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PubMed1991

Ciclosporin metabolite pattern in blood and urine of kidney graft patients in relation to liver function.

Ciclosporin, an immunosuppressant, is metabolized by the liver cytochrome P450 system. Changes in the pattern of its metabolites in blood and urine in patients with disturbed liver function have been studied. Forty seven kidney graft patients receiving 2.9 mg/kg/d ciclosporin b.i.d., and no additional medication that would interfere with ciclosporin metabolism, were allocated to three groups according to liver function: I with normal liver function (n = 19), II with elevated liver enzyme activity or bilirubin concentration in serum (n = 20), and III with cholestasis (n = 8). Ciclosporin and 17 metabolites were determined in blood and 24 h-urine. In blood the trough concentrations of metabolites M19 and M1A were significantly higher in group III than in groups I and II. The total quantity of metabolites excreted in 24 h-urine was significantly different for H230, M4N69 and M1A (group III greater than I = II). Renal excretion of the daily dose of ciclosporin in patients in group I was 2.7%, group II 3% and group III 5.7%. In group III compared to group I the ciclosporin metabolite pattern was shifted to a relatively higher concentration of M19 in blood and of H 230, M19 and M1A in urine. Since high ciclosporin metabolite concentrations appear to be associated with nephrotoxicity, the metabolite pattern in patients with impaired liver function should be monitored.

Alanine Transaminase↗
PubMed1995

The relationship between the morphology of nucleus of liver cells and the liver functions and prognosis of portal hypertension due to hepatic cirrhosis.

The morphology of nucleus of liver cells from 30 patients with portal hypertension due to hepatic cirrhosis and 5 normal persons were measured using an image analyzer coupled with a computer. It was found that the diameters, perimeters, areas and form factor (FF) of the nucleus of liver cirrhosis portal hypertension patients were significantly increased as compared with those of the normal subjects (P < 0.05 or P < 0.01). There was a very significant difference in this parameters between the normal persons and patients with Child-Pugh A liver function or patients with Child-Pugh C liver function (P < 0.01 for both). Significant difference in these parameters existed between the normal persons or patients with Child-Pugh A liver function and patients with liver function of Child-Pugh B (P < 0.05). No significant difference in the parameter of optic density (OD) were found between the normal persons and patients with impairment of liver function of varying degrees (Child-Pugh Classification) (P > 0.05). Our results suggest that the hepatocytes of patients with portal hypertension due to hepatic cirrhosis became juvenile and the morphology of the hepatocytes of patients with impairment of liver function of Child-Pugh C changed obviously. The enlargement and sparsity of nucleus of hepatocytes as revealed by pathological examination is a sign of severe impairment of liver function.

Adult↗
PubMed2004

Preoperative assessment of postoperative remnant liver function using hepatobiliary scintigraphy.

UNLABELLED: Hepatic resection is the therapy of choice for malignant and symptomatic benign hepatobiliary tumors. The concept of remnant liver volume (RLV) has been introduced and can be assessed with CT. However, inhomogeneous liver function distribution and a lack of correlation between morphologic hypertrophy and functional recovery fuelled the enthusiasm for functional imaging. The aim of the present study was to assess liver function reserve (LFR) and remnant liver function (RLF) before and after major liver surgery with hepatobiliary scintigraphy (HBS) and to compare scintigraphic results with volumetric CT data and indocyanine-green (ICG) clearance test results. Furthermore, HBS was used to assess functional recovery of liver function, and results were compared with volumetric data. METHODS: Fifteen patients with a partial liver resection were included. HBS was performed before, 1 d after, and 3 mo after surgery. ICG clearance and CT were performed before and 3 mo after surgery. Liver function determined with HBS was compared with ICG and volumetric data. RESULTS: Liver function determination using HBS was highly reproducible. A strong positive association (r = 0.84) was found between LFR determined with HBS and ICG clearance. Little or no association (r = 0.27) was found between CT volumetric analysis and corresponding ICG clearance. A strong positive association (r = 0.95) was found between the RLF determined preoperatively on HBS and the actually measured value postoperatively. A weak positive association (r = 0.61) was found between functional liver regeneration and liver volume regeneration in the 3 mo after partial liver resection. CONCLUSION: HBS offers a unique combination of functional liver uptake and excretion with the ability to assess the preoperative LFR and to estimate the RLF preoperatively. Determination of the RLF instead of the RLV might clarify some of the discrepancies observed in the literature between RLV and clinical outcome in patients with an inhomogeneous liver function. Finally, liver function regeneration can be monitored using HBS.

Adult↗
PubMed2006

Possible relations between thyroid function, endothelium, and kidney and liver function in kidney allograft recipients.

BACKGROUND: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes. AIM AND METHODS: This cross-sectional study examined thyroid hormones in relation to markers of endothelial damage and inflammation among 80 kidney allograft recipients and 29 healthy volunteers. Thyroid hormones, markers of endothelial damage (vWF, thrombomodulin, intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146), markers of inflammation (hsCRP), other hemostatic parameters (thrombin-antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet glycoprotein [V-GPV]) as well as P-selectin were measured using commercially available kits. RESULTS: Total T3 was significantly lower among kidney allograft recipients, whereas markers of endothelial dysfunction and inflammation were significantly elevated over controls. In kidney allograft recipients total T3 was independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin, urea, eGFR, dose of cyclosporine and treatment with mycophenolate mofetil/azathioprine. Total T4 was related to aspartate and alanine aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and cyclosporine dose. In healthy volunteers GPV was related only to TSH. CONCLUSIONS: We described novel relations between thyroid hormones and markers of endothelial dysfunction in kidney transplant recipients. In kidney transplant recipients thyroid function metrics were associated with endothelial damage, immunosuppressive treatment, liver and kidney function. Therefore, the relations between thyroid axis and endothelium in kidney allograft recipients merit additional studies.

Adult↗
PubMed1996

Liver function in early Lyme disease.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

Adult↗
PubMed1989

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Aged↗
PubMed2006

Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis.

BACKGROUND/AIMS: Mammalian target of rapamycin (mTOR) signalling is central in the activation of hepatic stellate cells (HSCs), the key source of extracellular matrix (ECM) in fibrotic liver. We tested the therapeutic potential of the mTOR inhibitor rapamycin in advanced cirrhosis. METHODS: Cirrhosis was induced by bile duct-ligation (BDL) or thioacetamide injections (TAA). Rats received oral rapamycin (0.5 mg/kg/day) for either 14 or 28 days. Untreated BDL and TAA-rats served as controls. Liver function was quantified by aminopyrine breath test. ECM and ECM-producing cells were quantified by morphometry. MMP-2 activity was measured by zymography. mRNA expression of procollagen-alpha1, transforming growth factor-beta1 (TGF-beta1) and beta2 was quantified by RT-PCR. RESULTS: Fourteen days of rapamycin improved liver function. Accumulation of ECM was decreased together with numbers of activated HSCs and MMP-2 activity in both animal models. TGF-beta1 mRNA was downregulated in TAA, TGF-beta2 mRNA was downregulated in BDL. 28 days of rapamycin treatment entailed a survival advantage of long-term treated BDL-rats. CONCLUSIONS: Low-dose rapamycin treatment is effectively antifibrotic and attenuates disease progression in advanced fibrosis. Our results warrant the clinical evaluation of rapamycin as an antifibrotic drug.

Administration, Oral↗
PubMed1994

Sodium retention does not occur at a critical threshold of liver function in alcoholic cirrhosis.

Sodium retention is triggered in rats with experimental liver injury at a critical threshold of liver function. We compared liver function and sodium retention in serially studied patients with alcoholic cirrhosis to determine whether a similar threshold exists in human beings. Antipyrine, caffeine, and cholic acid clearance were measured in 35 men with alcoholic liver disease. Nineteen patients were evaluated on two or more occasions; between studies, 28 remained in sodium balance (group NN), six spontaneously developed sodium retention and ascites formation (group NY), and seven spontaneously lost ascites (group YN). A threshold between patients with and without sodium retention did not exist for any of the clearance measurements. Indeed, values overlapped widely between the two groups. Antipyrine and cholate clearance were significantly reduced in patients with sodium retention, but caffeine clearance was similar in the two groups. Antipyrine and caffeine clearance declined significantly between the first and second study in group NY; cholate clearance did not change. No significant differences were observed between studies in group YN. In several patients of this group, liver function worsened as ascites spontaneously resolved. Impaired liver function commonly but not invariably accompanies sodium retention in patients with cirrhosis. A threshold at which sodium retention occurs or resolves does not exist.

Antipyrine↗
PubMed1992

Hemodynamic and liver function predictors of serum hyaluronan in alcoholic liver disease.

To define hepatic predictors of serum hyaluronan in patients with chronic liver disease, 62 patients with alcoholic liver disease were evaluated. In group 1, 30 patients had concurrent assessment of serum hyaluronan, liver function tests, Pugh grade and hemodynamic indices. A second, overlapping group of 42 patients (group 2) also had antipyrine clearance measured but without hemodynamic assessment. All but six patients had elevated serum hyaluronan levels. In both groups, serum hyaluronan levels differed between Pugh grades and, in each group, was significantly greater in Pugh grade C compared with those in Pugh grade A (p less than 0.05, Kruskal-Wallis test). When analyzed by correlation, serum hyaluronan was significantly associated with several indices in group 1, but on multivariate linear regression only three statistically independent predictors of serum hyaluronan were identified: serum albumin (p = 0.008), indocyanine green clearance (p = 0.024) and indocyanine green extraction (p = 0.036). The overall R2 for these correlates was 65%. In the second group, antipyrine clearance was not significantly associated with serum hyaluronan (r = 0.29, p = 0.06), but other associations were similar to the first group. On multivariate analysis, only serum albumin predicted serum hyaluronan (p less than 0.001; R2 = 43%). In conclusion, indices of hepatocyte synthetic function, sinusoidal blood flow and degree of intrahepatic shunting are independent predictors of serum hyaluronan in alcoholic liver disease. These data show the unique nature of serum hyaluronan and suggest its potential application to the assessment of acute hemodynamic changes in patients with liver disease.

Adult↗
PubMedDate not supplied

Tumor markers, liver function tests and symptoms in 115 patients with isolated colorectal liver metastases.

Development of the hybridoma technique has made the identification of several new tumor antigens possible. Although it was hoped that they would be more tumor-specific, none of these markers are found exclusively in tumor or in serum of tumor patients. Compared with carcinoembryionic antigen (CEA) and liver function tests, the roles of these markers (CA 19-9, CA 125, CA 15-3) were prospectively evaluated in 115 patients with colorectal liver metastases. Patients were classified according to tumor volume (T1 less than 25%, T2 25-75%, T3 greater than 75%), and the extension of infiltration (solitary/multiple/diffuse; unilateral, bilateral). Patients with benign liver or biliary disease served as a control group (n = 63). Overall sensitivity was 87% for *1, 50% for *2 and 38% for *3, with a significant correlation with tumor size. CEA serum levels were elevated in 88% of all patients. CA 19-9 was less sensitive: positive in 59%. Because of some complementary elevations, the combined use of CEA, CA 19-9 and CA 125 raised sensitivity to 94%. CA 19-9 and LDH could be useful for confirmation because of their higher specificity; however, the specificity of CEA rose to 93% on using a cut-off of 10 ng/ml instead of 3 ng/ml. The results indicate that CEA and CA 19-9 as well as liver function tests are helpful for preoperative staging in conjunction with imaging procedures before liver resection or regional chemotherapy.

Antigens, Neoplasm↗
PubMed1993

Improved liver function following treatment with an extracorporeal liver assist device.

A 68-year-old woman with fulminant hepatic failure of unknown etiology was treated with a bioartificial liver assist device. Prior to treatment, she had a number of clinical and laboratory features that suggested a hopeless outcome. Treatment was associated with a dramatic change in her mental status, and her clinical picture improved progressively during 6 days of continuous therapy. Evidence of recovery of native liver function allowed the discontinuation of treatment, and she continued to improve for a further 3 1/2 days before her demise from septic shock. We propose that a metabolically active liver assist device is a logical and practical method for treating the critical phase of fulminant hepatic failure.

Aged↗
PubMed1999

Analysis of whole blood tacrolimus concentrations in liver transplant patients exhibiting impaired liver function.

In transplant patients with impaired liver function, HPLC methodologies have been suggested for monitoring whole blood tacrolimus concentrations because of the reported inaccuracy of immunoassay for whole blood tacrolimus concentrations. One hundred fifty whole blood samples from 50 subjects enrolled in a multicenter liver transplant trial were chosen for HPLC/MS/MS analysis without consideration of the clinical status of the patient at the time of sampling. These samples were chosen to represent the sampling intervals during the 12-week posttransplantation period. Retrospectively, the authors identified a subset of 39 samples from 27 subjects exhibiting impaired liver function as demonstrated by bilirubin concentrations > 3.0 mg/dL (mean +/-SD = 7.5 +/- 5.6 mg/dL). The authors compared the agreement of concentrations obtained from the PRO-Trac II ELISA and HPLC/MS/MS by least squares linear regression analysis and Bland/Altman analysis, in this subset against the agreement of concentrations for 76 samples with normal bilirubin. In the samples obtained from patients with impaired liver function the resulting regression equation was: ELISA = 1.19(HPLC) + 0.7; r = 0.9. The mean difference (HPLC/MS/MS - ELISA) was -2.5 ng/mL +/- 2.9 ng/mL (mean +/- SD). While 71% of samples agreed within 3 ng/mL, 3% (n = 1) exhibited a difference >10 ng/ml. The corresponding evaluation of the samples with normal bilirubin concentrations resulted in the regression equation ELISA = 0.96(HPLC) + 0.9; r = 0.9, and a mean difference of -0.6 ng/mL +/- 2.3 ng/mL. The authors conclude that while a small subset of patients with cholestasis may require closer evaluation with a more specific methodology, the majority of the patients may be satisfactorily monitored with the PRO-Trac II ELISA.

Adult↗
PubMed2002

Rocuronium plasma concentrations during three phases of liver transplantation: relationship with early postoperative graft liver function.

BACKGROUND: Previous studies have suggested that neuromuscular blocking agents might be used to assess liver function during liver transplantation. This study examines changes in rocuronium plasma concentration during liver transplantation, to assess graft function. METHODS: A constant-rate infusion of rocuronium was administered to 17 adult patients undergoing liver transplantation. Blood samples were taken at 30-min intervals throughout the procedure, which was divided into three phases: paleo-, an-, and neohepatic. Assay of plasma concentrations of rocuronium was by a gas chromatographic-mass spectrometry technique. Postoperative liver function was followed for up to five days by measuring plasma aminotransferases. RESULTS: In 14 of the 15 patients who survived the transplantation procedure, there was a 7-50% decrease in rocuronium concentration during the neohepatic phase compared with the anhepatic phase. In contrast, rocuronium concentrations increased in the two patients who died after surgery, one as a result of primary non-function and one from massive bleeding. In one patient who survived there was no change in rocuronium concentration. The increase in plasma rocuronium concentration during the neohepatic phase in the two patients who died was consistent with high levels of plasma aminotransferases. CONCLUSIONS: Comparison of changes in plasma rocuronium concentration during the neohepatic phase with early postoperative liver function tests suggests the potential use of rocuronium as a pharmacokinetic probe for predicting liver function during liver transplantation. Further study of rocuronium's potential as an intraoperative pharmacodynamic probe of liver function by measuring neuromuscular paralysis is suggested.

Adult↗
PubMed2005

Imaging of liver function with dedicated animal dynamic pinhole scintigraphy in rats.

BACKGROUND: Non-invasive evaluation of liver function in small animal models remains a challenge. Hepatobiliary scintigraphy (HBS) enables the assessment of total and regional liver function for both uptake and excretion in larger species. AIM: To validate quantitative liver function assessment with dedicated pinhole HBS in rats. To illustrate an application of this technique, liver function was assessed in two surgical models of liver regeneration. METHODS: HBS was performed in 12 rats with 99mTc-mebrofenin on a dedicated animal pinhole gamma camera. The hepatic uptake rate was calculated twice by different observers to establish a normal range and the reproducibility of processing. The degree of hepatocellular injury and synthesis function were assessed by serum liver tests. Liver function was compared with liver weight. Subsequently, three groups of three rats were scanned on three separate days to assess the reproducibility of HBS. Finally, to illustrate an application of this technique, liver function was assessed in two surgical models of liver regeneration. RESULTS: HBS in rats was feasible without mortality. The mean liver uptake rate was 77.29+/-1.29% . min(-1). Calculation of the liver uptake (% . min(-1)) was highly reproducible (r=0.95, P<0.001). There was a good correlation between liver weight and function measured by HBS at baseline and after partial resection (r=0.94, P<0.001). CONCLUSION: HBS offers a unique combination of functional liver uptake and excretion assessment with the ability to determine the liver function reserve before and after an intervention in rats.

Aniline Compounds↗
PubMed1984

Effects of desipramine on clinical liver function tests.

Results of liver function tests in 46 depressed patients changed little during treatment with desipramine and were uncorrelated with drug plasma levels. The findings suggest that tricyclic-associated hepatitis, rather than being dose dependent, is an uncommon, idiosyncratic phenomenon.

Adult↗