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PubMed1975

Studies of liver function and structure in patients with gallstones before and during treatment with chenodeoxycholic acid.

Twelve patients with gallstones were treated with chenodeoxycholic acid (CDCA) for 3 to 22 months. Liver function and structure were studied before and during treatment. No signs of hepatotoxicity were observed. Activities of several enzymes, including transaminases, GLDH, and gamma-GT were frequently abnormal in this group of patients. But there was no statistical difference between treatment and pre-treatment levels. Serum bilirubin and protein electrophoresis remained normal throughout the study. The BSP retention test was not significantly altered by CDCA treatment. Light microscopic examination in 8 patients revealed no changes of liver structure during 3 to 19 months of CDCA administration except, however, for a decrease of fatty changes in 3 patients. The ultrastructure of liver cells was found to be normal in 5 patients, in whom electron microscopy was done as well.

Adult↗
PubMed2003

Liver function testing in patients on HMG-CoA reductase inhibitors.

PURPOSE: The Food and Drug Administration currently requires the labeling of HMG-CoA reductase inhibitors to recommend liver function tests (LFTs) before the start of therapy and at various intervals during therapy, depending on the specific agent. We sought to determine the frequency and patterns of LFT screening in patients receiving HMG-CoA reductase inhibitors. METHODS: A retrospective study was conducted at a staff-model health maintenance organization among 4178 new users of HMG-CoA reductase inhibitors during the period 1 January 1991 through 31 December 1996. The number and proportions of HMG-CoA reductase inhibitor therapy courses with baseline LFTs (within 180 days prior to dispensing), follow-up LFTs and LFT abnormalities were calculated. RESULTS: For the initial HMG-CoA reductase inhibitor dispensed, 1947 patients (47%) had at least one screening LFT at baseline and 3063 (73%) had at least one follow-up LFT. Twenty-seven (0.9%) patients with at least one follow-up LFT performed had a level greater than 3 times the upper limit of normal. In a random sample of 100 discontinued patients, none discontinued due to elevated LFTs or liver disease. CONCLUSIONS: A large proportion of patients dispensed HMG-CoA reductase inhibitors in this managed care setting did not have baseline and follow-up LFTs performed. Modest LFT abnormalities were common among users of HMG-CoA reductase inhibitors; however, in this population, serious abnormalities were rare.

Aged↗
PubMed2000

The effect of desflurane on liver function markers in infants and children. Report of a study and a pertinent case report.

BACKGROUND: In an open-labelled clinical trial, the effect of desflurane anaesthesia on liver function markers in paediatric patients was monitored. METHODS: Fifty infants and children, 37 male, scheduled for elective cleft plate surgery were included in the study. Median age was 0.57 (0.25-5.45) years (range), mean desflurane exposure was 2.29 +/- 0.75 MAC-h. Function markers were determined within 24 h prior to and within 24-48 h after anaesthesia. Complete data sets were available for total bilirubin 29, aspartate aminotransferase (ASAT) 36, alanine aminotransferase (ALAT) 35, and for alkaline phosphatase (AP) 28. Pre- and postanaesthetic function tests were compared by means of Wilcoxon's matched-pairs test. RESULTS: Only for AP could a statistically significant reduction of the postanaesthetic values be observed, while the other parameters showed no significant changes. Postanaesthetic ASAT and ALAT were clearly reduced in three children who had unspecific highly elevated preanaesthetic values. After the study, this observation could be repeated in at least one child, who received a further anaesthesia with desflurane within 3 months. CONCLUSION: The data suggest that desflurane does not affect excretory or structural liver integrity in infants and children.

Alanine Transaminase↗
PubMed1982

Effects of certain antibilharzial and contraceptive drugs on liver functions in rats.

Effects of single and combined administration of contraceptive drug (microvlar-30) and anti-urinary bilharzial drug (metriphonate) as well as anti-intestinal bilharzial drug (oxamniquine) on the liver functions of female albino rats were studied. Metriphonate increased serum globulin content and caused no change in the hepatic cells. Oxamniquine significantly increased the activities of serum transaminases and alkaline phosphatase and caused necrosis in some liver cells. Microvlar-30 exhibited no change on the serum enzymes, while marked increase was found in serum triglyceride and protein levels. The combined administration of metriphonate or oxamniquine with microvlar-30 prevented the increase in the levels of serum triglycerides and proteins. Histopathological examination confirmed the results obtained by chemical analysis.

Alanine Transaminase↗
PubMed2006

Hyaluronic acid and aspartate aminotransferase levels normalized by liver function can reflect sinusoidal impairment in chronic liver disease.

BACKGROUND/AIM: To evaluate the relationship between hyaluronic acid/aminopyrine breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate aminotransferase (AST)/ABT in relation to the HA/ABT. METHODS: We studied 48 patients with histologically proven chronic hepatitis C (CHC) and 35 patients with compensated cirrhosis (CIR). RESULTS: HA/ABT and AST/ABT showed a more significant correlation with the fibrosis score than HA or ABT or AST alone in the 48 CHC patients: r=0.568 (P<0.0001), r=0.610 (P<0.0001), r=0.450 (P=0.0021), r=-0.449 (P=0.0021), and r=0.472(P=0.0012), respectively. Progressive liver damage (fibrosis 1-2 vs fibrosis 3-6 vs cirrhosis) was significantly (P<0.05) reflected by both HA/ABT (mean+/-SEM: 4.0+/-0.9 vs 18.1+/-4.2 vs 149.9+/-33.1) and AST/ABT (6.3+/-1.8 vs 12.7+/-1.6 vs 42.1+/-14.6). A strong relationship was found between HA/ABT and AST/ABT (r=0.755 P<0.0001). In cirrhotic patients, the most significant relationship was observed between HA/ABT and CTP r=0.483 and P=0.0049, and MELD r=0.523 and P=0.0023. CONCLUSION: Considering that HA levels in chronic hepatitis depend on the progressive impairment of sinusoidal endothelial cells (SEC), related to progressive fibrosis, HA/ABT ratio would seem to be the most specific reflection of progressive impairment of the SEC. AST/ABT could be used as a possible surrogate of HA in identifying SEC impairment in chronic hepatitis.

Adult↗
PubMed1976

Comparison of sulfobromophthalein (BSP) and sulfobromophthalein glutathione (BSP-GSH) disposition under conditions of altered liver function and in the isolated perfused rat liver.

Disposition of sulfobromophthalein (BSP) and sulfobromophthalein glutathione (BSP-GSH) was compared in control, phenobarbital, or alpha-naphthylisothiocyanate-(ANIT)-treated rats, and in the isolated perfused rat liver preparation. After dye administration, BSP-GSH was found to have a more rapid early plasma disappearance rate, a more rapid appearance in the liver, and a greater rate of biliary excretion both in vivo and in the isolated perfused liver, than that of BSP. In considering these observations, it is concluded that hepatic uptake as well as biliary excretion of BSP-GSH is faster than that of BSP. Comparing BSP and phenobarbital, augmentation or reduction in plasma dye concentration, mean plasma half-life (2 to 30 minutes), hepatic dye content, and bile dye concentration, were of the same order of magnitude for both dyes. However, with dye infusion of 3.6 mumoles per kilogram per minute, phenobarbital significantly enhanced the rate of biliary excretion of BSP but not BSP-GSH and ANIT treatment had a greater inhibitory effect on biliary excretion of BSP-GSH than BSP.

1-Naphthylisothiocyanate↗
PubMed1994

Role of hepatic copper-metallothionein on liver function of Long-Evans cinnamon rats with a new mutation causing hereditary hepatitis.

Liver slices from Wistar and Long-Evans Cinnamon (LEC) rats were incubated while open to the atmosphere to assess the liver function in LEC rats. Leakages of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) into the medium were significantly lower in the LEC rat than in the Wistar rat. Furthermore, no pronounced enhancement of the concentration of thiobarbituric acid-reactive substances (TBARS) was found in the LEC rat. Hepatic Cu and Cu-metallothionein (Cu-MT) concentrations were 355.0 +/- 18.7 micrograms/g liver and 2559 +/- 181 micrograms/g protein in the LEC rats, whereas Wistar rats showed 4.1 +/- 0.1 Cu microgram/g liver accompanied by 16 +/- 4 micrograms/g protein of MT. The decrease of intrahepatic Cu-MT in LEC rats was stimulated by incubation with Fenitrilotriacetate (Fe-NTA). There was a direct correlation between the enhancement of TBARS and disappearance of Cu-MT. Our results suggest that hepatic Cu-MT in LEC rats protects against liver injury stimulated by oxidative stress.

Animals↗
PubMedDate not supplied

Overnight salivary caffeine clearance: a liver function test suitable for routine use.

The feasibility of measuring caffeine clearance from saliva (SCl) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o. in decaffeinated coffee powder between noon and 4 p.m., and caffeine concentrations were measured in saliva (using an enzyme immunoassay) before bedtime and upon arising. In the cirrhotics (n = 29), SCl was 0.58 +/- S.D. 0.45 ml per min X kg, thus being reduced to approximately one-third of drug-free, nonsmoking controls (1.53 +/- 0.46, n = 18); although patients with noncirrhotic liver disease showed intermediate values (0.95 +/- 0.47), their reduction in SCl was significant (p less than 0.001). SCl was correlated with indocyanine green fractional clearance, galactose elimination capacity and aminopyrine breath test; however, the closest relationship (Rs = 0.80) was observed with the aminopyrine breath test. It is suggested that the measurement of SCl represents a noninvasive and innocuous procedure for quantifying hepatic microsomal function, and is suitable for routine use. Since a.m. saliva concentrations of caffeine are highly correlated (Rs = -0.94) with SCl, further simplification of the test to a single-point measurement appears possible.

Ambulatory Care↗
PubMed1999

Progressive liver functional impairment is associated with an increase in AST/ALT ratio.

The ratio of serum aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) has been proposed as a noninvasive method of assessing liver fibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosing cirrhosis noninvasively as well as to verify the existence of a relationship between the ratio and liver functional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) were retrospectively evaluated and the AST/ALT ratio was related to monoethyl glycine xylidide (MEGX) formation. Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio and indocyanine green clearance and half-life. The AST/ALT ratio was able to separate patients with mild fibrosis from those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity, and platelet count were selected by multivariate analysis as variables associated with cirrhosis. The AST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine green clearance and half-life. The alterations of indocyanine green kinetics, which depend upon liver blood flow and uptake, were likely due to progressive fibrosis. These findings might partially explain the increase in the AST/ALT ratio as disease progresses.

Adult↗
PubMedDate not supplied

Liver function in rats treated individually and with a combination of xylene, toluene and methanol.

The individual and combined influences of three industrial solvents (namely xylene, toluene, and methanol) on certain parameters of liver function in laboratory rats have been studied. Although individual treatments with all three solvents elevated activities of serum enzymes (i.e., GOT, GTP, and alkaline phosphatase), and did manifest hyperbilirubinemia, nevertheless metabolic interaction occurring after their combined treatment suggested a weak antagonistic mechanism. This assumption has been supported by the fact that the detoxification ability of the liver, as indicated by the formation of hippuric acid, improved after the combined treatment.

Alanine Transaminase↗
PubMed1996

Influence of age, frailty and liver function on the pharmacokinetics of brofaromine.

OBJECTIVE: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y). METHODS: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). RESULTS: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001). CONCLUSION: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.

Administration, Oral↗
PubMed2002

Biliary atresia, the next generation: a review of liver function, social activity, and sexual development in the late postoperative period.

PURPOSE: The current study aimed to establish the management for biliary atresia (BA) patients in the late postoperative period. METHODS: Of 165 BA patients operated on in the authors' department, 44 patients (16 boys, 28 girls) with a follow-up period of more than 15 years were reviewed retrospectively. RESULTS: Forty-one of 44 patients (93.2%) currently are employed or highly educated, 7 are married, whereas 2 (4.5%) died, and 10 (22.7%) required liver transplantation after puberty. Four babies have been born from BA parents without congenital anomalies. Four girls conceived 5 times and delivered 3 newborns weighing 2,330 to 2,474 g including one delivered after transplantation. Maternal portal hypertension uniformly deteriorated during pregnancy, and one pregnancy was terminated. Menstrual disorder correlated significantly with the biochemical data related to liver function at puberty such as serum choline esterase (266 +/- 70.4 in 19 normal patients v 159 +/- 34.3 IU/L in 9 abnormal patients, P =.00057), asparate aminotransferase (42 +/- 30.8 v 96.0 +/- 63.6 IU/L; P =.0031), and serum albumin (4.6 +/- 0.4 v 3.9 +/- 0.6 g/dL; P =.013). CONCLUSIONS: The long-term survivors of Kasai's operation, with or without liver transplantation, have reached the next generation. Transgenerational follow-up and management including conception and perinatal care should be required for BA patients.

Adolescent↗
PubMedDate not supplied

Changes in liver function tests in patients with inflammatory bowel disease on enteral nutrition.

Morphologic and functional hepatic changes occur in inflammatory bowel disease (IBD). Patients with this disease often require the administration of artificial nutritional support. Liver function tests (LFT) derangement is a widely recognized side-effect of total parenteral nutrition (TPN). Therefore, the use of this modality of nutritional support may be an additional factor to cause hepatic damage in IBD patients. However whether or not the same occurs in patients receiving total enteral nutrition (TEN) is not well-established. The aim of the present study was to evaluate the effect of TEN upon LFT in patients with moderate to severe acute attacks of IBD, by means of a prospective, controlled, and nonrandomized design. Forty-nine patients were included; 29 (11 patients with ulcerative colitis and 18 with Crohn's disease) received TEN, and 20 (11 with ulcerative colitis and 9 with Crohn's disease) did not. Both groups were homogeneous regarding age, sex, disease activity index, nutritional status, and length of the study (24.8 +/- 1.3 vs 23.9 +/- 16.8 days). In all cases, weekly measurements of serum alkaline phosphatase, GOT, and GPT were performed. There were no significant differences in LFT at the beginning of the study between groups. The percentage of patients showing derangement of some LFT during the study did not differ between both groups: six of 29 (20.6%) in TEN group vs three of 20 (15%) in control group. Six out of the nine patients (in both groups) who developed LFT derangement had one or more causes, other than TEN for explaining hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Update on the use of metabolic probes to quantify liver function: caffeine versus lidocaine.

The search for continues for a safe, accurate and reliable method to quantify liver function similar in principle to renal creatinine clearance or pulmonary function spirometry tests. When evaluating patients in the more advanced stages of chronic liver disease, one's clinical judgement regarding the degree of liver dysfunction usually suffices, but in patients with early or only intermediate disease, and estimate based on routine blood tests and/or clinical severity scores is often unreliable. A more quantitative approach under investigation at present has been to monitor specific pharmacokinetic parameters of 'probe' drugs metabolized primarily by hepatic cytochrome P-450. These parameters include the plasma or salivary clearance rate of the parent compound and/or the formation rate of its metabolites. Following a review of basic hepatic pharmacology relevant to this topic, we shall explore the advantages and disadvantages of two 'metabolic probes' that have shown the most promise to date, caffeine and lidocaine.

Caffeine↗
PubMed1985

Effects of high hepatic acetaldehyde level following simultaneous administration of ethanol and cyanamide on liver function in rats.

Extremely high concentrations of hepatic acetaldehyde were induced in rats by the intragastric administration of ethanol and cyanamide, an aldehyde dehydrogenase inhibitor; and these high levels were maintained for 4 weeks. Liver function tests, including mitochondrial ornithine carbamoyltransferase (OCT) and GOT activities, were within normal limits, and no increase in either hepatic triglyceride or collagen contents was observed. These results suggest that hepatotoxic effects of ethanol are not derived from the high acetaldehyde levels in the liver.

Acetaldehyde↗