Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C
Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C
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DOI：
10.1007/s00535-010-0358-6
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发表时间：
2011-04-01
影响因子：
6.3
通讯作者：
Kumada, Hiromitsu
中科院分区：
文献类型：
--
作者：
Chayama, Kazuaki;Hayes, C. Nelson;Kumada, Hiromitsu
通过将聚乙二醇干扰素加利巴韦林联合治疗延长至72周，我们分析了非结构蛋白（NS）核心蛋白和干扰素敏感性决定区（ISDR）的氨基酸（aa）替换，840例1b基因型高病毒载量慢性丙型肝炎患者的5A。我们使用逻辑回归和分类回归树（CART）分析来确定接受72周治疗的患者持续病毒学应答（SVR）的预测因素，当使用多变量逻辑回归对患者进行治疗持续时间单独分析时，几个因素，包括性别、年龄、病毒载量和核心aa 70和ISDR置换，（P = 0.0003，P = 0.02，P = 0.01，P = 0.0001，和P = 0.0004）是治疗48周后SVR的显著预测因素，而年龄、既往干扰素治疗史和ISDR替代（分别为P = 0.03、P = 0.01和P = 0.02）是72周治疗的唯一显著预测因素。使用CART分析，生成了一个决策树，确定年龄，胆固醇，性别，治疗时间，和aa 70和ISDR取代作为最重要的预测因素。CART模型的敏感性为69.2%，特异性为60%，阳性预测值为68.4%，采用补充统计学和数据挖掘方法确定可能从72周治疗中获益的患者亚组。
Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy.We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment.When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%.Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.