Pár Alajos, Roth Erzsébet, Miseta Attila, Hegedüs Géza, Pár Gabriella, Hunyady Béla, Vincze Aron
Pécsi Tudományegyetem, Altalános Orvostudományi Kar I. Belgyógyászati Klinika, Pécs.
Orv Hetil. 2009 Jan 11;150(2):73-9. doi: 10.1556/OH.2009.28517.
Since oxidative stress may play a pathogenetic role in chronic hepatitis C, and sustained virological response to antiviral therapy is limited in HCV1 genotype infection, a double blind study was performed in HCV1 patients treated with pegylated interferon + ribavirin, to assess the efficacy of supplementation with the antioxidant flavonoid silymarin.
Thirty-two naive HCV1 positive patients with biopsy proven chronic hepatitis C, to be treated with pegylated interferon + ribavirin, have been randomized: group A): 16 patients have been given the antiviral therapy for 6-12 months plus placebo for the first 3 months; group B): 16 patients have been treated with pegylated interferon + ribavirin for 6-12 months plus silymarin, 2 x 166 mg/day, was given for 3 months. Serum alanine aminotransferase and HCV-RNA levels as well as parameters of oxidative stress such as plasma or red blood cell hemolysate, malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase and myeloperoxidase were determined after 0, 1, 3, 6 and 12 months during the treatment. Sustained virological response as undetectable serum HCV RNA was evaluated 24 weeks after the end of therapy.
In the silymarin group, a more rapid decrease in the malondialdehyde level as well as a marked decrease in superoxide dismutase and an increase in myeloperoxidase activity after month 12 were found, alanine aminotransferase normalized in 6/16 (vs control 9/16) cases, and sustained virological response occurred in 3/16 (vs 7/16) patients.
DISCUSSION/CONCLUSION: Although silymarin supportation to antiviral therapy improved oxidative stress, it was able to affect favourably neither the alanine aminotransferase nor the sustained virological response. These contradictory findings may be related to randomization bias as patients in study group B had more negative predictors of response: they were older with higher fibrosis score and even with more severe pretreatment baseline oxidative stress. Regarding the recently published in vitro experiments with silybinin on HCV replication as well as the newest convincing clinical observations, we do suggest further studies with more than three times higher doses of silymarin in controlled trials to assess the value of this supplementation in antivirally treated HCV patients.
由于氧化应激可能在慢性丙型肝炎的发病机制中起作用，并且在HCV1基因型感染中对抗病毒治疗的持续病毒学应答有限，因此对接受聚乙二醇化干扰素+利巴韦林治疗的HCV1患者进行了一项双盲研究，以评估补充抗氧化剂类黄酮水飞蓟宾的疗效。
32例经活检证实为慢性丙型肝炎的初治HCV1阳性患者，将接受聚乙二醇化干扰素+利巴韦林治疗，已被随机分组：A组：16例患者接受抗病毒治疗6 - 12个月，前3个月加用安慰剂；B组：16例患者接受聚乙二醇化干扰素+利巴韦林治疗6 - 12个月，加用水飞蓟宾，2×166毫克/天，服用3个月。在治疗的0、1、3、6和12个月后测定血清丙氨酸氨基转移酶和HCV - RNA水平以及氧化应激参数，如血浆或红细胞溶血产物、丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶和髓过氧化物酶。在治疗结束后24周评估持续病毒学应答，即血清HCV RNA检测不到。
在水飞蓟宾组中，发现丙二醛水平下降更快以及12个月后超氧化物歧化酶显著下降和髓过氧化物酶活性增加，丙氨酸氨基转移酶在6/16例（对照组为9/16例）中恢复正常，3/16例（对照组为7/16例）患者出现持续病毒学应答。
讨论/结论：尽管水飞蓟宾支持抗病毒治疗改善了氧化应激，但它对丙氨酸氨基转移酶和持续病毒学应答均无有利影响。这些相互矛盾的结果可能与随机化偏倚有关，因为B组患者有更多的阴性应答预测因素：他们年龄较大，纤维化评分较高，甚至预处理基线氧化应激更严重。鉴于最近发表的关于水飞蓟宾对HCV复制的体外实验以及最新的令人信服的临床观察结果，我们确实建议在对照试验中用超过三倍剂量的水飞蓟宾进行进一步研究，以评估这种补充剂在接受抗病毒治疗的HCV患者中的价值。
