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PubMed1991

Theophylline pharmacokinetics and liver function indexes in chronic liver disease.

Since patients with chronic liver disease present with greatly varying theophylline disposal reductions, in cirrhotics the acute theophylline dose schedule must be guided by an index of liver function that predicts theophylline pharmacokinetics. We therefore studied 26 patients with severe chronic liver disease to ascertain the efficacy of the routinely used clinical and biochemical liver function tests in predicting theophylline pharmacokinetics. The prealbumin plasma level, recently proposed as a valuable index of liver function, was also considered. With respect to 10 controls, theophylline clearance was found to be significantly reduced (30 +/- 2 vs. 75 +/- 11 ml/kg/h, mean +/- SD, p less than 0.01). However, only 7 patients had a reduction great enough to require a reduced intravenous theophylline dose schedule. An analysis of clinical utility, made on the basis of ROC curves, showed that the albumin/globulin ratio was the most effective index for identifying patients requiring lower doses of theophylline. Prealbumin and albumin were also useful, whereas bilirubin, prothrombin time, pseudocholinesterase, the presence of ascites and Pugh-Child's classification of the severity of liver disease were found to be worthless.

Adult↗
PubMed1986

Effect of acute portal hypertension on hepatosplanchnic hemodynamics and liver function.

Acute prehepatic portal hypertension was mechanically induced in Göttingen minipigs. A 125% increase in portal pressure resulted in a significant decrease in estimated hepatic blood flow. The decrease in blood flow was accompanied by a 25% reduction in the 'true' clearance of indocyanine green and an 18% decrease in splanchnic oxygen consumption. Judged from the splanchnic elimination rate of galactose, the functional liver cell mass was not altered by portal banding, and an unaltered lactate to pyruvate ratio in hepatic venous blood indicated that no functional parts of the liver became severely hypoxic.

Animals↗
PubMed2001

Liver function tests during amoebic liver abscess formation in indomethacin-treated hamsters.

Establishment of Entamoeba histolytica infection is facilitated through macrophage effector disruption by a prostaglandin E2 (PGE2)-mediated mechanism. Infection severity may be measured by weight of abscess formed. Indomethacin (Indo) treatment of infected hamsters reduced abscess weight by 30% at 7 days post-infection presumably by inhibition of PGE2. To explain reductions in abscess development by Indo treatment, we determined liver functionality in Indo-treated or untreated animals, either healthy or infected. Determinations of serum glutamic oxaloacetic (SGOT) and glutamic pyruvic (SGPT) transaminases, serum alkaline phosphatase (SAP), total serum protein (TSP), and bilirubinemia were done. SGOT, SGPT, and SAP activities showed a significant increase in their values by 600% at seven days post-infection in infected animals in both conditions; nonstatistical differences were found between animals treated or not. This increase did not correlate with the percentage of damage. Infected nontreated hamsters showed TSP levels 30% below normal group (P < 0.05). Infected Indo-treated hamsters had no significant differences compared to normal values. Infected nontreated animals showed an increase in bilirubin, particularly in indirect bilirubin, whereas infected Indo-treated hamsters showed total bilirubin values lower than normals (P < 0.05), with a decrease in direct bilirubin levels. Our results demonstrated that E. histolytica infection in hamsters produces similar abnormalities in liver function as it does in humans, and that the beneficial effect of Indo treatment on amoebic abscess development is not related with an improvement of liver functionality.

Animals↗
PubMed1984

Interpreting the profile of liver-function tests in pediatric liver transplants.

Results of traditional laboratory tests of liver function were correlated with the clinical course in 26 pediatric patients after liver transplantation. On the basis of clinical outcome after transplantation, the patients were divided into two groups: (a) uncomplicated course with short hospital stay, and (b) post-transplantation course complicated by multiple clinical problems. The patterns of results for tests reflecting liver function--bilirubin (total and conjugated), aspartate (EC 2.6.1.1) and alanine (EC 2.6.1.2) aminotransferases, and gamma-glutamyltransferase (gamma GT, EC 2.3.2.2)--were consistent with the clinical findings in these patients. Values for alkaline phosphatase (EC 3.1.3.1), however, were only rarely increased, even when there was clinical evidence of biliary obstruction. Not only was serum gamma GT increased in obstructive jaundice, but this sometimes was the only test giving results outside the normal limits. We suggest that the persistent and marked increases of gamma GT observed in half of the patients may have resulted from immune-mediated damage to the transplanted liver.

Adolescent↗
PubMed1987

Markers of allograft viability in the rat. Relationship between transplantation viability and liver function in the isolated perfused liver.

The relationship between transplant viability and liver function has been examined. Wistar rat livers were preserved at 4 degrees C for increasing intervals and then transplanted into Wistar rat recipients. Two critical times were identified, the longest preservation period with 100% transplantation success (4 hr) and the shortest preservation period with 100% transplant failure (8 hr). The comparable critical times were also identified in livers preserved at 37 degrees C (1 hr and 2 hr). Liver functions were studied by the isolated perfused liver technique in other rat livers stored at 4 degrees C or 37 degrees C for the critical times. Two liver function tests, AST and LDH concentration in perfusate, discriminated between viable and nonviable livers across as well as within preservation groups. AST gave the best separation between viable and nonviable livers. Some functions such as ALT concentration in perfusate separated viable from non viable allografts only within preservation groups. Other liver functions were more sensitive to preservation temperature than allograft viability. Oxygen consumption after cold preservation for either critical time was about twice control levels. Urea production was far below control levels in warm-preserved livers but almost normal in cold-preserved livers. Our results indicate that AST release into perfusate can be used as a screening technique to optimize preservation methods, reserving transplantation for confirming the most promising results.

Animals↗
PubMed2001

"Liver function tests" are not always tests of liver function.

A child with Wilm's tumor and a child with immune thrombocytopenic purpura (ITP) were each noted to have persistent elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). Both children underwent thorough evaluation for liver disease and, as a result, experienced delays in treatment of the Wilm's tumor and ITP. Eventually both children were found to have extremely elevated serum creatine kinase (CK). Muscle biopsy confirmed diagnoses of Duchenne's muscular dystrophy in one child, and Becker's muscular dystrophy in the second. Hematologists/oncologists should consider obtaining a serum CK to rule out muscle disease in patients with unexplained elevations of AST, ALT, and LDH.

Alanine Transaminase↗
PubMed2005

Phosphorus-31 MR spectroscopy in pediatric liver transplant recipients: a noninvasive assessment of graft status with correlation with liver function tests and liver biopsy.

OBJECTIVE: Noninvasive in vivo hepatic phosphorus-31 MR spectroscopy has recently been shown to provide information about hepatic functional status. We sought to show the correlation of phosphorus-31 MR spectroscopy with blood biochemistry and liver biopsy results in pediatric patients after liver transplantation. MATERIALS AND METHODS: Eleven pediatric transplant recipients (eight with good graft function, two with chronic hepatitis, and one with acute rejection) and four healthy control subjects were studied with in vivo 31P MR spectroscopy. Ratios of phosphomonoesters (PME) to total phosphorus (TP), phosphodiester (PDE) to TP, nucleotide triphosphates (NTP), inorganic phosphate (Pi), and intracellular acid-base status (pH) were measured. Liver function test (n = 11) and biopsy (n = 3) results were obtained for correlation with spectroscopic findings. RESULTS: The eight patients with good graft function displayed spectral profiles similar to those of the healthy subjects, and no significant difference in the metabolic ratios of these patients compared with the control subjects was detected. Three patients with abnormal liver function and biopsy-proven hepatic complications showed elevated PME/TP ratios when compared with those of both the control subjects and the group with good graft function. CONCLUSION: Phosphorus-31 MR spectroscopy is a feasible technique for the noninvasive assessment of host-related complications in pediatric patients after liver transplantation. Our preliminary data suggest that the technique may be integrated with MRI for the investigation of impaired liver function in transplant recipients when neither a biliary complication nor a vascular complication is identified.

Adolescent↗
PubMed2003

Presence of methylated arginine derivatives in orthotopic human liver transplantation: relevance for liver function.

Orthotopic liver transplantation (OLT) is a frequent option in the treatment of liver diseases. During the cold ischemia period of the donor liver, there is an accumulation of metabolites that are potent inhibitors of the cytokine-inducible and endothelial nitric oxide synthase isoenzymes. We identified the presence of L-N-monomethylarginine and asymmetric dimethylarginine (ADMA) as the main inhibitors by means of analytic high-pressure liquid chromatography and mass spectrometry techniques. An average ADMA concentration of 450 micromol/L was measured in the preservation medium of donor livers with poor outcomes after OLT. A statistically significant relationship was observed between the concentration of methylated arginine derivatives in the graft and liver function after OLT. These data suggest that measurement of methylated arginine, released after liver protein catabolism, might provide an indication of functional status of the liver that can help the development of strategies intended to improve graft viability.

Animals↗
PubMed2007

Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis.

BACKGROUND AND OBJECTIVE: To assess the influence of hepatitis C virus (HCV) co-infection and the extent of liver fibrosis on lopinavir/ritonavir pharmacokinetics in HIV-infected patients without liver function impairment. METHODS: Cross-sectional, comparative study enrolling HIV-infected adults receiving lopinavir/ritonavir (400 mg/100 mg twice daily). HIV/HCV co-infected patients were grouped as having advanced fibrosis (HCV+/FIB+, n=7) or not (HCV+/FIB-, n=8) based on the FIB-4 index. A full concentration-time profile was obtained for each patient, and blood samples were collected before (0), and 1, 2, 4, 6, 8, 10 and 12 hours after a lopinavir/ritonavir dose. Lopinavir and ritonavir concentrations in plasma were determined by high-performance liquid chromatography. Maximum and minimum plasma concentrations (Cmax and Cmin), area under the plasma concentration-time curve from 0 to 12 hours (AUC12), apparent oral clearance at steady state (CLss/F), and apparent volume of distribution after oral administration (Vd/F) were calculated for each individual using a non-compartmental approach. RESULTS: Twenty-six HCV- and 22 HCV+patients were enrolled. Lopinavir and ritonavir pharmacokinetics were comparable between HCV- and HCV+patients. However, the Vd/F of lopinavir was 125% higher in HCV+/FIB+patients than in HCV-patients (p=0.015) and 107% higher than in HCV+/FIB-(p=0.040) patients. The CLss/F of ritonavir was 40% lower in HCV+/FIB+patients than in HCV-patients (p=0.005) and 44% lower than in HCV+/FIB-patients (p=0.040). Thus, for ritonavir AUC12, Cmax and Cmin in HCV+/FIB+patients were 63%, 86% and 100% higher, respectively, when compared with those parameters in HCV-patients (p=0.005, p=0.012 and p=0.015, respectively), and 80%, 86% and 100% higher, respectively, when compared with levels in HCV+/FIB- patients (p=0.040, p=0.040 and p=0.029, respectively). CONCLUSION: Lopinavir exposure is similar in HIV-infected patients with or without HCV co-infection and without liver function impairment. However, ritonavir exposure may be higher in this setting, particularly in individuals with advanced liver fibrosis.

Area Under Curve↗