Child-Turcotte Score Research Articles

PWE-106 Is functional sarcopenia associated with hepatic encephalopathy and severity of cirrhosis?

Introduction The original Child-Turcotte score to assess stage severity of cirrhosis included an assessment of nutritional status. Loss of muscle mass (sarcopaenia) is increasingly recognised in patients with end-stage liver disease (ESLD) and skeletal muscle is recognised as a source of ammonia metabolism. The aim was to determine if there was an association with functional sarcopaenia, MELD score, hepatic encephalopathy (HE) and risk of death. Method A pilot retrospective-prospective cohort analysis of inpatients with ESLD presenting at the Royal Liverpool Hospital Between January 2014–June 2014. Patients with cirrhosis had a nutritional assessment including: BMI, hand-grip strength (HGS), biochemical assessment, MELD calculation and clinical assessment for HE. End points were to assess if there was an association with HGS with liver cirrhosis severity (MELD), HE, and death. Follow-up was completed January 2015. Results 64 patients were included in the final analysis. Male 39 (61%), median age 54 (IQR47–61 yrs). Disease aetiology was: ALD 56 (87.5%), NASH 3 (4.7%), HCV 3 (4.7%), HFE 1 (1.6%), AIH 1 (1.6%). 12 patients (19%) had HE. There were 12 deaths over the study period (19%). There was no association with HE and death on fishers exact test (p=NS). On univariate analysis the following factors were assessed for risk of death: MELD p = 0.002, Vitamin D p = 0.6, HGS p = 0,16, age p = 0.21. There was a correlation between hand grip strength and MELD (spearmans test 0=0.04), and there was also a correlation between HGS strength and HE (spearmans p = 0.03). Conclusion There is a correlation with HGS with liver disease severity and HE. No association was proven with HGS and survival in this small pilot study. HGS could be used to refine prognosis in ESLD. Large studies investigating the mechanisms and role of sarcopaenia in ESLD are required. Disclosure of interest None Declared.

TIMP-1 in patients with cirrhosis: relation to liver dysfunction, portal hypertension, and hemodynamic changes

Objective. Cirrhotic portal hypertensive patients often develop hemodynamic complications and the diagnosis is often based on liver biopsy and measurements of the hepatic venous pressure gradient (HVPG). Potential noninvasive biomarkers for the severity of cirrhosis are the matrix metalloproteinase and their specific inhibitors such as tissue inhibitor of metalloproteinases-1 (TIMP-1). The aim of the study was to investigate TIMP-1 levels in cirrhosis in relation to the degree of liver dysfunction, portal hypertension, and hemodynamic changes. Materials and methods. We retrospectively studied 84 patients with cirrhosis and 14 controls without liver disease. All individuals underwent a liver vein catheterization with a hemodynamic assessment. TIMP-1 was determined in arterial and hepatic venous plasma using an MAC-15 TIMP-1 ELISA. Results. Hepatic venous concentrations of TIMP-1 were significantly increased in patients compared to controls: 336 (166) ng/ml versus 145 (100) (median/IQ range) (p < 0.001) with a progressive increase throughout the Child classes (p < 0.001). Circulating TIMP-1 correlated significantly with indocyanine green clearance (r = –0.44, p < 0.0001), Child Turcotte score (r = 0.50, p < 0.0001), HVPG (r = 0.40, p < 0.0001), mean arterial pressure (r = –0.29, p = 0.008), and systemic vascular resistance (r = –0.23, p = 0.03). Receiver operating characteristic curve analysis enabled us to establish cutoff values for TIMP-1 with regard to portal hypertension. Conclusions. TIMP-1 is significantly increased in patients with cirrhosis and correlates with the severity of the disease, degree of portal hypertension, and vasodilatory state. TIMP-1 is therefore a promising new noninvasive marker to predict hemodynamic-related complications in cirrhosis.

Arterial pressure profile in patients with cirrhosis: Fourier analysis of arterial pulse in relation to pressure level, stroke volume, and severity of disease: On the reduction of afterload in the hyperdynamic syndrome

Objective.Patients with cirrhosis have cardiovascular dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyze the arterial pressure curve in relation to mean arterial pressure level, stroke volume, and severity of liver disease. Materials and methods.Forty-one patients with cirrhosis (Child–Turcotte classes A/B/C = 13/15/13) were studied during a hemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. We applied fast Fourier analysis to quantify the pressure components of the arterial curve, the harmonic Fourier coefficients (HFC). Results.Mean arterial pressure was significantly reduced (91 vs. 98 mmHg, p < 0.001) and stroke volume was significantly increased (94 vs. 78 ml, p < 0.001) in patients with cirrhosis versus controls. The HFC were significantly lower in patients with cirrhosis than in controls (–15 to –24%, p < 0.002), except for the fourth HFC, which was significantly increased (+28%, p < 0.02). In contrast to controls, which showed a highly significant effect of the level of arterial pressure on their HFC (p < 0.001), patients with cirrhosis did not show pressure or stroke volume dependence on their HFC, indicating an overall compliant and slow reflective arterial vascular bed. The initial rise in pulse pressure (dP/dt) was inversely related to the Child–Turcotte score (p < 0.05), and the HFC were borderline significantly related to this score (p = 0.07). Conclusions.The arterial pulsation in cirrhosis is qualitatively changed with reduced pulse reflections, which may protect against manifest cardiac failure in patients with advanced cirrhosis.

Child-Turcotte score versus MELD for prognosis in a randomized controlled trial of emergency treatment of bleeding esophageal varices in cirrhosis

Background and AimsBleeding esophageal varices is responsible for much of the high mortality rate in cirrhosis. An important objective of management of bleeding varices is to develop reliable tools for predicting survival, controlling bleeding and encephalopathy, and improve quality of life. This study compared two widely used prognostic tools, the model for end-stage liver disease (MELD) and the Child-Turcotte (C-T) score, in a randomized controlled trial of emergency treatment of bleeding varices. MethodsWe randomized 211 unselected consecutive patients with cirrhosis and bleeding varices to endoscopic sclerotherapy (n = 106) or emergency portacaval shunt (n = 105). Diagnosis and treatment were accomplished within 20 hours. Follow-up was 100% for 10 y. We compared the prognostic powers of MELD and C-T upon entry, and then monthly for the first year and every 3 months thereafter. Statistical analysis included computation of receiver operating curves, the area under the curve, and the proportion of variability. ResultsIn baseline determinations of MELD versus C-T, there were no significant differences in predicting survival, recurrent encephalopathy, and rebleeding. The Child-Turcotte score was a stronger predictor than MELD of hospital readmissions and readmission days. In serial determinations over years, the prognostic power of both MELD and C-T was substantial, but C-T was significantly more effective in predicting survival and time to recurrent encephalopathy. ConclusionsIn this first long-term comparison of MELD versus C-T in cirrhosis with bleeding varices, C-T was consistently as effective as MELD in predicting survival, encephalopathy, rebleeding, hospital readmissions, and readmission days. In some measures, C-T was a more effective prognostic tool than MELD.

Reduced baroreflex sensitivity and pulmonary dysfunction in alcoholic cirrhosis: effect of hyperoxia

Patients with cirrhosis exhibit impaired regulation of the arterial blood pressure, reduced baroreflex sensitivity (BRS), and prolonged QT interval. In addition, a considerable number of patients have a pulmonary dysfunction with hypoxemia, impaired lung diffusing capacity (Dl(CO)), and presence of hepatopulmonary syndrome (HPS). BRS is reduced at exposure to chronic hypoxia such as during sojourn in high altitudes. In this study, we assessed the relation of BRS to pulmonary dysfunction and cardiovascular characteristics and the effects of hyperoxia. Forty-three patients with cirrhosis and 12 healthy matched controls underwent hemodynamic and pulmonary investigations. BRS was assessed by cross-spectral analysis of variabilities between blood pressure and heart rate time series. A 100% oxygen test was performed with the assessment of arterial oxygen tensions (Pa(O(2))) and alveolar-arterial oxygen gradient. Baseline BRS was significantly reduced in the cirrhotic patients compared with the controls (4.7 +/- 0.8 vs. 10.3 +/- 2.0 ms/mmHg; P < 0.001). The frequency-corrected QT interval was significantly prolonged in the cirrhotic patients (P < 0.05). There was no significant difference in BRS according to presence of HPS, Pa(O(2)), Dl(CO), or Child-Turcotte score, but BRS correlated with metabolic and hemodynamic characteristics. After 100% oxygen inhalation, BRS and the QT interval remained unchanged in the cirrhotic patients. In conclusion, BRS is significantly reduced in patients with cirrhosis compared with controls, but it is unrelated to the degree of pulmonary dysfunction and portal hypertension. Acute hyperoxia does not significantly revert the low BRS or the prolonged QT interval in cirrhosis.

Clinical application of TcGSA

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoprotein. The 99mTc-labeled asialoglycoprotein analog, TcGSA (galactosyl-human serum albumin-diethylenetriamine-pentaacetic acid) has been applied to human hepatic receptor imaging. This method is unique and provides information that is totally independent of the ICG test or Child-Turcotte Score. However, simple parameters, HH15 or LHL15 are no better than conventional Child-Turcotte Score. Parameters obtained from kinetic modeling were useful in detecting liver cirrhosis or postoperative liver failure. They provide quantitative data on functioning liver mass. Considering the moderate cost and widespread availability of gamma cameras, a TcGSA test should be performed on patients whose liver function are not adequately estimated by an ICG test or a Child-Turcotte score.

The acid-labile subunit of the ternary insulin-like growth factor complex in cirrhosis: relation to liver dysfunction

Background/Aims: In the circulation, insulin-like growth factor-I (IGF-I) is bound in a trimeric complex of 150 kDa with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). Whereas circulating IGF-I and IGFBP-3 are reported to be low in patients with chronic liver failure, the level of ALS has not been described in relation to hepatic dysfunction. The aim of the present study was therefore to measure circulating and hepatic venous concentrations of ALS in relation to hepatic function and the IGF axis.Methods: Twenty-five patients with cirrhosis (Child class A/B/C:5/10/10) and 30 controls with normal liver function were studied. During a haemodynamic investigation, blood samples were collected from the hepatic vein and femoral artery, and the plasma concentrations of ALS, IGF-I and IGFBP-3 were determined.Results: Hepatic venous and arterial concentrations of ALS were significantly decreased in the cirrhotic patients compared with the controls (−69% and −68%, respectively, both p<0.001). IGF-I and IGFBP-3 were similarly decreased in the cirrhotic patients (−51%, p<0.001). A significant hepatic extraction of ALS was found in the controls (6%, p<0.01) and in the cirrhotic patients (8%, p=0.08). ALS correlated significantly with indicators of liver dysfunction, including the Child-Turcotte score (r=−0.69, p<0.0001), IGF-I (r=0.82, p<0.0001) and IGFBP-3 (r=0.74, p<0.0001).Conclusions: Circulating and hepatic venous ALS are decreased in patients with cirrhosis with significant relations to liver dysfunction and other components of the IGF complex. A small hepatic extraction was found in controls, which suggests extrahepatic production of ALS. Future studies should focus on organspecific removal of ALS.

Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene—related peptide

Increased circulating levels of the neuropeptide calcitonin gene-related peptide (CGRP) have recently been described in cirrhosis. CGRP is formed by alternative transcription of the calcitonin/alpha-CGRP gene, which also gives rise to calcitonin (CT). This study was undertaken to determine circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte classes A/B/C, n = 10/22/7) were studied under a hemodynamic investigation and compared with 13 control subjects without liver disease. CT and CGRP in arterial and organ venous plasma were determined by radioimmunoassays. In patients with cirrhosis, circulating CT was significantly increased versus control (12.1 v 6.9 pmol/L, P < .001) and a direct relation to the Child-Turcotte score was found (P < .005). The increased circulating CT was directly correlated with increased CGRP (r = .29, P < .05). No significant arteriovenous extraction of circulating CT was observed in the kidneys, hepatosplanchnic system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P < .005). It is concluded that in addition to thyroid production, increased circulating CT in cirrhosis is most likely due to overexpression of the calcitonin/alpha-CGRP gene, with relation to the severity of disease and possibly to an accompanying pulmonary dysfunction.

Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: Role of splanchnic and renal passage and liver function

Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 ± 0.8 pg/mL, 19.1 ± 0.9 pg/mL, and 16.8 ± 0.8 pg/mL) were significantly ( P < .001) higher than in controls (9.2 ± 1.7 pg/mL, 9.0 ± 2.0 pg/mL, and 8.4 ± 1.9 pg/mL, respectively). The same held true for the corresponding ET-3 plasma concentrations in cirrhosis (19.3 ± 1.6 pg/mL, 20.5 ± 1.5 pg/mL, and 18.4 ± 1.5 pg/mL, respectively) compared with controls (11.1 ± 1.8 pg/mL, 11.3 ± 1.5 pg/mL, and 10.1 ± 1.7 pg/mL, respectively; P < .01). There was a significant ( P < .05) renal net extraction of ET-1 and ET-3 in cirrhosis. In contrast, a significant ( P < .05) net release of ET-1 and ET-3 (2.40 ± 0.80 ng/min and 1.75 ± 1.16 ng/ min) during splanchnic passage was observed in cirrhosis, but not in controls (−0.24 ± 0.51 ng/min, and −0.46 ± 0.64 ng/min). Plasma concentrations of ET-3 in cirrhosis were correlated to the Child-Turcotte score ( r = .66, P < .01) and inversely to the functional liver cell mass, determined by the galactose elimination capacity ( r = −.72, P < .01). Hepatic venous ET-1 concentrations correlated to the hepatic blood flow assessed by the indocyanine green clearance ( r = .48; P < .05). Net splanchnic release may contribute to elevated ET-1 and ET-3 plasma concentrations in patients with cirrhosis. Splanchnic ET-1 and ET-3 handling in cirrhosis may be influenced by different mechanisms.

Albumin synthesis rates in cirrhosis: Correlation with Child-Turcotte classification

Albumin-synthesis rates were measured in nine patients with stable cirrhosis and compared with those of eight healthy volunteers by means of a new technique using stable isotopes. Four grams of L-[1-13C]leucine was injected over 10 min, and blood samples were drawn at intervals. Serum free [13C]leucine enrichment, taken to be the precursor for albumin synthesis, and 13C enrichment of leucine in albumin, isolated with differential solubility in absolute ethanol from trichloroacetic acid–precipitated serum proteins, were measured on mass spectrometry. Albumin synthesis, expressed as a fractional rate, was 7.9% ± 0.3%/day in the controls and 7.9% ± 1.1%/day in the cirrhotic patients. Albumin synthesis, expressed as an absolute rate, was lower in the cirrhotic group (cirrhotic, 119 ± 17 mg/kg/day controls, 146 ± 8 mg/kg/day), but because of the relatively small number of patients the difference was not significant. However, the absolute rate of albumin synthesis significantly correlated with the Child-Turcotte score (p = 0.024) and its Pugh modification (p = 0.027). The rate of albumin synthesis also correlated with serum phenylalanine concentration but not with serum albumin concentration and intravascular albumin mass or with other clinical indexes of liver function or integrity when taken separately. However, the significant correlation between albumin synthesis and Child score suggests that albumin synthesis might be useful for the clinical judgment of patients with cirrhosis. (HEPATOLOGY 1993;18:292–297).

Albumin synthesis rates in cirrhosis: Correlation with child-turcotte classification

Albumin-synthesis rates were measured in nine patients with stable cirrhosis and compared with those of eight healthy volunteers by means of a new technique using stable isotopes. Four grams of L-[1-13C]leucine was injected over 10 min, and blood samples were drawn at intervals. Serum free [13C]leucine enrichment, taken to be the precursor for albumin synthesis, and 13C enrichment of leucine in albumin, isolated with differential solubility in absolute ethanol from trichloracetic acid-precipitated serum proteins, were measured on mass spectrometry. Albumin synthesis, expressed as a fractional rate, was 7.9% +/- 0.3%/day in the controls and 7.9% +/- 1.1%/day in the cirrhotic patients. Albumin synthesis, expressed as an absolute rate, was lower in the cirrhotic group (cirrhotic, 119 +/- 17 mg/kg/day; controls, 146 +/- 8 mg/kg/day), but because of the relatively small number of patients the difference was not significant. However, the absolute rate of albumin synthesis significantly correlated with the Child-Turcotte score (p = 0.024) and its Pugh modification (p = 0.027). The rate of albumin synthesis also correlated with serum phenylalanine concentration but not with serum albumin concentration and intravascular albumin mass or with other clinical indexes of liver function or integrity when taken separately. However, the significant correlation between albumin synthesis and Child score suggests that albumin synthesis might be useful for the clinical judgment of patients with cirrhosis.

Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis

Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis and to correlate these both to clinical and biochemical characteristics and survival rate. Urinary GH excretion, IGF-1, and other biochemical parameters were measured in 36 patients with alcoholic cirrhosis, while in the control group of 34 healthy individuals only U-GH excretion was measured. U-GH excretion was significantly higher in patients than in the healthy controls (p < 0.00001), and increased with deteriorating liver function assessed by modified Child-Turcotte score (p < 0.01). The highest U-GH excretions were found in patients with hepatic encephalopathy (p < 0.003). IGF-1 levels were reduced in cirrhosis and correlated with liver function (p < 0.001). Serum IGF-1 concentrations below 3.1 nmol/l were associated with a poor prognosis (p < 0.004). The elevated U-GH in patients with alcoholic cirrhosis may reflect high serum levels of GH due to increased pituitary secretion or decreased hepatic degradation of GH. In addition, the IGF-1 levels reflect the degree of hepatic insufficiency and, thus, seem to provide new prognostic information.