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Neuromuscular paralysis as a pharmacodynamic probe to assess organ function during liver transplantation.

Potential for assessing liver function during liver transplantation surgery by monitoring muscle paralysis from nondepolarizing neuromuscular blockers that are hepatically cleared is critically assessed. Rocuronium is strongly favored as a promising pharmacodynamic probe for predicting allograft liver function because it is predominantly eliminated via the liver and its putative metabolites are not active. Prolongation of recovery from rocuronium paralysis is closely correlated with allograft liver function postoperatively. Vecuronium, pancuronium, and perhaps pipecuronium may also prove to be useful probes, but the two former blockers have active metabolites. Further prospective studies are necessary with more precise measurement of neuromuscular function to confirm the predictive value of this method. Alterations in neuromuscular blocker plasma concentrations that are correlated with changes in liver function and either the dose required or the intensity or duration of paralysis needs to be demonstrated for this technique to be clinically useful.

Androstanols↗

Differential diagnosis of cholestasis following allogeneic hematopoietic stem cell transplantation in children: the contribution of serum bile acid levels in relation to other liver function tests.

Hepatic complications associated with cholestasis occur frequently in hematopoietic stem cell transplant recipients. Since bile acid seems to be a sensitive indicator of beginning cholestasis, the authors monitored total serum bile acid levels in addition to the standard liver function tests in 23 recipients of allogeneic transplants between June 1999 and September 2000. The observations suggest that bile acid is an early and sensitive marker of hepatic GvHD but not as specific as bilirubin. For cholestasis in absence of hepatic GvHD bile acid seems to be more sensitive than bilirubin. Routinely monitoring of bile acid after hematopoietic stem cell transplantation is not indicated.

Adolescent↗

Impaired liver function in stable renal allograft recipients.

Hepatic failure as a cause of death is increased in stable renal allograft recipients when compared with patients on dialysis. In order to assess the magnitude and the natural history of the hepatic functional derangement, the kinetics of xenobiotics which are metabolized by cytosolic (galactose) or microsomal (prednisolone, cyclosporine A) enzymes were determined in 28 consecutive stable kidney transplant patients 1 month and 1 year after transplantation. Renal transplant patients had a decreased mean (+/- S.D.) galactose elimination capacity at 1 month (6.26 +/- 0.94 mg per min x kg) and at 1 year (5.93 +/- 0.96 mg per min x kg), when compared with a different group of 28 healthy control subjects (7.52 +/- 0.78 mg per min x kg, p less than 0.001) and a decreased total body clearance of prednisolone at 1 month (2.13 +/- 0.34 ml per min x kg vs. 2.71 +/- 0.43 ml per min x kg in controls, p less than 0.001), which further decreased over the following year to 1.76 +/- 0.32 ml per min x kg (p less than 0.001). The clearance of cyclosporine A declined significantly during the first year of successful transplantation (5.9 +/- 2.1 ml per min x kg vs. 4.9 +/- 1.2 ml per min x kg, p less than 0.05). In conclusion, a substantial proportion of stable renal transplant recipients have decreased cytosolic and microsomal liver functions despite the absence of clinical and laboratory evidence of significant liver disease.

Cyclosporins↗

Routine liver function tests and serum amylase determinations after biliary lithotripsy: are they necessary?

Shock-wave-induced soft-tissue damage after biliary extracorporeal shock-wave lithotripsy (BESWL) has been reported. Every patient treated in Vancouver has, therefore, had liver function tests and serum amylase levels measured before and within 6 days after BESWL. All patients had symptomatic cholecystolithiasis with normal pre-BESWL biochemistry. Analysis of 311 patients after treatment with the Siemens Lithostar unit showed elevation of one or more laboratory value in 19% (60/311). Serum aspartate transaminase level was most frequently abnormal (38 cases). The majority of abnormalities were mild, less than two times normal levels. Clinically significant complications occurred in five patients (three pancreatitis, one cholecystitis, one common bile duct obstruction); four of these occurred 1 week or more after treatment. The results of routine laboratory tests could not be used to predict complications. No correlation was seen between abnormal values and number of shock waves administered or peak shock-wave pressure. Of 112 patients surveyed at the time of post-BESWL enzyme measurement, 49 (44%) reported a degree of pain, which was severe in eight cases. Presence of severe pain correlated strongly (p less than .001) with abnormal laboratory findings, however not with the degree of abnormality. As results of these laboratory tests are nonspecific, have not been shown to correlate with the degree of severity of BESWL-induced tissue damage, and do not predict complications, the tests are of little value in the absence of clinical signs and symptoms. These conclusions, however, apply only to the Siemens Lithostar Plus with patients treated in the steep left posterior oblique position. Cost savings can be expected if routine post-BESWL biochemical tests are abandoned.

Adolescent↗

Liver function tests and urinary albumin in house painters with previous heavy exposure to organic solvents.

The serum activities or concentrations of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), albumin, gamma-glutamyl transpeptidase (GGT), bilirubin (BIL), cholic acid (CHOL), chenodeoxycholic acid (CHENO), and transferrin with isoelectric point 5.7, and the urinary excretion of albumin were determined among male current or former house painters (n = 135) and house carpenters (n = 71) who had worked in their trades for at least 10 years before 1970. Workers who showed a value above the 90th percentile among the carpenters in at least one of the tests ASAT, ALAT, GGT, BIL, CHOL, or CHENO were regarded as showing "possible signs of liver dysfunction". Each participant's lifetime solvent exposure was evaluated by interview. The painters were divided into categories with low, intermediate, and heavy cumulative exposure during life (LTSE) or during the most exposed year (MEYSE). All participants stated none or slight recent exposure. The prevalence of possible signs of liver dysfunction increased with solvent exposure category according to LTSE as well as MEYSE with a numerically higher risk estimate in the heavy exposure category for MEYSE than for LTSE. ALP activity increased with exposure category according to both exposure estimates. This increase seemed to be due to an interaction between exposure to solvents and current or previous long term intake of medicines potentially toxic to the liver. None of these results was affected by whether or not the subjects had been exposed to solvents during the year before the investigation. The exposure to solvents was not significantly related to any other outcome variable. It is concluded that long term heavy exposure to solvents may elicit changes in conventional liver function tests indicative of a mild chronic effect on the liver. The findings also suggest that heavy solvent exposure during short time periods is a more likely cause of the findings than lifetime cumulative solvent exposure and that an interaction between solvent exposure and medicines potentially harmful to the liver may be important in the causation of the effects.

Aged↗

[Liver function test impairment induced by propafenone in a 73 year old woman].

Propafenone hydrochloride is a drug used for treating arrhythmia. The drug is usually well tolerated, although there are cardiovascular as well as non-cardiovascular side effects. The latter usually occur in the digestive tract and the neurological system. The rarest side effect is cholestasis. The literature cites five reported cases. This phenomenon is generally accompanied by clinical symptoms and upon discontinuation of the treatment with propafenone, the liver function tests return to the normal range. We review the literature dealing with liver damage resulting from treatment using propafenone. This is a case study of a 73-year old woman with three exposures of cholestasis connected to treatment with propafenone. The literature background and the case history were presented in order to heighten the physician's awareness of this rare phenomenon.

Aged↗

Antenatal detection of abnormal liver function tests - a marker for poor perinatal outcome.

The purpose of this study was to examine (a) the incidence of liver disease diagnosed in our antenatal population, (b) the diagnostic value of initial symptoms and liver function tests (LFTs), (c) the adequacy of investigation and management of the liver disorder and (d) the obstetric and neonatal outcome in this group of patients. Women with abnormal LFTs that delivered at our hospital over a 2-year period were identified from computerised hospital records and data was obtained from chart review. Forty-six out of a total of 13 181 (0.35%) women had liver disease diagnosed in pregnancy: Diagnoses included intrahepatic cholestasis of pregnancy (13), pre-eclampsia and the HELLP syndrome (eight), acute fatty liver of pregnancy (three), hyperemesis gravidarum (one), hepatitis C (13), B (four) and hepatitis A (one), cholelithiasis (two) and hepatitis of unknown aetiology (one). Symptoms at presentation were more predictive of the final diagnosis than the initial LFT profile. Investigation of the liver disorder was incomplete in 50% of cases. One mother required intensive care for 6 weeks postpartum and three others had significant postpartum haemorrhage. There was one neonatal death and 24 neonates were admitted to the special care baby unit. Eighteen women attended for their postnatal check up at 6 weeks. Eight of these women were referred to a hepatologist. Detection of liver disease in pregnancy identifies a group at risk of poor neonatal and maternal outcome. Structured guidelines should be implemented in obstetric units to facilitate appropriate investigation, treatment and referral patterns for these women.

Journal Article↗

Effects of colchicine on liver functions of cirrhotic rats: beneficial effects result from stellate cell inactivation and inhibition of TGF beta1 expression.

Liver cirrhosis (LC) is a chronic disease with high mortality rate and its pathophysiology includes hepatic parenchymal cell destruction, connective tissue formation, and nodular regeneration. Colchicine has been used in liver diseases as an anti-inflammatory and anti-fibrotic drug. However, there is controversy over the beneficial effects of colchicine in LC treatment. In the present study, we injected rats with multiple doses of dimethylnitrosamine for 4 weeks and used rats with severe LC to determine whether colchicine treatment improved liver functions and resolved cirrhotic nodules. Colchicine (30-150microg/kg per day, i.p., for 4 weeks) failed to significantly increase the survival rate of LC rats. Animals were subjected to blood biochemical, liver histopathological and immunochemical analyses. The plasma albumin level, decreased in cirrhotic rats, was restored by colchicine treatment along with reduction of ascites. Colchicine decreased the accumulated extracellular matrix and the multiple fibrotic nodules formed in cirrhotic liver, and eliminated alpha-smooth muscle actin (alpha-SMA)-positive cells. In activated stellate cells, colchicine inhibited alpha-SMA and transforming growth factor-beta1 (TGFbeta1) expression. The results of the present study showed that colchicine resolves cirrhotic nodules and accumulated fibers in the liver of LC rats, but failed to significantly improve the survival rate of LC animals, and that the beneficial effects of colchicine in cirrhotic animals result from stellate cell inactivation and inhibition of TGFbeta1 expression.

Animals↗

[Disorder of liver functions in a schizophrenic patient after long-term risperidone treatment--case report].

We present a 51-year old man with an 18-year history of chronic paranoid schizophrenia. The last four years he was treated only with risperidone at a dose of 3 mg per day. He was admitted to hospital due to a psychotic decompensation. Jaundice and skin pruritus were also observed at admission. Laboratory tests revealed elevated liver enzymes. Cholestatic and viral hepatitis were excluded. Risperidone was changed to other antipsychotic drugs. After 7 weeks of treatment the patient was discharged with significant improvement of his mental condition. The liver function test results returned to normal values except for the slightly increased total bilirubin level. Regular liver monitoring was suggested. In this case liver dysfunction was possibly correlated with long-term risperidone therapy.

Antipsychotic Agents↗

[Studies of biotransformation and liver function from the occupational medicine viewpoint].

General principles of biotransformation are described. Using examples from literature interindividual differences in the biotransformation capacity (induction and disposition) are discussed, especially concerning the combined effect of several xenobiotics (i.e., chemical working materials, ethanol, and drugs). The indocyanine greene excretion rate, the galactose elimination capacity and the 14C-aminopyrine breath test are described in detail as quantitative liver function tests.

Breath Tests↗

Effects of medroxyprogesterone on the liver function and drug metabolism of patients with primary biliary cirrhosis and chronic active hepatitis.

Effects of medroxyprogesterone acetate on the clinical course of six patients with primary biliary cirrhosis (PBC) and chronic active hepatitis (CAH) were investigated. The response in all subjects was good; the subjective symptoms decreased, the liver function tests showed a tendency towards normal values. Furthermore, the levels of serum antibodies declined and the hepatic metabolic ability, as tested by serum albumin levels and indices of drug metabolism, improved. The beneficial influence of progesterone on the patients may be due to the immunosuppressive effect and enhancement of protein synthesis. The results suggest that medroxyprogesterone may be a valuable alternative for patients with autoimmune liver disease, particularly in cases developing resistance or undesirable reactions to the previous therapy.

Adult↗