Grammatikos Georgios, Lange Christian, Susser Simone, Schwendy Susanne, Dikopoulos Nektarios, Buggisch Peter, Encke Jens, Teuber Gerlinde, Goeser Tobias, Thimme Robert, Klinker Hartwig, Boecher Wulf O, Schulte-Frohlinde Ewert, Penna-Martinez Marissa, Badenhoop Klaus, Zeuzem Stefan, Berg Thomas, Sarrazin Christoph
J. W. Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
Uniklinik TU München, München, Germany.
PLoS One. 2014 Feb 7;9(2):e87974. doi: 10.1371/journal.pone.0087974. eCollection 2014.
Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed.
In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome.
Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response.
While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.
已确定不同参数用于预测接受聚乙二醇干扰素、利巴韦林联合治疗的丙型肝炎病毒1型感染患者的治疗结果。关于维生素D水平重要性的结果相互矛盾。在本研究中，在其他已知治疗预测指标的背景下，对治疗前和治疗期间的维生素D水平以及参与维生素D代谢的单核苷酸多态性进行了综合分析。
在一个特征明确的前瞻性队列中，对398例接受聚乙二醇干扰素-α和利巴韦林治疗24 - 72周的1型感染患者（INDIV - 2研究），分析了25 - 羟基维生素D水平、不同的单核苷酸多态性以及已知的生化参数，以与病毒学治疗结果进行相关性分析。
在抗病毒治疗过程中，66%（39%）的患者观察到25 - 羟基维生素D水平波动超过5（10）ng/ml，治疗前和治疗期间的25 - 羟基维生素D水平均与治疗结果无关。7 - 脱氢胆固醇还原酶内的DHCR7 - TT多态性在单因素分析中显示与持续病毒应答有显著关联（P = 0.031）。在分析的众多其他参数中，我们发现年龄（OR = 1.028，CI = 1.002 - 1.056，P = 0.035）、胆固醇（OR = 0.983，CI = 0.975 - 0.991，P < 0.001）、铁蛋白（OR = 1.002，CI = 1.000 - 1.004，P = 0.033）、γ - 谷氨酰转移酶（OR = 1.467，CI = 1.073 - 2.006，P = 0.016）和IL28B基因型（OR = 2.442，CI = 1.271 - 4.695，P = 0.007）是治疗反应的最强预测指标。
虽然在长期抗病毒治疗过程中25 - 羟基维生素D水平有相当大的变化，但在1型感染患者中它们与治疗结果没有任何显著关联。
