氨甲酰磷酸合成酶-Ⅰ和鸟氨酸氨基甲酰转移酶与肝性脑病的关系

目的 探讨血清氨甲酰磷酸合成酶Ⅰ(CPS-Ⅰ)和鸟氨酸氨基甲酰转移酶(OCT)在肝性脑病(HE)发生中的作用.方法 2008年1月-2009年12月在我院住院的120例肝硬化患者,其中HE患者25例,非肝性脑病(非HE)患者95例.对照组为我院健康体检正常者60例.收集研究对象的血清和血浆,采用酶联免疫吸附试验方法测定血清CPS-Ⅰ、OCT,VITROS-250干化学分析仪测定血氨.分析HE组、非HE组、对照组CPS-Ⅰ和OCT水平;分析肝硬化患者CPS-Ⅰ、OCT与肝功能及血氨的相关性;分析CPS-Ⅰ、OCT水平与肝硬化患者Child-Pugh分级之间的相关性.应用SPSS15.0软件进行数据分析,采用x2和t检验,计量资料两组间比较采用成组t检验,多组间的比较采用方差分析、q检验,两变量相关分析采用Pearson相关分析法.结果 HE组血清CPS-Ⅰ、OCT水平分别为(143.3±48.5)U/L和(297.0±102.6)×10 U/L,非HE组分别为(180.3±51.5)U/L和(351.8±109.0)×10 U/L,t值分别为2.53和2.78,P值均＜0.01;HE组、非HE组血清CPS-Ⅰ、OCT水平均低于正常对照组,t值分别为3.21、4.16和2.12、3.15,P值均＜0.05.CPS-Ⅰ与OCT相关性好,r=0.946,P＜0.05;CPS-Ⅰ、OCT与ALT、AST呈负相关,r值分别为-0.284、-0.239、-0.303、-0.322,P值均＜0.05.肝硬化患者CPS-Ⅰ、OCT水平和Child分级密切相关,F值分别为10.13,20.28,P值均＜0.01.结论 肝硬化患者CPS-Ⅰ和OCT活性影响血氨水平,CPS-Ⅰ和OCT与肝性脑病的发生密切相关.     

Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy

Serum levels of the potent inhibitory neurotransmitter gamma aminobutyric acid (GABA) were measured in 10 patients with chronic liver disease and hepatic encephalopathy, 11 patients with chronic liver disease and no evidence of hepatic encephalopathy, 7 patients with end-stage renal disease and 11 healthy volunteers. Serum GABA levels were elevated in all 10 patients with hepatic encephalopathy, 5/11 with liver disease and no encephalopathy and 4/7 renal disease patients. The mean serum GABA level for the encephalopathic patients (0.92 +/- 0.13 microM, mean +/- SEM) was significantly greater than the mean for liver disease patients without encephalopathy (0.48 +/- 0.05 microM, p less than 0.05), renal disease patients (0.46 +/- 0.04 microM, p less than 0.05) and healthy volunteers (0.39 +/- 0.03 microM, p less than 0.001). These results would tend to support the hypothesis that GABA may play a role in the pathogenesis of hepatic encephalopathy.     

Portal hypertension and ascites in acute hepatitis: clinical, hemodynamic and histological correlations

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 +/- 3.4 vs. 8.4 +/- 3.6 mmHg, respectively; p less than 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg. We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p less than 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p less than 0.01). We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.     

Atrial natriuretic factor, catecholamines and the renin-angiotensin system in cardiac insufficiency. Relation to hemodynamic parameters

Plasma concentrations of atrial natriuretic factor (ANF), catecholamines (adrenaline, noradrenaline, dopamine) and aldosterone, and plasma renin activity (PRA) were measured in a group of 20 patients with moderate to medium heart failure (NYHA class II 7 patients, class III 13 patients), 24 hours after treatment was discontinued. Compared with a control group, plasma concentrations of ANF (p less than 0.01), noradrenaline (p less than 0.05), aldosterone (p less than 0.01) and PRA (p less than 0.01) were significantly increased. There was a significant difference between class II patients and class III patients in plasma ANF (p less than 0.01) and noradrenaline (p less than 0.02) concentrations, but not in PRA and aldosterone levels. A significant correlation was observed between plasma ANF concentration and left ventricular end-diastolic pressure (r = 0.68, p less than 0.001), pulmonary arterial pressure (r = 0.59, p less than 0.01), pulmonary capillary pressure (r = 0.51, p less than 0.02), cardiac index (r = 0.46, p less than 0.05) and left ventricular end-diastolic volume (r = 0.50, p less than 0.05). However, ANF concentration was not correlated with mean right atrial pressure. Plasma adrenaline concentration correlated with systemic arterial resistance (r = 0.80, p less than 0.001), pulmonary arterial pressure (r = 0.57, p less than 0.02), mean pulmonary capillary pressure (r = 0.62, p less than 0.001), cardiac index (r = 0.53, p less than 0.05) and left ventricular end-diastolic pressure (r = 0.58, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Function of the autonomic nervous system in patients with hepatic encephalopathy

To obtain further pathophysiological details concerning the development of cardiovascular disturbances in severe liver disease, the state of the autonomic nervous system, the function of the baroreceptor reflex pathway and the responsiveness of the cardiovascular system to noradrenaline, angiotensin II and isoprenaline were investigated in 11 patients with hepatic encephalopathy and in 10 healthy control subjects. Increased plasma levels of noradrenaline and adrenaline and an attenuated increase in heart rate in response to atropine were found in patients with hepatic encephalopathy. These changes and the hemodynamic disturbances tended to be more pronounced in patients with hepatic encephalopathy Grades III-IV as compared to hepatic encephalopathy Grades I-II. The increase in systolic blood pressure induced by infusion of noradrenaline (400 ng per kg per min) and angiotensin II (20 ng per kg per min) was higher in the patients than in healthy control subjects (hepatic encephalopathy Grades I-II: p less than 0.001; hepatic encephalopathy Grades III-IV: p less than 0.02). The changes in mean and diastolic blood pressure in response to angiotensin II were more pronounced in hepatic encephalopathy grades I-II than in hepatic encephalopathy Grades III-IV (p less than 0.02). The decrease of heart rate in response to blood pressure increase in patients with hepatic encephalopathy was not different from control subjects except a smaller decrease during angiotensin II infusion in hepatic encephalopathy grades III-IV (p less than 0.05). The responsiveness to isoprenaline was diminished (p less than 0.001). The present results indicate that the increased activity of the sympathetic nervous system in hepatic encephalopathy is associated with decreased parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between urinary sialylated saccharides, serum amyloid A protein, and C-reactive protein in rheumatoid arthritis and systemic lupus erythematosus.

The urinary excretion of sialic-acid-containing oligosaccharides, total sialic acid, serum amyloid A protein (SAA), and C-reactive protein (CRP) has been studied in 48 patients with rheumatoid arthritis (RA) and in 17 patients with systemic lupus erythematosus (SLE). Linear regression analysis revealed a close positive correlation between serum SAA and CRP levels in both RA (r = 0.71, p less than 0.001) and SLE (r = 0.86, p less than 0.001). The urinary excretion of sialyl lactose showed a positive correlation with the serum levels of SAA and CRP in RA (r = 0.45 and r = 0.45, respectively, p less than 0.01) but not in SLE (r = 0.05 and r = 0.10 respectively). Changes in serum total sialic acid levels paralleled those in CRP and SAA in RA as well as in SLE. Patients with very active RA had higher urinary sialyl oligosaccharide excretion (p less than 0.001), higher CRP levels (p less than 0.01), and higher SAA levels ( p less than 0.05) than those with moderately active disease.     

Mechanism for the Abnormal Liver Scan in Acute Alcoholic Liver Injury

The mechanism of liver scan abnormality was investigated in patients with acute alcoholic liver injury evaluated shortly after admission (18 patients) with repeat examination 1 month later (14 patients). Indocyanine green (ICG) and Tc99 sulfur colloid extraction ratios (ERICG and ERSC), elimination rate constants (KICG and KSC), total body clearance (TBCICG and TBCSC), and hepatic clearance of sulfur colloid (HCSC) were determined from sequential blood samples obtained at the time of hepatic vein catheterization after the intravenous injection of ICG and Tc99 sulfur colloid. Liver size and sulfur colloid redistribution expressed as a scan score (SS) and redistribution ratio (RR) were assessed from an external scan immediately after the procedure. Improvement in hepatic tests and function was noted between the first and second study. At both the first and second study, the SS (or RR) correlated with the hepatic removal of sulfur colloid (ERSC; r = -0.59; p less than 0.001; HCSC: r = -0.56; p = 0.003) and ICG (ERICG: r = -0.85; p less than 0.001; KICG: r = -0.83; p less than 0.001). ERSC correlated with ERICG (r = 0.76; p less than 0.007) and both correlated with SS and RR consistent with intrahepatic shunting as the mechanism of decreased hepatic clearance and of sulfur colloid redistribution. However, the systemic clearance of sulfur colloid (KSC) did not correlate with redistribution (SS: r = -0.25; NS) at either study period or to ICG clearance (r = 0.23; p = NS) in the first period. The KSC/KICG ratio in both study periods correlated with serum bilirubin (r = 0.83; p less than 0.001 and r = 0.73; p less than 0.001), but was significantly higher in the first period (3.37 +/- 2.37 versus 2.00 +/- 0.75; p less than 0.01). This lack of correlation between intrahepatic shunting and systemic clearance of sulfur colloid is consistent with an increase in the nonhepatic clearance of sulfur colloid in patients with alcoholic liver injury and deep jaundice. A decrease in liver size between the first and second study correlated inversely with change in portal pressure (r = -0.67; p = 0.004) and SS (r = -0.49; p = 0.038) and directly with change in KICG (r = 0.48; p = 0.04). By virtue of these relationships, redistribution of Tc99 sulfur colloid by liver scan may have prognostic significance in patients with alcoholic liver disease.     

The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin-mediated glucose disposal, basal and glucose-stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01). Fasting C-peptide correlated negatively with HDL-cholesterol (r = -0.76, p less than 0.01), HDL2-cholesterol (r = -0.80, p less than 0.001) and apoprotein A1 (r = -0.56, p less than 0.05) and positively with total: HDL-cholesterol ratio (r = 0.64, p less than 0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose-stimulated plasma insulin and C-peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL-cholesterol independent of insulin insensitivity. In addition, fasting C-peptide alone accounted for 70% of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL-cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.     

Digoxin-like immunoreactive substances in chronic liver disease

Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 +/- 0.05 ng per ml, p less than 0.01) was higher than that of controls (0.02 +/- 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 +/- 0.17 ng per ml, p less than 0.001), hepatorenal syndrome (0.57 +/- 0.20 ng per ml, p less than 0.001) and hepatic encephalopathy (0.43 +/- 0.20 ng per ml, p less than 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 +/- 0.06 ng per ml, p less than 0.001) before the development of clinically detectable ascites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis.

Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.     

Determinants of drug disposition in patients with cirrhosis

The effects of alterations of the hepatic blood flow, the intrinsic clearance, and the anatomy of the portal circulation on drug disposition were investigated in 53 cirrhotic patients with portal hypertension using indocyanine green (ICG) and lidocaine as model drugs. ICG disposition was studied by sampling from an artery and one hepatic vein following i.v. injection, with determination of systemic and intrinsic clearances and hepatic blood flow. Lidocaine disposition was studied following i.v. and oral administration from peripheral vein disappearance curves, with determination of systemic and intrinsic clearances and systemic availability. The shunted fraction of intestinal blood flow (f) was measured from the combined ICG and lidocaine disposition studies. In the 53 patients, systemic clearances of ICG and lidocaine varied widely and were significantly correlated with each other (r = 0.725, p less than 0.001). The systemic clearances of both ICG and lidocaine were not related to hepatic blood flow but were significantly correlated to their respective intrinsic clearances (for ICG: r = 0.948, p less than 0.001; for lidocaine: r = 0.873, p less than 0.001). Lidocaine systemic availability was also found to vary widely from 0.2 to 1.0. In 28 patients, f was less than 0.1 indicating minimal extrahepatic shunting and in these patients, lidocaine systemic availability was related to its intrinsic clearance (r = -0.717, p less than 0.001); in the 25 other patients with significant extrahepatic shunting (f greater than 0.1), the extent of lidocaine systemic availability was related to both intrinsic clearance (r = -0.819, p less than 0.001) and extrahepatic shunting (r = 0.913, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased Serum Type IV Collagen 7-S Levels in Patients with Hepatic Metastasis

Objective: The purpose of this study was to assess scrum type IV collagen 7-S domain (IV 7-S) levels in colorectal cancer patients with hepatic metastasis and to investigate the relation between serum IV 7-S levels and type IV collagenase activities in tumor tissue. Methods: Tissue type IV collagena.se activity and serum IV 7-S were measured in 50 colorectal cancer patients without hepatic metastasis and in 26 patients with hepatic metastasis. Results: Type IV collagenase showed significantly higher activities in colorectal cancer (n = 36) than in colorectal normal mucosa (n = 36) ( p < 0.001), but significantly lower activities were shown in the hepatic metastatic tumor (n = 18) than in the primary tumor (n = 36) and normal liver tissue (n = 18) ( p < 0.001). No significant correlation was (bund between type IV collagenase activities in the tumor and serum IV 7-S levels. Colorectal cancer patients with hepatic metastasis (n = 26) had significantly higher serum IV 7-S levels than those without hepatic metastasis (n = 50) ( p < 0.001). Moreover, serum IV 7-S levels correlated significantly with hepatic metastatic tumor volume in patients with synchronous ( r = 0.719, p < 0.001, n = 26) and in patients with metachronous ( r = 0.910, p < 0.001, n = 16) hepatic metastasis. Conclusion: We suggest that serum IV 7-S levels may increase in hepatic metastasis, not by the degradation of type IV collagen in the primary and secondary tumors, but by the enhanced production of type IV collagen responsive to hepatic metastasis. The measurement of serum IV 7-S levels might be a useful tumor marker of hepatic metastasis reflecting hepatic metastatic tumor volume.     

Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy

BACKGROUND/AIMS: To compare venous, arterial and partial pressure of ammonia (pNH(3)) in 27 consecutive cirrhotics with hepatic encephalopathy, 15 cirrhotics without hepatic encephalopathy and nine controls; to reevaluate all parameters after the improvement of encephalopathy. METHODS: Patients were studied by clinical examination and psychometric testing. pNH(3) was calculated from arterial ammonia and pH. RESULTS: In patients with encephalopathy, each form of ammonia was higher than in both controls and patients without encephalopathy. The correlation with the severity of hepatic encephalopathy was similar for venous (r=0.72), arterial ammonia (r=0.76) and pNH(3) (r=0.75). The sensitivity and specificity of each variable in correctly classifying the patients as having or not having hepatic encephalopathy was also similar. Each form of ammonia decreased after the resolution or amelioration of symptoms. However, even in the 17 patients with complete resolution of hepatic encephalopathy, all three ammonia determinations resulted unchanged or increased in some patients. CONCLUSIONS: Despite the significant correlation between pNH(3) and hepatic encephalopathy, our study suggests that neither pNH(3) nor arterial ammonia are, from a clinical point of view, more useful than venous ammonia: all three determinations being limited both for the diagnosis of hepatic encephalopathy and for the clinical management of the patients.     

Response of fibronectin to liver regeneration after hepatectomy

The relationship between plasma fibronectin concentration and the regenerative process in liver remnants after hepatectomy was studied in 12 patients and in male Sprague-Dawley rats with and without cirrhosis. Plasma fibronectin levels were reduced immediately after hepatectomy in humans and rats. Patients and rats without cirrhosis displayed preoperative fibronectin levels within 1 mo and 1 wk, respectively, but low fibronectin levels persisted longer in those with cirrhosis. Plasma fibronectin levels correlated well with the degree of hepatic regeneration in the patients with cirrhosis (r = 0.4227; p less than 0.05) and without cirrhosis (r = 0.8148; p less than 0.001), and also with the percentage of change in liver weight during regeneration in the rat with thioacetamide-induced cirrhosis (r = 0.4905; p less than 0.01) or in the rat without cirrhosis (r = 0.6422; p less than 0.001). These results suggest that plasma fibronectin is a useful marker for the detection of regenerating liver.     

Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the 1H-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters. METHODS: In a prospective study, localized 1H-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20). RESULTS: Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r = -0.50; p < 0.001) and linearly (r = 0.50; p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myo-inositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE. CONCLUSIONS: The abnormalities seen on the 1H-MRS of the brain of patients with liver cirrhosis are not likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve.     

Septic encephalopathy. Evidence for altered phenylalanine metabolism and comparison with hepatic encephalopathy

We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with septic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entities differ in other respects.     

Brain natriuretic peptide and severity of disease in non-alcoholic cirrhotic patients

BACKGROUND: Cirrhotic patients have a hyperdynamic systemic circulation. They have insidious cardiac problems besides well-known complications. Brain natriuretic peptide (BNP) relaxes vascular smooth muscle and has a portal hypotensive action. The relations between BNP levels and severity of disease, cardiac dysfunction and esophageal varices were studied in non-alcoholic cirrhotic patients. METHODS: Fifty-two non-alcoholic cirrhotic patients were evaluated for decompensation component of cirrhosis. The BNP concentration of echocardiographically examined patients was determined. RESULTS: The BNP levels were significantly higher in ascites, spontaneous bacterial peritonitis and hepatic encephalopathy history group (P = 0.033, P < 0.001, P = 0.014, respectively), but no significant difference were observed for presence of esophageal varices and bleeding history (P = 0.267, P = 0.429). A significant correlation was observed between BNP concentration and Child score (r = 0.427, P = 0.012), interventricular septal thickness (r = 0.497, P < 0.001) and left ventricular posterior wall thickness (r = 0.526, P < 0.001). According to Child-Pugh classification there were no significant difference between groups for echocardiographic measurements and blood pressure (P > 0.05), but plasma BNP levels were significantly higher in Child class B and C patients compared with class A patients (P < 0.05). CONCLUSION: Increased levels of BNP are more likely related to the severity of disease in non-alcoholic cirrhotic patients. The advanced cirrhosis is associated with more advanced cardiac dysfunction and BNP has prognostic value in progression of cirrhosis.     

Correlation between ammonia levels and the severity of hepatic encephalopathy

PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r(s)) were calculated. RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r(s) = 0.61, P < or = 0.001), venous total ammonia (r(s) = 0.56, P < or = 0.001), arterial partial pressure of ammonia (r(s) = 0.55, P < or = 0.001), and venous partial pressure of ammonia (r(s) = 0.52, P < or = 0.001). CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.     

Serum levels of the apoptosis-associated molecules, tumor necrosis factor-alpha/tumor necrosis factor type-I receptor and Fas/FasL, in sepsis

STUDY OBJECTIVE:s: Numerous reports suggest that apoptosis may play an important role in the sepsis syndrome. The objective of the present study was to examine the levels of molecules associated with apoptosis belonging to the tumor necrosis factor (TNF)-alpha/TNF type-I receptor (TNFRI) and Fas ligand (FasL)/Fas receptor (Fas) pathways in patients with sepsis. PATIENTS AND METHODS: Twenty-two patients with sepsis (14 patients with severe sepsis and 8 patients with sepsis), and 6 healthy volunteers were evaluated. Sequential analysis of the serum levels of TNF-alpha, TNFRI, FasL, and Fas were performed in these patients using enzyme-linked immunosorbent assays. RESULTS: Detectable levels of TNF-alpha were found in only 8 of 14 patients with severe sepsis. Patients with severe sepsis and sepsis had similarly increased levels of FasL, compared with healthy individuals (p < 0.05). Higher levels of TNFRI and Fas were found in patients with severe sepsis than in patients with sepsis and healthy volunteers (p < 0.001 and p < 0.01, respectively). Fas levels were also higher in patients who died than in those who survived (p < 0.01). A direct relationship was found between serum levels of TNFRI and Fas, and multiorgan dysfunction (sequential organ failure assessment score) [p < 0.0001]. CONCLUSIONS: These results suggest that the TNF-alpha/TNFRI and FasL/Fas systems may be involved in the pathogenesis of sepsis. Serum levels of the death-receptors, TNFRI and Fas, could serve as potential markers of the severity of human sepsis.     

Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis

Objective: Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters. Methods: Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon γ, interleukin-1, interleukin-6, tumor necrosis factor α, endotoxin, and nitrates-nitrites were determined. Results: Mean arterial pressure was lower and interleukin-6, tumor necrosis factor α, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor α, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor α and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r ≥ 0.4, p < 0.005). Conclusions: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.