Zografos Theodoros A, Liaskos Christos, Rigopoulou Eirini I, Togousidis Elias, Makaritsis Kostantinos, Germenis Anastasios, Dalekos George N
Department of Medicine (Research Laboratory of Internal Medicine), Medical School, University of Thessaly, Larissa, Greece.
Am J Gastroenterol. 2008 Mar;103(3):605-14. doi: 10.1111/j.1572-0241.2007.01729.x. Epub 2008 Jan 8.
To compare serum adiponectin and tumor necrosis factor (TNF)-alpha among patients with viral liver diseases; to investigate associations of serum adiponectin and TNF-alpha with histological or viral characteristics of chronic hepatitis C (CHC); to investigate adiponectin and TNF-alpha alterations during interferon (IFN)-alpha treatment; and to assess the relationship between serum adiponectin and TNF-alpha and response rates to treatment.
Adiponectin (mug/mL) and TNF-alpha (pg/mL) determinations by enzyme-linked immunosorbent assay (ELISA) in serial samples (before, the middle, the end, and 6 months after the end of treatment) from 83 CHC and 59 chronic hepatitis B (CHB) patients. Forty-three blood donors served as healthy controls. Patients were treated with IFN-alpha (4.5 MU/t.i.w.) for 12 months in CHB cases, and IFN-alpha (3 MU/t.i.w.) plus ribavirin for 6-12 months according to hepatitis C virus (HCV) genotype in CHC cases.
After adjustment for gender and body mass index (BMI), HCV genotype 3 overweight patients (BMI > 25 kg/m(2)) had significantly lower adiponectin (7.3 +/- 2.7) at baseline compared with non-3 HCV genotype overweight patients (P < 0.05). Lower adiponectin (HCV genotype 3, P= 0.02 and HCV genotype 1, P= 0.025) and higher TNF-alpha (P= 0.025) at baseline were identified as independent predictors of liver steatosis in CHC patients. Lower adiponectin was also identified as an independent predictor of no virological response at the end of treatment (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.66-0.87, P < 0.001). At the end of IFN-alpha therapy, only HCV genotype 3 patients had significantly higher serum adiponectin (10.4 +/- 6.3) compared with its levels before treatment (8.7 +/- 4.7, P < 0.05).
This study suggests that HCV genotype 3 may directly affect adiponectin. This is further supported by the significant increase in adiponectin at the end of treatment only in HCV genotype 3 patients. Serum adiponectin at baseline appears to be an independent predictor of liver steatosis and for the achievement of end-of-treatment virological response, while serum TNF-alpha at baseline was identified as an independent predictor only of liver steatosis.
比较病毒性肝病患者血清脂联素和肿瘤坏死因子(TNF)-α水平;研究血清脂联素和TNF-α与慢性丙型肝炎(CHC)组织学或病毒学特征的相关性;研究干扰素(IFN)-α治疗期间脂联素和TNF-α的变化;评估血清脂联素和TNF-α与治疗反应率之间的关系。
采用酶联免疫吸附测定(ELISA)法测定83例CHC患者和59例慢性乙型肝炎(CHB)患者系列样本(治疗前、治疗中期、治疗结束时及治疗结束后6个月)中的脂联素(μg/mL)和TNF-α(pg/mL)。43名献血者作为健康对照。CHB患者接受IFN-α(4.5 MU/隔日1次)治疗12个月,CHC患者根据丙型肝炎病毒(HCV)基因型接受IFN-α(3 MU/隔日1次)联合利巴韦林治疗6至12个月。
校正性别和体重指数(BMI)后,HCV基因3型超重患者(BMI>25 kg/m²)基线时脂联素水平(7.3±2.7)显著低于非3型HCV基因型超重患者(P<0.05)。基线时较低的脂联素水平(HCV基因3型,P = 0.02;HCV基因1型,P = 0.025)和较高的TNF-α水平(P = 0.025)被确定为CHC患者肝脂肪变性的独立预测因素。较低的脂联素水平也被确定为治疗结束时无病毒学应答的独立预测因素(比值比[OR]0.76,95%置信区间[CI]0.66 - 0.87,P<0.001)。IFN-α治疗结束时,仅HCV基因3型患者血清脂联素水平(10.4±6.3)显著高于治疗前水平(8.7±4.7,P<0.05)。
本研究提示HCV基因3型可能直接影响脂联素。仅HCV基因3型患者治疗结束时脂联素显著升高进一步支持了这一点。基线时血清脂联素似乎是肝脂肪变性和实现治疗结束时病毒学应答的独立预测因素,而基线时血清TNF-α仅被确定为肝脂肪变性的独立预测因素。