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Serum biochemical indicators of liver function in neonatal foals.
Serum biochemical indicators of liver function were determined in healthy, age-matched foals during the first 270 days of life. Values were compared with those of healthy adult horses and with those determined on the day of birth (less than 12 hours old). Serum alkaline phosphatase, gamma-glutamyl transferase, and L-iditol dehydrogenase activities were increased during the first 2 weeks of life. Serum cholesterol, triglyceride, and total and unconjugated bilirubin concentrations peaked during this same period. During the early neonatal period (less than 12 hours old), globulin concentrations (mainly beta 2 and gamma fractions) were low and albumin/globulin ratios were high. However, individual values for all analytes were varied.
Liver function tests and electrophoretic pattern of serum protein in hepatic amoebiasis.
The liver function tests and the electrophoretic pattern of serum protein in a series of 11 patients admitted to Bernhard Nocht Institut with hepatic amoebiasis were reviewed. A constant pattern of hypoalbuminaemia and elevated alpha2 globulins were demonstrated in all patients. LDH enzyme levels were raised in all cases admitted with amoebic liver abscess. The pathogenesis of these disturbances was discussed.
Studies in cholestasis of pregnancy. V. Gallbladder disease, liver function tests, serum lipids and fatty acid composition of serum lecithin in the non-pregnant state.
Women from an earlier series of cholestasis of pregnancy (CP) were called for a retrospective study to consider presence of gallstones in the gallbladder (evaluated by cholecystography), liver function tests, serum lipids and lipoproteins and the relative fatty acid composition of serum lecithin (as determined by GLC). The attendance in the retrospective study was 60%. Estimated on the total series (assuming that none of the non-responders would have a positive X-ray), the incidence of gallbladder disease was 23.7%. Among women with previous cholestasis of pregnancy and with a positive X-ray finding no characteristic changes in liver function tests or serum lipids were revealed. The women with positive X-ray had, however, a lower alpha-lipoprotein cholesterol than women with negative X-ray. A characteristic finding among women with positive X-ray was furthermore the low relative content of palmitic acid (16:0) in serum lecithin. Also women with negative X-ray had a lower relative content of palmitic acid than controls. It is suggested that the low palmitic acid content is expressive of an influence on liver lecithin synthesis pathways and that the serum lecithin fatty acid composition reflects similar changes in bile lecithin. The "basic defect" in CP influencing liver lecithin synthesis might be the primary cause for disturbed cholesterol solubility in bile and of the frequent occurrence of gallstones in CP.
Modulating influence of cytochrome P-450 MspI polymorphism on serum liver function profiles in coke oven workers.
OBJECTIVES: It was reported previously that topside oven workers with heavy exposure to coke oven emissions had increased serum activities of hepatic aminotransferase in one coke oven plant. This study was conducted to investigate the modifying effect of CYP1A1 MspI polymorphism on liver function profiles in coke oven workers. METHODS: 88 coke oven workers from a large steel company in Taiwan were studied in 1995-6. Exposure was categorised by work area: topside oven workers and sideoven workers. Liver function profiles including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), r-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL) were examined in the morning after personal exposure measurements. The MspI polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Five of 23 (22%) topside oven workers and seven of 65 (11%) sideoven workers had the CYP1A1 MspI homozygous variant genotype. With sideoven workers with the combined wild type and heterozygous variant as the reference group in multiple regression models, it was found that topside oven workers with the combined traits had mean AST and ALT activities that were 21% and 46% higher (95% confidence interval (95% CI) 4% to 42% and 12% to 91%, respectively) than the reference group after adjusting for appropriate confounders. Also, topside oven workers with the homozygous variant trait had mean AST, ALT, and GGT activities that were 59%, 68%, and 157% higher (95% CI 21% to 109%, 6% to 168%, and 39% to 374%, respectively) than the reference group. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/l or ALT > 39 IU/l) was more common in the topside oven workers with the homozygous variant than in the sideoven workers with the other combined genotypes (adjusted odds ratio 9.9, 95% CI 1.2 to 82.3) after adjusting for appropriate confounders. CONCLUSIONS: The CYP1A1 MspI polymorphism may modify the biotransformation of coke oven emissions, which results in hepatocellular damage in coke oven workers.
Balloon-occluded retrograde transvenous obliteration improves liver function in patients with cirrhosis and portal hypertension.
BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (B-RTO) is a novel therapeutic method for the treatment of large gastric fundal varices with spontaneous splenorenal shunt (SRS). However, the effects of B-RTO on liver function remain unknown. METHODS: Fourteen patients with portal hypertension and gastric varices with SRS were studied, consisting of four patients with acute bleeding, five with high-risk varices, and five with refractory portosystemic encephalopathy. Hepatic venous catheterization was performed to evaluate hepatic blood flow and liver function using the continuous indocyanine green (ICG) infusion method. To assess the metabolic activity of the hepatocyte, the intrinsic clearance of ICG was calculated. In all patients, endoscopic study was performed before and 1 week and 1 month after the B-RTO, and followed every 6 months thereafter. After baseline measurements, B-RTO was performed. Four weeks after the B-RTO, the same catheter measurements were repeated. RESULTS: The B-RTO was successful in all patients. Contrast-enhanced computed tomography showed complete obliteration of the SRS prior to the follow-up measurements. Endoscopic eradication of the fundal varices was obtained 6 months after B-RTO in all patients and encephalopathy was improved within 1 week after B-RTO. Following the B-RTO, hepatic blood flow (441 +/- 214 vs 668 +/- 299 mL/min, P < 0.0001) and the intrinsic clearance of ICG (233 +/- 123 vs 285 +/- 148 mL/min, P < 0.05) were significantly increased. Furthermore, intrahepatic resistance decreased after the B-RTO (P < 0.005). CONCLUSION: From short-term assessment, B-RTO increases hepatic blood flow and improves the metabolic activity of the liver in patients with portal hypertension.
Interleukin 6 in bile as an indicator of liver function after hepatectomy in patients with biliary tract carcinoma.
BACKGROUND: Interleukin (IL) 6 is one of the important components of the early signalling pathways leading to liver regeneration, and has been detected in the bile after liver transplantation. IL-6 concentrations in the bile were studied in an attempt to predict liver function after major hepatectomy for biliary tract carcinoma. METHODS: This study involved 24 patients without cirrhosis who underwent major hepatectomy for biliary tract carcinoma. The bile was sampled regularly through external biliary drainage tubes. IL-6 concentrations in bile and serum were measured using an enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 concentrations increased 37-fold (from mean(s.e.) 56(13) pg/ml before hepatectomy to 2071(398) pg/ml on day 1 after operation) in patients without liver failure after hepatectomy (n = 18) and increased sevenfold (from 71(24) to 530(76) pg/ml) in patients with liver failure after hepatectomy (n = 6). The values were significantly lower in patients with liver failure than in those without liver failure (P < 0.05). The bile IL-6 concentration on day 1 after operation exhibited a significant negative correlation with the maximum serum total bilirubin concentration after hepatectomy. Although serum IL-6 concentrations were also increased in both groups after hepatectomy, there was no significant correlation with postoperative liver function. CONCLUSION: Increased bile IL-6 concentrations after hepatectomy may reflect liver regenerative capacity. Measurement of bile IL-6 concentrations may be clinically useful for the early identification of liver failure after hepatectomy.
Neuropsychologic effects of diazepam related to single dose kinetics and liver function.
The neurophysiologic and neuropsychologic effects and their relation to the kinetics of diazepam (DZ) were studied in 10 patients with impaired liver function of various degrees and in three normal subjects after 10 mg DZ i.v. The plasma concentration data were treated according to a two-compartment open model. Neurophysiologic effect measurements were obtained from galvanic skin response, continuous reaction times (CRT), heart rate, and averaged evoked potentials; neuropsychologic measurements were obtained from trail making A + B, hidden pattern, word fluency, and subtraction tests; in addition, clinical effects were rated by Beechers Mood Scale and Spielbergers Anxiety Scale. Except for trail making A and word fluency all tests discriminated well between the experimental conditions with or without diazepam. No difference from normal in the response to acute diazepam administration could be detected in patients with reduced liver function. A linear correlation between prolongation in CRT and DZ log plasma concentration was demonstrated in the entire, heterogenous patient material. In the clinical ratings only items of a predominantly sedative and autonomic significance responded to the diazepam injection, while predominantly anxiolytic items did not.
Reliability of total overnight salivary caffeine assessment (TOSCA) for liver function evaluation in compensated cirrhotic patients.
BACKGROUND AND AIMS: Systemic caffeine clearance is considered the gold standard for phenotyping cytochrome P450 1A2 in epidemiological studies, and has been recommended for the non-invasive assessment of liver function in chronic liver disease. Our aim was to find a valid, simple and reliable alternative to this method, and therefore focused our attention on the measurement of an unique salivary caffeine concentration, without drug exposure. METHODS: Our evaluation included 36 healthy controls, 47 patients with compensated liver cirrhosis of viral origin, and 48 obese and diabetic patients with cryptogenetic (likely metabolic) cirrhosis. All shared the same caffeine consumption habits (regular daily use of caffeinated beverages, mainly coffee). The total overnight salivary caffeine assessment (TOSCA) was determined by using a single-point concentration of salivary caffeine, after an overnight period of abstinence. RESULTS: Daily routine caffeine intake of our population was adequate for studying the TOSCA. This single-point concentration correlated well with caffeine clearance, measured by salivary concentrations of caffeine. Mean TOSCA in cirrhotic patients was significantly higher than in controls (p<0.001; sensitivity (%) 84.2 and specificity (%) 97.2; negative likelihood ratio=0.16 and positive likelihood ratio=30.32). A cut-off set at 4.2 microg/ml (sensitivity (%) 95.8 and specificity (%) 68.1; negative likelihood ratio=0.06 and positive likelihood ratio=3.0) successfully differentiated the type of cirrhosis. Rapid (with higher metabolism of caffeine) metabolizers were more frequent in the group of patients with cirrhosis of metabolic origin (70.8%; p<0.0001), and the opposite was true for the group of patients with cirrhosis of viral origin, which comprised many poor metabolizers (85.1%; p<0.001). Serum transforming growth factor-beta 1 concentration, mirroring ongoing fibrosis, ranked high in poor metabolizers. The association between overnight assessment and homeostasis model assessment in rapid metabolizers could result from similar roles for cytochrome P450 1A2 and insulin resistance in determining metabolic liver cirrhosis. CONCLUSION: The TOSCA, although differential between the viral and metabolic etiologies, could be considered a good diagnostic use to verify the presence and eventually the type of compensated liver cirrhosis.
Use of external conduit impairs liver function in patients with biliary atresia.
An external conduit (stoma) for patients with biliary atresia has been used to prevent postoperative cholangitis. Thirty-two patients with biliary atresia who had hepatic portoenterostomies with external conduits were studied retrospectively with respect to frequency and severity of postoperative cholangitis or stoma bleeding. Changes in their liver enzyme levels, and total bilirubin (TB) levels were measured before and after closure of the stoma. Cholangitis was observed in 20 patients (62.5%), and major hemorrhage from the stoma site was seen in 14 patients (43.8%) prior to closure. Levels of liver enzymes such as glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), gamma-glutamyl transpeptidase (gamma-GTP), and alkaline phosphatase (ALP) improved significantly within 1 month after closure of the stoma, and remained low thereafter. The TB concentration was the only liver function that did not change significantly following closure. In summary, the authors do not recommend an external conduit in patients with biliary atresia because it is not an effective way of reducing the incidence of postoperative cholangitis, and it may be deleterious to liver function.
Abnormal liver function tests in a patient fed with total parenteral nutrition and treated with octreotide.
Octreotide is a long-acting analog of somatostatin, a hypothalamic release-inhibiting hormone. It is sometimes used therapeutically to relieve symptoms associated with acromegaly and gastroenteropancreatic endocrine tumors. It has also been used in the treatment of short-bowel syndrome and gastrointestinal and biliary fistulae. We report a patient with biliary leakage due to Marizzi's syndrome treated with total parenteral nutrition and octreotide who developed abnormal liver function tests that improved when the two treatments were stopped. We also review the literature regarding abnormal liver function tests in patients on total parenteral nutrition.
Insulin and glucagon levels in living related liver transplantation: their interaction with the recovery of graft liver function.
Insulin and glucagon have opposite effects on various hepatic functions, including energy metabolism, which is essential for hepatic viability. To evaluate the effects of insulin and glucagon on the recovery of graft liver function, changes in these levels were investigated in relation to arterial ketone body ration (AKBR) during a 30-h period after graft liver reperfusion in 29 recipients of living related liver transplants. Insulin levels did not change significantly throughout this study, while glucagon levels decreased immediately after reperfusion, indicating a rapid degradation of glucagon by the graft liver. The insulin/glucagon (I/G) ratio increased after reperfusion concomitantly with AKBR. In addition, the I/G ratio was significantly correlated with AKBR after reperfusion. It is concluded that the increase in the I/G ratio was closely related to the recovery of graft liver function as reflected by the AKBR in living related liver transplantation.
Caffeine: a model compound for measuring liver function.
The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14CO2 following i.v. injection of 2 mu Ci of [3-methyl-14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for Cl (2.02 +/- S.D. 0.68 ml per min per kg) and t1/2 (3.8 +/- 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in Cl (to 0.76 +/- 0.40) and prolongation in t1/2 (to 13.7 +/- 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 +/- 0.16 vs. 0.64 +/- 0.13 liter per kg in normals). Cumulative 14CO2 production and specific activity of 14CO2 in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t1/2; however, 14CO2 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs = 0.83) of cumulative 14CO2 excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.
Does acetaminophen affect liver function in alcoholic patients?
Acetaminophen in doses of 4 g/d did not affect liver function of alcoholic patients in this randomized study. These results do not rule out the possibility of acetaminophen-induced liver failure in alcoholic patients, especially patients with pre-existing liver disease or those who continue to drink. Patient-oriented outcomes (ie, studying chronic acetaminophen use in alcoholics to determine the incidence of developing hepatic failure) ultimately would resolve this controversy. However, these data do cast doubt on the medical myth (based on case reports) that acetaminophen use in alcoholics causes hepatotoxicity.
Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume.
AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and Child-Pugh's classification, and to discuss its value of clinical application. METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a history of haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia. A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4 times before and after intravenous D-sorbitol infusion. The hepatic clearance (CL(H)) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (Q(TOTAL)) and intrahepatic shunt (R(INS)) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively. RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358+/-0.064) mmol x L(-1) in cirrhotic group and (0.189+/-0.05) mmol x L(-1) in control group (P<0.01). CL(H) =(812.7+/-112.4) ml x min(-1), Q(TOTAL) =(1280.6+/-131.4) ml x min(-1), and R(INS) =(36.54+/-10.65) % in cirrhotic group and CL(H)=(1248.3+/-210.5) ml x min(-1), Q(TOTAL)=(1362.4+/-126.9) ml x min(-1), and R(INS)=(8.37+/-3.32) % in control group (P<0.01). The liver volume of cirrhotic group was 1057+/-249 cm(3), 851+/-148 cm(3) and 663+/-77 cm(3) in Child A, B and C group respectively with significant difference (P<0.001). The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P<0.001). The patient, whose liver volume decreased by 40 % with the CLH below 600 ml x min(-1), would have a higher incidence of postoperative complications. There was no strict correspondent relationship between CL(H), liver volume and Child-Pugh's classification. CONCLUSION: The hepatic clearance of D-sorbitol, CT measured liver volume can be reliably used for the evaluation of hepatic functional blood flow and liver metabolic volume. Combined with the Child-Pugh's classification, it could be very useful for further understanding the liver functional reserve, therefore help determine reasonable therapeutic plan, choose surgical procedures and operating time.
Hepatitis B virus infection and liver function in patients with systemic lupus erythematosus.
One hundred patients with systemic lupus erythematosus (SLE) were investigated for serological markers of hepatitis B virus (HBV) and had liver function evaluated. One patient had hepatitis B surface antigen and 25 had antibodies to HBsAg which is not significantly different from normal blood donor controls. Minor liver function abnormalities were found in 35 patients and there was no difference between those with and without anti-HBs. A single patient without HBV markers had more severe liver enzyme elevation. Our data do not show a relationship between SLE and HBV and support the contention that liver diseases in lupus is mild.
High-dose naltrexone and liver function safety.
Studies have found naltrexone useful in the treatment of diseases other than opiate addiction in which endogenous opioids presumably play a role, such as alcoholism and eating disorders. Some of these studies involve high doses (100-200 mg bid). Because investigational studies with high doses (300 mg/day) reported clinically significant increases in liver enzyme levels, the authors measured a spectrum of liver function parameters in response to high doses of naltrexone in a double-blind, crossover trial (100 mg bid) followed by an open-label period (200 mg bid). They observed no adverse clinical or laboratory changes in liver function in association with high-dose naltrexone therapy in eating disorders.
The effect of continuous vasopressin infusion on splanchnic blood flow, liver function, and portal and central venous pressures in patients with cirrhosis.
Continuous vasopressin infusion has been shown to control bleeding from oesophageal varices in patients with cirrhosis of the liver. The mortality, however, has not been changed. To investigate whether reduction of portal blood flow over a period of hours deteriorates the liver function, we measured the splanchnic blood flow and galactose and oxygen consumption in five cirrhotic patients during liver vein catheterization. Vasopressin was given as a continuous infusion of 0.2 units per min for three h. The splanchnic blood flow was reduced to 70% of control values and remained so throughout the infusion. After three h no impairment of the liver function was found. The wedged hepatic pressure (portal pressure) rose slightly, probably due to the increase of the central venous pressure reflecting impaired cardiac function. The reported beneficial effect of vasopressin on varix bleeding probably depends on the reduced portal flow per se.