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PubMed2003

Copper supplementation has no effect on markers of DNA damage and liver function in healthy adults (FOODCUE project).

BACKGROUND/AIMS: Copper is routinely used in the laboratory to promote oxidation in vitro. However, copper concentrations are million-fold higher than physiological concentrations and, in contrast, accumulating evidence suggests that copper may have an antioxidant role in vivo. The aim of this study was to provide data on how increased intake of copper affected mononuclear leukocyte DNA damage and liver function in healthy young free-living men and women. METHODS: The study design was a double-blind repeated crossover trial with treatment and intervening placebo periods, each of 6 weeks' duration. The following supplementations were given orally in sequence: CuSO(4) at a dose of 3 mg copper/day and copper amino acid chelates at doses of 3 and 6 mg copper/day. Oxidative DNA damage was assessed using a modification of the alkaline Comet assay incorporating an endonuclease III digestion step. The assessment of liver function was by measurement of the liver enzymes, alanine aminotransferase and L-gamma-glutamyltransferase. RESULTS: There was no significant alteration in mononuclear leukocyte DNA damage or on liver function after 6 weeks of copper supplementation at two doses (3 and 6 mg/day). CONCLUSIONS: Copper supplementation (giving total copper intake at the highest level of 7 mg/day) did not induce DNA damage or adversely affect liver function in healthy adults.

Adult↗
PubMed1983

Value of profiling liver function in the elderly.

The value of measuring three routine tests of liver function was assessed prospectively in 523 geriatric patients. Abnormalities were found in 27% of patients and were clinically helpful in half of these cases. Profiling liver function, without clinical indication, revealed abnormal results in 17% of patients and was important in one-third of these (6% of total). The two most important diagnoses were unsuspected osteomalacia and gall stone disease.

Aged↗
PubMed1991

Role of carcinoembryonic antigen and liver function tests in the detection of recurrent colorectal carcinoma.

The optimal laboratory evaluation for the early detection of liver metastases from colorectal cancer is controversial. This investigation was undertaken to compare the efficacy of liver function tests (LFTs) with that of carcinoembryonic antigen (CEA) levels for the early detection of liver metastases. Patients who developed liver metastases after potentially curative resections of adenocarcinoma of the colorectum between 1974 and 1988 were reviewed. The following laboratory tests were serially evaluated during the follow-up period: CEA, alkaline phosphatase (AP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and lactic dehydrogenase (LDH). These values were retrospectively assessed from the time of documented liver metastases to identify which lab value(s) were elevated initially. Ninety-two patients were available for study. Average time for the occurrence of liver metastases was 20 months (range, 3-72 months). The incidence of elevation of individual tests at the time of suspicion of liver metastasis was: CEA, 94.6 percent (P less than 0.25, chi-squared); AP, 18.5 percent; SGOT, 12.0 percent; SGPT, 5.4 percent; and LDH, 29.3 percent. When comparing CEA with a battery of LFTs at the time of suspicion of liver metastasis, CEA was elevated with normal LFTs in 64.1 percent (P less than 0.05, chi-squared), the most frequent occurrence. At least one LFT was elevated with a normal CEA in only 2.2 percent; CEA and at least one LFT were increased in 30.4 percent; and both tests were normal in only 3.3 percent. These results indicate that, of the individual laboratory tests performed, CEA elevation heralds liver metastases significantly more frequently. LDH is the liver function test most frequently elevated when liver metastases are first suspected. When CEA is directly compared with a battery of LFTs, CEA is statistically significantly more frequently elevated. In fact, suspicion of liver metastases would have been delayed by the omission of LFTs in only 2.2 percent of patients. Therefore, we conclude that LFTs should be deleted from the follow-up of colorectal cancer patients, decreasing costs without significantly decreasing accuracy.

Adenocarcinoma↗
PubMed1989

[Which factors affect the liver function most after gastrectomy in the gastric cancer patients?].

We examined the factors which influence the postoperative liver function in the gastric cancer patients who received gastrectomy by a particular surgeon. One hundred and five patients had no history of liver diseases, no blood transfusions, and no infection after the operation. They also had normal liver function preoperatively. They were anesthetized with halothane-nitrous oxide oxygen or enflurane-nitrous oxide oxygen with epidural anesthesia by the same group of anesthesiologists. GOT was followed for one month after the operation to evaluate the liver function. In 44 patients, GOT went up to above 50 IU.l-1. The maximal GOT correlated with low hemoglobin level on the 1st postoperative day, the duration of hypotension below 80 mmHg of the systolic blood pressure, and duration of the operation. These results suggest that special attention should be paid to correct hemoglobin level and to avoid hypotension during anesthesia.

Adult↗
PubMed1996

Alcoholism, hepatitis B and C viral infections, and impaired liver function among Taiwanese aboriginal groups.

Viral hepatitis and alcoholism prevail in four major Taiwanese aboriginal groups. To study the relative importance of the acquisition of hepatitis B virus or hepatitis C virus infection and alcoholism to the presence of impaired liver function in these groups, the authors conducted a semistructured clinical interview for alcoholism and test for seromarkers for viral hepatitis among 993 cohort members enrolled in 1990-1992 in an ongoing prospective study (Taiwan Aboriginal Study Project). The subjects' blood specimens were tested for serum alanine aminotransferase/aspartate aminotransferase levels and for the presence of hepatitis B surface antigen and anti-hepatitis C virus antibody. The prevalence of a combination of an alanine aminotransferase level of > 35 IU/liter and an aspartate aminotransferase level of > 40 IU/liter, implying impaired liver function or advanced liver disease, was 4.3% overall. Univariate and multiple logistic regression analysis showed that, rather than chronic hepatitis B virus infection, hepatitis C virus infection and alcoholism were the two dominant risk factors that signalled the risk of liver damage among these Taiwanese aborigines. In addition, these two contributing factors were able to act synergistically to cause impaired liver function.

Alcoholism↗
PubMed2001

Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function.

OBJECTIVES: Altered small-bowel motility, lengthening of the orocecal transit time, and small-intestinal bacterial overgrowth have been described in patients with liver cirrhosis. These changes might be related to the progressive course and poor prognosis of the disease. We investigated the effect of a long-term treatment with cisapride and an antibiotic regimen on small-intestinal motor activity, orocecal transit time, bacterial overgrowth, and some parameters of liver function. METHODS: Thirty-four patients with liver cirrhosis of different etiology entered in the study. They were randomly allocated to receive cisapride (12), an alternating regimen of norfloxacin and neomycin (12), or placebo (10) during a period of 6 months. At entry and at 3 and 6 months, a stationary small-intestinal manometry was performed, and orocecal transit time and small-intestinal bacterial overgrowth were also investigated using the H2 breath test. Liver function was estimated with clinical and laboratory measurements (Child-Pugh score). RESULTS: After 6 months, both cisapride and antibiotics significantly improved fasting cyclic activity, reduced the duration of orocecal transit time, and decreased small-intestinal bacterial overgrowth. Cisapride administration was followed also by an increase in the amplitude of contractions. No statistically significant variations in these parameters were observed with placebo. An improvement of liver function was observed at 3 and 6 months with both cisapride and antibiotics. CONCLUSIONS: Long-term treatment with cisapride or antibiotics reversed altered small-intestinal motility and bacterial overgrowth in patients with liver cirrhosis. These findings suggest a possible role for prokinetics and antibiotics as a modality of treatment in selected cases of decompensated cirrhosis.

Adult↗
PubMed1994

The influence of chronic lobular hepatitis on pharmacokinetics of cefoperazone--a novel galactose single-point method as a measure of residual liver function.

Cefoperazone is a semisynthetic cephalosporin antibiotic containing a piperazine side chain, which results in antipseudomonal activity. Unlike the other cephalosporins, it is mainly cleared by the liver (60-80%) and it may be more sensitive to changes in the liver function and/or plasma protein binding than other cephalosporins, which are not primarily cleared by the liver. In order to study the influence of chronic lobular hepatitis on the pharmacokinetics of cefoperazone, a dose of 1 g of cefoperazone was administered to 11 normal, healthy volunteers and 16 subjects with chronic lobular hepatitis. In each volunteer or patient, a novel galactose single-point (GSP) method, the galactose elimination capacity (GEC) test, and the modified galactose elimination capacity (MGEC) test were also performed as a measure of residual liver function. Cefoperazone was administered intravenously over a period of 3-5 min. Blood and urine samples were collected at appropriate intervals after drug administration and stored at -30 degrees C until high-pressure liquid chromatographic (HPLC) analysis. The cefoperazone hepatic clearance, mean residence time, and renal clearance in hepatitis patients were significantly different from those of normal healthy volunteers, whereas the plasma protein binding was unaltered between the two groups. Urinary excretion of cefoperazone showed a highly significant increase in patients, 23.95 +/- 5.06% and 37.54 +/- 13.61% for normal men and hepatitis patients respectively. Hepatic clearance and fraction excreted in urine significantly correlated with values of GSP and MGEC respectively (p < 0.05). These results suggest (i) cefoperazone kinetics was significantly altered in patients with chronic lobular hepatitis; (ii) GSP, a novel simple, clinically useful quantitative liver function test, can predict the cefoperazone hepatic clearance in patients with liver dysfunction.

Adult↗
PubMed2001

Troglitazone and liver function abnormalities: lessons from a prescription event monitoring study and spontaneous reporting.

OBJECTIVES: To investigate whether there were any cases of liver function abnormalities possibly associated with troglitazone use in general practice in England. DESIGN: A prescription-event monitoring (PEM) study was undertaken between October 1997 and December 1997. SETTING: Data from prescriptions were obtained electronically for the troglitazone cohort in the immediate postmarketing period. STUDY PARTICIPANTS: Event data were obtained for a total of 1344 patients. RESULTS: Troglitazone was effective in 394 (75%) of the 529 patients for whom an opinion was given. The most frequent reasons for stopping treatment related to drug tolerability were malaise/lassitude (16 reports), abnormal liver function tests (II reports) and nausea/vomiting (9 reports). The major cause of stopping troglitazone was because the drug was withdrawn from the market (1101 reports). 30 patients with liver dysfunction were identified from the cohort. In 9 of these patients there were alternative explanations for the liver dysfunction and hence these patients were not followed up further. 21 patients were followed up, for whom 19 questionnaires were returned. In 5 patients their liver dysfunction was assessed as possibly related to troglitazone, in 6 patients the liver dysfunction was unlikely to be attributed to troglitazone, while in 7 patients it was difficult to assess the causality because of limited information and confounding factors. The remaining patient was not included as this individual did not fit the inclusion criteria of the study. CONCLUSION: Although the cohort is small (the drug was available for only 3 months in the UK), 5 patients with abnormal liver function, considered possibly related to troglitazone were detected in this PEM study. It is possible for PEM to contribute to the elucidation of safety signals in the UK.

Adult↗
PubMed2004

Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function.

OBJECTIVES: This study was designed (1) to evaluate the effect of a cytochrome P450 (CYP) 1A2 inhibitor, fluvoxamine, on the pharmacokinetics of intravenous lidocaine and its 2 pharmacologically active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), to confirm recent in vitro results indicating that CYP1A2 is the main isoform responsible for lidocaine biotransformation and (2) to assess whether liver function has any influence on the fluvoxamine-lidocaine interaction. METHODS: The study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild (Child grade A) and 10 with severe (Child grade C) liver dysfunction, according to a randomized, double-blind, 2-phase, crossover design. In one phase all participants received placebo for 6 days; in the other phase they received 50 mg fluvoxamine for 2 days and 100 mg fluvoxamine for the next 4 days. On day 6, a 1-mg/kg lidocaine dose was administered intravenously 2 hours after the last dose of fluvoxamine or placebo. Plasma concentrations of lidocaine, MEGX, GX, and fluvoxamine were measured up to 12 hours after lidocaine injection. RESULTS: The effects of fluvoxamine coadministration were dependent on liver function. Lidocaine clearance was decreased on average by 60% (from 12.1 mL/min.kg to 4.85 mL/min.kg, P <.001) in healthy subjects and by 44% (from 9.83 mL/min.kg to 5.06 mL/min.kg, P <.001) in patients with mild liver dysfunction, with proportional increases in terminal half-lives, whereas virtually no effect was produced in patients with severe liver dysfunction (4.21 mL/min.kg versus 3.65 mL/min.kg, P >.05). Analogous effects were observed on MEGX and GX formation kinetics, which were drastically impaired in healthy subjects and patients with mild liver cirrhosis but virtually unaffected in patients with severe cirrhosis. CONCLUSION: CYP1A2 is the enzyme principally responsible for the metabolic disposition of lidocaine in subjects with normal liver function. The extent of fluvoxamine-lidocaine interaction decreases as liver function worsens, most likely because of the concomitant decrease in the hepatic level of CYP1A2. These observations indicate that results obtained in healthy subjects cannot be extended a priori to patients with liver dysfunction, but the clinical consequences of inhibition of drug metabolism must also be assessed in such patients.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Liver function tests in diabetic patients.

Nine different liver function tests (LFT) were assessed in 175 unselected diabetic outpatients stabilized on diet, insulin, or oral hypoglycemic drugs. In another group of 72 diabetic inpatients having diagnostic liver biopsy, relationships between LFT and histologic changes in the liver were investigated. Abnormalities in at least one of the tests were noted in 57% of the outpatients, and two tests gave pathologic results in 27%. The non-insulin-dependent diabetic patients more often had abnormal LFT results than did the insulin-dependent diabetic patients. Serum chenodeoxycholic acid concentrations were increased in 27%, gamma-glutamyl transpeptidase (gGT) activities in 19%, and alanine aminotransferase (Alt) activities in 17% of the outpatients, but the increases were rarely more than twice the upper limit of normal. In multivariate analysis, outpatients who were overweight, showed poor diabetes control during a short duration of diabetes controlled by treatment with diet or oral agents, and had a mature age at onset of diabetes displayed the most significant clinical explanatory variables associated with abnormal Alt. In the inpatients, the percentages of abnormal Alt and gGT results were augmented, along with increasing severity of histologic changes, but the mean values of Alt and gGT did not differ significantly between the various histologic groups. In addition, the diabetic patients with nonspecific inflammatory changes or increase in liver fibrosis often showed normal or only minor elevations in these test values.

Adult↗
PubMed1991

Abnormal results of biochemical liver function tests in breast-fed infants with prolonged indirect hyperbilirubinaemia.

To clarify the relationship between hyperbilirubinaemia and abnormal results of biochemical liver function tests in infants with breast milk jaundice (BMJ), 58 breast-fed infants with indirect hyperbilirubinaemia were enrolled in this study. Sera obtained from the above infants were subjected to routine liver function tests. Although serum transaminases were within normal limits in all 58 patients, serum alkaline phosphatase levels were abnormally increased in 13, gamma-glutamyltranspeptidase in 8 and total bile acids in 11 out of all patients examined. A total of 18 (31%) patients had abnormal results in at least one item of the liver function tests. The intrinsic bile acid loading test showed postprandial increases in bile acids in 5 of 16 (31%) patients examined at either 60 or 120 min, while all 13 breast-fed, age-matched controls had no abnormal results. The decrease in rate of serum bilirubin levels after the 3-day discontinuation of breast-feeding was significantly less in patients with increased fasting bile acids than in patients with normal fasting levels of serum bile acids. These results may suggest that mild hepatic dysfunction or cholestasis is associated with indirect hyperbilirubinaemia in some infants with BMJ.

Alkaline Phosphatase↗
PubMed1988

Long-term effect of nadolol on quantitative liver function tests in patients with cirrhosis.

Nadolol, a non-cardioselective beta adrenoreceptor blocking agent, has been reported to decrease portal pressure without affecting liver function in cirrhotic patients treated for 1 month. There were no data about the long-term effects of nadolol on liver function. In 11 patients with cirrhosis and portal hypertension galactose eliminating capacity, aminopyrine metabolic capacity, ICG clearance and IGC intrinsic hepatic clearance according to the "parallel tube" model were measured before and after 6 months of treatment with nadolol at a dose reducing resting heart rate by approximately 25%. No significant variation in any of these parameters was found. Thus 6 months of continuous oral administration of nadolol did not further impair liver function in cirrhotics.

Adult↗
PubMed1989

Protective effect of vasodilators on liver function after long hypothermic preservation: a study in the isolated perfused rat liver.

The effects of two vasodilators, papaverine and pentoxifylline (a methylxanthine derivative), on liver function after 19 hr hypothermic preservation were investigated. Hypothermic preservation was performed according to the standard technique, and liver hemodynamics and function were studied during 70 min immediately after reperfusion in an isolated perfused rat liver system. No significant changes occurred after hypothermic storage for 5 hr. However, when the storage was prolonged to 19 hr, bile flow and taurocholate intrinsic clearance were significantly reduced; transaminase release was markedly increased and histological studies demonstrated centrilobular necrosis. Concomitantly, liver blood flow was significantly reduced and intrahepatic vascular resistance was increased. Papaverine and pentoxifylline administered during preservation and at the time of reperfusion significantly improved all parameters. The improvement was more pronounced after pentoxifylline, and this group showed no significant difference in any of the studied parameters from the control livers. The results show that two vasodilators significantly protect the liver during long hypothermic preservation. The data suggest that abnormalities of liver microcirculation are of major importance in the pathogenesis of liver injury after hypothermic storage.

Animals↗
PubMed1984

[Grading of tricuspid regurgitation by pulsed Doppler echocardiography and liver function tests].

Recently, pulsed Doppler echocardiography has been used for the quantitative evaluation of tricuspid regurgitation (TR). However, there are some problems about the clinical significance of TR diagnosed by Doppler examination probably because of the excellent sensitivity in detecting TR. In the present study, we used liver function tests as an indicator of the visceral damage caused by TR and compared them to the severity of TR estimated by Doppler examination. Forty Doppler examinations were performed in 33 cardiac patients including seven, in which the examinations were repeated because the severity of TR changed during the clinical course. The severity of TR was classified into four grades according to the maximal extent of the regurgitant signal. Abnormal liver function was defined by the abnormalities of at least one of the following six tests: cholinesterase (CHE), gamma-GTP, leucine aminopeptidase (LAP), total bilirubin, alkaline phosphatase and GPT. Abnormal liver function tests were present in one of eight patients without TR, two of 10 with 1 + TR, four of seven with 2 + TR, seven of eight with 3 + TR, and six of seven with 4 + TR. The incidence of abnormal liver function tests increased parallel to the grade of TR and was very frequent in patients with 3 + or 4 + TR. TR diagnosed as greater than 3 + by Doppler examination is considered to have an important clinical significance and an indication of the intensive therapy.

Cholinesterases↗
PubMed1989

Disturbed liver function in heart transplantation candidates: two case reports.

Heart transplantation candidates frequently have a disturbed liver function. Two cases with jaundice are described in whom the cause and prognosis of the associated liver disease were analysed. In the 4-yr period during which heart transplantation patients with a disturbed liver function were investigated, "cirrose cardiaque" was not encountered; liver tests usually normalized after a successful heart transplant.

Adult↗