Nikolaidis Nikolaos L, Giouleme Olga I, Tziomalos Konstantinos A, Saveriadis Adamos S, Grammatikos Nikolaos, Doukelis Panagiotis, Voutsas Anastasios D, Vassiliadis Themistoklis, Patsiaoura Kalliopi, Orfanou-Koumerkeridou Eleni, Balaska Aikaterini, Eugenidis Nikolaos P
Gastroenterology and Hepatology Section of Second Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
J Gastroenterol Hepatol. 2005 Nov;20(11):1721-5. doi: 10.1111/j.1440-1746.2005.04029.x.
Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance.
In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely.
Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively.
Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.
对于大多数抗HBe阳性的慢性乙型肝炎患者，使用单一抗病毒药物进行单药治疗不足以控制乙型肝炎病毒感染。对干扰素/长期拉米夫定联合治疗进行了评估，以确定该策略是否会提高治疗效果并减少拉米夫定耐药性的出现。
总共36例连续的抗HBe阳性患者接受了干扰素（皮下注射3MU，每周3次）和拉米夫定（口服100mg，每天1次）治疗12个月。联合治疗完成后，所有患者继续无限期接受拉米夫定单药治疗。
总体而言，35例患者（97%）在12个月时出现病毒学应答。4例患者（11%）清除了HBsAg并产生了抗-HBs。在随访期间，停用干扰素后，随访时间为30±12个月（范围：7 - 57个月），13例患者（36%）出现突破性感染。治疗1、2、3和4年结束时突破性感染的累积发生率分别为0%、14%、32%和59%。
联合治疗似乎有效，也可能延迟拉米夫定耐药变异株的选择。然而，确实需要进行对照试验以阐明联合抗病毒治疗相对于单药治疗的潜在益处。
