Sperl Jan, Frankova Sona, Senkerikova Renata, Neroldova Magdalena, Hejda Vaclav, Volfova Miroslava, Merta Dusan, Viklicky Ondrej, Spicak Julius, Jirsa Milan
Jan Sperl, Sona Frankova, Renata Senkerikova, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
World J Gastroenterol. 2015 May 14;21(18):5496-504. doi: 10.3748/wjg.v21.i18.5496.
To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.
The sustained virological response (SVR) rate, IL28B genotype, IFNL4 genotype, initial viral load (IVL) and other pretreatment variables in 39 end-stage renal disease patients (ESRD) on maintenance haemodialysis (HD) infected with hepatitis C virus (HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment naïve and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a (PegIFN-α) weekly and a reduced dose of ribavirin (RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/dL. Control group patients were given standard doses of PegIFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ(2) test compared the frequencies. Logistic regression was used to determine significant predictors of SVR. Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.
The distribution of IL28B rs12979860 CC, CT and TT genotypes in the ESRD group was 28.2%, 64.1% and 7.7%, respectively, and 19.3%, 62.4% and 18.3% in the controls. The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B. The proportion of patients with a low IVL (< 600000 IU/mL) was significantly higher in the ESRD group than in the controls (28/39, 71.8% vs 51/109, 46.8%, P = 0.009), as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group (10/11, 90.9% vs 18/28, 64.3%, P = 0.0035). This difference was not found in the controls (7/22, 31.8% vs 44/87, 50.6%, P = 0.9). The overall SVR rate was 64.1% (25/39) in the ESRD group and 50.5% (55/109) in the control group (P = 0.19). 11/11 (100%) and 19/22 (86.4%) IL28B CC patients achieved SVR in the ESRD and control groups, respectively. A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups. The ESRD patients who achieved SVR showed the lowest IVL [median 21000, interquartile range (IQR): 6000-23000 IU/mL], compared with ESRD individuals without SVR (1680000, IQR: 481000-6880000, P = 0.001), controls with SVR (387000, IQR: 111000-1253000) and controls without SVR (905000, IQR: 451000-3020000). In ESRD, an IVL < 600000 IU/mL was strongly associated with SVR: 24/28 (85.7%) patients who achieved SVR had viraemia below this threshold.
Haemodialysis decreases the viral load, especially in IL28B CC genotype carriers. A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.
确定接受聚乙二醇干扰素α治疗的1型慢性丙型肝炎血液透析患者持续病毒学应答的预测因素。
比较39例接受维持性血液透析（HD）的终末期肾病（ESRD）患者（感染1b型丙型肝炎病毒（HCV））的持续病毒学应答（SVR）率、IL28B基因型、IFNL4基因型、初始病毒载量（IVL）和其他治疗前变量，与同期治疗的109例肾功能正常的对照组患者进行比较。所有患者均未接受过治疗，且肝病代偿良好。ESRD患者每周接受135μg聚乙二醇化干扰素α-2a（PegIFN-α），23/39例初始血红蛋白水平>10g/dL的患者给予减量的利巴韦林（RBV）。对照组患者给予标准剂量的PegIFN-α和RBV。SVR评估为治疗后24周HCV RNA阴性。采用t检验或方差分析比较均值，采用χ(2)检验比较频率。采用逻辑回归确定SVR的显著预测因素。连续变量的截断值通过受试者工作特征分析获得。
ESRD组中IL28B rs12979860 CC、CT和TT基因型的分布分别为28.2%、64.1%和7.7%，对照组中分别为19.3%、62.4%和18.3%。IFNL4基因型与IL28B几乎完全连锁不平衡。ESRD组中低IVL（<600000 IU/mL）患者的比例显著高于对照组（28/39，71.8%对51/109，46.8%，P = 0.009），ESRD组中IL28B CC携带者的低IVL患者比例与非CC携带者相比也更高（10/11，90.9%对18/28，64.3%，P = 0.0035）。对照组未发现这种差异（7/22，31.8%对44/87，50.6%，P = 0.9）。ESRD组的总体SVR率为64.1%（25/39），对照组为50.5%（55/109）（P = 0.19）。ESRD组和对照组中分别有11/11（100%）和19/22（86.4%）的IL28B CC患者实现了SVR。两组中均发现SVR与IL28B和IFNL4变异之间存在统计学显著关联。实现SVR的ESRD患者的IVL最低[中位数21000，四分位间距（IQR）：6000 - 23000 IU/mL]，与未实现SVR的ESRD个体（1680000，IQR：481000 - 6880000，P = 0.001）、实现SVR的对照组（387000，IQR：111000 - 1253000）和未实现SVR的对照组（905000，IQR：451000 - 3020000）相比。在ESRD中，IVL < 600000 IU/mL与SVR密切相关：24/28（85.7%）实现SVR的患者病毒血症低于此阈值。
血液透析可降低病毒载量，尤其是在IL28B CC基因型携带者中。多变量分析确定低IVL是ESRD患者SVR的最强预测因素。
