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Known liver function tests (activities of ASAT = L-Aspartate: 2-oxoglutarate aminotransferase, ALAT = L-Alanine: 2-oxoglutarate aminotransferase, GLDH = Glutamate-dehydrogenase, LDH = Lactate-dehydrogenase in serum) are not qualified for detecting minimal histopathological liver alterations induced by aminophenazon.
BACKGROUND: Spider angioma is a common sign in patients with liver cirrhosis, but the pathogenesis is still unclear. Alcohol and hyperestrogenemia are both possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with liver cirrhosis to alcohol, liver function test results, and plasma levels of sex hormones. METHODS: Eighty-two patients with liver cirrhosis and 18 healthy subjects were enrolled in this study. The number, size, and location of the spider angiomas were recorded for all subjects. Plasma levels of estradiol and testosterone were measured. RESULTS: Cirrhotic patients had significantly higher estradiol/testosterone ratios (26.8 +/- 5.1 x 10(-3) versus 8.8 +/- 2.0 x 10(-3); P = 0.002) than healthy controls. Twenty-seven (33%) of the 82 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas were younger (56 +/- 3 versus 66 +/- 1 years; P = 0.002) and had higher serum bilirubin levels (3.3 +/- 0.6 versus 1.7 +/- 0.2 mg/dl; P = 0.002), longer prothrombin time (16.8 +/- 0.8 versus 14.8 +/- 0.4 sec; P = 0.01), and higher prevalence of alcoholism (41% versus 20%; P = 0.04) than those without. Stepwise logistic regression showed that alcoholism and serum bilirubin level were the only significant and independent predictors associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.5; 95% confidence interval = 1.2-10.8; P = 0.03, and odds ratio = 2.8; 95% confidence interval = 1.3-5.7; P = 0.006, respectively). CONCLUSIONS: Alcoholism and impaired liver function are important predictors of the presence of spider angiomas in patients with liver cirrhosis.
Kupffer cells are the tissue macrophages in the liver and play an important role in the defense mechanisms of the body. However, their role in liver function and hepatocellular activity remains unclear. This study was therefore undertaken to investigate the effect of gadolinium chloride-induced Kupffer cell dysfunction on liver function and hepatocellular signaling activity in mice and to establish an animal model for studying the role of Kupffer cells in vivo. Kunming mice were intraperitoneally injected with different doses of gadolinium chloride (GdCl3), a selective inhibitor of Kupffer cells, and the mice were sacrificed at different time periods following the drug administration. Hepatotoxicity and Kupffer cell function, as well as the levels of signaling molecules and inflammatory mediators in liver tissue, were measured. We demonstrated that the administration of 10-20 mg/kg GdCl3 caused apoptosis of Kupffer cells and blocked the Kupffer cell effector function, as shown by a decrease in CD68 expression and phagocytic activity. In addition, the NO, PGE2 and cAMP levels in the liver were also reduced significantly. Furthermore, 20 mg/kg GdCl3 decreased the levels of cNOS, PKC and NF-kappaB p65 expression by 26.6, 68 and 64%, respectively. In contrast, hepatotoxicity was not observed when the same doses of GdCl3 were used. Moreover, we found that Kupffer cell function and the NO, PGE2 and cAMP contents, as well as PKC and NF-kappaB p65 levels in the liver were only partially, but not fully recovered in up to six days following 20 mg/kg GdCl3 injection. However, the administration of higher doses of GdCl3 (40 mg/kg) caused both hepatotoxicity and Kupffer cell necrosis, as well as an increased release of TNF, NO, and PGE2 in the liver. These results indicate that administration of suitable doses of GdCl3 blocked the effector function of Kupffer cells selectively, but did not cause liver parenchymal cell toxicity, and provide a frame-work for the establishment of an animal model for studying the role of Kupffer cells in signaling in the liver. Lastly, the present study also provides evidence that shows there is a positive association between the expression of cAMP, PKC, or NF-kappaB and the levels of NO, PGE2 and TNF in the liver of Kupffer-cell-blocked mice, and suggests that Kupffer cells may play a part in mediating liver function and hepatocellular activity.
The effects of vasopressin and of its analogues on liver function, and their possible mechanisms of action, are poorly understood. This study was designed to assess the effect of triglycyl-lysin-vasopressin on liver function, evaluated by two quantitative tests independent of liver blood flow, i.e., indocyanine green intrinsic hepatic clearance and galactose elimination capacity. Indocyanine green intrinsic hepatic clearance and galactose elimination capacity were determined before and after administration of 2 mg triglycyl-lysin-vasopressin to (respectively) 10 and 12 patients with cirrhosis. Eighteen additional patients with cirrhosis were studied before and after infusion of placebo. No significant variation in either test was observed in placebo-treated patients. A significant decrease in indocyanine green intrinsic hepatic clearance, averaging 22%, was observed in patients receiving the drug (p = 0.04). Conversely, galactose elimination capacity remained unchanged after the drug. These results are compatible with the hypothesis that the drug produced a preferential decrease in perfusion in functioning areas of the liver, with relative maintenance of blood flow in non-functioning areas.
BACKGROUND: In this study, we investigated the influence of brain death on inflammatory response and the effects of brain death on liver function both directly after explantation and after reoxygenation. METHODS: The influence of brain death on liver function was studied in rats using a brain death model and the liver slice model to mimic reoxygenation. Liver function was assessed by measuring the ATP content and the ATP-driven urea synthesis. The activation of non-parenchymal cells was studied by measuring mRNA levels of IL-10, cytokine production (IL-10 and IL-1 beta) and inducible nitric oxide synthases (iNOS) upregulation (mRNA) and protein level. RESULTS: Brain death had no direct influence on the ATP content of the liver. However, it led to induction of several cytokines because of activation of non-parenchymal cells, which led to upregulation of iNOS and to nitric oxide metabolites production. It is known that cytokine production may influence the drug metabolism capacity; however, no influence of brain death on drug metabolism was observed. An explanation may be the relatively short experimental period. CONCLUSIONS: Kupffer cells seem to be activated during the onset of brain death induction; however, they become quiescent when liver slices of brain dead rats were reoxygenated during incubation. Other non-parenchymal cells, possibly the endothelial cells, remain activated during incubation and reoxygenation in slices from brain death donors but not in slices from control livers. Future experiments in our rat liver transplantation model need to elucidate the implications of these findings.
The relationship between dexamethasone suppression test (DST) response, depressive symptoms and liver function tests was investigated in 15 male alcohol-dependent patients for 2 weeks during alcohol withdrawal. Six of the patients relapsed into drinking within the investigation period. There was no association between DST response and relapse, which suggests that abnormal DST response has no predictive value for relapse into drinking. About 50% of the patients had abnormal DST responses during the first week of alcohol withdrawal. There was no relationship between DST response and depression or depressive symptoms. Depression remitted within 1-2 weeks, whereas DST responses remained abnormal for at least 2 weeks in 2 of the non-relapsing 9 patients. Abnormal DST response in alcohol withdrawal is unlikely to be due to alterations in liver function but may be attributable to the effect of alcohol on the hypothalamic-pituitary-adrenocortical axis.
Sex differences exist in the metabolism of histidine, drugs and steroids by the liver. These differences are controlled, at least in the rat, by the hypothalamo-pituitary axis. Histidase is controlled by growth hormone, giving an increase in the male to the female level. Drug and steroid metabolism are controlled directly from the pituitary in the female rat by means of an unidientified hormone designated "feminizing factor". In the male rat, androgens derived from the testes and adrenals are involved in the regulation of liver function, probably by a feedback action on the pituitary secretion of feminizing factor. The thyroid glands are involved in the control of liver function in both males and females. Regulation of lactogenic receptors in rat liver is very similar to that of drug and steroid metabolism. The secretion of feminizing factor is regulated by the hypothalamus and probably involves higher centres, notably the amygdala.
The present study was conducted in 50 patients of various subtypes of leprosy (Lepromatous, Tuberculoid, Borderline borderline) and 25 healthy control, for detection of Australia antigen and various liver function tests (serum protein, cholesterol, alkaline phosphates, SGOT, SGPT, bilirubin and liver biopsy) to see incidence of Australia Antigen and derangement in liver function. It was concluded that incidence of Australia antigen in study and control group was zero. Total serum protein and serum globulin was increased in lepromatous leprosy. A/G ratio was reversed in 34.3% and 50% in lepromatous and tuberculoid leprosy respectively. Granulomatous hepatitis was seen in 66.66% and 50% cases of lepromatous and tuberculoid leprosy respectively. No relationships was established between hepatic lesion, Australia antigen and liver function test.
A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2) may influence alcohol-induced liver injury because of higher production of acetaldehyde in the liver. In the present study, we examined relationships between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. Study subjects were 385 male workers in a metal plant in Japan, who were free from hepatic viruses and did not have higher aminotransferase activities (<100). The subjects completed a questionnaire on alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined by the PCR method followed by restriction-enzyme digestion. In the moderately and heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower levels than those with ALDH2*1/*1 for all three parameters of liver function, whereas no such differences were observed in the least-drinking group. Multiple linear-regression analysis, adjusting for age, obesity, and smoking habits, revealed that aspartate aminotransferase activity was positively associated with alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine transferase activity was negatively associated with alcohol intake only in those with ALDH2*1/*2. The present study indicates that effects of alcohol intake on liver-function biomarkers are likely to be modified by the ALDH2 genotype in adult males.
In an attempt to design a liver function test which takes into account both portal-systemic shunting and hepatocellular dysfunction, we investigated a group of patients with cirrhosis with or without surgical porta-caval shunt for d-propoxyphene and its major metabolite, norpropoxyphene kinetics. A small dose of d-propoxyphene (0.7 mg/kg body weight) was given orally to seven normal subjects, 15 patients with cirrhosis and seven patients with cirrhosis and surgical portacaval shunt. D-propoxyphene and norpropoxyphene areas under the plasma concentration-time from 0 to 4-h (AUC) were determined by the trapezoidal method. As d-propoxyphene is a high extraction drug and since the production of norpropoxyphene should reflect the amount of d-propoxyphene available to the hepatocytes, we tested the hypothesis that norpropoxyphene/d-propoxyphene AUC ratios should reflect both the degree of portal-systemic shunting and the severity of hepatocyte dysfunction. Norpropoxyphene/d-propoxyphene AUC ratios were significantly lower in patients with cirrhosis (mean +/- S.D.: 0.92 +/- 0.59) than in controls (2.51 +/- 0.45) and also significantly lower in patients with cirrhosis and a surgical shunt (0.53 +/- 0.23) than in patients with cirrhosis but without surgical shunt (1.10 +/- 0.63). Moreover, there was an overall statistically significant correlation between norpropoxyphene/d-propoxyphene AUC ratios and branched to aromatic amino acids ratios (rs = 0.91) and fasting venous NH4 (rs = -0.63). On the other hand, there was only a weak correlation between norpropoxyphene/d-propoxyphene AUC ratios and the 14C-aminopyrine breath test (rs = 0.43). These data suggest that the norpropoxyphene/d-propoxyphene AUC ratio reflects both shunting and reduced hepatocellular function.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND/AIMS: Surgical resection of liver metastases is performed increasingly frequently after chemotherapy, which can induce fatty degeneration, possibly modifying the postoperative course after hepatectomy. This study evaluated the effect of chemotherapy on postoperative liver function tests according to the use of preoperative chemotherapy or not. METHODOLOGY: Thirty-two patients were operated on for isolated breast cancer hepatic metastases, after stabilization or complete response to systemic therapy. The first group included 20 patients operated on after chemotherapy (9 major and 11 minor hepatic resections). The second group included 12 patients operated on without chemotherapy (3 major and 9 minor hepatic resections). RESULTS: Histological examination after chemotherapy confirmed micronodular fatty degeneration in 85% of cases, versus none in the control group (P = 0.05). Fall in prothrombin time on day 1 (D1) was more marked in the chemotherapy group (58%) versus control group (74%) (P = 0.001). gamma-glutamyl transpeptidase did not rise on D7 in the chemotherapy group (1.4 x N), even after major hepatectomy (1.6 x N), in contrast with the control group, in which the mean gamma-glutamyl transpeptidase on D7 was 4.6 x N after major hepatectomy and 2 x N after minor hepatectomy (P = 0.05). CONCLUSIONS: Chemotherapy induces almost constant fatty degeneration of the liver. Hepatic regeneration in the postchemotherapy liver is delayed, as reflected by a later and lower elevation of gamma-glutamyl transpeptidase. The predictive risk of liver failure, reflected by prothrombin time, following minor hepatectomy on postchemotherapy liver is similar to that of major hepatectomy to healthy liver.
Proteins (total, albumin, globulin and their subfractions), carbohydrate (intravenous glucose tolerance test), lipids (serum cholesterol, triglycerides and phospholipids), and liver function tests (alkaline phosphatase, lactic dehydrogenase and aspartate aminotransferase activities in the serum, bromsulphathalein retention test and serum bilirubin) were studied in 12 non-lactating healthy Thai subjects before, and subsequently at 3 weeks and 3, 6, 9 and 12 months after the initiation of treatment with injectable medroxyprogesterone acetate (150 mg I.M. every 90 days). Serum protein and lipid levels, and the results of liver function and I.V. glucose tolerance tests, remained unchanged in all subjects throughout the one-year study period. However, a significant and persistent increased insulin level was noted in all subjects, after initiation of the hormone treatment, during the first thirty minutes of intravenous glucose load. It is concluded that injectable medroxyprogesterone acetate used as a contraceptive agent does not interfere with glucose tolerance, lipid and protein metabolism, and that the liver function remains normal during its administration.
In view of increasing therapeutic possibilities interest focuses on prognosis of liver cirrhosis. Until nowadays studies on prognosis revealed significant importance only for some parameters: Ascites, encephalopathy and portal hypertension as signs of decompensation, bilirubin, albumin and prothrombin time as laboratory indices of decreasing liver function. The commonly used Child-Pugh-score is based on these parameters and allows a reasonable classification of diseased patients. Cholestasis and inflammation seem to be of minor prognostic importance. Assessment of liver function by quantitative tests is desirable (e.g. aminopyrine breath test, bile acids). The prognostic value, however, has not yet been proven in large studies. Use of these tests should therefore be restricted to studies (prognosis, therapy, indication to liver transplantation).
The changes of biotransformation enzyme system (b.e.s.) activity and capacity in liver diseases significantly influence the metabolism of various xenobiotics. Lidocaine is metabolised through oxidative N-deethylation by b.e.s. resulting in the production of monoethylglycinexylide (MEGX). The aim of this study was the determination of serum MEGX concentration as a model substance for indirect evaluation of liver b.e.s. function in patients with liver steatofibrosis and cirrhosis and the assessment of the possibilities to use it as a quantitave test of liver functional state. The study group consisted of 53 patients, 36 of them with liver disease of different etiology (postviral, ethyltoxic, cryptogenic, liver cirrhosis on the basis of autoimmune hepatitis, liver cirrhosis induced by primary sclerosing cholangitis, primary biliary cirrhosis in the stage of cirrhosis, Wilson's disease in the stage of cirrhosis), 7 patients with liver steatofibrosis and 10 control persons. After intravenous administration of lidocaine (1 mg/kg of body weight), concentration of MEGX was assessed by fluorescence polarization immunoassay (FPIA) using Tdx system in venous blood. The concentration was assesed prior to administration of lidocaine and 15 and 30 minutes after. In the group of liver steatofibrosis the concentrations in the 15th minute after administration were lower comparing to controls, in the 30th minute the difference was less significant. The values of MEGX in cirrhosis group were significantly decreased 15 and 30 minutes after lidocaine administration in comparison with control group. The cirrhosis group was divided into two subgroups: compensated (Ci c) and decompensated (Ci d) and independently of this division into three parts according to score system of Child-Pugh classification (Ci A, Ci B, Ci C). The concentrations 15 and 30 minutes after lidocaine administration in patients with Ci c and Ci d were significantly different, similarly there were statistically significant differences among Ci A, Ci B and Ci C. Statistically significant differences were also between the group of steatofibrosis and whole group of cirrhosis. The concentration of MEGX 15 and 30 minutes after lidocaine administration correlated significantly with the values of albumin, prothrombin time, cholinesterase, Child-Plugh score and bilirubin. MEGX test represents an appropriate and rapid method for the determination of functional liver capacity in patients with liver cirrhosis and liver steatofibrosis, not yet used in Slovak republic. It is a noninvasive test, low time consuming, and when repeated it may provide prognostic information about further development of the disease. MEGX test is an appropriate index of liver function and may contribute to early treatment of chronic liver diseases. (Tab. 9, Fig. 10, Ref. 47.)
Biliary lipids, faecal steroids, and serum bile acids were studied in patients with chronic active hepatitis and primary biliary cirrhosis. The results were correlated with excretory and parenchymal liver function tests and with the presence or absence of orcein-positive copper-protein complexes in histological liver specimens. In general, faecal bile acids, but not neutral and total sterols, correlated negatively with the percentage of biliary cholic acid, serum cholesterol, and serum bile acids and positively with the percentage of biliary deoxycholic acid. In orcein-positive subjects-indicative of long-standing cholestasis-the bile was undersaturated with cholesterol, biliary deoxycholic acid was subnormal, cholic acid correspondingly increased, and serum cholesterol and bile acids were raised. Only patients with marked impairment of both excretory and parenchymal liver functions had a decreased output of neutral sterols, bile acids, and total steroids, and, thus, low bile acid and cholesterol synthesis. The findings indicate that mild disturbances in parenchymal liver function infrequently cause major changes in cholesterol metabolism, while abnormalities in secretory liver function-in orcein-positive subjects especially-are frequently associated with proportionate changes in parameters of cholesterol metabolism.
BACKGROUND/AIMS: The aim of this study was to investigate the long term effect of prophylactic endoscopic injection sclerotherapy (EIS) on liver function. METHODOLOGY: This study was a retrospective investigation of seventy-eight patients with liver cirrhosis, whose liver function was classified as Child's A before follow-up. Laboratory data were retrospectively examined before and after follow-up, and a comparison was made between the EIS group (n=21) and the non-treated group (n=57). RESULTS: In the 3 or more years of follow-up, cholinesterase and total cholesterol levels deteriorated in several severe-variceal cases. However, these levels did not deteriorate over the 3 or more years of follow-up in the EIS group. CONCLUSION: Prophylactic endoscopic injection sclerotherapy among patients with early stage LC may prevent the deterioration of liver function.
In 20 patients with cirrhosis we studied the relationship among the efficiency of beta-adrenergic blockade induced by oral administration of 40 mg propranolol, the plasma level of propranolol, and the liver function. The beta-adrenergic blockade was studied 2 h and 8 h after propranolol administration and assessed by the cardiac chronotropic response to isoprenaline. Liver function was evaluated by a standard liver function test and the Child-Turcotte or Pugh score. The beta-adrenergic blockade and propranolol plasma concentration were higher 2 h than 8 h after propranolol administration. The beta-adrenergic blockade and the propranolol plasma concentration varied widely among patients. No significant correlation was found between the efficiency of beta-blockade and propranolol concentration. The beta-adrenergic response before propranolol administration was correlated with bilirubin level and Child scores, but no significant correlation was found between the beta-blockade and the severity of liver disease. These results suggest that in patients with cirrhosis, differences in response to propranolol are not related to differences in the severity of the liver disease or to differences in propranolol concentration.
We investigated sex- and age-specific prevalences of hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe) in 1,163 carriers of hepatitis B surface antigen (HBsAg) in Okinawa, Japan, and followed them up for longer than one year in correlation with liver function abnormalities. Elevated serum transaminase levels were found in 160 (13.8%) of them. The prevalence of liver function abnormalities was significantly higher in male carriers (127/690, 18.4%) than in female carriers (33/473, 7.0%) at a P value of 0.001. In asymptomatic carriers, the prevalence of HBeAg was 13.2% and that of anti-HBe 80.0%, significantly different from 41.9% and 54.4%, respectively, in carriers with elevated transaminase levels (P less than 0.001). In asymptomatic carriers, the mean age of HBeAg-positive carriers was 16.7 years which was much lower than the 22.8 years in carriers with liver function abnormalities. The prevalence of elevated transaminase levels was significantly higher in carriers with HBeAg than in those with anti-HBe (33.8% vs. 9.7%, P less than 0.001). Based on these results, the prolonged positivity for serum HBeAg would qualify as a predictor for deteriorating liver function among HBsAg carriers.