Niederau Claus, Mauss Stefan, Schober Andreas, Stoehr Albrecht, Zimmermann Tim, Waizmann Michael, Moog Gero, Pape Stefan, Weber Bernd, Isernhagen Konrad, Sandow Petra, Bokemeyer Bernd, Alshuth Ulrich, Steffens Hermann, Hüppe Dietrich
Clinic for Internal Medicine, St. Josef Hospital, Oberhausen, Germany.
Center for HIV and Hepatogastroenterology, Duesseldorf, Germany.
PLoS One. 2014 Sep 19;9(9):e107592. doi: 10.1371/journal.pone.0107592. eCollection 2014.
Previous trials have often defined genotype 2 and 3 patients as an "easy to treat" group and guidelines recommend similar management.
The present study looks for differences between the two genotypes and analyzes predictive factors for SVR.
Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012.
When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p<0.0001, respectively), and a higher APRI score (p<0.005). SVR was higher in genotype 2 when compared with genotype 3 (64.7% vs. 56.9%, p = 0.004). By multivariate analysis of genotype 2 patients, low baseline γ -GT and RVR predicted SVR. In genotype 3 age ≤45 years, cholesterol>130 mg/dl, a low APRI score, and a γ-GT ≥3-times ULN, RVR, and RBV starting dose were associated with SVR by multivariate analysis.
The present study corroborates that liver fibrosis is more pronounced in genotype 3 vs. 2. SVR is higher in genotype 2 versus genotype 3 partly because of follow-up problems in genotype 3 patients, in particular in those infected by drug use. Thus, subgroups of genotype 3 patients have adherence problems and need special attention also because they often have significant liver fibrosis.
Verband Forschender Arzneimittelhersteller e.V., Berlin, Germany ML21645 ClinicalTrials.gov NCT02106156.
既往试验常将基因2型和3型患者定义为“易于治疗”组,且指南推荐类似的管理方式。
本研究探寻这两种基因型之间的差异,并分析持续病毒学应答(SVR)的预测因素。
一项基于社区的前瞻性队列研究,涉及德国各地的421名医生。分析纳入了2007年8月至2012年7月期间接受聚乙二醇干扰素α-2a联合利巴韦林治疗的2347例未经治疗的慢性丙型肝炎基因2型(n = 391)和3型(n = 1956)感染患者。
与基因2型患者相比,基因3型患者更年轻,感染持续时间更短,总胆固醇、低密度脂蛋白胆固醇和体重指数值更低,经静脉吸毒作为感染途径的频率更高且男性居多(分别为p < 0.0001),天冬氨酸氨基转移酶与血小板比值指数(APRI)评分更高(p < 0.005)。基因2型患者的SVR高于基因3型患者(64.7%对56.9%,p = 0.004)。对基因2型患者进行多因素分析,低基线γ-谷氨酰转移酶(γ-GT)和快速病毒学应答(RVR)可预测SVR。在基因3型患者中,多因素分析显示年龄≤45岁、胆固醇>130 mg/dl、低APRI评分、γ-GT≥正常上限(ULN)的3倍、RVR以及利巴韦林起始剂量与SVR相关。
本研究证实基因3型患者的肝纤维化比基因2型更明显。基因2型患者的SVR高于基因3型,部分原因是基因3型患者存在随访问题,尤其是经静脉吸毒感染的患者。因此,基因3型患者亚组存在依从性问题,也需要特别关注,因为他们往往有明显的肝纤维化。
德国柏林药物研究协会ML21645 美国国立医学图书馆临床试验注册中心NCT02106156。