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PubMed1991

A prospective study of liver function in infants and children exposed to daily isoflurane for several weeks.

Eleven infants and children presenting for daily radiotherapy for a period of at least 2 weeks were anaesthetised with isoflurane in 33% oxygen and nitrous oxide. They were unpremedicated and given no other agents to supplement anaesthesia. The average number of exposures was 24 (SD 11; range 10-39) and the total anaesthetic time per exposure varied between 15 and 30 minutes. Liver function was assessed by determining serum total bilirubin, aspartate amino transferase, gamma glutamyl transferase and alkaline phosphatase before the start of treatment and at 5-daily intervals thereafter. There was no measurable change in any of these determinants of liver function. All children accepted daily induction of anaesthesia with isoflurane. Induction, maintenance and recovery from anaesthesia were uncomplicated.

Alkaline Phosphatase↗
PubMed1994

Vecuronium neuromuscular blockade reflects liver function during hepatic autotransplantation in pigs.

BACKGROUND: Rapid assessment of hepatic function early after reperfusion of the liver graft is of great importance, because it may allow for prompt detection of incipient hepatic graft failure. The current study was undertaken to determine whether the continuous recording of neuromuscular transmission could be used as an on-line assessment of hepatic function during liver transplantation when a muscle relaxant with high hepatic uptake is used. METHODS: We quantified and compared the effect of liver exclusion and graft reperfusion on the level of vecuronium-induced neuromuscular blockade in nine pigs studied twice within 3 days. During the 1st day (control session), an intravenous infusion of vecuronium was administered to maintain a constant 90-95% twitch depression during 180 min. The twitch response was then allowed to recover spontaneously to 75% of its prerelaxant value. Neuromuscular transmission was continuously measured on the right anterior leg using an acceleration transducer. During the same time period, the metabolic rate of 14C-labeled aminopyrine (a well-established quantitative test of the liver microsomal function) was determined by measuring the excretion of 14CO2 in expired air after administration of an intravenous bolus of 14C-labeled aminopyrine. Two days later, the pigs underwent a hepatic autotransplantation, during which vecuronium was administered to maintain a constant 90-95% twitch depression. After reperfusion of the liver graft, the vecuronium infusion rate was maintained at its anhepatic level, and the recovery index of the neuromuscular blockade (the time from 25% to 75% recovery of twitch height) was calculated. The aminopyrine breath test was performed during the last 30 min of the anhepatic phase, and during 3 h after reperfusion of the liver graft. RESULTS: During control studies, the mean infusion rate of vecuronium was 1.30 +/- 0.33 mg.kg-1.h-1 and the recovery index was 3.4 +/- 0.5 min. During liver dissection, the infusion rate of vecuronium was similar to the control value (1.18 +/- 0.16 mg.kg-1.h-1), then considerably decreased to 0.05 +/- 0.03 mg.kg-1.h-1 during the anhepatic phase. After reperfusion of the liver graft, the recovery index was markedly prolonged to 35.5 +/- 15.8 min, indicating a prolongation of the recovery of neuromuscular blockade by a factor of 10.4. Excretion of 14CO2 was equal to zero during the anhepatic phase and then increased to 0.19 +/- 0.11% during the 1st h after reperfusion of the liver graft, an excretion rate corresponding to 11.2% of control conditions. The relationship between individual changes in the recovery index of the neuromuscular blockade and 14CO2 excretion in expired air after reperfusion of the liver graft showed a strong significant correlation (r2 = 0.71). CONCLUSIONS: These results indicate that, compared with the control studies, there is a similar decrease in the recovery rate of vecuronium-induced neuromuscular blockade and in the metabolic rate of 14C-labeled aminopyrine during the progressive recovery of hepatic function immediately after unclamping of the liver vessels. Metabolism of 14C-labeled aminopyrine increased progressively during the reperfusion phase. Therefore, recording of neuromuscular transmission during liver transplantation could serve as a continuous and easy to perform assessment of liver graft function provided that a muscle relaxant with a high hepatic uptake is used for neuromuscular blockade.

Aminopyrine↗
PubMed1990

Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population.

In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A). Sputum positive patients receive regimen A plus rifampicin (regimen B). Both groups continue treatment with isoniazid and thiacetazone. 21 patients on regimen A and 19 on regimen B had clinical assessment and liver function tests performed at weeks 0, 2, 4, 8, and 12 weeks of treatment (during and four weeks after, the intensive phase of 8 weeks). Acetylator status was also assessed, no significant difference was found between patients on regimen A or B (41 per cent and 45 per cent fast acetylators respectively). Liver function tests results (alanine aminotransferase and alkaline phosphatase) showed a persisting rise during the intensive phase on both regimens, and further rise after four weeks in the continuation phase, this further rise reaching statistical significance in regimen B. These results are unexpected when compared to other studies but the regimens under investigation are not used elsewhere. The significant rise after stopping intensive therapy in regimen B suggests some protective effect of rifampicin against the hepatotoxicity of the regimen, possibly the isoniazid/thiacetazone component. Acetylator status did not influence the degree of hepatotoxicity.

Alanine Transaminase↗
PubMed1997

Quantitative liver function tests as surrogate markers for end-points in controlled clinical trials: a retrospective feasibility study.

Quantitative liver function tests such as the determination of galactose elimination capacity (GEC) or the aminopyrine breath test (ABT) may have the potential to serve as refined entry criteria and surrogate markers for end-points in controlled clinical trials. The magnitude of a statistically detectable difference in test results and the period of observation required to document such a difference must be known to properly design such trials. Therefore, we explored retrospectively the time course of changes in GEC and ABT and their reproducibility from a cohort of patients with alcoholic cirrhosis followed for 12 to 42 months, with a median of 34 months. In 15 patients who stopped drinking, GEC improved significantly by 0.64 mg/min/kg within 1 year (mean; 95% confidence interval [CI]: 0.42; 0.86). In contrast, it deteriorated by 0.53 mg/min/kg within 1 year (95% CI: 0.32; 0.74) in another 17 patients who continued to drink (P < .01). The residual standard deviation of the changes in GEC with respect to the patients' initial values was 0.43 mg/min/kg (95% CI: 0.32; 0.52). In addition, ABT improved significantly by 0.14% dose x kg/mmol CO2 (95% CI: 0.09; 0.18) in the abstinent group, and deteriorated by 0.09% dose x kg/mmol CO2 (95% CI: 0.06; 0.13) in the nonabstinent group (P < .01). The residual standard deviation in the above sense for ABT was 0.08% dose x kg/mmol CO2 (95% CI: 0.06; 0.10). These data indicate that clinical trials with a sample size of n = 20 in each group must achieve absolute differences (ADs) in GEC of 0.6 mg/min/kg and of 0.7 mg/min/kg to reach statistical significance at the 5% and 1% level, respectively. In the present study, a period of 11 and 12 months was necessary to observe such differences. The corresponding results for the ABT are 0.11% dose x kg/mmol CO2 (9 months of follow-up; 5% level) and 0.13% dose x kg/mmol CO2 (11 months of observation; 1% level), respectively. Provided that patients with liver diseases treated with drugs are similar to the abstinent and nonabstinent patients with alcoholic liver disease investigated in this study, such numbers could serve for the planning of controlled clinical trials, in which the control group is likely to deteriorate and the treated group is expected to improve. Trials based on GEC or ABT would require only 37 or 30 patient years of observation compared with a median of 444 patient years (range, 50-2,100 patient years) reported for various published controlled clinical trials using survival analysis.

Adult↗
PubMed1991

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting.

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.

Adult↗
PubMed2001

Abdominal cross-sectional imaging for inpatients with abnormal liver function test results: yield and usefulness.

BACKGROUND: Abdominal cross-sectional imaging is often performed to evaluate abnormal liver function test (LFT) results in hospitalized patients. However, few data are available regarding the yield and usefulness of imaging inpatients for the indication of abnormal LFT results, the process of requesting abdominal imaging studies, or the response to their findings. METHODS: We retrospectively reviewed abdominal imaging scans that were obtained during a 27-month period. We matched the imaging studies done with the indication of abnormal LFT results; all scans were requested using computerized physician order entry. Reports were coded for interpretation and associated process step results. To determine the usefulness of the imaging studies, a random sample of patient charts with positively coded imaging studies were reviewed. Imaging examinations were considered useful if they provided new diagnostic information and/or changed subsequent patient care. RESULTS: Of 6494 abdominal imaging studies, 856 were performed for the indication of abnormal LFT results and matched to both image reports and laboratory results. Report coding judged 37% of interpretations as clinically significant, including 27% with "positive" (abnormal results and explain the abnormal LFT results) examinations. Among the positive examinations, the most common diagnoses were biliary obstruction (25%), cholecystitis (21%), malignancy (20%), and cirrhosis (14%). Positively coded reports provided new clinical information in 63% of these studies and changed patient care in 42% of cases. Process measures assessed provision of additional information to and from radiologists (69% and 8%, respectively) and the frequency with which the findings of current abdominal imaging studies were compared with those of prior studies (59%). CONCLUSION: Abdominal cross-sectional imaging studies performed on inpatients with abnormal LFT results had a high diagnostic yield and frequently changed patient care.

Abdomen↗
PubMed1997

Expression of liver functions following sub-lethal and non-lethal doses of allyl alcohol and acetaminophen in the rat.

BACKGROUND/AIMS: To relate severity of intoxication with allyl alcohol and acetaminophen to modulated hepatic gene expression of liver functions and regeneration. METHODS: Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g per kg body weight, or allyl alcohol 100 or 125 microl by gastric tube, doses producing no and about 30% mortality, respectively, within 2 days. In the morning 2, 6, 12, 24, and 36 h after intoxication, RNA was extracted from liver tissue. By slot blot hybridization mRNA levels were determined for acute phase proteins, enzymes involved in ammonia elimination and urea synthesis, and for proteins related to liver regeneration. RESULTS: After allyl alcohol, mRNA of "positive" acute phase proteins was higher than after acetaminophen and increased with the dose, whereas after acetaminophen it decreased with the dose. The mRNA of the urea cycle enzymes and glutamine synthetase was uniformly reduced by allyl alcohol, whereas that of most urea cycle enzymes was above the controls after the non-lethal, but not after the sub-lethal, dose of acetaminophen. The mRNA of glutamine synthetase was significantly more reduced by acetaminophen than by allyl alcohol. The mRNA of cell-cycle dependent proteins was greatly reduced after both toxins, more after the higher dose. CONCLUSIONS: The study shows that acetaminophen intoxication inhibits or fails to induce the expression of acute phase proteins in contrast to allyl alcohol intoxication. Allyl alcohol suppressed the expression of urea cycle enzymes, whereas that of the rate limiting enzymes carbamoylphosphate synthase and argininosuccinate synthetase was increased by the non-lethal but not by the sub-lethal dose of acetaminophen. The expression of the cell-cycle dependent proteins was more suppressed after the sub-lethal than after the non-lethal dose of both toxins. The data support the view that a fatal outcome of the intoxications depends more on the ability to regenerate than on the maintenance of liver-specific functions.

1-Propanol↗
PubMed2005

Pharmacokinetic and clinical phase II trial of imatinib in patients with impaired liver function and advanced hepatocellular carcinoma.

OBJECTIVES: No effective chemotherapy for advanced hepatocellular carcinoma (HCC) exists. Expression of the platelet-derived growth factor receptor (PDGFR) has been demonstrated in HCC, which may derive from hepatic stem cells that express c-kit. The aim of this trial was to evaluate imatinib, a tyrosine kinase inhibitor of PDGFR and c-kit, in patients with advanced HCC and impaired liver function. PATIENTS AND METHODS: Patients were treated with 400-600 mg imatinib daily. Immunohistochemical staining was performed for PDGFR and c-kit. Response was assessed by CT scans every 8 weeks. For pharmacokinetics studies, 74 plasma samples were assessed. RESULTS: Of the 17 patients enrolled in the study, 15 were evaluable for response. Only 1 tumor was positive for PDGFR and none was positive for c-kit. Grade 3/4 neutropenia occurred in 2 patients (1 had neutropenic fever). There was no objective response, and 5 (33%) patients had stable disease. Median time to treatment failure was 1.8 months in the whole study cohort and 3.7 months in the patients with stable disease. Patients treated with 400 mg imatinib did not significantly differ in pharmacokinetics from patients with chronic myelogenous leukemia (CML). CONCLUSION: In this small group of patients with advanced, mostly PDGFR- and c-kit-negative HCC, imatinib showed no therapeutic effect. In contrast to CML patients, the pharmacokinetics of imatinib were not significantly affected by impaired liver function.

Adult↗
PubMed1986

Influence of protein intake and liver function on acid base balance in premature infants.

In 43 patients with late metabolic acidosis (LMA) the factors promoting LMA were investigated. Postnatal adaptation was distributed in all cases, in 35 patients acidosis developed after introduction of formula feeding. Whereas no differences were observed in renal function (urine volume and renal molar excretion) between acidotic and non-acidotic patients, there was a significantly higher concentration of bile acids in serum (26.1 +/- 9.6 vs 98.6 +/- 21.6 mumol/l), a significantly increased fractional volume of stools (8.2 +/- 1.3 vs 11.4 +/- 1.9% of intake, and higher faecal fat excretion (26.5 +/- 5.2 vs 39.1 +/- 6.6% of faecal weight) in LMA patients than non-acidotic formula-fed infants. It is suggested that impaired postnatal development of liver function caused by severe disturbances of postnatal adaptation (respiratory distress, persistent fetal circulation, sepsis) is one of the most important factors in the pathogenesis of LMA. Thus, liver function should be checked before a protein intake surpassing that of a breastfed infant is introduced. Concentration of the serum bile acid level seems a reliable marker of LMA.

Acidosis↗
PubMed2003

Study of liver function in healthy elderly subjects using the 13C-methacetin breath test.

BACKGROUND: The issue of whether or not liver function is compromised in the healthy elderly population remains unsolved. AIM: To investigate the putative age-related modifications of hepatic function using the 13C-methacetin breath test. Because endogenous CO2 production changes with age, motor activity and nutrition, a different form of processing the results was investigated. PATIENTS AND METHODS: Twenty-nine elderly subjects (mean age, 79.8 +/- 7.9 years; female/male ratio, 17/12) and 28 adult subjects (mean age, 40.6 +/- 12.3 years; female/male ratio, 13/15) underwent 13C-methacetin breath test and trans-abdominal echosonography with Doppler pulsed wave analysis of the coeliac axis and portal vein. RESULTS: Although the 13CO2 peak occurred within 15-30 min in both elderly and adult subjects, it was significantly decreased in the former (30.66% +/- 9.2% vs. 38.33% +/- 6.05%; P < 0.001), as was the cumulative excretion (33.07% +/- 7.06% vs. 39.81% +/- 5.68%; P < 0.001). When correcting for the effects of CO2 excretion by age, the age-related modification of the cumulative dose became more evident (elderly group 30.15% +/- 6.46% vs. adult group 37.97% +/- 5.92%; P < 0.0001). The elderly group also showed an increase in the intra-hepatic resistance index using Doppler pulsed wave analysis, which inversely correlated with the results of the breath test. CONCLUSIONS: Hepatic function is not well preserved in healthy humans throughout life and may be due to an increase in vascular resistance.

Acetamides↗
PubMed2006

Changes in the liver function tests during the attacks of familial Mediterranean fever.

The present study aims to investigate whether or not FMF patients display abnormal liver functions during attack periods. About 41 consecutive FMF patients with attacks were enrolled on this study. Bilirubin levels, liver transaminases, erythrocyte sedimentation rate and C-reactive protein (C-RP) levels were determined within the first 72 h after the onset of attacks. This procedure could be performed on only 28 of these 41 FMF patients, 4 weeks after the attack of the patients' had completely disappeared. As for the disease control group, 44 patients were determined to be eligible for the study. Another 31 healthy individuals were also included. Hyperbilirubinemia was determined in 11 of the 41 patients (26.8%) with FMF. The number of FMF patients with hyperbilirubinemia was significantly higher than in DC and HC (P < 0.001, P = 0.03, respectively). Levels of liver transaminases slightly increased in four patients with FMF during the attack and two of these four patients had also mild hyperbilirubinemia. A significant correlation was found between C-RP levels and total and unconjugated bilirubin levels in FMF patients with attack (r = 0.43, P = 0.01; r = 0.40, P = 0.02, respectively). In conclusion, mild hyperbilirubinemia may occur in one-fourth of the patients with FMF during the attack period.

Adult↗
PubMed1990

Effect on liver function of acetonaemia and the fat cow syndrome in cattle.

The effect of fatty infiltration on liver function was studied in 29 dairy cows aged 6 +/- 0.4 (SEM) years with primary acetonaemia, secondary acetonaemia or the fat cow syndrome. The average interval from calving at diagnosis was 16.4 +/- 2.0 days and the animals had been anorexic for a mean of 5.6 +/- 0.8 days. Fatty infiltration of the liver occurred well before calving and was associated with severe clinical illness and intercurrent infections. The percentage of fatty infiltration in the liver (mean 53.1 +/- 2.8 per cent) was significantly correlated with both the degree of clinical illness (P less than 0.001) and the period of anorexia (P less than 0.05). Alterations in uptake, conjugation and excretion at the hepatocyte level were determined by measuring bromsulphthalein clearance, and plasma total bilirubin and total bile acid concentrations. Values for all three were positively correlated with the extent of fatty infiltration. Plasma albumin, urea and glucose concentrations were reliable indicators of the liver's synthetic function and together with plasma aspartate aminotransferase, iditol and glutamate dehydrogenase were correlated with the degree of hepatic lipidosis.

Animals↗