Elevated adiponectin and sTNFRII serum levels can predict progression to hepatocellular carcinoma in patients with compensated HCV1 cirrhosis
Elevated adiponectin and sTNFRII serum levels can predict progression to hepatocellular carcinoma in patients with compensated HCV1 cirrhosis
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DOI：
10.1684/ecn.2018.0413
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发表时间：
2018-09-01
影响因子：
2.8
通讯作者：
Di Martino, Vincent
中科院分区：
文献类型：
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作者：
Bastard, Jean-Philippe;Fellahi, Soraya;Di Martino, Vincent
背景和目的：肥胖相关的脂肪组织分泌改变被认为是丙型肝炎病毒(丙型肝炎病毒)肝硬变患者发生肝细胞癌的危险因素。然而，还没有前瞻性研究检验循环脂肪因子和免疫炎症生物标记物对这种风险的预测价值。方法：这是一项嵌套在法国国家前瞻性队列中的病例对照研究，研究对象为经活检证实为代偿性肝硬变的丙型肝炎病毒感染患者。我们选择了56名后来发展为肝癌的HCV1感染患者(病例)，以及96名年龄、性别和糖尿病相匹配的对照组，这些患者在类似时期后没有发展为肝癌。在基线冰冻血清样本上测定脂肪因子和免疫炎症生物标志物。结果：患者多为男性(62.5%)，丙型肝炎病毒复制活跃(83%)，平均随访时间为6.3年，其中44.4%获得持续病毒应答。病例组脂联素水平明显高于对照组(P=0.01)。免疫炎症标记物水平除sTNFRII和GT；5,000 pg/mL外，两组相似(52%的病例与24%的对照组；P=0.001)。没有与组织学脂肪变性相关的标志物。在多变量分析中，基线脂联素和sTNFRII水平与肝细胞癌的发生独立相关，并与既往过量饮酒和丙型肝炎病毒载量有关。结论：高基线循环脂联素和sTNFRII水平与HCV1肝硬变患者发生肝细胞癌的风险增加相关，与其丙型肝炎病毒复制状态无关。
Background and aims: An obesity-related altered adipose tissue secretion is suggested as a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) cirrhosis. However, no prospective study has yet examined the predictive value of circulating adipokines and immuno-inflammatory biomarkers regarding this risk. Methods: This was a case-control study nested in a prospective French national cohort of HCV-infected patients with biopsy-proven compensated cirrhosis. We selected 56 HCV1-infected patients who subsequently developed HCC (cases), and 96 controls matched for age, gender and diabetes, not developing HCC after a similar period. Adipokines and immuno-inflammatory biomarkers were determined on baseline frozen serum samples. Their influence on the occurrence of HCC was assessed using a mixed logistic regression model under univariate analysis and a backward stepwise procedure under multivariate analysis.Results: The patients were mostly male (62.5 %) with active HCV replication (83 %) and had been followed for a median duration of 6.3 years during which 44.4% achieved a sustained viral response. Higher adiponectinemia levels were found in cases than in controls (P = 0.01). Levels of the immuno-inflammatory markers were similar in both groups except sTNFRII >5,000 pg/mL (52% cases versus 24% controls; P= 0.001). No marker was associated with histological steatosis. Under multivariate analysis, baseline adiponectin and sTNFRII levels were independently associated with the occurrence of HCC, alongside previous excessive alcohol intake and HCV viral load. Conclusions: High baseline circulating adiponectin and sTNFRII levels were associated with an increased risk of HCC in patients with HCV1 cirrhosis, independently of their HCV replication status.