背景和目的：体重指数≥30kg/㎡的慢性丙型肝炎患者应用干扰素和利巴韦林治疗时一般无应答，但肥胖降低治疗效果的有关细节机制仍不清楚
方法：在该项III期完成治疗分析研究中，共纳入303例2型或3型丙肝患者，目的在于评价肥胖对预后以及标准方案治疗后血药浓度的影响，方案为聚乙二醇化干扰素180ug每周一次，利巴韦林800mg，每日一次。结果：随访24周，BMI大于30kg/m2患者疗效较差，持续病毒应答率明显低于对照组（62% vs 89%，P= 0.006），此外，肥胖患者脂肪肝分级（P=0.002）、胰岛素抵抗指数（P<0.0001）、甘油三酯水平（P=0.0002）及基线病毒载量（P=0.028）均显著升高。肥胖与治疗第3天（P=0.02）、7天（P=0.0017） 及29天（P<0.0001）干扰素血药浓度低及第29天利巴韦林血药浓度低（P=0.025）显著相关，而低干扰素血药浓度患者初始治疗HCV RNA降低不显著。多因素分析结果表明，随访24周，治疗第12周利巴韦林浓度、治疗第29天干扰素浓度及基线HCV RNA是患者能否获得SVR的独立预后因素。结论：干扰素和利巴韦林生物利用度的减少与高基线病毒载量是肥胖的慢性丙型肝炎患者治疗失败的主要危险因素。
Impact of Obesity on the Bioavailability of Peginterferon-a2a and Ribavirin and Treatment Outcome for Chronic Hepatitis C Genotype 2 or 3
Background and Aims：Having a body mass index above or equalt 30kg/m2 in conjunction with chronic hepatitis C virus infection isassociated with non-responsiveness to treatment with interferon and ribavirin, but details regarding the mechanisms whereby obesity reduces the efficacy of therapy remain unclear. Methods ：This study evaluated impact of obesity on outcome as well as interferon and ribavirin concentrations following standard-of-care fixed dosing with peginterferon-a2a 180 ug once weekly and ribavirin 800 mg daily among 303 HCV genotype 2/3-infected patients enrolled in the per-protocol analysis of a recently completed phase III trial. Results: Patients with BMI ≥30 kg/m2 showed poorer outcome following 24 weeks of therapy (SVR 62% vs. 89% for BMI＜30 vs. 30; P = 0.006) along with significantly higher steatosis grade (P = 0.002), HOMA-IR (P,0.0001), triglyceride levels (P = 0.0002), and baseline viral load (P = 0.028). Obesity was also significantly associated with lower plasma interferon concentrations on days 3, 7, and 29 (P = 0.02, P = 0.0017, and P,0.0001, respectively) and lower plasma ribavirin concentrations day 29 (P = 0.025), and lower concentration of interferon in turn was associated with a poorer first phase reduction in HCV RNA (P,0.0001). In multivariate analysis, ribavirin concentrations week 12, interferon concentrations day 29, and baseline HCV RNA levels were independent predictors of achieving SVR among patients treated for 24 weeks. Conclusions: Reduced bioavailability of interferon and ribavirin along with higher baseline viral load are dominant risk factors for treatment failure in obese patients with chronic hepatitis C.
方法：在该项III期完成治疗分析研究中，共纳入303例2型或3型丙肝患者，目的在于评价肥胖对预后以及标准方案治疗后血药浓度的影响，方案为聚乙二醇化干扰素180ug每周一次，利巴韦林800mg，每日一次。结果：随访24周，BMI大于30kg/m2患者疗效较差，持续病毒应答率明显低于对照组（62% vs 89%，P= 0.006），此外，肥胖患者脂肪肝分级（P=0.002）、胰岛素抵抗指数（P<0.0001）、甘油三酯水平（P=0.0002）及基线病毒载量（P=0.028）均显著升高。肥胖与治疗第3天（P=0.02）、7天（P=0.0017） 及29天（P<0.0001）干扰素血药浓度低及第29天利巴韦林血药浓度低（P=0.025）显著相关，而低干扰素血药浓度患者初始治疗HCV RNA降低不显著。多因素分析结果表明，随访24周，治疗第12周利巴韦林浓度、治疗第29天干扰素浓度及基线HCV RNA是患者能否获得SVR的独立预后因素。结论：干扰素和利巴韦林生物利用度的减少与高基线病毒载量是肥胖的慢性丙型肝炎患者治疗失败的主要危险因素。
吉林大学第一医院肝胆胰内科 徐鹤摘译
本文首次发表于[PLoS ONE, 2012,7(5):e37521]
本文首次发表于[PLoS ONE, 2012,7(5):e37521]
Impact of Obesity on the Bioavailability of Peginterferon-a2a and Ribavirin and Treatment Outcome for Chronic Hepatitis C Genotype 2 or 3
