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PubMedDate not supplied

The evolution of changes in quantitative liver function tests in a rat model of biliary cirrhosis: correlation with morphometric measurement of hepatocyte mass.

The aim of this study was to determine the prognostic significance of functional changes in the liver during progression of cirrhosis. Liver function was quantitated weekly by the aminopyrine breath test (measuring microsomal function) and the galactose breath test (measuring cytosolic function) in rats made cirrhotic by bile duct ligation (n = 14) and in sham-surgery controls (n = 9). Nine rats died spontaneously of cirrhosis. Both the aminopyrine breath test and galactose breath test were sensitive (89%) predictors of death within 1 week, but the galactose breath test was more specific (83%). Morphometric measurements of livers from surviving cirrhotic animals and controls (n = 5 each) showed that mean hepatocyte mass was maintained in the cirrhotic livers [cirrhosis (17.0 +/- 2.0) vs. controls (13.9 +/- 0.9 gm)]. The galactose breath test was also maintained, whereas the aminopyrine breath test was significantly decreased in the surviving cirrhotics. The galactose breath test, but not the aminopyrine breath test, correlated with hepatocyte mass (r = 0.67). The aminopyrine breath test correlated with microsomal aminopyrine N-demethylase activity (r = 0.78). Serial use of quantitative liver tests allows prediction of time of death from cirrhosis in this model.

Aminopyrine↗
PubMed2005

Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy.

AIM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF). METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n = 8), interferon/ribavirin (n = 19) or peg-interferon/ribavirin (n = 23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCl) and indocyanine green clearance (ICG) was performed before and 3 mo after initiation of antiviral therapy. RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCV-RNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 mo. Parameters of liver perfusion (SCl and ICG) were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION: ICG and SCl remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.

Adult↗
PubMed1994

[Clinical evaluation of kinetic model for the quantification of liver function with Tc-99m PMT and dynamic scintigraphy].

The purpose of this study was to quantify the uptake and excretion of Tc-99m-N-pyridoxyl-5-methyltryptophan (PMT) by hepatocytes using a tracer kinetic modeling approach, and to clarify the pathophysiological changes of diffuse parenchymal liver diseases. Fifty-two patients with liver diseases and seven normal subjects were studied. Studies were performed using an intravenous bolus injection of 185 MBq of PMT. Our compartment model consisted of three compartments. These parameters were calculated using the non-linear least-square method. The fitting curves agreed well with the measured ones. K1 correlated with blood tests of liver function better than parameters from the two-compartment model such as ku. K1 correlated especially closely with K-ICG (r = 0.898). K1 reflected hepatic blood flow, and the decrease of K1 was associated with hepatic dysfunction. Although K3 correlated poorly with serum bilirubin (r = -0.447), it correlated well with MTT (deconvolutional analysis) (r = -0.833). K3 reflected excretory function, and did not decrease until liver function was moderately damaged. By using three-compartment analysis, we were better able to explain the pathophysiological status of the liver. Our model is more useful for the assessment of liver function than the simple model.

Adult↗
PubMed2004

Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.

Adult↗
PubMed1999

Estimation of functional liver reserve in patients before cardiac surgery using antipyrine plasma clearance test.

BACKGROUND: Hyperbilirubinemia is not uncommon and is sometimes fatal after valvular surgery. One important cause of it is a poor functional liver reserve, however, conventional tests reflect hepatic blood flow and do not offer precise evaluation of the pure functional liver reserve. Antipyrine has particular pharmacological properties, and its plasma clearance represents quantitatively the functional capacity of the liver. In this study, we measured antipyrine plasma clearance in cardiac surgical patients and evaluated the feasibility of using this parameter as a predictor of the risk of postoperative hyperbilirubinemia. METHODS: The plasma clearance of antipyrine was measured preoperatively in 40 cardiac patients undergoing mitral and/or tricuspid valvular surgery and its relations with hemodynamics or postoperative course were studied. RESULTS: Antipyrine clearance in preoperative patients was 0.365+/-0.175 (mean +/- SD) ml/min/kg, lower than the normal range (0.405+/-0.04 ml/min/kg), and showed no correlation with cardiac index, while the plasma disappearance rate of indocyanine green depended on the cardiac index. The maximum postoperative total bilirubin level showed significant correlation with antipyrine clearance (r=-0.699); this correlation coefficient was greater than that with indocyanine green (-0.477). The correlation was more prominent in patients with cardiac dysfunction. Furthermore, antipyrine clearance showed significant predictability of the duration of ICU stay. CONCLUSIONS: Antipyrine clearance provides a precise estimate of functional liver reserve which is independent of hemodynamics and predicts the risk of postoperative hyperbilirubinemia in preoperative cardiac patients.

Adult↗
PubMed1983

Safety studies evaluating the effect of mebendazole on liver function in dogs.

The effect of repeated and exaggerated mebendazole administration was evaluated in dogs with and without experimentally induced altered liver function. Irish Setters and Toy Poodles were dosed at 1, 3, and 5 times the therapeutic dose (22 mg/kg) of mebendazole for 17 days, without any effect on the liver. Mixed breed dogs that received increasing doses of mebendazole at 11 to 110 times the therapeutic dose for 2 months did not show adverse effects and remained in good health throughout the experiment. There was not substantial evidence that carbon tetrachloride-induced liver changes were exacerbated by subsequent repeated treatments with mebendazole at 15 times the therapeutic dose. Additionally, in dogs whose liver function was compromised experimentally by glutathione depletion and microsomal enzyme induction, administration of mebendazole at this same dosage for 30 days did not result in any hepatotoxic effect. When mebendazole was given at 15 times the therapeutic dose prior to an hypoxic episode in dogs pretreated with a barbiturate and high protein diet, there was no evidence of any adverse effect on liver function. These metabolic manipulations, in conjunction with mebendazole administration, failed to reveal any mechanism of hepatic dysfunction associated with mebendazole treatment. Unrecognized factors appear to be involved with the rare cases of hepatic dysfunction that have been reported after mebendazole administration. Only careful documentation of field cases and further laboratory research can identify these factors.

Animals↗
PubMed1997

Assessment of liver function: pre- and peritransplant evaluation.

Liver transplantation has been demonstrated to be a successful therapeutic modality for patients with end-stage liver disease. The high rate of survival for an otherwise terminal condition has resulted in significant expansion of the indications and diseases treated by this procedure, and is hampered only by the limited numbers of organs available for transplantation. Efforts in clinical and laboratory medicine should be directed to identify candidates who would benefit most from this procedure, to provide better means for accurate assessment of liver reserve and the appropriate timing for transplantation, to identify quality liver grafts that would have the potential to tolerate cold preservation and reperfusion injury, and to assist in accurate monitoring of graft function immediately after transplantation. The aim of this manuscript is to describe the existing pathways for clinical and laboratory assessment of pretransplant residual liver function, the donor liver graft, and immediate posttransplantation function.

Humans↗
PubMed1978

Liver function tests after ligation of hepatic artery.

Nine patients with unresectable primary and secondary malignancy of the liver underwent ligation of the hepatic artery (HAL) distal to the gastroduodenal artery as a therapeutic measure. Another patient had a similar operation for hepatic artery aneurysm. Their postoperative liver function tests are studied in detail, and the patterns of change are compared with three other patients who had extensive resection of tissues but without HAL. It appears that liver function tests rarely became abnormal after major operations, whereas HAL produced an immediate rise of lactic dehydrogenase and transaminase (up to 5--60 times normal value), and creatine phosphokinase (4--15 times normal). All elevated enzymes returned to preoperative levels within a week. Alkaline phosphatase and bilirubin rose mildly after HAL and returned to preoperative range in about one week. However, if the patient had repeated surgical stress, anoxic insult, or maximal loss of the hepatic parenchyma, serum enzymes rose only slightly after HAL.

Adult↗
PubMed2004

Abdominal ultrasound in the evaluation of the asymptomatic patient with abnormal liver function tests.

We retrospectively evaluated abdominal ultrasound studies of 273 asymptomatic patients with abnormal liver function tests over an 18-month period to assess the value of abdominal ultrasound as an initial investigation. In-patients, out-patients and general practitioner referrals were included. 143 (53%) examinations were normal. Those with significant abnormality (n=13, 5%) were referred for further investigation/treatment. Those with alterations in hepatic echogenicity (n=117, 42%) underwent clinical and biochemical follow-up, radiological follow-up or biopsy. 20% of patients underwent further radiological investigation. Ultrasound is a non-invasive, cost effective first-line investigation in the evaluation of asymptomatic patients with abnormal liver function tests.

Abdomen↗
PubMed1988

Rapid 31P NMR test of liver function.

The 31P NMR spectrum of perfused rat liver was found to be dependent on the exogenous carbon available to the tissue. When pyruvate was supplied to liver initially perfused with lactate, Pi decreased, phosphoenol pyruvate and phosphomonoesters increased, and nucleotide pools remained the same. It is proposed that these changes can be used to evaluate liver function.

Animals↗
PubMed2001

Does age affect liver function and the hepatic acute phase response after major abdominal surgery?

OBJECTIVE: The liver plays a key role in the inflammatory response during major surgery or infection. The influence of age on liver function and hepatic acute phase protein (APP) synthesis should be serially studied in elderly patients undergoing major abdominal surgery. DESIGN AND SETTING: Prospective and descriptive study over 3 days. Clinical investigation in the operating room and surgical intensive care unit (ICU) of a tertiary care hospital. PATIENTS AND INTERVENTIONS: 42 consecutive patients were grouped according to age: less than 60 years ("adult") or over 65 years ("elderly") and prospectively studied. All patients received standardized general anesthesia and were treated afterwards according to the standard protocols of our ICU. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. MEASUREMENTS AND RESULTS: Concentrations of interleukin (IL)-6, serum amyloid A (SAA), C-reactive protein (CRP), alpha1-antitrypsin (alpha1-AT), and haptoglobin were measured to assess the APP response. Liver function was evaluated by the monoethylglycinexylidide (MEGX) test and by measuring alpha-glutathione S-transferase (alpha-GST). All measurements were performed at induction of anesthesia (T0), at the end of surgery (T1), and 2 h (T2), 24 h (T3), and 48 h (T4) postoperatively. There was no difference in the incidence of postoperative septic complications between the two groups. Baseline values of IL-6 and the four APPs were normal in all patients and did not differ between the groups. IL-6 levels increased significantly in all patients at T1 and T2, with a significantly higher increase in the older patients (elderly: from 7.4+/-3.4 pg/ml to 220.6+/-49.5 pg/ml; adult: from 6.2+/-2.5 pg/ml to 189.9+/-36.8 pg/ml). A return to baseline values was seen at T3 in both groups. Concentrations of all APPs, except for haptoglobin, started to increase at T3. Peak concentrations were significantly lower in the elderly patients (elderly: SAA 358+/-133 microg/l, CRP 5.1+/-2.3 mg/dl, alpha1-AT 160+/-96 mg/dl; adult: SAA 444+/-100 microg/l, CRP 8.5+/-3.2 mg/dl, alpha1-AT 223+/-85 mg/dl). Baseline alpha-GST and MEGX concentrations were normal in all patients. Alpha-GST concentrations increased in both groups at T1 and T2, with a significantly higher increase in the older patients (elderly: 3.7+/-1.4 microg/l to 10.2+/-2.9 microg/l; adult 4.5+/-2.1 microg/l to 8.5+/-1.7 microg/l). A return to baseline values was seen at T3 in both groups. MEGX concentrations were significantly lower and abnormal (<50 ng/ml) in the older patients at T3 and T4. CONCLUSIONS: Our observations suggest that the postoperative hepatic acute phase response is reduced in elderly patients undergoing major abdominal surgery. The decreased release of liver-synthesized APPs was associated with an impaired hepatocyte function and a disturbance of hepatocellular integrity. Further work needs to be done to determine whether these findings might have an impact on the incidence of postoperative septic complications or prognostic significance for survival in aged patients.

Abdomen↗
PubMed1988

[Radionuclide study of liver function in polycythemia vera and other types of polycythemia].

Clinico-laboratory and radionuclide (radio-hepatography with 131I-rose bengal and liver scanning with 198Au colloid solution) investigation of liver function was performed in 110 patients with polycythemia vera during exacerbation, in 16 patients with symptomatic erythrocytosis (10--chronic pulmonary disease, 3--polycystic kidney, 2--obesity, 1--peptic ulcer), and in 11 patients with a polycythemic form of myelofibrosis. The results of the radionuclide method showed disturbed liver function in 51 (46.3%) patients with polycythemia, in 4 patients with myelofibrosis and in 3 with erythrocytosis which were characterized by a decrease in hepatocytic absorptive-excretory function and a decrease in the activity of the reticulo-histiocytic stroma. Liver changes depended on a stage of disease and were detected earlier than with the use of biochemical methods. As distinct from erythrocytes, one-type disorders were noted in the patients with myelofibrosis. Correlation in the lever of RP accumulation in the spleen, its sizes and stage of disease was established. Liver function returned to normal after cytostatic therapy in the patients with stage IIA polycythemia, partially IIB stage, during remission.

Adult↗
PubMed1995

Functional liver imaging with asialoglycoprotein receptors and serum hyaluronate in a patient with amyloidosis.

A 47-year-old man with primary amyloidosis was admitted with abdominal pain. A new radionuclide liver imaging technique using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was performed and the serum hyaluronate concentration was measured. Although ordinary laboratory tests revealed only slight abnormalities, the uptake of the radiolabelled ligand for hepatocyte asialo-glycoprotein receptors was decreased, and marked hepatomegaly was revealed. Furthermore, the serum hyaluronate level was elevated. Histological examination of a hepatic needle biopsy specimen revealed a marked deposition of amyloid in the hepatic perisinusoidal spaces. These results indicate that this new radionuclide liver imaging technique (using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin) and the measurement of serum hyaluronate may be useful supplementary tools for identifying amyloid deposition in the hepatic perisinusoidal spaces in patients with amyloidosis.

Amyloidosis↗
PubMed2002

Endotoxin tolerance in rats: influence on LPS-induced changes in excretory liver function.

OBJECTIVE AND DESIGN: We investigated in a rat model of endotoxic shock whether endotoxin tolerance (ETT) prevents lipopolysaccharide (LPS) associated lethality and studied the initial function of liver response to LPS. ANIMALS: Male Sprague-Dawley rats. TREATMENT: ETT was induced by i.p. injection of LPS (Salmonella friedenau) intraperitoneally over 5 days. Rats (n = 6 each group) received 1 mg LPS/kg b. w. intravenously (Salmonella friedenau). The common bile duct was then canalized and bile was collected every 60 min for 6 h. 1 h after LPS-application liver biopsies were taken for determination of TNF-alpha by RT-PCR. Sham operated animals (n = 6 each group) were treated identically but without application of LPS. RESULTS: All ETT animals survived the duration of the experiment whereas non-tolerant animals (NETT) died before the end of the experiment (5/6). NETT animals showed a continuous decrease in bile flow after 240 min. The amount of bile acids was significantly lower (ANOVA) in NETT animals than in sham operated controls or ETT-animals. Analysis of TNF-alpha mRNA expression in the liver revealed an upregulation 1 h after LPS application, which was significantly lower in LPS-tolerant animals. CONCLUSIONS: Our results show that excretory liver failure and death subsequent to intravenous LPS application can be successfully counteracted by induction of ETT.

Animals↗
PubMedDate not supplied

Functional liver damage during laparoscopic cholecystectomy as the sign of the late common bile duct stricture development.

BACKGROUND/AIMS: Thermal trauma is hypothesized as a major cause of late common bile duct stricture. Dispersion of electric energy through the tissues during electrocautery is not controlled and may cause necrosis even in remote tissues. Changes in liver enzymes may be used as indirect indicators of common bile duct damage, because of the close proximity of these structures in the liver porta. METHODOLOGY: Laparoscopic cholecystectomy was performed in 20 patients using a monopolar cutter (thermal device), and in another 20 patients using a harmonic scalpel (non-thermal device). Changes in liver enzymes, as well as histology of gallbladder wall were assessed. RESULTS: There was a significant rise in liver enzymes (AST and ALT) after surgery in both groups, but postoperative values of these two enzymes were significantly higher in patients operated using the monopolar cutter. There were no significant differences in postoperative levels of hemoglobin and red blood cell count between these two groups. CONCLUSIONS: Thermal trauma of the liver parenchyma was significantly greater in patients operated using the monopolar cutter, suggesting possible detrimental effects to the common bile duct.

Adult↗