Age-dependency of galactose elimination capacity in healthy children and children with chronic liver disease

Abstract

Objective. Galactose elimination capacity (GEC) is used as a quantitative measure of liver metabolic function with prognostic value in adults with acute and chronic liver failure. Almost no data are available regarding GEC in children, however. This study thus aims to meet the previously unmet clinical need for age-related data on GEC in children. Material and methods. We studied galactose elimination in 10 healthy children (median age 10.7 years; range 7 months to 16 years) and 30 children with chronic liver disease (median age 8.6 years; range 3 months to 16 years). GEC was estimated from the linear decrease in concentration of galactose in arterialized capillary blood from the ear following intravenous infusion of galactose. Results. In both groups of children, GEC (μmol/min/kg body weight) was highest in the youngest children and decreased with age, although at a significantly lower level in the children with liver disease (p = 0.05). GEC was significantly higher in healthy children than in healthy adults, diminishing to the adult level by the age of 16 years. Conclusions. GEC was found to be higher in children than in adults until the age of 16 years. Moreover, GEC was significantly lower in children with chronic liver disease than in healthy children, underlining that GEC testing also has potential clinical usefulness as a quantitative measure of liver metabolic function in children.     

吲哚菁绿清除试验对乙型肝炎肝硬化患者肝脏储备功能的评估价值

目的通过吲哚菁绿(ICG)清除试验评估乙型肝炎肝硬化患者肝脏储备功能,探讨ICG清除试验与Child-TurcottePugh(CTP)分级和MELD评分评价肝功能之间的关系。方法收集福建医科大学附属第一医院2012年1月-2015年1月住院的乙型肝炎肝硬化患者127例,进行ICG清除试验,计算患者的ICG血浆清除率值(K值)、有效肝血流量(EHBF)、ICG 15 min滞留率(ICG R15),以及CTP分级和MELD评分。组间比较采用方差分析,进一步两两比较采用LSD-t检验;相关性比较采用Spearman等级相关性分析;采用受试者工作特征曲线下面积(AUC)比较肝脏储备功能。结果乙型肝炎肝硬化患者CTP分级:A级患者63例,B级患者45例,C级患者19例。随着CTP分级升高,ICG R15逐渐增高,而EHBF和K值则逐渐降低,差异均有统计学意义(F值分别为146.96、91.26、40.94,P值均分别为0.001、0.003、0.005)。在评价肝功能方面ICG R15与MELD评分及CTP分级呈正相关(r值分别为0.525、0.838,P值均0.01),与EHBF及K值呈负相关(r值分别为-0.703、-0.901,P值均0.01)。ICG R15AUC为0.85,MELD评分AUC为0.65。结论 ICG消除试验能够准确动态反应肝脏储备功能,ICG R15评估肝脏储备功能优于CTP分级及MELD评分。     

吲哚菁绿15分钟滞留率对HBV相关慢加急性肝衰竭患者病情及预后的评估价值

目的分析吲哚菁绿15 min滞留率(ICG R15)对慢加急性肝衰竭(ACLF)病情及临床预后的评估价值,为ACLF患者的病情评估及预后评价提供参考指标。方法以中国医科大学附属盛京医院2013年8月-2016年1月收治的127例ACLF患者为研究对象,按照临床分期分为早期组、中期组、晚期组,比较不同临床分期患者ICG R15、MELD评分及PT的差异,并按照患者90 d预后分为存活组、死亡组,比较两组患者上述指标间差异,总结ICG R15评价患者病情及预后的临床价值。计量资料组间比较采用独立样本t检验或单因素方差分析,采用LSD-t检验进行两两比较;计数资料组间比较采用χ2检验。结果不同临床分期组间ICG R15、PT、MELD评分差异均有统计学意义(F值分别为7.036、3.217、5.883,P值均0.05),其中中期组、晚期组ICG R15、PT、MELD评分[(53.96±10.01)%、(26.87±6.84)s、(31.56±4.17)分,(54.23±9.21)%、(28.43±3.61)s、(32.87±3.28)分]均高于早期组[(44.00±9.21)%、(19.79±2.82)s、(24.00±3.85)分],差异均有统计学意义(P值均0.05)。死亡组ICG R15、PT、MELD评分[(53.91±5.83)%、(29.85±3.52)s、(33.81±4.67)分]均高于存活组[(45.03±4.33)%、(21.35±3.18)s、(25.30±4.02)分],差异均有统计学意义(t值分别为9.85、14.20、10.99,P值均0.05)。以ICG R15=52%、PT=29 s、MELD评分=32分为截断值,不同指标水平患者病死率比较(22.39%vs 63.33%,25.71%vs 61.40%,21.54%vs 62.90%),差异均有统计学意义(χ2值分别为8.831、6.263、7.583,P值均0.05)。结论随着ACLF患者病情的加重与预后质量的下降,其PT、MELD评分逐渐升高,且ICG R15亦有所上升,根据上述指标变化能够早期全面评估患者病情及临床预后。     

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis

BACKGROUND:The indocyanine green(ICG)clearance test(clearance rate(K)and retention rate at 15 minutes (R15))is a sensitive indicator to evaluate liver function. The model for end-stage liver disease(MELD)score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity.In this study,we investigated the correlation between the ICG clearance test and MELD score of patient...     

ICGR15在肝硬化断流术前评估肝脏储备功能的应用价值

目的 探讨吲哚菁绿试验15 min滞留率(ICGR15)在评估肝硬化断流术前肝脏储备功能的应用价值.方法 回顾性分析我院收治的75例肝硬化行断流术的患者,Child - Pugh A级患者55例,Child - Pugh B级患者20例.手术方式均为贲门周围血管离断术.对Child - Pugh A、B级两组患者术前测定的ICGR15及肝功能良好组和肝功能不全组间年龄、ALT、TBil、PT、Alb、ICGR15值、Child - Pugh评分进行比较,并应用ROC曲线评价ICGR15值的评估价值.结果 Child - Pugh A、B级两组ICGR15值分别为(17.98±12.12)％、(34.19 ±9.90)％,两组间差异具有统计学意义(P＜0.01);肝功能良好组和肝功能不全组间ICGR15值、Child - Pugh评分差异存在统计学意义(P＜0.01),年龄、ALT、TBil、PT、Alb差异无统计学意义(P＞0.01);ROC曲线下面积为0.971,差异有统计学意义(P =0.000).结论 ICGR15值是肝硬化断流术前评估肝脏储备功能较好的指标.     

吲哚菁绿清除试验对急性/慢加急性肝衰竭患者预后的评价

目的通过观察肝衰竭患者吲哚菁绿清除试验15 min滞留率(ICG R15)与其他常用肝脏储备功能指标变化,评判ICGR15对预测肝衰竭患者预后的价值。方法对32例肝衰竭患者采用脉搏光度分析法(即PDD法),检测入院时ICG R15,同时检测常用肝功能指标,包括ALT、AST、TBil、Alb、GGT、胆碱酯酶(CHE)、凝血酶原活动度(PTA)和胆固醇(CHO)。计算MELD评分。同时选取15例慢性肝炎患者、94例肝硬化患者作为对照,检测ICG R15及同期Alb、CHE、PTA和CHO。对肝衰竭组患者进行了3个月随访,确定存活及死亡情况,并对ICG R15、MELD评分进行受试者工作特征曲线(ROC曲线)分析,探讨其对预后的判断意义。结果(1)在慢性肝炎、肝硬化和肝衰竭组ICG R15、Alb、PTA、CHE、CHO在3组间差异均有统计学意义(P<0.05),其中ICG R15,Alb,CHE,PTA在慢性肝炎和肝硬化组差异有统计学意义(P<0.05);ICG R15、PTA、CHO在肝硬化和肝衰竭组差异有统计学意义(P<0.05)。(2)3个月时肝衰竭存活组与死亡组ICG R15分别为(50.05±9.04)%、(56.27±5.65)%,差异有统计学意义(P<0.05)。(3)对肝衰竭组ICG R15和MELD评分进行ROC曲线分析,二者曲线下面积分别为75.9%和60.4%,ICG R15对预后的判断优于MELD评分;当ICG R15为52.5%时对预后判断的敏感性为80%,特异性为70.6%。(4)肝衰竭组入院时ICG R15≤50%10例,3个月时死亡2例,病死率20%;>50%22例,3个月时死亡14例,病死率63.6%。结论 (1)在慢性肝炎、肝硬化和肝衰竭组,随着病情加重PTA逐渐下降,ICG R15逐渐升高,两者反映病情的严重程度优于其他指标。(2)比较ICG R15和MELD评分对肝衰竭患者的预后判别作用,ICG R15对3个月预后的判断优于MELD评分。(3)肝衰竭患者ICG R15>50%时预后较差。     

Prognostic value of the aminopyrine breath test in cirrhotic patients

The aminopyrine breath test has been proposed as a quantitative test of hepatic function, but its long-term prognostic value in patients with cirrhosis has not been determined. The aim of this study was to examine the usefulness of the aminopyrine breath test in assessing prognosis and to compare it with traditional methods of evaluating liver function. One-hundred eighty-seven patients with histologically confirmed cirrhosis were studied prospectively. An aminopyrine breath test was obtained at the time of inclusion in the study and results were expressed as per cent of the dose excreted in 2 hr. At inclusion, the severity of liver disease was also assessed according to the Pugh modification of the Child-Turcotte classification based on ascites, neurological status, serum albumin, serum bilirubin and prothrombin time. Mean follow-up was 844 days. During that period, 59 of 187 patients died of their liver disease. Two-year survival decreased with increasing Child-Turcotte classification score: survival was 98% in Child Class A patients (n = 62), 66% in Child Class B (n = 76) and 36% in Child Class C (n = 49) (chi 2 = 65.6, p less than 0.001). Two-year survival also decreased significantly with increasing degree of aminopyrine breath test abnormalities: survival was 90% in patients with aminopyrine breath test greater than 4% (n = 56); 78% in patients with aminopyrine breath test = 2 to 4% (n = 66), and 43% in patients with aminopyrine breath test less than 2% (n = 65) (chi 2 = 36.9, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value of (13)C-phenylalanine breath test on predicting survival in patients with chronic liver failure

AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival.CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease.     

吲哚菁绿清除试验对肝硬化及肝衰竭患者肝脏储备功能的评估及预后的判断

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慢性肝炎肝硬化和肝衰竭患者吲哚菁绿清除试验的变化及其临床意义

目的 探讨吲哚菁绿(ICG)清除试验对不同程度慢性肝病患者肝脏储备功能的评估价值。方法 2017年11月～2019年8月山西医科大学第一医院感染病科住院治疗的肝病患者87例,其中慢性病毒性肝炎9例,肝硬化69例,慢性肝衰竭9例,使用日本DDG-3300K分析仪及配套分析软件检测ICG15分钟滞留率(ICG-R15)、ICG血浆清除率(K值)和有效肝脏血流量(EHBF),同时检测肝功能、血常规、腹部彩超、腹部CT或MRI,计算肝功能Child-Turcotte-Pugh(CTP)评分并对肝硬化患者分级。结果 慢性肝衰竭组ICG-R15为(54.2±11.6)%,K值为(0.04±0.01)/min,EHBF为(0.2±0.1)L/min,与慢性肝炎组比,差异显著【分别为(7.4±1.7)%、(0.22±0.05)/min和(0.9±0.3)L/min,P<0.05】;11例CTP C级患者ICG-R15为(39.3±8.9)%,K值为(0.06±0.02)/min,EHBF为(0.3±0.1)L/min,与39例CTP B级【分别为(28.8±12.6)%、(0.10±0.03)/min和(0.4±0.2)L/min,P<0.05】或19例CTP A级【分别为(12.2±2.8)%、(0.16±0.05)/min和(0.7±0.2)L/min,P<0.05】比,差异显著。结论 ICG清除试验能动态反映肝脏储备功能,弥补CTP分级的不足,尝试作为早期诊断肝硬化的参考指标,值得进一步研究。     

原发性胆汁性肝硬化预后判断及其治疗方案

原发性胆汁性肝硬化(PBC)患者的预后评判以及如何改善预后一直备受关注,预后不佳PBC患者的进一步治疗方案成为临床及科研的研究方向。归纳了PBC患者基线指标与预后的关系及熊去氧胆酸(UDCA)治疗中患者预后的评价,介绍了对UDCA应答不佳患者联合布地耐德、贝特类药物及奥贝胆酸的治疗现状,以及正在研究开发的药物,分析了可能影响预后和UDCA疗效的其他因素。认为PBC患者UDCA治疗前及治疗中需对预后及疗效进行评价,及时调整治疗方案,改善预后。     

IRIS13C-美沙西汀呼气试验与Child-Pugh分级、MELD评分评估肝硬化患者肝功能的比较

目的通过比较肝硬化患者13C-美沙西汀呼气试验、Child-Pugh分级及MELD评分,结合腹部CT测量肝脾体积以探讨13C-美沙西汀呼气试验评价肝脏储备和代偿功能的临床应用价值。方法 139例肝硬化患者行13C-美沙西汀呼气试验、Child-Pugh分级及MELD评分,分析各组13C-美沙西汀呼气试验的呼气参数值之间的相互关系,比较乙型肝炎肝硬化患者肝脏、脾脏体积变化以进一步评估13C-美沙西汀呼气试验反映肝细胞储备和代偿功能的作用。结果13C-美沙西汀呼气试验肝脏功能分级与肝硬化患者传统的Child-Pugh分级判定肝功能状况具有良好一致性(κ=0.55,P<0.05),与MELD评分比较具有一致性(κ=0.41,P<0.05);肝脏病变程度越重,13C-美沙西汀呼气试验量化值越小,肝硬化患者呼气参数值显著下降(P<0.05),肝细胞储备和代偿功能越差;呼气试验参数与Child-Pugh分级计分、MELD评分、血清总胆红素、国际标准化比值(INR)呈明显负相关(P<0.01),与血清白蛋白、前白蛋白、凝血酶原活动度、胆碱酯酶呈正相关(P<0.01),与肝硬化患者脾脏体积呈负相关(P<0.05),与血肌酐、ALT、肝脏体积无显著相关性(P>0.05)。68例乙型肝炎肝硬化患者中Child-Pugh分级、MELD评分越高,肝脏体积越小;13C-美沙西汀呼气试验量化值与乙型肝炎肝硬化患者肝脏体积呈正相关(P<0.05)。结论 IRIS13C(红外线同位素13C)-美沙西汀呼气试验可准确反应肝硬化患者肝脏储备及代偿功能。     

无创心脏血流动力检测对乙型肝炎肝硬化预后的评价价值

目的无创血流动力检测法研究不同阶段乙型肝炎肝硬化患者心脏血流动力学变化,探讨心脏泵功能与肝硬化预后的关系。方法 20例慢性乙型肝炎患者作为对照,以45例乙型肝炎肝硬化患者为研究对象,根据Child-Pugh分级分为A级组(12例)、B级组(17例)和C级组(16例),根据食管静脉曲张程度分为轻度组(10例)、中度组(17例)和重度组(18例),根据病毒载量分为高病毒载量组(105拷贝/ml)(19例)和低病毒载量组(≤105拷贝/ml)(26例),采用无创血流动力检测仪测定心脏血流动力学参数。结果随着肝功能恶化,平均动脉压(MAP)、每搏出量(SV)、每搏指数(SI)、心输出量(CO)、心脏指数(CI)、左心作功(LCW)和左心作功指数(LCWI)呈降低趋势,其中C级组明显低于A级组(P<0.05)。随着食管静脉曲张程度的加重,MAP、SV、SI、CO、CI、LCW和LCWI呈降低趋势,其中重度组明显低于轻度组(P<0.05)。不同病毒载量组间MAP、SV、SI、CO、CI、LCW和LCWI差异无统计学意义(P>0.05)。结论心脏血流动力学参数可有效判断乙型肝炎肝硬化病变进展程度,心脏泵功能随肝硬化Child-Pugh分级升高及食管静脉曲张程度加重呈进行性减退。     

Quantitative liver function in the elderly assessed by galactose elimination capacity, aminopyrine demethylation and caffeine clearance

Hepatic function was assessed in 13 healthy elderly subjects, 71-88 years of age, with three quantitative tests of liver function. The galactose elimination capacity was significantly (P less than 0.05) lower in the elderly (6.08 +/- 1.30 mg X min-1 X kg-1, mean +/- SD) than in a group of 70 subjects under 40 (7.48 +/- 0.94 mg X min-1 X kg-1) and 11 subjects between the age of 40 and 70 (7.08 +/- 0.68 mg X min-1 X kg-1). The demethylation of aminopyrine as assessed by the aminopyrine breath test, and the systemic clearance of caffeine, two measures of microsomal function, demonstrated a comparable decrease but showed much more interindividual variation. Caffeine clearance decreased from 1.49 +/- 0.44 ml X min-1 X kg-1 in young adults to 0.97 +/- 0.39 ml X min-1 X kg-1 (P less than 0.01) in the elderly, and the demethylation of aminopyrine decreased from 0.79 +/- 0.15 to 0.62 +/- 0.20% dose X kg X mmol-1 (P less than 0.05). Our data indicate that aging is associated with a loss of the functioning mass of hepatocytes. The decrease in drug metabolism parallels the loss of functional mass but shows more interindividual variation probably reflecting the many genetic and environmental factors influencing these tests of microsomal function.     

吲哚菁绿清除试验对肝硬化患者肝脏储备功能的评估价值

目的 探讨吲哚菁绿（ICG）清除试验对肝硬化患者肝脏储备功能的评估价值。方法 在64例肝硬化患者和50例正常体检人员,使用日本DDG‐3300K分析仪及配套分析软件检测ICG 15分钟滞留率（ICGR15）,同时检测肝功能、血常规、腹部B超等,计算肝功能Child-Turcotte-Pugh（CTP）评分并分级;采用直线相关分析或Spearman等级相关分析。结果 肝硬化患者ICGR15为（28.5±18.3）%,显著高于正常对照组[（4.7±1.2）%,P<0.05];随着 CTP分级升高,肝硬化患者ICGR15越高,差异具有统计学意义（F=40.97,P<0.05）;ICGR15与CTP分级呈正相关（r=0.650,P<0.05）,与肝血流量或血浆清除率呈负相关（r=-0.715、r=-0.817,P<0.05）;不同ICGR15的肝硬化患者血小板计数、凝血酶原时间国际标准化比值、ALT、前白蛋白、白蛋白和总蛋白之间差异具有统计学意义（F=23.44、F=14.05、F=33.63、F=25.3、F=10.58、F=23.51,P<0.05）,ICGR15与凝血酶原时间和总蛋白水平呈正相关（r=0.537、r=0.487,P<0.05）,与前白蛋白、白蛋白和ALT呈负相关（r=-0.498、r=-0.497、r=-0.272,P<0.05）,其中与凝血酶原时间和前白蛋白相关性最强。结论 ICG清除试验能够较准确地动态反映肝脏储备功能,使用ICGRl5评估肝脏储备功能优于CTP分级。     

Prognostic value of clinical variables and liver histology for development of fibrosis and cirrhosis in autoimmune hepatitis

Objective: In autoimmune hepatitis, data on the prognostic value of baseline liver biopsy and the sequential histology is controversial. Our aim was to evaluate the prognostic value of clinical variables and biopsy at the time of diagnosis and during the disease course.

Materials and methods: All 98 patients in our hospital during 1995–2012 were included. Sequential biopsies were available in 66 patients. Analyses based on clinical and histological variables were performed to find parameters predicting the progression of fibrosis, and development of cirrhosis.

Results: At the time of diagnosis, 7% were cirrhotic. Fibrosis progressed in 28 (42%) patients, remained stable in 26 (39%) and resolved in 12 (18%) patients. Findings which predicted fibrosis progression, were baseline total inflammation (odds ratio 1.7, 95% CI 1.01–2.8), cumulative total inflammation (1.8, 95% CI 1.01–3.2, rosette formation (2.8, 95% CI 1.1–7.1), absence of pericholangitis (0.4, 95% CI 0.1–1.0) and necrosis (1.4, 95% CI 1.0–2.0). Risk factors for the development of cirrhosis were cholestasis (4.6, 95% CI 1.2–16.9), interphase inflammation (3.4, 95% CI 1.1–10.4), and necrosis (3.3, 95% CI 1.2–9.7). In a cumulative model, cumulative total inflammation (4.5, 95% CI 1.4–15.0), necrosis (6.7, 95% CI 1.3–34.6), or cumulative immunoglobulin G load (61.8, 95% CI 2.0–1954.3) were risk factors. None of the patients with histological pericholangitis or granulomas developed cirrhosis.

Conclusions: The histology provides prognostic information regarding progression of fibrosis or the development of cirrhosis. The total cumulative inflammatory activity predicts the progression of fibrosis, whereas baseline fibrosis, interphase inflammation, cholestasis, necrosis, as well as the cumulative total inflammation and cumulative immunoglobulin G, are risk factors for cirrhosis.     

终末期肝病模型对肝硬化患者预后评估价值的研究进展

客观、准确地判断肝硬化患者的病情及预后有助于指导临床医生选择正确的治疗方案。终末期肝病模型（MELD）是目前被广泛认可的评估终末期肝病严重程度的评分体系。近年来各种基于MELD评分发展而来的新评分系统不断涌现。加入新的变量例如血清钠可进一步提高MELD的预测能力,此文就MELD的研究现状作一综述。