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.

中文翻译：

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HCV1代偿性肝硬化患者中脂联素和sTNFRII血清水平升高可预测其进展为肝细胞癌。

背景和目标

肥胖相关的脂肪组织分泌改变被认为是丙型肝炎病毒（HCV）肝硬化患者肝细胞癌（HCC）的危险因素。但是，尚无前瞻性研究检查循环脂肪因子和免疫炎性生物标记物对这种风险的预测价值。

方法

这是一项病例对照研究，嵌套在法国全国HCV感染并经活检证实为肝硬化的患者的前瞻性队列中，我们选择了56例HCV1感染的患者，这些患者随后发展为HCC（病例），并选择了96例年龄，性别和糖尿病，在相似的时期后没有发展成肝癌。在基线冷冻血清样品上测定了脂肪因子和免疫炎性生物标志物。在单变量分析下使用混合逻辑回归模型，在多变量分析下使用后向逐步程序，评估它们对肝癌发生的影响。

结果

患者主要为男性（62.5％），具有活跃的HCV复制（83％），随访时间中位数为6.3年，其中44.4％实现了持续的病毒反应。病例中脂联素血症水平高于对照组（P = 0.01）。除sTNFRII> 5,000 pg / mL外，两组的免疫炎症标记物水平均相似（52％的病例与24％的对照；P = 0.001）。没有标志物与组织学脂肪变性相关。在多变量分析中，基线脂联素和sTNFRII水平与肝癌的发生，既往酒精摄入过多和HCV病毒载量独立相关。

结论

高基线循环脂联素和sTNFRII水平与HCV1肝硬化患者的HCC风险增加相关，而与HCV复制状态无关。