Chen Chi-Ling, Yang Wei-Shiung, Yang Hwai-I, Chen Chuen-Fei, You San-Lin, Wang Li-Yu, Lu Sheng-Nan, Liu Chun-Jen, Kao Jia-Horng, Chen Pei-Jer, Chen Ding-Shinn, Chen Chien-Jen
Graduate Institute of Clinical Medicine, College of Medicine; Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University;
Graduate Institute of Clinical Medicine, College of Medicine; Department of Internal Medicine; Hepatitis Research Center, National Taiwan University Hospital;
Cancer Epidemiol Biomarkers Prev. 2014 Aug;23(8):1659-71. doi: 10.1158/1055-9965.EPI-14-0161. Epub 2014 Jun 3.
Obesity is considered a risk factor for hepatocellular carcinoma (HCC). The relationship between adipocytokine and HCC in hepatitis B virus (HBV) carriers remains unclear. We prospectively investigated the association of adiponectin, leptin, and visfatin levels with HCC.
We conducted a nested case-control study in a community-based cohort with 187 incident HCC and 374 HCC-free HBV carriers. Unconditional logistic regression was conducted to estimate the ORs and 95% confidence intervals (CI).
Adiponectin, but not leptin and visfatin, levels were associated with an increased risk of HCC after adjustment for other metabolic factors and HBV-related factors. The risk was increased [OR = 0.51; 95% CI, 0.12-2.11; OR = 4.88 (1.46-16.3); OR = 3.79 (1.10-13.0); OR = 4.13 (1.13-15.1) with each additional quintiles, respectively] with a significant dose-response trend (P(trend) = 0.003). HCC risk associated with higher adiponectin level was higher in HBV carriers with ultrasonographic fatty liver, genotype C infection, higher viral load, and with elevated alanine aminotransferase. Longitudinally, participants with higher adiponectin were less likely to achieve surface antigen of hepatitis B virus (HBsAg) seroclearance and more likely to have persistently higher HBV DNA. Eventually, they were more likely to develop liver cirrhosis [OR = 1.65 (0.62-4.39); OR = 3.85 (1.47-10.1); OR = 2.56 (0.96-6.84); OR = 3.76 (1.33-10.7) for the second, third, fourth, and fifth quintiles, respectively; P(trend) = 0.017] before HCC.
Elevated adiponectin levels were independently associated with an increased risk of HCC.
Adiponectin may play different roles in the virus-induced and metabolic-related liver diseases, but the underlying mechanism remains unknown.
肥胖被认为是肝细胞癌（HCC）的一个风险因素。乙肝病毒（HBV）携带者中脂肪细胞因子与HCC之间的关系仍不清楚。我们前瞻性地研究了脂联素、瘦素和内脂素水平与HCC的关联。
我们在一个基于社区的队列中进行了一项巢式病例对照研究，其中有187例新发HCC患者和374例未患HCC的HBV携带者。采用无条件逻辑回归来估计比值比（OR）和95%置信区间（CI）。
在调整了其他代谢因素和HBV相关因素后，脂联素水平而非瘦素和内脂素水平与HCC风险增加相关。随着脂联素水平每增加一个五分位数，风险增加[OR分别为0.51；95%CI，0.12 - 2.11；OR = 4.88（1.46 - 16.3）；OR = 3.79（1.10 - 13.0）；OR = 4.13（1.13 - 15.1）]，具有显著的剂量反应趋势（P趋势 = 0.003）。在超声检查有脂肪肝、基因型C感染、病毒载量较高以及丙氨酸氨基转移酶升高的HBV携带者中，与较高脂联素水平相关的HCC风险更高。纵向来看，脂联素水平较高的参与者乙肝表面抗原（HBsAg）血清清除的可能性较小，且HBV DNA持续较高的可能性较大。最终，他们在发生HCC之前发生肝硬化的可能性更大[第二、第三、第四和第五五分位数的OR分别为1.65（0.62 - 4.39）；OR = 3.85（1.47 - 10.1）；OR = 2.56（0.96 - 6.84）；OR = 3.76（1.33 - 10.7）；P趋势 = 0.017]。
脂联素水平升高与HCC风险增加独立相关。
脂联素可能在病毒诱导的和代谢相关的肝脏疾病中发挥不同作用，但其潜在机制仍不清楚。
