Angelico Mario, Koehler-Horst Beate, Piccolo Paola, Angelico Francesco, Gentile Silvia, Francioso Simona, Tarquini Pierluigi, Vecchia Roberto Della, Ponti Laura, Pilleri Giampaolo, Barlattani Angelo, Grieco Antonio, Soccorsi Francesco, Guarascio Paolo, Demelia Luigi, Sorbello Orazio, Rossi Zaccaria, Forlini Giuseppe, Zaru Salvatore, Bandiera Franco
Hepatology Unit, Tor Vergata University, Rome, Italy.
Eur J Gastroenterol Hepatol. 2008 Jul;20(7):680-7. doi: 10.1097/MEG.0b013e3282f5196c.
The objective of this study was to compare the efficacy of anti-hepatitis C virus (anti-HCV) treatment schedules on the basis of an early virological response (EVR), defined as undetectable serum HCV-RNA (<50 IU/ml) after a 12-week induction course of peginterferon alpha-2a (PEG-IFN) 180 mcg/week.
A total of 210 interferon-naïve patients (69% male; median age, 42 years) with histologically proven chronic hepatitis C infection (genotype 1: 62%) received PEG-IFN 180 mcg/week for 12 weeks. Patients with EVR (58%) were randomized to continue PEG-IFN monotherapy (n=64) or to add ribavirin (RBV), 800 mg/day (n=57), for 36 additional weeks. Patients without EVR (42%) were randomized to add RBV (n=42), or RBV plus amantadine, 200 mg/day (n=47), for 36 additional weeks. Sustained virological response (SVR, undetectable HCV-RNA 24 weeks after treatment completion) was compared among treatment groups.
Patients with EVR: SVR rate was 60.3% in the PEG-IFN group versus 67.2% in the PEG-IFN+RBV group (NS). In genotypes 2/3, SVR rates were 66.7 versus 73.1% (NS); in genotypes 1/4, SVR rates were 51.6 versus 61.3%, respectively (NS). Patients without EVR: SVR was 16.7% in the PEG-IFN+RBV group versus 31.9% in the triple therapy group (P=0.07). In patients with genotypes 1/4, SVR rates were 9.4 versus 29.7% (P=0.041).
In genotypes 1/4 patients without EVR, triple therapy results in higher SVR rates than standard dual therapy. This study confirms that addition of amantadine is beneficial in early-recognized 'difficult-to-treat' patients.
本研究的目的是基于早期病毒学应答（EVR）比较抗丙型肝炎病毒（抗-HCV）治疗方案的疗效，EVR定义为在接受每周180微克聚乙二醇干扰素α-2a（PEG-IFN）诱导治疗12周后血清HCV-RNA检测不到（<50 IU/ml）。
总共210例初治的丙型肝炎患者（69%为男性；中位年龄42岁），经组织学证实为慢性丙型肝炎感染（基因型1：62%），接受每周180微克PEG-IFN治疗12周。有EVR的患者（58%）被随机分为继续接受PEG-IFN单药治疗（n = 64）或加用利巴韦林（RBV），800毫克/天（n = 57），再治疗36周。无EVR的患者（42%）被随机分为加用RBV（n = 42），或加用RBV加金刚烷胺，200毫克/天（n = 47），再治疗36周。比较各治疗组的持续病毒学应答（SVR，治疗完成后24周HCV-RNA检测不到）情况。
有EVR的患者：PEG-IFN组的SVR率为60.3%，而PEG-IFN + RBV组为67.2%（无统计学差异）。在基因型2/3中，SVR率分别为66.7%和73.1%（无统计学差异）；在基因型1/4中，SVR率分别为51.6%和61.3%（无统计学差异）。无EVR的患者：PEG-IFN + RBV组的SVR为16.7%，而三联疗法组为31.9%（P = 0.07）。在基因型1/4的患者中，SVR率分别为9.4%和29.7%（P = 0.041）。
在基因型1/4且无EVR的患者中，三联疗法的SVR率高于标准的双联疗法。本研究证实，加用金刚烷胺对早期识别的“难治性”患者有益。
