慢性HCV基因型-1感染的肥胖患者抗病毒治疗无应答与肝脏SOCS-3的表达上调有关

作     者：Walsh M.J. Jonsson J.R. Richardson M.M. E.E.Powell 陈瑜 

作者机构：Princess Alexandra HospitalIpswich RdWoolloongabbaQLD 4102AustraliaDr 

出 版 物：《世界核心医学期刊文摘（胃肠病学分册）》 (Core Journals in Gastroenterology)

年 卷 期：2006年第2卷第10期

页      面：38-38页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：SOCS-3 抗病毒 HCV基因 宿主因素 干扰素α 肝活检 信号转导 细胞因子 慢性丙型肝炎 胰岛 

摘      要：Background: Interferon α(IFN-α) activated cellular sign- aling is negatively regulated by inhibitory factors, including the suppressor of cytokine signaling (SOCS) family. The effects of host factors such as obesity on hepatic expression of these inhibitory factors in subjects with chronic hepatitis C virus (HCV) are unknown. Objectives: To assess the independent effects of obesity, insulin resistance, and steatosis on response to IFN-αtherapy and to determine hepatic expression of factors inhibiting IFN-αsignaling in obese and non-obese subjects with chronic HCV. Methods: A total of 145 subjects were analysed to determine host factors associated with non-response to antiviral therapy. Treatment comprised IFN-αor peginterferon alpha, either alone or in combination with ribavirin. In a separate cohort of 73 patients, real time-polymerase chain reaction was performed to analyse hepatic mRNA expression. Immunohistochemistry for SOCS-3 was performed on liver biopsy samples from 38 patients with viral genotype 1 who had received antiviral treatment. Results: Non-response (NR) to treatment occurred in 55%of patients with HCV genotypes 1 or 4 and 22%with genotypes 2 or 3. Factors independently associated with NR were viral genotype 1/4 (p 0.001), cirrhosis on pretreatment biopsy (p = 0.025), and body mass index ≥30 kg/m2 (p = 0.010). Obese subjects with viral genotype 1 had increased hepatic mRNA expression of phosphoenolpyruvate carboxy kinase (p = 0.01) and SOCS-3 (p = 0.047), in comparison with lean subjects. Following multivariate analysis, SOCS-3 mRNA expression remained independently associated with obesity (p = 0.023). SOCS-3 immunoreactivity was significantly increased in obesity (p = 0.013) and in non-responders compared with responders (p = 0.014). Conclusions: In patients with chronic HCV viral genotype 1, increased expression of factors that inhibit interferon signaling may be one mechanism by which obesity reduces the biological response to IFN-α.