【作者】 杨光；

【导师】 王楠娅；

【作者基本信息】 吉林大学 ， 临床医学（专业学位）， 2020， 硕士

【摘要】 目的:生物电阻抗分析(bioelectrical impedance analysis,BIA)是一种测定人体成分的技术,被广泛应用于人体成分检查及营养状态评估的临床实践。相位角(phase angle,PA)是由BIA得出的一项营养状态评估指标,与细胞内、外液及细胞膜稳定性有关。研究表明,PA数值高低是影响乳腺癌、头颈部肿瘤等多个肿瘤生存的因素之一,低PA不仅提示营养状况不佳,还与预后不佳有关。但PA数值与原发性肝癌的预后之间的关系未见报道。本研究拟探讨原发性肝癌患者PA数值与人体成分分析其他指标及预后的关系,进一步明确PA检测对原发性肝癌患者的临床意义。方法:回顾性分析2015年1月至2019年12月期间就诊于吉林大学第一医院肿瘤中心并进行生物电阻抗分析的248例原发性肝癌患者。收集患者基本临床资料(性别、年龄、身高、体重)、肿瘤相关资料(BCLC分期、转移)、实验室相关指标资料(血红蛋白、转铁蛋白、C反应蛋白、视黄醇结合蛋白、门冬氨酸氨基转移酶、丙氨酸氨基转移酶、γ-谷氨酰转肽酶、碱性磷酸酶、甲胎蛋白、肝炎病毒定量等)和生存资料。根据PA中位数进行分组,比较两组患者总生存期(OS)、人体成分分析其他指标的差异及对影响生存的因素进行统计分析。结果:1.一般特征比较:共纳入248例原发性肝癌患者,其中男性190例,女性58例,年龄26~84岁,平均年龄67.6岁。肝功能Child-Pugh分级A级209例,B级25例,C级14例。BCLC分期A期84例,B期85例,C期79例。根据相位角的中位数分组,低PA组与高PA组相比,细胞内水分(20.45L vs 23.56L,P=0.038)、细胞外水分(13.38L vs14.57L,P=0.004)、肌肉量(43.23 kg vs 48.87 kg,P=0.031)、去脂体重(45.88 kg vs 51.72 kg,P=0.036)均较低。低PA组门冬氨酸氨基转移酶、γ-谷氨酰转肽酶、总胆红素、直接胆红素水、胆固醇水平均高于高PA组(78.36U/L vs47.71U/L,P=0.021;138.48 U/L vs108.45U/L,P=0.018;30.7μmol/L vs19.76μmol/L,P=0.001;13.92μmol/L vs6.49μmol/L,P<0.001;4.31mmol/l vs4.04mmol/l,P<0.001)。低PA组血红蛋白水平低于高PA组(129.72g/L vs144.31g/L,P=0.042)。2.相关性:将PA与上述指标进行Pearson相关性分析。结果显示:PA与身高(r=0.196,P=0.002)、体重(r=0.342,P<0.001)、腹围(r=0.250,P<0.001)、白蛋白(r=0.286,P<0.001)、胆碱酯酶(r=0.319,P<0.001)、血红蛋白(r=0.391,P<0.001)、细胞内水分(r=0.499,P<0.001)、细胞外水分(r=0.300,P<0.001)、蛋白质(r=0.494,P<0.001)、无机盐(r=309,P<0.001)、肌肉量(r=0.438,P<0.001)、去脂体重(r=0.431,P<0.001)、上臂围度(r=0.28,P<0.001)、身体质量指数(r=0.303,P<0.001)、基础代谢率(r=0.281,P<0.001)、身体细胞量(r=0.380,P<0.001)呈正相关;与总胆红素(r=-0.127,P=0.046)、直接胆红素(r=-0.145,P=0.023)、年龄(r=-0.309,P<0.001)、性别(r=-0.295,P<0.001)、PG-SGA评分(r=-0.233,P=0.001)呈负相关;与门冬氨酸氨基转移酶、丙氨酸氨基转移酶、γ-谷氨酰转肽酶、碱性磷酸酶、总蛋白、转铁蛋白、视黄醇结合蛋白、胆固醇、甘油三酯、体脂肪、骨矿物质含量、内脏脂肪面积无相关性。3.生存资料:对患者自行人体成分分析时起至死亡或观察终点(随访时间截止至2019年12月)进行随访,中位随访时间为53.5个月。248例患者m OS为70个月,高PA组与低PA组比较m OS差异具体统计学意义(70个月vs 54.6个月,P=0.004)。亚组分析显示在BCLC分期A、B期中,高PA与低PA比较生存差异具体统计学意义(P=0.0006、0.025)。4.多因素分析:以出现死亡为结局,将单因素分析中差异有统计学意义的变量纳入,进行COX多因素回归分析,多因素分析结果示:门冬氨酸氨基转移酶、总胆红素、临床分期是影响原发性肝癌患者预后的独立危险因素(P=0.02,0.025,<0.001)。5.亚组分析:在BCLC分期A中,高PA组与低PA组比较m OS差异具体统计学意义(70个月vs 60个月,P<0.001),将单因素分析中差异有统计学意义的变量进行COX多因素回归分析,结果显示PA是影响原发性肝癌BCLC分期A期患者预后的独立危险因素(P=0.026);在分期B中,低PA组m OS为60个月,高PA组m OS为70.2个月,差异具有统计学意义(P=0.025),将单因素分析中差异有统计学意义的变量进行COX多因素回归分析,结果显示PA是影响原发性肝癌BCLC分期B期患者预后的独立危险因素(P=0.039)。结论:1.根据相位角的中位数分组,两组患者体成分分析中细胞内水分、细胞外水分、肌肉量和去脂体重具有差异。血液学指标方面,低PA组门冬氨酸氨基转移酶、γ-谷氨酰转肽酶、总胆红素、直接胆红素水、胆固醇水平均高于高PA组,血红蛋白水平低于高PA组。2.PA与身高、体重、腹围、白蛋白、胆碱酯酶、血红蛋白、人体成分分析中其他指标呈正相关;与年龄、性别、PG-SGA评分、总胆红素、直接胆红素呈负相关。3.低PA组患者生存期较高PA组患者生存期短,PA是影响原发性肝癌BCLC分期A期和B期患者预后的独立危险因素。更多还原

【Abstract】 Objective:Bioelectrical impedance analysis(BIA)is a technique for measuring human moisture,and is widely used in clinical practice of body composition inspection and nutritional status assessment.Phase angle(PA)is an indicator of nutritional status derived from BIA,which is related to the stability of intracellular,extracellular fluid,and cell membranes.Studies have shown that PA is one of the factors affecting the survival of multiple tumors such as breast cancer and head and neck tumors.Low PA not only indicates poor nutritional status,but also is associated with poor prognosis.However,the significance of PA value in the assessment of primary liver cancer prognosis have not been reported.This study intends to explore the relationship between the PA of patients with primary liver cancer and body composition analysis other indicators and prognosis of patients,and further clarify the clinical significance of PA detection in patients with primary liver cancer.Methods:A retrospective analysis of 248 primary liver cancer patients who were admitted at the First Hospital of Jilin University from January 2015 to December 2019 and underwent bioelectrical impedance analysis.Collect patients’ basic clinical data(gender,age,height,weight),tumor-related data(BCLC stage,metastasis),laboratory-related index data(hemoglobin,transferrin,C-reactive protein,retinol Binding protein,aspartate aminotransferase,alanine aminotransferase,γ-glutamyl transpeptidase,alkaline phosphatase,alpha-fetoprotein,quantification of hepatitis virus,etc.)and survival data.Group according to the median phase angle(PA),compare the overall survival(OS),body composition analysis and other indicators of the two groups of patients and statistical analysis of factors affecting survival.Results:1.Normal information: A total of 248 patients with liver cancer were included,including 190 males and 58 females,aged 26 to 84 years,with an average age of 67.6 years.In the Child-Pugh classification of liver function,there were 209 in grade A,25 in grade B,and 14 in grade C.In the BCLC stage,there were 84 people in stage A,85 in stage B,and 79 in stage C.Group by median of phase angle,compared with the high PA group,the low PA group had lower intracellular water(20.45 L vs 23.56 L,P =0.038),extracellular water(13.38 L vs 14.57 L,P = 0.004),muscle mass(43.23 kg vs 48.87 kg,P=0.031),and lean body mass(45.88 kg vs 51.72 kg,P = 0.036).Aspartate aminotransferase,γ-glutamyl transpeptidase,total bilirubin,direct bilirubin water,and cholesterol levels in low PA group were higher than those in high PA group(78.36U/L vs47.71U/L,P = 0.021;138.48 U/L vs108.45U/L,P = 0.018;30.7μmol/L vs19.76 μmol/L,P = 0.001;13.92μmol/L vs6.49 μmol/L,P = 0.000;4.31 mmol/l vs 4.04 mmol/l,P<0.001).Compared with the high PA group,the hemoglobin level in low PA group was lower(129.72g/L vs 144.31g/L,P = 0.042).2.Correlation: Pearson correlation analysis of the phase angle(PA)with the above indicators.The results showed: PA and albumin(r=0.286,P < 0.001),cholinesterase(r=0.319,P < 0.001),hemoglobin(r=0.391,P<0.001),height(r=0.196,P=0.002),body weight(r=0.342,P<0.001),intracellular water(r=0.499,P<0.001),extracellular water(r=0.300,P < 0.001),protein(r=0.494,P < 0.001),Inorganic salt(r=309,P < 0.001),muscle mass(r=0.438,P < 0.001),fat-free body weight(r=0.431,P < 0.001),upper arm circumference(r=0.28,P <0.001),body mass index(r=0.303,P < 0.001),basal metabolic rate(r=0.281,P<0.001),body cell mass(r=0.380,P<0.001),abdominal circumference(r=0.250,P < 0.001)are positively correlated;with prealbumin(r=-0.148,P=0.027),total bilirubin(r=-0.127,P=0.046),direct bilirubin(r=-0.145,P=0.023),age(r=-0.309,P<0.001),gender(r=-0.295,P < 0.001),PG-SGA score(r=-0.233,P=0.001)were negatively correlated;AST,ALT,γ-GT,alkaline phosphatase,total protein,transferrin,retinol-binding protein,cholesterol,triglycerides,body fat,bone mineral content,and visceral fat area were not related.3.Survival data: The patients were followed up from the time of their own body composition analysis to death or observation end point(the follow-up time ended in December 2019).The median follow-up time was 53.5 months.The m OS of 248 patients was 70 months.The difference in m OS between the high PA group and the low PA group was statistically significant(70 months vs 54.6 months,P=0.004).The subgroup analysis showed that in BCLC stage A and B,the difference in survival between high PA and low PA was statistically significant(P = 0.0006,0.025).4.Multivariate analysis: Taking death as the outcome,the variables with statistical significance in univariate analysis were included,and COX regression analysis was performed.The results of multivariate analysis showed that aspartate aminotransferase,total bilirubin and clinical stage are independent risk factor that affect the prognosis of patients with primary liver cancer(P= 0.02,0.025,<0.001).5.Subgroup analysis: In BCLC stage A,the difference in m OS between the high PA group and the low PA group was statistically significant(70 months vs 60 months,P <0.001).The COX multivariate regression analysis of the variables showed that PA was an independent risk factor affecting the prognosis of patients with primary liver cancer BCLC stage A(P = 0.026);in stage B,the m OS in the low PA group was 60 months,and the high PA The m OS of the group was 70.2 months,and the difference was statistically significant(P = 0.025).The variables with statistical significance in the univariate analysis were analyzed by COX multivariate regression analysis.The results showed that PA was affecting the BCLC stage B of primary liver cancer Independent risk factors for patients’ prognosis(P = 0.039).Conclusion: 1.Grouped according to the median of the phase angle,the intracellular water content,extracellular water content,muscle mass,and lean body mass of the two groups of patients were different.In terms of hematological indicators,aspartate aminotransferase,γ-glutamyl transpeptidase,total bilirubin,direct bilirubin water,and cholesterol levels in the low PA group were higher than those in the high PA group,and the hemoglobin level in the low PA group Lower than the high PA group.2.PA is positively correlated with height,weight,abdominal circumference,albumin,cholinesterase,hemoglobin,and other indicators in the analysis of human composition;negatively correlated with age,gender,PG-SGA score,total bilirubin,and direct bilirubin.3.Patients in the low PA group had a higher survival time and patients in the PA group had a shorter survival time.PA is an independent risk factor affecting the prognosis of patients with primary liver cancer BCLC stage A and B.更多还原