Aizawa Yoshio, Shimada Noritomo, Abe Hiroshi, Seki Nobuyoshi, Aida Yuta, Ishiguro Haruya, Ika Makiko, Kato Keizo, Tsubota Akihito
Department of Gastroenterology and Hepatology, Jikei University School of Medicine, Tokyo, Japan.
Hepat Mon. 2013 May 27;13(5):e8988. doi: 10.5812/hepatmon.8988. eCollection 2013 May.
Abnormal serum lipid profiles have been noted in patients with chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b infection who have an unfavorable response to pegylated interferon (peg-IFN) plus ribavirin (RBV) combination therapy. However, after the discovery of single nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent predictive factors affecting the response to peg-IFN plus RBV, lipid factors are thought to be confounding factors.
To re-examine the significance of lipoprotein profiles on virological response to peg-IFN plus RBV combination therapy in patients with chronic HCV G1b infection, we examined cholesterol and triglyceride concentrations in each lipoprotein fraction separated by high performance liquid chromatography.
Lipoprotein profiles were examined using fasting sera from 108 patients infected with HCV G1b who had chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles and clinical data, including IL28B genotype and amino acid substitution at aa70 of HCV G1b, were compared between patients with a sustained virological response (SVR) and non-SVR or a non-virological response (NVR) and virological responses other than NVR (non-NVR). In addition, significant predictive factors independently associated with virological response to peg-IFNα-2b plus RBV were determined by logistic regression analysis.
An increased ratio of cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917 (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In contrast, lipid factors were not elucidated as independent predictive factors for NVR.
Examination of the fasting lipid profile has clinical importance in predicting the efficacy of peg-IFN-α-2b plus RBV combination therapy for patients with HCV G1b even after the discovery of the IL28 genotype as a potent predictive factor.
慢性丙型肝炎病毒(HCV)感染患者存在血清脂质谱异常。此外,许多报告表明,在对聚乙二醇化干扰素(peg-IFN)加利巴韦林(RBV)联合治疗反应不佳的HCV G1b感染患者中,血清脂蛋白谱的扭曲更为严重。然而,在发现IL28B基因附近的单核苷酸多态性(rs8099917和rs12979860)作为影响peg-IFN加RBV反应的有效预测因素后,脂质因素被认为是混杂因素。
为了重新审视脂蛋白谱对慢性HCV G1b感染患者peg-IFN加RBV联合治疗病毒学反应的意义,我们检测了通过高效液相色谱分离的各脂蛋白组分中的胆固醇和甘油三酯浓度。
使用108例经肝活检确诊为慢性肝炎的HCV G1b感染患者的空腹血清检测脂蛋白谱。比较持续病毒学应答(SVR)患者与非SVR或非病毒学应答(NVR)患者以及除NVR以外的病毒学应答(非NVR)患者的脂蛋白谱结果和临床数据,包括IL28B基因型和HCV G1b第70位氨基酸替换情况。此外,通过逻辑回归分析确定与peg-IFNα-2b加RBV病毒学反应独立相关的显著预测因素。
极低密度脂蛋白中胆固醇/甘油三酯比值升高(优势比(OR)3.03;95%置信区间(CI)1.01 - 9.44)以及rs8099917的主要基因型(OR 9.09;95% CI 2.94 - 33.33)是SVR的独立预测因素。相比之下,脂质因素未被阐明为NVR的独立预测因素。
即使在发现IL28基因型作为有效预测因素之后,检测空腹血脂谱对于预测peg-IFN-α-2b加RBV联合治疗HCV G1b患者的疗效仍具有临床重要性。