Zilly M, Lingenauber C, Desch S, Väth T, Klinker H, Langmann P
Department of Internal Medicine, University of Würzburg, Medizinische Poliklinik, Standort Luitpoldkrankenhaus, Division of Hepatology and Infectiology, Germany.
Eur J Med Res. 2002 Apr 30;7(4):149-54.
Therapy options for patients with chronic hepatitis C who failed prior treatment are needed. In recent studies triple antiviral therapy with Interferon-alpha, ribavirin, and amantadine seemed to increase sustained virological response rates in this group.
To evaluate efficacy, side effects and safety of a triple re-therapy in an open labeled prospective study, we compared 23 nonresponders to interferon monotherapy (9 nonresponders, 3 relapsers, 11 with breakthrough) with 23 nonresponders to standard combination therapy (interferon plus ribavirin) (16 nonresponders, 7 breakthroughs). All outpatients enrolled for re-therapy received interferon-alpha 2a (6 mega units [MU] three times in week), ribavirin (1000-1200 mg daily in divided doses) and amantadine (200 mg daily) for six months. In case of virological re-therapy response (negative qualitative HCV RNA) study medication was continued with interferon monotherapy for another six months.
Sustained virological response was achieved in 16 (35%) out of 46 prior therapy nonresponders. Response rates were dependent on pretreatment outcome. In the standard combination therapy group only 1 (6%) primary nonresponder achieved sustained response, but none of the 9 monotherapy nonresponders did. After primary breakthrough sustained response was seen in 8 of 11 (73%) patients in the interferon monotherapy and in 5 of 7 (71%) in the combination therapy group. Of 3 monotherapy relapsers 2 (66%) did also clear the virus sustained. Safety profile under triple therapy was similar to the previous therapy. Compliance was higher and side effects lower in those patients already experienced in combination therapy.
In patients with a breakthrough or relapse after interferon monotherapy or standard combination therapy with interferon and ribavirin a re-therapy with a triple combination of interferon, ribavirin, and amantadine results in a high rate of sustained virological response.
对于既往治疗失败的慢性丙型肝炎患者，需要有新的治疗方案。在最近的研究中，α干扰素、利巴韦林和金刚烷胺的三联抗病毒疗法似乎能提高该组患者的持续病毒学应答率。
为了在一项开放标签的前瞻性研究中评估三联再治疗的疗效、副作用和安全性，我们将23例对干扰素单药治疗无应答的患者（9例无应答者、3例复发者、11例出现突破者）与23例对标准联合治疗（干扰素加利巴韦林）无应答的患者（16例无应答者、7例出现突破者）进行了比较。所有登记接受再治疗的门诊患者接受α干扰素2a（每周三次，每次6百万单位[MU]）、利巴韦林（每日1000 - 1200mg，分剂量服用）和金刚烷胺（每日200mg），疗程为6个月。如果出现病毒学再治疗应答（定性HCV RNA阴性），则继续使用干扰素单药治疗6个月。
46例既往治疗无应答者中有16例（35%）实现了持续病毒学应答。应答率取决于治疗前的结果。在标准联合治疗组中，只有1例（6%）初治无应答者实现了持续应答，但9例单药治疗无应答者均未实现。初治突破后，干扰素单药治疗组11例患者中有8例（73%）出现持续应答，联合治疗组7例患者中有5例（71%）出现持续应答。3例单药治疗复发者中有2例（66%）也实现了病毒持续清除。三联治疗的安全性与既往治疗相似。联合治疗经验丰富的患者依从性更高，副作用更低。
对于干扰素单药治疗或干扰素与利巴韦林的标准联合治疗后出现突破或复发的患者，使用干扰素、利巴韦林和金刚烷胺的三联组合进行再治疗可获得较高的持续病毒学应答率。
