Piccolo Paola, Lenci Ilaria, Demelia Luigi, Bandiera Franco, Piras Maria R, Antonucci Giorgio, Nosotti Lorenzo, Mari Terenzio, De Santis Adriano, Ponti Maria L, Sorbello Orazio, Iacomi Fabio, Angelico Mario
Hepatology Unit, Tor Vergata University, Rome, Italy.
Antivir Ther. 2009;14(8):1165-74. doi: 10.3851/IMP1466.
Pegylated interferon (PEG-IFN)-alpha monotherapy is the current standard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We aimed to assess the safety and efficacy of PEG-IFN-alpha plus adefovir dipivoxil (ADV) versus PEG-IFN-alpha monotherapy for compensated HBeAg-negative CHB.
A multicentre randomized controlled trial was performed in eight outpatient hepatology/infectious disease clinics in central Italy. A total of 60 patients (67% male and median age 48 years) with biopsy-proven HBeAg-negative compensated CHB (mean alanine aminotranferase [ALT] levels 3.3 +/-3x the upper normal limit and serum hepatitis B virus [HBV] DNA 5.8 +/-0.9 log(10) IU/ml) were randomized at baseline to receive PEG-IFN-alpha2a 180 microg/week plus ADV 10 mg/day or PEG-IFN-alpha2a monotherapy for 48 weeks. Post-treatment follow-up was for 24 additional weeks. The primary end point was sustained HBV DNA suppression defined as serum HBV DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up. The secondary end point was ALT normalization at the end of follow-up.
At week 48, HBV DNA was undetectable in 20/30 (67%) in the combination group versus 11/30 (37%) patients in the monotherapy group (P=0.02). ALT normalization was achieved in 17/30 (57%) versus 10/30 (30%) patients, respectively (P=0.03). At week 72, sustained virological response was achieved in 7/30 (23.3%) in the combination group versus 6/30 (20%) patients in the monotherapy group (P=0.75); 5 (16%) patients in each group dropped out because of adverse events or non-compliance.
In HBeAg-negative CHB, combination PEG-IFN-alpha2a plus ADV for 48 weeks is safe and resulted in greater on-treatment efficacy than PEG-IFN-alpha2a monotherapy. No difference in sustained virological and biochemical response rates were observed between the two treatment regimens.
聚乙二醇化干扰素（PEG-IFN）-α单药治疗是目前乙肝e抗原（HBeAg）阴性慢性乙型肝炎（CHB）短期抗病毒治疗的标准疗法。我们旨在评估PEG-IFN-α联合阿德福韦酯（ADV）对比PEG-IFN-α单药治疗对代偿期HBeAg阴性CHB的安全性和疗效。
在意大利中部的8个门诊肝病/传染病诊所进行了一项多中心随机对照试验。共有60例经活检证实为HBeAg阴性代偿期CHB的患者（67%为男性，中位年龄48岁）（平均丙氨酸转氨酶[ALT]水平为正常上限的3.3±3倍，血清乙肝病毒[HBV] DNA为5.8±0.9 log₁₀ IU/ml）在基线时随机分组，接受每周180μg的PEG-IFN-α2a联合每日10mg的ADV治疗或PEG-IFN-α2a单药治疗48周。治疗后随访额外进行24周。主要终点是持续HBV DNA抑制，定义为治疗后随访24周时血清HBV DNA<2000 IU/ml。次要终点是随访结束时ALT正常化。
在第48周时，联合治疗组30例中有20例（67%）HBV DNA检测不到，而单药治疗组30例中有11例（37%）（P=0.02）。ALT正常化分别在联合治疗组30例中的17例（57%）和单药治疗组30例中的10例（30%）患者中实现（P=0.03）。在第72周时，联合治疗组30例中有7例（23.3%）实现了持续病毒学应答，而单药治疗组30例中有6例（20%）（P=0.75）；每组各有5例（16%）患者因不良事件或不依从退出。
在HBeAg阴性CHB中，PEG-IFN-α2a联合ADV治疗48周是安全的，且治疗期疗效优于PEG-IFN-α2a单药治疗。两种治疗方案在持续病毒学和生化应答率方面未观察到差异。
