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Antipyrine clearance and its correlation to routine liver function tests in patients with liver disease.

Antipyrine clearance was determined in five healthy volunteers, 10 patients with viral hepatitis and 15 patients with cirrhosis of the liver. The antipyrine clearance in controls was 30.1 +/- 2.5 ml/kg/h (S.E.M.), in patients with viral hepatitis 30.3 +/- 3.9 ml/kg/h and in liver cirrhosis 20.4 +/- 2.7 ml/kg/h. In the patients with liver disease no correlation could be demonstrated between the routine liver function tests and antipyrine clearance. The results are compared to similar studies reported previously. Antipyrine pharmacokinetics do not appear to be a clinically useful index for the hepatic drug metabolizing capacity in the individual patient with liver disease.

Adult↗

Biochemical effect of antioxidants on lipids and liver function in experimentally-induced liver damage.

Recent studies demonstrated the role of antioxidants in preventing organ damage caused by free radicals. The present study was conducted to find out the modulatory effect of some antioxidants on lipid patterns in experimentally-induced liver damage. Rats chronically intoxicated with carbon tetrachloride (CCl4) were used as a model of liver injury terminating with fibrosis or cirrhosis. One hundred and sixty six albino rats were classified into five groups: one served as a control group; the second was subjected to oral administration of CCl4 (200 microL/100 g body weight) twice a week; the other three groups, in addition to CCl4, received oral doses of silymarin (30 mg/kg), vitamin E (200 IU/kg) and vitamin C (50 mg/kg) respectively. At the end of the experiment, the animals were killed, blood was collected and liver was taken for histopathological examination. Liver function tests, disturbed by CCl4 were significantly modulated by antioxidants, and histopathological examination showed that antioxidants ameliorated the necrotic and fibrotic changes caused by CCl4. Treatment with antioxidants was also shown to modulate the toxic effect of CCl4 on the lipid profile and malondialdehyde content. Administration of antioxidants could play an important role in prophylaxis against lipid peroxidation and consequently liver fibrosis caused by free radicals.

Animals↗

Susceptibility of the liver and biliary tract to anaerobic infection in extrahepatic biliary tract obstruction. II. Liver function and morphology of the liver and biliary tract--an experimental study in rabbits.

Biliary tract infection with anaerobic bacteria (B. fragilis or Fusobacterium mortiferum) was produced in rabbits by common duct ligation (c.d.l.) 3 days prior to intravenous bacterial inoculation. Animals were investigated 1, 4 or 7 days after inoculation. Histopathological investigations included the liver, the common duct, and the gallbladder, while liver function was evaluated by bilirubin, alkaline phosphatase (AP), and L-alanine aminotransferase (GPT) in serum. Rabbits with c.d.l. and biliary tract infection were compared to rabbits with c.d.l. in which bacterial inoculation failed to produce infection, to inoculated rabbits without c.d.l., and to uninoculated rabbits with c.d.l. Anaerobic biliary tract infection in rabbits with c.d.l. caused a significant increase in liver abscesses, a significant increased infiltration with granulocytes in the gallbladder, and a significant increase in serum levels of bilirubin, AP, and GPT, but failed to produce signs of cholangitis in the liver and intramural abscesses in the gallbladder. A material is presented of normal values for bilirubin, AP, and GPT in serum in rabbits.

Alkaline Phosphatase↗

13C-breath tests in the study of microsomal liver function.

Conventional liver tests can be used to estimate a mixture of injury and function but none of these may be regarded as a reliable marker either to quantify functional hepatic reserve or to reflect life-threatening complications of acute and chronic liver diseases. To overcome this limit, many dynamic tests have been developed in order to evaluate the "hepatic functional mass". Among these tests we can include breath tests with 13C-labeled substrates undergoing different metabolic pathways. As concerning the evaluation of microsomal function, two main categories of breath tests have been developed based on the limiting step in the different substrates metabolism. The first group include aminopyrine, caffeine and diazepam, all substrates with a metabolism independent from hepatic blood flow and dependent almost exclusively from the enzymatic activity of different cytochromes P450. The other group is composed of substrates with flow dependent metabolism like methacetin, phenacetin, erythromycin. The aim of this review is to describe the clinical applications of microsomal liver breath tests in different hepatic diseases.

Acetamides↗

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors.

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurements with the volume of the resected liver mass. The correlation coefficient between these methods was 0.899 (P less than 0.01). Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days the liver had regenerated maximally to a volume of 75 +/- 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 +/- 10% for the caffeine clearance and to 100 +/- 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. Our study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy.

Adult↗

[The effects of exercise on liver function in patients with chronic liver disease].

This study examined the effect of exercise on liver function in patients with chronic liver disease (CLD). 1) Twenty-five patients with CLD (21 with chronic hepatitis (CH) and 4 with liver cirrhosis (LC] and 10 healthy subjects were administered an exercise test employing a treadmill. The load applied was 6.5 Mets and was administered for a period of 10 min. The serum levels of S-GOT, S-GPT, LDH, CPK, triglyceride, GOTm and GLDH were measured before exercise and 1 h, 24 h and 7 days after exercise in the patients with CLD, and before and 24 h after exercise in the healthy subjects. i. The patients with CLD showed an increase in GLDH 24 h after exercise (p less than 0.005), a decline in LDH 1 h (p less than 0.05) and 24 h (p less than 0.01) after exercise, and a decrease in triglyceride 24 h after exercise (p less than 0.005) as compared with pre-exercise values. No significant changes were observed in S-GOT, S-GPT, CPK or GOTm levels. ii. The mean values and standard deviations (SD) of S-GOT and S-GPT during the 3-month period immediately preceding the study were calculated for all 25 patients. Increases in S-GOT of more than 1 SD were observed after exercise in 5 patients (20%); another 5 patients (20%) showed similar increases in S-GPT. The number of overlapping cases in which increases in both S-GOT and S-GPT were observed was 2 (8%). iii. No significant differences were found in mean HR during exercise/predicted max HR, or mean BP during exercise between patients with increased S-GOT and those without, or between patients with increased S-GPT and those without. iv. In the healthy subjects, there was a significant increase in GOTm (p less than 0.05) following exercise, but no such increase in S-GOT, S-GPT, CPK or GLDH. 2) The number of steps taken per day measured by a pedometer was selected as a parameter of daily exercise and examined in 14 patients with CLD (9 with CH and 5 with LC). No significant correlation was found between mean number of walking steps and S-GOT and S-GPT levels for patients with either type of CLD. The results of this study indicate that moderate exercise was well tolerated in the majority of patients with CLD.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Liver regeneration and restoration of liver function after partial hepatectomy: the relation of fibrosis of the liver parenchyma.

BACKGROUND/AIMS: Patients who survive partial hepatectomy sometimes have unsatisfactory liver regeneration and restoration of liver function. Although the extent of resection should be adjusted to attain favorable liver regeneration and restoration of liver function, a guiding principle for this has not been established. METHODOLOGY: Seventy patients with hepatic tumors associated with liver disorders of various severity who underwent hepatectomy were studied. We calculated the removal rate of the liver and the regeneration rate of the remnant liver using computed tomography. The liver function was investigated using ICG R-15 (retention rate of indocyanine green). Liver disorder was classified into 4 groups, according to the severity of fibrosis. RESULTS: The regeneration rates of the remnant liver indicated a significant decline in patients with severe fibrosis. In the no fibrosis and mild fibrosis groups, an increased removal rate was associated with increased regeneration rate, and post-operative ICG R-15 improved with time. However, in the moderate fibrosis and severe fibrosis groups, an increased removal rate was not associated with increased regeneration rate, and post-operative ICG R-15 showed no change or became worse with time. CONCLUSIONS: Severe fibrosis of the liver parenchyma is associated with poorer regeneration of the remnant liver leading to poor restoration of post-operative liver function. The severity of fibrosis is useful as a predictive factor for liver regeneration and restoration of liver function after partial hepatectomy.

Adult↗

The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function.

Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of which leads to liver damage.

Adult↗

Effect of rifampicin on liver function in man.

Liver function and serum concentrations of rifampicin, a highly cholephilic antibiotic, have been studied after ingestion of a single dose of 600 mg of rifampicin in 12 patients, six of them having a normal liver and six a cirrhotic, and during treatment with 600 mg of rifampicin per day for 17 days in eight patients, four of them having a normal liver and four a cirrhotic. Rifampicin produced competition for the elimination of bilirubin and bromsulphalein by the liver. This competition, which seemed to involve mainly the uptake by the liver cell, was always rapidly reversible when treatment was discontinued. It makes it impossible, however, to interpret a bromsulphalein test during treatment with rifampicin. In the eight patients treated for 17 days, apart from the competition already mentioned, no clinical, biological, or morphological abnormalities of the liver were ascertained. But in this limited number of patients it is not possible to exclude the fact that rifampicin could provoke jaundice by idiosyncrasy in a small percentage of cases. The serum concentrations of rifampicin were higher in cirrhotic patients than in patients with normal livers, especially after one or two weeks of treatment. It is suggested that efficient blood concentrations of rifampicin would be achieved with small doses in case of previous hepatocellular insufficiency.

Adult↗

Changes in portal vein flow after adult living-donor liver transplantation: does it influence postoperative liver function?

In adult living donor liver transplantation, using small grafts in cirrhotic patients with severe portal hypertension may have unpredictable consequences. The so-called small-for-size syndrome is present in most series worldwide. The goal of this study was to prospectively evaluate the influence of hemodynamic changes on postoperative liver function and on the percentage of liver volume increase, in the setting of living donor liver transplantation. Twenty-two consecutive adult living donor liver transplantations were performed at our institution in a 2-year period. We measured right portal flow and right hepatic arterial flow with an ultrasonic flow meter in the donor, and then in the recipient 1 hour after reperfusion. Postoperative liver function was measured by daily laboratory work. We also performed duplex ultrasounds on postoperative days 1, 2, and 7. Liver volume increase was estimated by magnetic resonance imaging graft volumetry at 2 months posttransplantation. We compared the blood flow results with the immediate liver function and its liver volume increase rate at 2 months. There was a significant increase in portal flow in the recipients compared with the donors (up to fourfold in some cases). Higher portal flow increase rates significantly correlated with faster prothrombin time normalization and faster liver volume increases. Median graft volume increase at 2 months was 44.9%. The increase in blood flow to the graft is well tolerated by the liver mass not affecting hepatocellular function as long as the graft-to body weight ratio is maintained (>0.8) and adequate outflow is provided.

Body Weight↗

Impaired liver function tests in patients treated with antithymocyte globulin: implication for liver transplantation.

Antithymocyte globulin (ATG) is traditionally used as a conventional immunosuppression agent in various pathological states including severe aplastic anaemia (SAA), graft versus host disease (GVHD), and for the prevention and treatment of graft rejection and GVHD post bone marrow and liver transplantation. We reviewed the liver functions of 16 haematological patients with no previous liver disorders who received ATG as part of their pre-bone marrow transplantation (BMT) conditioning regimen, and the liver function tests of five SAA patients who received ATG as part of their treatment. Liver functions were evaluated at day -1 pre-, and days +3 and +10 post-ATG treatment. All patients had normal liver functions before treatment. In the haematological patients, the mean serum lactic dehydrogenase (LDH) levels increased from 408.7 +/- 37.7 U/l pre-treatment to 1394.4 +/- 488.7 U/l 3 days post-treatment (n = 16; p < 0.029), and then declined to 561.4 +/- 61.3 U/l 10 days post-treatment (n = 16; p < 0.043). The mean alanine aminotransferase (ALT) levels increased from 51.9 +/- 11.3 U to 184.6 +/- 74.6 U (n = 16; p < 0.036), and then declined to 121.9 +/- 61.3 U (n = 16; NS). The mean aspartate amino transferase (AST) levels increased from 31.2 + 5.7 U to 152.0 +/- 67.0 U (n = 16; p < 0.44) and then declined to 46.0 +/- 14 (n = 16; p < 0.049). The mean tau-glutamyltransferase (GTP) levels increased from 93.0 +/- 34 to 188.0 +/- 36 (n = 16; p < 0.02), and were 168.0 +/- 37.0 at day +10 (n = 16; NS). The mean bilirubin levels increased from 18.0 +/- 1.9 microM l(-1) to 22.7 +/- 2.8 (n = 16); NS), at day +3 and to 31.9 +/- 6.9 at day +10 (n = 16; NS). In contrast, no significant changes in liver function tests were demonstrated in the SAA patients treated with ATG. The possible pathophysiologic mechanisms and the clinical implications for liver transplantation are discussed.

Adolescent↗

[Quantitative assay of metabolic rate of para-aminobenzoic acid combining glycine for the assessment of rabbit liver function].

OBJECTIVE: To evaluate liver function by the assessment of the capacity of glycine combining para-aminobenzoic acid (PABA) to form hippuric acid in rabbits with acute liver injury. METHODS: Thirty rabbits were randomly divided into two groups: experiment group (n=20) received D-galactosamine to be subject to acute liver necrosis, and control group (n=10) received saline as placebo. Serum concentrations of PABA, para-aminohippuric acid (PAHA), para-acetamidobenzoic acid (PAABA), and para-acetamidohippuric acid (PAAHA) were measured by high pressure liquid chromatography (HPLC). RESULTS: Compared with control group, the serum concentrations of PAHA and PAAHA were significantly reduced in experimental group, which were correlated with the degree of liver injury. CONCLUSIONS: The metabolic rate of glycine combining PABA is a sensitive index for quantitative test of liver function and assessment of acute liver necrosis.

4-Aminobenzoic Acid↗

[Hepatic arterial infusion of high-dose 5-FU to liver metastases--case reports of 6 patients with abnormal laboratory data on liver function].

Six patients with metastatic liver cancer (H3) and abnormal laboratory data for liver function underwent intra-hepatic arterial infusion (H.A.I.) therapy of high dose 5-FU (1 g/body/day, 6 days/week, 1q for 2 patients, 2q for 4 patients, with at least a one week interval). No serious side effects were observed in any case. Even in 2 cases with suspicious partial obstruction of the portal vein, no remarkable change in liver function was observed after high dose 5-FU H.A.I. therapy. Four patients who received 12 g of 5-FU showed a reduction in the abnormal data after a short transient rise in some cases. In 2 cases the reduction rate was high and the laboratory data were normalized in 3 months. A long PR was obtained in these cases. The other 2 cases, on the other hand, showed a low reduction rate and the liver function relapsed in a week. Tumor markers also returned to previous levels in a short period. These findings together imply that the reduction rate of abnormal liver function data might predict the efficacy of high dose 5-FU H.A.I. therapy.

Aged↗

Liver damage after paracetamol overdose. Comparison of liver-function tests, fasting serum bile acids, and liver histology.

54 patients have been studied after paracetamol (acetaminophen) overdose. Liver-function tests and fasting serum bile-acids were measured daily; liver biopsy was done in all cases, and slides were examined "blind" to assess liver damage. The plasma-paracetamol was measured on one occasion. A histological abnormality was present in the livers of 53 of the 54 patients, and was minor in 23, moderate in 16, and severe in 14. In 6 patients with moderate and 18 with mild histological abnormality liver-function tests were normal. A serum-aspartate-aminotransferase above 400 units/1 was always associated with severe histological liver damage. Fasting serum bile-acids were raised in 51 of the patients with abnormal liver histology; the serum-bile-acid seemed to be a more sensitive indicator of mild liver-cell damage than was the transaminase level. There was, however, little correlation between increase in bile-acid concentration and the degree of histological abnormality. As a result of these investigations empirically determined levels of plasma-paracetamol have been drawn which give a guide to the likelihood of liver damage after paracetamol overdose.

Acetaminophen↗

Identifying prognostic factors in binary outcome data: an application using liver function tests and age to predict liver metastases.

A frequent issue confronting the medical scientist is the detection of important prognostic variables, or covariates, that affect the outcome variable. In this paper we propose specific guidelines for the analysis of binary outcome data based on recent developments in statistical methodology and on less formal graphical techniques. By incorporating these methods into the process of fitting the standard logistic regression model, one can assess covariate selection and model specification more thoroughly and obtain a more balanced view of a model's predictive capabilities. We apply the methods to the evaluation of non-invasive liver function tests and age to predict the presence of liver metastases in patients with small cell lung cancer.

Age Factors↗

The effect of low-dose combined oral contraceptive pills versus injectable contraceptive (Depot Provera) on liver function tests of women with compensated bilharzial liver fibrosis.

This was an open comparative trial of two types of hormonal contraceptives, a low-dose combined oral contraceptive and the injectable depot-medroxyprogerone acetate, with a control group using an intrauterine device (copper T-380). Clients were recruited from bilharzial patients attending the maternal-child health and family centers affiliated with the National Liver Institute. Clients with compensated bilharzial liver disease were chosen and were divided into three subgroups according to their own preference for the method of contraception. Baseline, 2-, and 4-months liver function tests were compared, and abdominal ultrasound scanning of the liver was done. There was a nonsignificant change in liver function tests, and the portal vein diameter measured by ultrasound scanning was not changed with steroidal contraceptives. The use of combined oral contraceptive containing low-dose estrogen or using depot medroxyprogertone acetate injectables are safe and can be prescribed in cases with compensated bilharzial hepatic fibrosis with normal function.

Alanine Transaminase↗