率高于NAs。……