Improvement of prognostic power of the Child-Pugh classification of liver cirrhosis by hyaluronan

BACKGROUND/AIMS: Modifications of the Child-Pugh classification of liver cirrhosis by incorporation of hyaluronan were tested to improve the prognostic power for long term evaluation of liver cirrhosis in 126 patients observed over a period of 10 years. METHODS: Serum concentrations of HA were determined at study entry. Statistical analysis included Kaplan-Meier life tables and stepwise multivariant Cox-regression analysis for each parameter of Child-Pugh classification and hyaluronan. Prognostic models were developed by exchanging prothrombin time, albumin and encephalopathy by HA in different combinations. RESULTS: Based on a good single correlation between hyaluronan (0.62) and clinical course (P<0.01) we conclude that models with hyaluronan instead of albumin or encephalopathy and with or without shifted threshold values of bilirubin and albumin are superior for the prediction of the long term prognosis. In Cox-regression analysis, apart from hyaluronan and bilirubin, no other parameters contributed to an improvement. CONCLUSIONS: We conclude that a modification of the Child-Pugh classification of liver cirrhosis by inclusion of HA significantly improves the predictive power of CP, especially in alcoholic etiology. A prospective validation of the newly defined scores needs to be done in the future.     

The relationship between conventional liver tests,quantitative function tests,and histopathology in cirrhosis

Thirty patients with cirrhosis were evaluated with the 2-hr [¹⁴C]aminopyrine breath test (score) and with conventional liver tests. Of the 30 patients, 24 also had current liver biopsies. There was a good correlation between necroinflammatory activity in the 24 cirrhotic liver biopsies and the 2-hr aminopyrine scores. All five patients who had at least grade 2 necroinflammatory activity on their biopsy had an abnormal prothrombin time (>3.5 sec above control) and their aminopyrine score was less than 2%. The correlation was good between the 2-hr aminopyrine score and the prothrombin time (seconds over control). No correlation was found between the 2-hr aminopyrine score and either the serum aspartate aminotransferase (SGOT) or any other liver test except for the prothrombin time. It seems that the 2-hr aminopyrine score and prothrombin time are more likely to give a quantitative estimate of total functioning parenchymal mass which is left unaffected by hepatocellular disease in cirrhosis, than the other commonly used liver tests.     

Prognostic value of quantitative liver function tests in viral cirrhosis: a prospective study

BACKGROUND AND AIMS: Widespread application of quantitative liver function tests as a prognostic tool is controversial. In this study we assessed the predictivity of serial evaluations of galactose elimination capacity (GEC) and the monoethylglycinexylidide (MEGX) test on survival in viral cirrhosis, and secondarily we compared these tests with Child-Turcotte-Pugh (CTP) and Model for End Stage Liver Disease (MELD) scores. METHODS: In a cohort of 35 patients with viral cirrhosis, GEC and MEGX were evaluated every 6 months for 24 months and compared with CTP and MELD scores at the same time intervals. The end points were patient death or liver transplantation. RESULTS: Statistically significant differences between dead/transplanted patients and survivors were found for basal values of GEC, MEGX, CTP and MELD. Receiver-operating characteristics curves of CTP and MELD scores showed a higher prognostic accuracy than GEC and MEGX. On multivariate analysis, neither GEC nor MEGX were independent predictors of survival. Repeated-measures analysis of GEC and MEGX did not increase the prognostic accuracy of these tests and did not add useful prognostic information on patient outcome during the following 6 months. CONCLUSIONS: Our data suggest that neither single nor repeated determinations of GEC and MEGX are superior to CTP and MELD scores in predicting prognosis of patients with viral cirrhosis.     

终末期肝病模型及Child—Pugh分级对失代偿期肝硬化患者的预后分析

目的探讨终末期肝病模型（MELD）及Child—Pugh评分对失代偿期肝硬化预后评估的应用价值。方法应用MELD评分公式及Child—Pugh分级对136例失代偿期肝硬化患者进行评分及分级,比较两种系统对肝硬化预后的评估。结果分别有19．85％和33．82％患者3个月和6个月内死亡,死亡组MELD和Child—Pugh评分均高于生存组（P〈0．001）;MELD评分在3个月预后评估的ROC曲线AUC高于Child—Pugh评分（P〈0．05）;生存分析表明MELD与Child—Pugh评分均可有效地分辨6个月内可能生存及死亡的患者（P〈0．005）;MELD评分与Child评分显著相关（r=0．67,P〈0．001）。结论MELD评分及Child—Pugh评分均可预测失代偿期肝硬化患者短期预后,MELD评分短期评估优于Child—Pugh分级。     

肝硬化患者肠黏膜通透性与Child—Pugh分级的相关性研究

目的探讨肝硬化患者肠黏膜通透性（IP）与Child—Pugh分级的相关性及肠道去污剂对肝硬化患者肠道屏障功能及肝功能状态的影响。方法按Child—Pugh分级标准将76例肝硬化患者分为A、B、C3组,并选择30例体检者作为对照组,采用高压液相色谱法检测各组患者尿液乳果糖／甘露醇排出比（L／M）;给予76例肝硬化患者选择性肠道去污剂,比较用药前后各组患者肝功能Child—Pugh分级和肠黏膜通透性。结果肝硬化患者尿乳果N／甘露醇排出比明显高于对照组（0．208±0．025vs0．057±0．019）,肝硬化患者按Child。Pugh分级各组尿乳果糖／甘露醇排出比也均明显高于对照组,差异有显著性（P〈0．01）;采用Spearman等级相关分析发现,肝功能Child—Pu巾评分与乳果糖／甘露醇排出比呈正相关（r=0．658,P〈0．05）;给予肠道去污药物2周后肝硬化Child-Pugh分级各组患者尿液乳果糖／甘露醇排出比与治疗前比较均明显下降（P〈0．05）,各组Child—Pugh评分均有改善。结论肝硬化患者的肠黏膜通透性与肝功能Child—Pugh评分呈正相关,即肠道通透性随肝功能下降而升高,肠黏膜通透性对于肝硬化患者的诊断和治疗有临床意义。     

Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients

BACKGROUND Reliable biomarkers of cirrhosis, hepatocellular carcinoma(HCC), or progression of chronic liver diseases are missing. In this context, Golgi protein-73(GP73) also called Golgi phosphoprotein-2, was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells. As a result, GP73 expression was found primarily in biliary epithelial cells, with only slight detection in hepatocytes. However, in patients with acute or chronic liver diseases and especially in HCC, the expression of GP73 is significantly up-regulated in hepatocytes. So far, few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA (QUANTA Lite~? GP73, Inova Diagnostics, Inc., Research Use Only) in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa, Greece(n = 366) and Debrecen, Hungary(n = 266). Aspartate aminotransferase(AST)/Platelets(PLT) ratio index(APRI) was also calculated at the relevant time points in all patients. Two hundred and three patients had chronic hepatitis B, 183 chronic hepatitis C, 198 alcoholic liver disease, 28 autoimmune cholestatic liver diseases, 15 autoimmune hepatitis, and 5 with other liver-related disorders. The duration of follow-up was 50(57) mo [median(interquartile range)]. The development of cirrhosis, liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines. In particular, the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP) determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73( 20 units) were detected at initial evaluation in 277 out of 632 patients(43.8%). GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4% vs 51.5%, P 0.001), decompensation of cirrhosis(60.3% vs 35.5%, P 0.001), presence of HCC(18.4% vs 7.9%, P 0.001) and advanced HCC stage(52.9% vs 14.8%, P = 0.002). GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score [Area under the curve(AUC)(95%CI): 0.909(0.885-0.934) vs 0.849(0.813-0.886), P = 0.003]. Combination of GP73 with APRI improved further the accuracy(AUC: 0.925) compared to GP73(AUC: 0.909, P = 0.005) or APRI alone(AUC: 0.849, P 0.001). GP73 levels were significantly higher in HCC patients compared to non-HCC [22.5(29.2) vs 16(20.3) units, P 0.001) and positively associated with BCLC stage [stage 0: 13.9(10.8); stage A: 17.1(16.8); stage B: 19.6(22.3); stage C: 32.2(30.8); stage D: 45.3(86.6) units, P 0.001] and tumor dimensions [very early: 13.9(10.8); intermediate: 19.6(18.4); advanced: 29.1(33.6) units, P = 0.004]. However, the discriminative ability for HCC diagnosis was relatively low [AUC(95%CI): 0.623(0.570-0.675)]. Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline, was prognostic of higher rates of decompensation(P = 0.036), HCC development(P = 0.08), and liver-related deaths(P 0.001) during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination. In combination with APRI, its diagnostic performance can be further improved. Most importantly, the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.     

Intrinsic hepatic clearance and Child-Turcotte classification for assessment of liver function in cirrhosis

Child-Turcotte classification (CTC) is an empirical but widely accepted approach for assessment of severity of cirrhosis. However, it is not known to what extent CTC reflects accurately the degree of impairment of hepatic function. In this study we compared CTC, standard liver tests and intrinsic hepatic clearance (IHC) of indocyanine green as means of assessing hepatic function in 63 cirrhotic patients. As compared to 10 control patients, IHC was significantly decreased in the cirrhotic group: (mean +/- SD) 0.270 +/- 0.141 l/min vs 1.227 +/- 0.312 l/min (P less than 0.001). Serum bilirubin (SB), prothrombin time (PT) and serum albumin were significantly correlated with the degree of IHC impairment while alkaline phosphatase, ALAT and clinical criteria of CTC were not. Multivariate analysis showed that SB and PT were the only 2 variables that significantly explained the impairment of IHC. The model which best explained IHC impairment was Z = 21.77 + 4.78 PT - 1.25 SB. The rate of IHC variance explained by this model, as determined by multiple correlation coefficient square (R2), was 42.6%. These results suggest that CTC provides only gross information about the degree of impairment of liver function in cirrhosis. To evaluate the role of liver function in the prognosis or in the response to treatments, it should therefore be preferable to employ direct measurement of liver function using a clearance technique.     

Hepatocellular carcinomas do not compromise quantitative tests of liver function

BACKGROUND/AIMS: Hepatocellular carcinoma, which usually develops in cirrhotic livers, is one of the most frequent cancers worldwide. If and how far hepatoma growth influences liver function is unclear. Therefore, we compared a broad panel of quantitative tests of liver function in cirrhotic patients with and without hepatocellular carcinoma. METHODOLOGY: Patients with (n=40) and without (n=40) hepatocellular carcinoma were matched according to Child-Pugh grade and subjected to testing of aminopyrine demethylation capacity, galactose elimination capacity, sorbitol clearance and indocyanine green clearance. RESULTS: Compared to healthy controls, patients with cirrhosis Child-Pugh grade B and grade C revealed reduced metabolic (aminopyrine demethylation capacity, galactose elimination capacity) and perfusion-dependent QTLF (sorbitol clearance, indocyanine green clearance). Comparing values of quantitative tests of liver function in matched patients with and without hepatocellular carcinoma, no differences in liver function parameters were observed. CONCLUSIONS: Quantitative tests of liver function correlated inversely with the Child-Pugh grade. Since these parameters are not affected by the occurrence of hepatocellular carcinoma, the emergence of hepatic neoplasia in cirrhotics does not appear to be determined by the degree of hepatic functional deterioration.     

Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis

OBJECTIVE: To investigate anterior pituitary function (adrenal, somatotropic, thyroid and gonadal axes, and prolactin) in relation to the Child-Pugh score in male patients with alcoholic and virus-related liver cirrhosis. METHOD: Anterior pituitary function was evaluated in 52 male cirrhotics (26 Child-Pugh class A (CPA), 16 Child-Pugh class B (CPB) and 10 Child-Pugh class C (CPC)) by a combined pituitary stimulation test, and was compared with 50 age-matched controls. RESULTS: A normal cortisol response to corticotropin-releasing hormone (CRH) stimulation was demonstrated in 57.6% of CPA patients, 31.1% of CPB patients and 20% of CPC patients, while basal levels of adrenocorticotropic hormone (ACTH) and cortisol in cirrhotics were comparable to those in controls. Levels of basal growth hormone (P < 0.001) and stimulated growth hormone (P < 0.01) were significantly higher in cirrhotics compared with controls, while levels of insulin-like growth factor 1 (IGF-1) were significantly lower (P < 0.001). Basal prolactin levels were elevated significantly in CPC patients (P < 0.01), while stimulated prolactin as well as basal and stimulated thyroid-stimulating hormone (TSH) levels were comparable. Basal luteinizing hormone levels were significantly higher in CPA (P < 0.001) and CPB (P < 0.001) patients, and stimulated luteinizing hormone levels were significantly lower in CPC patients than in controls (P < 0.005). Basal and stimulated follicle-stimulating hormone (FSH) levels were comparable in all groups. Child-Pugh score was correlated positively to prolactin and was correlated negatively to IGF-1, stimulated luteinizing hormone and free testosterone. CONCLUSIONS: In cirrhotics, the hypothalamic-pituitary-adrenal and -gonadal axes and prolactin secretion are impaired. Growth hormone response to growth hormone-releasing hormone (GHRH) is accelerated in cirrhotics. Thus, elevated basal and stimulated levels of growth hormone probably reflect compensation for low levels of IGF-1, which are associated with deteriorating liver function. The aetiology of cirrhosis was found to have no influence on the degree of alteration of the hypothalamic-pituitary-glandular axes.     

Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis

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检测门脉高压程度评估肝硬化严重程度研究进展

<正>肝硬化是由一种或多种原因引起的、肝组织弥漫性纤维化、假小叶和再生结节为组织学特征的进行性慢性肝病,临床以门静脉高压和肝功能减退为特征,常并发上消化道出血、肝性脑病、继发感染等而死亡。门脉高压常导致食管胃底静脉曲张出血、腹水、脾肿大、脾功能亢进、肝肾综合征、肝肺综合征等,被认为是继病因之后的促进肝功能减退的重要病理生理环节,是肝硬化的主要死亡原因之一。     

Noninvasive quantitative testing of liver function using ultrasonography in patients with cirrhosis

BACKGROUND/AIMS: Chronic liver disease is characterized by progressive hepatic fibrosis and changes in hepatic hemodynamics. Although there are sufficient hemodynamic ultrasonography data about patients with liver cirrhosis, reports of combinations of these data are insufficient. This study aimed to address the possibility of noninvasive diagnosis for the degree of hepatic fibrosis by evaluating the ultrasonography score, HCI (Hepatic Circulation Index), A/P (The peak velocity of hepatic artery/The peak velocity of portal vein), and CAT (hepatic vein circulation time) in patients with cirrhosis. METHODOLOGY: 53 cirrhosis patients underwent ultrasonographically-guided liver biopsy to confirm the diagnosis of cirrhosis. Values were correlated with the ultrasonography score, blood fibrosis makers, metabolic liver function tests and Child-Pugh classification. RESULTS: 53 patients participated in this study. The fibrosis stage of a total of 53 patients was > or = S2; 22.6% of the patients (n= 12) had cirrhosis of Child-Pugh grade A, 41.5% of grade B (n=22) and 35.9% of grade C (n=19). Liver function showed a steady decrease from Child-Pugh grade A to grade B and to grade C. In contrast, ultrasonography score was significantly increased in Child-Pugh grade A, B and C patients compared to healthy controls. Differences between the three Child grades were significant. CONCLUSIONS: Ultrasonography score and A/P correlated with Child-Pugh grades and HCI, CAT correlated inversely with Child-Pugh grades so they may be useful tools to predict prognosis or complications in cirrhosis.     

失代偿期肝硬化死亡概率预测模型的建立

如何判断肝硬化患者的预后一直是临床医生们关注的问题,而准确评价失代偿期肝硬化患者的病情也有利于为患者选择个体化的治疗方案.近年来,随着肝移植技术的发展,越来越多的患者选择肝移植,但供体有限,临床医生需要更准确评估患者的预后,以合理选择进行肝移植的病例.目前在美国和欧洲国家等都采用终末期肝病模型(MELD)评分作为肝移植的标准.有研究者认为它剔除了门静脉高压的并发症,如腹水、静脉曲张破裂出血、自发性腹膜炎和肝性脑病这些影响肝硬化患者预后的重要因素而不是很合理[1].因此,人们仍在继续寻找更完善的评分系统.我们更全面地考虑与肝硬化预后相关的各项指标,期望建立一个更有效的评估失代偿期肝硬化预后的模型.     

Role of des-gamma-carboxy prothrombin in assessment of liver function and prognosis of patients with liver cirrhosis

正Objective To investigate the role of des-gammacarboxy prothrombin (DCP) in assessment of liver function and prognosis of patients with liver cirrhosis.Meth-o dsFrom January 2013 to August 2016, a total of 137patients with liver cirrhosis in Shanghai Changzheng Hospital were enrolled. The serum DCP level was measured,the clinical data was collected and the complication and     

Diffusion-weighted magnetic resonance imaging of the liver in hepatitis B patients with Child-Pugh a cirrhosis

The purpose of this study was to test the hypothesis that cirrhotic change of liver in hepatitis B patients observed in Child-Pugh classification based on clinical assessment would be reflected in the apparent diffusion coefficient (ADC) values calculated from diffusion-weighted magnetic resonance (MR) imaging. Twenty-seven patients with hepatitis B Child-Pugh class A cirrhosis and 10 control subjects were referred for measurement values of the liver on a 3.0-T MR unit. The results revealed that ADCs were significantly lower in hepatitis B patients with Child-Pugh class A compared with control subjects (p < 0.01). In conclusion, our preliminary study showed that hepatitis B patients with Child-Pugh class A had reduced ADC values in liver vis-a-vis normal subjects.