肝细胞癌进展:代谢综合征相关危险因素研究

doi:10.3969/j.issn.1672-5069.2022.06.030

摘要/Abstract

摘要： 目的分析代谢综合征(MetS)对肝细胞癌(HCC)进展的影响。方法 2013年1月～2021年12月中山大学附属第八医院肝胆胰外科收治的HCC患者203例,其中合并MetS者89例,未合并者114例。将存在肝内转移、血管侵犯、肿瘤最大径＞5 cm、淋巴转移和远处转移等肿瘤生物学特征定义为肿瘤进展,应用多因素Logistic回归分析影响肝癌进展的独立危险因素。结果合并MetS组血糖、血清总胆红素、高密度脂蛋白和甘油三酯水平分别为(6.6±1.4)mmol/L、(48.3±16.2)μmol/L、(0.9±0.3)mmol/L和(1.5±0.8)mmol/L,与未合并组比,差异显著【分别为(5.4±1.9)mmol/L、(22.9±7.2)μmol/L、(1.2±0.3)mmol/L和(1.0±0.5)mmol/L,P<0.05】;合并组HBV感染、发生肿瘤肝内转移、淋巴转移、中心型肥胖和血压升高发生率分别为73.0%、52.8%、32.6%、78.7%和69.7%,与未合并组比,差异显著(分别为86.8%、29.8%、20.2%、39.5%和29.8%,P＜0.05);合并MetS组分患者更容易发生肿瘤进展(P<0.05),经多因素Logistic回归分析显示,低HDL、血糖升高和血压升高是HCC发生肿瘤进展的独立危险因素(P<0.05)。结论 MetS促进HCC患者肝内肿瘤转移和淋巴结转移,导致肿瘤进展,而控制MetS组分是否能帮助抑制或减少肿瘤进展,值得研究。

关键词: 肝细胞癌, 肿瘤进展, 代谢综合征, Logistic回归分析, 危险因素

Abstract: Objective The aim of this study was to analyze the metabolic syndrome (MetS) relevant risk factors for disease progression in patients with hepatocellular carcinoma (HCC). Methods A retrospective study was performed on the clinical data of 203 patients with HCC admitted to the Department of Hepatobiliary Pancreatic Surgery, Eighth Hospital Affiliated to Sun Yat-sen University between January 2013 and December 2021, and out of them, the concomitant MetS was found in 89 cases, and wasn’t in 114 cases. The disease progression was defined as intrahepatic tumor metastasis, blood vessel invasion, tumor diameter larger than 5 cm, lymph node metastasis and remote metastasis. The multivariate Logistic regression analysis was applied to reveal the risk factors. Results The fasting plasma glucose (FPG), serum bilirubin, high-density lipoprotein (HDL) and triglyceride levels in patients with MetS were (6.6±1.4)mmol/L, (48.3±16.2)μmol/L, (0.9±0.3)mmol/L and (1.5±0.8)mmol/L, significantly different as compared to [(5.4±1.9)mmol/L, (22.9±7.2)μmol/L, (1.2±0.3) mmol/L and (1.0±0.5)mmol/L, respectively, P<0.05] in HCC patients without; the incidences of hepatitis B viral infection, intrahepatic tumor metastasis, lymph node metastasis, central obesity and blood hypertension in patients with MetS were 73.0%, 52.8%, 32.6%, 78.7% and 69.7%, significantly different compared to 86.8%, 29.8%, 20.2%, 39.5% and 29.8% (P＜0.05) in patients without; the HCC patients with MetS were prone to having disease progression (P<0.05), and the multivariate Logistic analysis showed that decreased serum HDL, increased FPG, and hypertension were the independent risk factors for disease progression in patients with HCC(P<0.05). Conclusion The MetS components could promote intrahepatic and lymph node tumor metastasis, leading to disease progression in patients with HCC, which warrants further investigation.

Key words: Hepatocellular carcinoma, Disease progression, Metabolic syndrome, Logistic regression, Risk factors

郑希彦, 杜飞, 林志群, 李瑞曦, 周正, 张广权, 周红, 何方平, 史宪杰. 肝细胞癌进展:代谢综合征相关危险因素研究[J]. 实用肝脏病杂志, 2022, 25(6): 877-880.

Zheng Xiyan, Du Fei, Lin Zhiqun, et al.. Metabolic syndrome-related risk factor for disease progression of patients with hepatocellular carcinoma[J]. Journal of Practical Hepatology, 2022, 25(6): 877-880.

参考文献

[1] Liu Z, Jiang Y, Yuan H, et al. The trends in incidence of primary liver cancer caused by specific etiologies: Results from the global burden of disease study 2016 and implications for liver cancer prevention. J Hepatol, 2019,70(4):674-683.
[2] 刘奇,郝吉庆.免疫联合治疗肝细胞癌研究进展.实用肝脏病杂志,2021,24(1):7-9.
[3] Przybycien-Gaweda PM, Gwee X, Gao Q, et al. Metabolic syndrome and cognition: follow-Up study of Chinese over-55-year-olds. Dement Geriatr Cogn Disord, 2020,49(2):129-137.
[4] Rochlani Y, Pothineni NV, Kovelamudi S, et al. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis,2017,11(8):215-225.
[5] Sohn W, Lee HW, Lee S, et al. Obesity and the risk of primary liver cancer: a systematic review and meta-analysis. Clin Mol Hepatol,2021,27(1):157-174.
[6] Zhu W, Peng Y, Wang L, et al. Identification ofα-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immunotherapy. Hepatology,2018,68(2):574-589.
[7] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版). 中华消化外科杂志,2020,19(1):1-20.
[8] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版).中华糖尿病杂志,2018,10(1):4-67.
[9] Mili N, Paschou SA, Goulis DG, et al. Obesity, metabolic syndrome, and cancer: pathophysiological and therapeutic associations. Endocrine, 2021,74(3):478-497.
[10] Nderitu P, Bosco C, Garmo H, et al. The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: a study in the Swedish amoris cohort. Int J Cancer,2017,141(6):1148-1160.
[11] 杨蕊旭,范建高.非酒精性脂肪性肝病相关肝细胞癌流行病学与筛查.实用肝脏病杂志,2022,25(2):153-156.
[12] Kai Zhang, Changcheng Tao, Fan Wu, et al. A practical nomogram from the SEER database to predict the prognosis of hepatocellular carcinoma in patients with lymph node metastasis. Ann Palliat Med,2021,10(4): 3847-63.
[13] Ben-Aicha S, Badimon L, Vilahur G. Advances in HDL: much more than Lipid transporters. Int J Mol Sci,2020,21(3):732-739.
[14] Zhang J, Cao X, Liu B,et al. The alterations of cholesterol, HDL-cholesterol and LDL-cholesterol in Chinese with hepatocellular carcinoma: a cross-sectional study. Asian J Surg,2019,42(10):938-939.
[15] Zhao L, Deng C, Lin Z, et al. Dietary fats, serum cholesterol and liver cancer risk: a systematic review and meta-analysis of prospective studies. Cancers (Basel),2021,13(7):1580-1593.
[16] Maruši M, Knobloch M, et al. NAFLD, insulin resistance, and diabetes mellitus type 2. Can J Gastroenterol Hepatol,2021,2(17):6613827-6613834.
[17] Liu GM, Zeng HD, Zhang CY, et al. Key genes associated with diabetes mellitus and hepatocellular carcinoma. Pathol Res Pract,2019,215(11):152510.
[18] 张利利,李玉芳,张驰,等.乙型肝炎肝硬化合并2型糖尿病发生原发性肝癌的风险研究.中华肝脏病杂志,2019,27(10):788-792.
[19] Petrelli F, Ghidini A, Cabiddu M,et al. Effects of hypertension on cancer survival: a meta-analysis. Eur J Clin Invest,2021,51(6):e13493-e13512.
[20] Angel-Korman A, Rapoport V, Leiba A. The relationship between hypertension and cancer. Isr Med Assoc J,2022,24(3):165-169.
[21] Li F, Liu Y, Ren L, et al. IGF-1 regulates ang ii and vegf signaling pathways in retinal neovascularization. Eur Rev Med Pharmacol Sci, 2018,22(19):6175-6180.
[22] An X, Li S, Weng X, et al. Maxingxiongting mixture attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the rho-kinase signaling pathway. J Tradit Chin Med, 2020,40(6):992-998.
[23] Jarvis H, Craig D, Backer R, et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies, PLoS Med,2020,17(4):e1003100.