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PubMed2006

Effect of commonly used vehicles on gastrointestinal, renal, and liver function in rats.

INTRODUCTION: Solubility is often a limiting factor when testing new compounds in animal experiments. Various solubilizing agents may be used, but each have their own pharmacological effects. We investigated the effects of selected vehicles having different chemical characteristics on gastrointestinal, renal, and liver function. METHODS: Rats were treated orally, intravenously or intraperitoneally and gastric emptying, intestinal transit, renal, and liver function were investigated. RESULTS: Gastrointestinal motility was influenced by hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD, DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400, Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical chemistry measurements in serum. Urinary function was modified by HPgammaCD, DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80. DISCUSSION: Most of the investigated vehicles changed gastrointestinal, renal, and/or liver parameters after application of a certain threshold dose for each assay. No "best" vehicle could be identified that may be used in each test system. Thus, vehicles must be selected not only on their chemical characteristics but also on their potential pharmacological activity in a given test system.

Animals↗
PubMed1982

Clinical significance of blood biochemical liver function tests in asymptomatic chronic HBs Ag carriers.

To date we have had 31 asymptomatic chronic HBs Ag carriers in whom the time of HBV infection can be assumed, HBs Ag in sera persisted for at least 6 months, laparoscopy with liver biopsy was performed within 6 to 21 months after the assumed HBV infection, and the clinical course after performance of laparoscopy with liver biopsy ranged from 6 months to 5 years has been observed, while with the lapse of time, blood biochemical liver function tests were examined once every 4 weeks. In 16 out of 31 cases, the results of blood biochemical liver function tests remained always in the normal range and in the remaining 15 cases, blood biochemistries fluctuated sometimes pathologically, but transiently. In the former group, the results of blood biochemical liver function tests showed no pathologic findings, although the histologic inflammatory processes were outstanding in cases of chronic aggressive hepatitis and liver cirrhosis. In the remaining 15 cases, blood biochemistries fluctuated transiently and slightly, although morphological findings corresponded to chronic aggressive hepatitis and liver cirrhosis. The dissociation between blood biochemistries and morphologic findings needs to be further clarified.

Adult↗
PubMed1999

Evaluation of liver function parameters by Tc-99m-GSA using multivariate analysis: a study of 47 clinical cases.

To investigate the correlation between nuclear medicine parameters determined by technetium-99m-DTPA-galactosyl-human serum albumin (Tc-99m-GSA) and liver function tests, canonical correlation analysis was performed. Tc-99m-GSA studies were performed on 47 patients with hepatocellular carcinoma (HCC) who had undergone transcatheter arterial embolization (TAE). The nuclear medicine parameters LU15, HH15 and LHL15, which are results of nuclear imaging tests, were chosen in combination with the following liver function tests: the serum bilirubin level (T.Bil), the serum albumin level (Alb), serum cholinesterase activity (Ch-E), the clearance rate of indocyanine green (KICG), the hepaplastin test (HPT) and the prothrombin time (PT). The canonical correlation coefficient was 0.7345 and the upper tail probability was 0.00167. A significant correlation was observed between the two sets of variables. The high structural coefficients of Ch-E, KICG and HPT indicated a close relationship with the nuclear medicine parameters, supporting the notion that these nuclear medicine parameters are useful for the estimation of liver damage. The structural coefficients of the nuclear medicine parameters were also high, with LU15 being a parameter as useful as both HH15 and LHL15. T.Bil may evaluate a liver function that is not measured by nuclear imaging techniques, so we should take T.Bil results into account before considering TAE.

Aged↗
PubMed2000

[Liver function tests during administration of triphasic contraceptives containing Norgestimate].

OBJECTIVE: To evaluate serum levels of liver enzymes and bilirubin before and after six cycles of use of a triphasic oral contraceptive containing 35 micrograms of ethinylestradiol and 180/215/250 micrograms of norgestimate (Pramino, Janssen-Cilag). DESIGN: A prospective, open-label, non-comparative, multicentric phase IV study. SETTING: Department of Obstetrics and Gynaecology, 1st Medical Faculty, Charles University, Prague. METHOD: Before the start and after six cycles of Pramino use, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GMT), and bilirubin were determined in women. As the analyses were performed in different laboratories, the evaluation involved: 1. Subgroups of women examined in laboratories with the same reference range; 2. A group of women examined in laboratories with the upper reference range within the mean +/- SD interval; 3. Percentage variations of the measured values from a concrete upper reference limit. RESULTS: When evaluating subgroups of women from laboratories with the same standards, significant decreases in AST and bilirubin were seen in some subgroups, a rise in GMT in one subgroup; the other changes were non-significant. When assessing the entire group and percentage variations from standard, a mild rise in GMT was again seen; however, the values remain deep within the normal range. Values above the upper reference limit at the start of the study either do not change significantly throughout the study, or they normalize spontaneously. CONCLUSION: No clinically significant changes in liver function tests occurred in users of a triphasic oral contraceptive containing norgestimate along with 35 micrograms EE over a period of six cycles of use. The results, as judged by their dynamics, suggest liver function tests are not a useful tool for routine monitoring a healthy combined oral contraceptive user.

Contraceptives, Oral, Combined↗
PubMedDate not supplied

Hepatic resection with and without surgical margins for hepatocellular carcinoma in patients with impaired liver function.

BACKGROUND/AIMS: The significance of a surgical margin for hepatic resection of hepatocellular carcinoma (HCC) in patients with impaired liver function was evaluated. METHODOLOGY: Sixty-eight patients, each with a solitary HCC, who had not received any prior treatments were divided into 2 groups, according to surgical margin: Group A included 25 patients who underwent resection with no margin (although the tumor was not exposed) and Group B included 43 patients with a sufficient surgical margin (mean distance: 9 mm). There were no significant differences in clinicopathologic variables between the 2 groups. The rate of stump recurrence, survival and recurrence-free survival were analyzed. RESULTS: Among the 38 patients who had cancer recurrence after a median follow-up of 58 months, 9 (Group A, n=4; Group B, n=5) (24%) had recurrent lesions at the stump. The surgical margin was not a significant factor related to survival or recurrence, irrespective of cirrhosis, capsule formation, cancer spread, or tumor size. CONCLUSIONS: Our results indicated that the HCC-free surgical margin is unlikely to be related to the survival of patients with impaired liver function unless the tumor is exposed on the raw liver surface.

Adult↗
PubMed1995

Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function.

OBJECTIVE: To evaluate glycine conjugation of para-aminobenzoic acid (PABA) to the hippurated metabolites, para-aminohippuric acid (PAHA), and para-acetamidohippuric acid (PAAHA) as a quantitative liver function test in patients with liver disease. DESIGN AND METHODS: Serum concentrations of PABA and metabolites were measured by high pressure liquid chromatography in 24 controls and 50 patients with hepatobiliary disease. RESULTS: Hippurate formation was significantly decreased in all patient groups with chronic liver disease versus controls. The hippurate ratio (% hippurated metabolites formed) correlated with severity of disease, serum albumin, and factor VII concentrations. PAHA concentration was a better prognostic indicator than factor VII concentrations in patients with acute liver disease; concentrations of zero correctly predicted a poor outcome in patients with fulminant liver failure. CONCLUSIONS: Glycine conjugation of PABA may be useful as a quantitative liver function test in patients with hepatobiliary disease and as a prognostic index in patients with fulminant liver failure.

4-Aminobenzoic Acid↗
PubMed1991

Relationship between hepatic histology and conventional biochemical liver function test in chronic alcoholic patients.

This paper explores the relationship between hepatic histology and conventional biochemical liver function tests in 125 chronic alcoholic patients. On the basis of the results obtained, it is suggested that abnormal biochemical liver function tests may offer important clues for further invasive investigations to establish the diagnosis of alcoholic liver disease.

Adult↗
PubMed1982

The aminopyrine breath test as a measure of liver function. A quantitative description of its metabolic basis in normal subjects.

The APBT is used widely as a measure of liver function. The development of the APBT into a liver function test of greater diagnostic value requires quantitative information on the processes involved in aminopyrine disposition and metabolism in man and on how APBT values reflect changes in these processes. A dual-isotope kinetic study of aminopyrine disposition and metabolism has been carried out on five normal adult subjects. Oral administration of 13C-aminopyrine (2 mg/kg) accompanied by simultaneous intravenous injection of 14C-aminopyrine was followed by serial measurements of aminopyrine and monomethylaminopyrine in plasma and urine over 6 hr. Timed collections of respiratory CO2 were analyzed for the content of excess 13CO2 and for 14CO2. On separate days, an intravenous bolus of 13C-labeled NaHCO3 was administered to obtain estimates of the kinetic parameters of CO2 elimination in each subject. These data were fitted simultaneously to a multicompartmental model that, in addition to providing hitherto unavailable quantitative information, has revealed that (1) demethylation is the major elimination pathway for aminopyrine; (2) a major alternative pathway not involving demethylation exists for monomethylaminopyrine; and (3) only 50% of the labeled carbon generated by demethylation eventually is oxidized to HCO3-. The sensitivity of seven types of APBT scores to 50% reductions in the rates of aminopyrine absorption, metabolism of monomethylaminoantipyrine, intermediate carbon metabolism, and bicarbonate kinetics was evaluated with breath test curves simulated using the APBT model. Every APBT score currently in use was affected by variations in both gastrointestinal output of aminopyrine and bicarbonate kinetics. There is a need for further development of selective scoring methods in the aminopyrine breath test.

Adult↗
PubMedDate not supplied

Hepatitis B or hepatitis C co-infection in individuals infected with human immunodeficiency virus and effect of anti-tuberculosis drugs on liver function.

BACKGROUND: Tuberculosis (TB) and hepatitis are the two common co-infections in patients infected with human immunodeficiency virus (HIV). Anti-tuberculosis treatment (ATT) may have an effect on the liver enzymes in these co-infected HIV patients. AIMS: To determine the prevalence of Hepatitis B and C virus coinfection in HIV infected patients in Tamilnadu and assess effects of anti-tuberculosis drugs on their liver function. SETTINGS: HIV positive subjects referred to the Tuberculosis Research Centre, Chennai. MATERIALS AND METHODS: All HIV infected patients referred to the Tuberculosis Research centre, from March 2000 to May 2004, were screened for Hepatitis B surface antigen (HBsAg) & Hepatitis C virus (HCV) antibodies by enzyme linked immunoabsorbent assay (ELISA). HIV infection was confirmed using two rapid tests and one ELISA. Patients were given either short-course anti-tuberculosis treatment or preventive therapy for tuberculosis, depending on the presence or absence of active TB, if their baseline liver functions were within normal limits. None of these patients were on antiretroviral therapy during the study period. STATISTICAL ANALYSIS: Paired t-test was used to find the significance between baseline and end of treatment liver enzymes levels, while logistic regression was done for assessing various associations. RESULTS: Of the 951 HIV-infected patients, 61 patients (6.4%) were HBsAg positive, 20 (2.1%) had demonstrable anti HCV antibodies in their blood. Serial estimation of liver enzymes in 140 HIV patients (81 being co-infected with either HBV or HCV) showed that 95% did not develop any liver toxicity while they were on anti-tuberculosis treatment or prophylaxis. CONCLUSIONS: The prevalence of hepatitis B and C coinfection was fairly high in this largely heterosexually infected population supporting the use of more careful screening for these viruses in HIV positive persons in this region. Anti-tuberculosis therapy as well as TB preventive therapy can be safely employed in HIV and hepatitis coinfected patients, if baseline liver function tests are within normal limits.

AIDS-Related Opportunistic Infections↗
PubMed1977

Short-term and prolonged treatment with oral contraceptives and liver function.

Experiments on female rats were performed to observe the effects of progesterone and two synthetic progestens: ethinodiol-diacetate and methylestrenolone on liver function. In acute experiments animals were treated for the duration of one sexual cycle. All three compounds prolonged the hexobarbital biotransformation time. This effect is reversible and normalised 48 h after stopping treatment. The testosterone inducement of microsomal mixed function oxydases remained at the level of controls after methylestrenolone pretreatments and was even higher in the ethinodiol-diacetate and progesterone pretreated animals. Subacute and chronical treatments lasting for two or more sexual cycles resulted in the same slight inhibition of hexobarbital biotransformation when performed with the two progestogens. Chronical progesterone administration prolonged significantly hexobarbital biotransformation time. This impairement is also reversible. Our results pertain to a moderate, transitive inhibition of hexobarbital metabolism during short-term and prolonged progesterone and progestogen treatment. This effect may be easily suspended by interrupting drug administration or inducing microsomal enzymes with a single dosage of testosterone. In our progesterone experiments the inhibition of liver function increased with dosage and exposition time. In case of the two examined progestogens exposition time has not been proven as a predisposing factor for impairing liver function.

Animals↗
PubMed1975

Effect of long-term estrogen treatment on liver function in patients with prostatic carcinoma.

To evaluate the effect on liver function of therapy with massive doses of synthetic female sex hormones a study was performed on the alterations in levels of serum zinc turbidity test, bilirubin, alkaline phosphatase, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase following antiandrogenic treatment with castration and synthetic female sex hormones in patients with prostatic carcinoma. Results included: 1) Irrespective or response to treatment the zinc turbidity test level tended to increase. 2) After 1 week of treatment some increase was observed in the alkaline phosphatase level and was more pronounced in poor response cases than in the fair ones. However, in general, no definite fluctuation was observed. 3) The bilirubin level tended to decrease in general but in poor response cases an early increase was observed. 4) The glutamic oxaloacetic transaminase level was significantly increased in the early phase and more pronounced in poor response cases than in the fair ones. 5) An increased glutamic pyruvic transaminase level was observed after 2 weeks of treatment but was not significant to the pre-treatment level and later returned to the neighborhood of the pre-treatment level. After 1 week of female sex hormone therapy many indices studied showed abnormality. However, except for a steady increase in the zinc turbidity test level no serious damage on liver functions evaluated was encountered during a year of massive dose therapy with female sex hormones.

Aged↗
PubMed1997

Splanchnic hemodynamic pattern and liver function in patients with cirrhosis and esophageal or gastric varices.

OBJECTIVES: This study was designed to characterize the splanchnic hemodynamic pattern and liver function in patients with cirrhosis and esophageal or gastric varices. METHODS: Forty control subjects and 112 patients with cirrhosis were studied. Portal inflow (the sum of superior mesenteric arterial and splenic arterial flows), portal venous flow, and collateral flow (the difference between portal inflow and portal venous flow) were measured using duplex ultrasonography. Endoscopic examination showed that 45 patients had no varices or small esophageal or gastric varices, 49 had large esophageal varices, and 18 had large gastric varices. Liver function was assessed by Pugh-Child score. RESULTS: Portal inflow was significantly greater in patients with large esophageal varices or large gastric varices than in control subjects and patients with no varices or small esophageal or gastric varices. Portal venous flow was significantly lower in patients with large gastric varices than in the other three groups. Collateral flow was significantly greater in patients with large gastric varices than in patients with large esophageal varices. The Pugh-Child score was significantly higher in patients with large gastric varices than in patients with large esophageal varices. The Pugh-Child score was also inversely correlated with portal venous flow (r = -0.35, p < 0.01) and directly correlated with collateral flow (r = 0.59, p < 0.01). CONCLUSIONS: Both patients with esophageal varices and those with gastric varices have increased portal inflow. However, patients with gastric varices, in contrast to patients with esophageal varices, have a reduced portal venous flow associated with an increased collateral flow. Such a portal outflow pattern may contribute to the worse liver function seen in patients with gastric varices.

Endoscopy, Digestive System↗
PubMed2004

Use of lidocaine metabolism to test liver function during the long-term follow-up of liver transplant recipients.

BACKGROUND/AIMS: The aim of this study was to assess the usefulness of the monoethylglycinexylidide (MEGX) test to monitoring the long-term function of liver allografts. METHODS: MEGX production was measured prospectively in 60 consecutive liver transplant recipients undergoing their annual review. RESULTS: Median MEGX values in liver recipients (54 ng/mL; range 10-146) were lower than those found in healthy controls (78 ng/mL; range 44-118). MEGX values correlated negatively with alanine aminotransferase (ALT) activity (p = 0.004) and with the overall histological score (p = 0.01), and positively with sulfobromophthalein (BSP) and indocyanine green (ICG) clearances (p = 0.0002 and p = 0.002, respectively). A stepwise decline was observed with worsening liver fibrosis, from 71 +/- 5 microg/L in patients with no fibrosis to 27 +/- 9 microg/L in patients with bridging fibrosis (p = 0.002). BSP and ICG clearances correlated more closely than the MEGX test with the overall histological score (p = 0.001 and p = 0.001, respectively) and portal fibrosis (p = 0.002 and p = 0.001). CONCLUSIONS: The measurement of MEGX formation is a simple and non-invasive method to monitor liver graft function. It may constitute a valuable tool for assessing the degree of fibrosis.

Adolescent↗
PubMed1985

[Foreign substances as indicators of liver function].

The need to use xenobiotics to quantify liver function is based on the fact that the serum levels of endogenous tracers (such as transaminases, alkaline phosphatase, bilirubin and bile acids) cannot be interpreted in pharmacokinetic terms, since information is lacking on volume of distribution and on rate of synthesis and of disposition. Methods are now available which allow practically non-invasive estimation of (minimal) hepatic perfusion by indocyanine green fractional clearance, of portosystemic shunt flow by finger pulse photometry following nitroglycerin administration, of microsomal capacity by the aminopyrine breath test (ABT) or caffeine clearance, and of cytosolic function by galactose elimination capacity (GEC). Assessment of inherited hydroxylation deficiency of the debrisoquine type is best performed with dextromethorphan, and of the acetylator phenotype with sulfadimidine. Recently, caffeine clearance in saliva has been studied extensively in this laboratory, and, on the basis of a constant relationship between caffeine concentrations in serum and saliva, overnight clearance measurements (requiring a saliva sample at bedtime and upon arising following a single oral dose of caffeine) have been shown to be closely related to ABT or GEC. This approach, which has been successfully used in children, may represent the first simple and innocuous test for quantifying of hepatic function in the pediatric age group. The clinical utility of these clearance tests is to assess severity of disease (or genetically determined impairment of function), thus yielding important clues to prognosis.

Aminopyrine↗
PubMedDate not supplied

Impaired liver function and long-term prognosis after hepatectomy for hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) show a wide variety of histologic changes in the noncancerous liver parenchyma, and these changes may affect the prognosis. In this study, we grouped patients according to the extent of liver impairment and investigated their long-term prognosis after hepatectomy for HCC. A total of 194 patients were divided into two groups according to their plasma clearance rate of indocyanine green (ICG-K) values: those with values < 0.13 min-1 (group A, n = 97) and those with values of > or = 0.13 min-1 (group B, n = 97). Eighty-nine patients with stage I or II HCC were also divided into two groups: those with values < 0.13 min-1 (group C, n = 52) and those with values of > or = 0.13 min-1 (group D, n = 37). Group B patients tended to survive longer than group A patients during 4 years after hepatectomy, and group D patients survived significantly longer than group C patients (p < 0.01). There was no significant difference in the recurrence-free survival rates between those in groups A and B or groups C and D. Because patients with poor liver function frequently had multiple recurrent lesions and limited therapeutic options, patients with good liver function received more intensive treatment. In conclusion, the extent of liver impairment is one of the factors determining long-term prognosis after hepatectomy for HCC, especially during the early stage of the disease.

Adult↗
PubMed2003

The influence of Enteral Nutrition in postoperative patients with poor liver function.

AIM: To investigate the safety, rationality and the practicality of enteral nutritional (EN) support in the postoperative patients with damaged liver function and the protective effect of EN on the gut barrier. METHODS: 135 patients with liver function of Child B or C grade were randomly allocated to enteral nutrition group (EN, 65 cases), total parenteral nutrition group (TPN, 40 cases) and control group (CON, 30 cases). Nutritional parameters, hepatic and kidney function indexes were measured at the day before operation, 5th and 10th day after the operation respectively. Comparison was made to evaluate the efficacy of different nutritional support. Urinary concentrations of lactulose(L) and mannitol(M) were measured by pulsed electrochemical detection(HPLC-PED) and the L/M ratio calculated to evaluate their effectiveness on protection of gut barrier. RESULTS: No significant damages in hepatic and kidney function were observed in both EN and TPN groups between pre- and postoperatively. EN group was the earliest one reaching the positive nitrogen balance after operation and with the lowest loss of body weight and there was no change in L/M ratio after the operation (0.026+/-0.004) at the day 1 before operation, 0.030+/-0.004 at the day 5 postoperative and 0.027+/-0.005 at the day 10 postoperative), but the change in TPN group was significant at the day 5 postoperative (0.027+/-0.003 vs 0.038+/-0.009,P<0.01). CONCLUSION: EN is a rational and effective method in patients with hepatic dysfunction after operation and has significant protection effect on the gut barrier.

Adult↗