派罗欣±拉米夫定治疗HBeAg阴性慢性乙肝患者HBV-DNA抑制的2年随访结果----百济新特药房肝病专科

　　背景：HbeAg慢性乙肝预后较差，治疗应答率低且复发率高，尤其是核苷类似物治疗更是如此。在一项大型国际研究中已证实接受派罗欣±拉米夫定治疗较拉米夫定单药治疗停药后24周的的应答率显著增高。

　　目的：评价派罗欣±拉米夫定治疗停药2年后病毒学和生化学应答的持久性。

　　方法：在初期研究中，HBeAg阴性慢性乙肝患者接受的治疗方案：派罗欣180μg，每周1次，联合安慰剂（每日1次）或拉米夫定100mg（每日1次），共48周，并在停药后6个月进行评价。在随后的长期观察性研究中，接受派罗欣联合安慰剂的患者中有116例（116/177，66%），派罗欣联合利巴韦林中有114例（114/179，64%）在停药后第6、9、12、24个月接受评估，包括：HBV-DNA<20,000拷贝/毫升、<10,000拷贝/毫升、<400拷贝/毫升，和ALT复常<1倍正常值上限（30或>30～≤50IU/L）

　　结果：HBV-DNA水平从停药后第9月至第24月保持稳定，派罗欣单药治疗和派罗欣联合拉米夫定治疗患者病毒学应答无显著差异。派罗欣单药治疗和派罗欣联合拉米夫定治疗患者停药后第1年和第2年的ALT复常率分别为50% vs 45%，32% vs 28%。研究期间接受派罗欣单药治疗的患者有11例出现HbsAg转阴，其中6例出现HbsAg抗体，在2年随访期间维持稳定。接受联合治疗的患者中14例出现HbsAg转阴，6例出现HbsAg抗体，其中2例在随访期间维持稳定。

　　结论：派罗欣治疗，在停药后随访2年期间有持久的ALT复常率和HBV-DNA抑制低于10,000拷贝/毫升，后者最近被证明可相当大地降低疾病并发症和肝癌的危险。复发的患者在随访早期即出现复发。

AASLD 2006 Abstract ID# 972

Suppression of HBV-DNA in Patients with HBeAg-negative CHB Treated with Peginterferon Alfa-2a (40KD) ± Lamivudine: 2-Year Follow-up Results

P. Marcellin1; F. Bonino2; G. K. Lau3; P. Farci4; C. Yurdaydin5; T. Piratvisuth6; K. Luo7; S. Gurel8; S. Hadziyannis9; Y. Wang10; M. Popescu11

1. Service d'Hepatologie, Hopital Beaujon, University of Paris, Paris, France.
2. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Maggiore di Milano Policlinico, Milan, Italy.
3. Department of Medicine, Queen Mary Hospital, Hong Kong, China.
4. Dipartimento di Scienze Mediche, Università di Cagliari, Monserrato, Italy.
5. Department of Gastroenterology, University of Ankara, Ankara, Turkey.
6. Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand.
7. Department of Infectious Diseases, Nanfang Hospital, Guangzhou, China.
8. Department of Gastroenterology, University of Uludag, Bursa, Turkey. f
9. Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece.
10. Infectious Disease Department, Xinan Hospital, Chongqing, China.
11. Pharmaceuticals Division, Roche, Basel, Switzerland.

Background: HBeAg-negative chronic hepatitis B (CHB) is associated with poor prognosis, low rates of treatment response and high rates of relapse, especially following treatment with nucleos(t)ide analogues. Significantly higher response rates 24 weeks post-treatment have been demonstrated in patients receiving peginterferon alfa-2a +/- lamivudine, versus lamivudine alone, in a large multinational trial.

Objective: To evaluate the durability of virological and biochemical response to peginterferon alfa-2a +/- lamivudine for up to 2 years post-treatment.

Methods: In the initial study, HBeAg-negative CHB patients received 180μg peginterferon alfa-2a (40KD) once-weekly (qw) plus either placebo daily (qd) or 100 mg lamivudine (qd) for 48 weeks, and were assessed 6 months post-treatment. In a roll-over long-term observational study, 116/177 (66%) of those receiving peginterferon alfa-2a plus placebo, and 114/179 (64%) receiving the combination with lamivudine, were assessed for HBV-DNA suppression to <20,000 cp/mL, <10,000 cp/mL and <400 cp/mL and ALT normalisation <1 X ULN, (30 or >30–≤ 50 IU/L) at 6, 9, 12 and 24 months post-treatment.

Results: HBV-DNA suppression at 1 and 2 years post-treatment is shown in the table below. HBV-DNA levels were stable from 9 months to 24 months post-treatment and there was no significant difference in the virological response between patients treated with peginterferon alfa-2a monotherapy and peginterferon alfa-2a plus lamivudine. ALT normalisation at 1 and 2 years post-treatment was 50% versus 45% and 32% versus 28% for patients treated with peginterferon alfa-2a monotherapy versus the combination with lamivudine, respectively. A total of 11/116 patients receiving peginterferon alfa-2a monotherapy lost HBsAg during the study, of whom six developed anti-HBs antibody, maintained over 2 years of follow-up. Of those receiving the combination with lamivudine, 14/114 lost HBsAg, and six developed anti-HBs antibody at some time during the study, which was maintained in two patients up to 2 years post-treatment.

Conclusions: Peginterferon alfa-2a provides durable ALT normalisation and HBV-DNA suppression to less than 10,000 cp/mL, a level that has recently been associated with a considerably reduced risk of disease complications and hepatocellular cancer, for up to 2 years post-treatment. Patients who relapsed, did so in the early months of follow-up.