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Interactive effects between CYP1A1 genotypes and environmental polychlorinated dibenzo-p-dioxins and dibenzofurans exposures on liver function profile.

Previous studies reported that polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) induced hepatic cytochrome P-4501A1 (CYP1A1). The aim of this study was to examine the interactive influence of CYP1A1 genotypes and PCDD/Fs exposure on liver function profile. PCDD/Fs levels and liver function parameters were determined in serum and correlated with genetic polymorphism of CYP1A1/Msp 1 in 225 human volunteers who had no or minimal occupational exposure to PCDD/F. The results showed that the highest glutamate pyruvate transaminase (GPT) activity levels were found in subjects with homozygous variant CYP1A1/Msp 1, followed by heterozygous variant, and finally homozygous wild type for those individuals whose serum PCDD/Fs levels were higher than 17.4 pg WHO-TEQ/g lipid. Data suggest that GPT activity levels may be modified by interaction of CYP1A1/Msp 1 genotype with dioxin after adjustment for age, alcohol consumption, and history of liver illness. Further studies are needed to characterize the variation in other related genes to verify whether a correlation exists between serum PCDD/Fs levels and adverse health effects.

Adolescent↗

Liver function profiles and their interpretation.

Plasma bilirubin, protein and enzyme measurements are used to evaluate hepatocellular function and integrity and bile duct patency. This 'liver function test' package is of value for the detection, confirmation, categorization and assessment of liver disease.

Alkaline Phosphatase↗

Antipyrine metabolism and liver function in patients treated with high-dose medroxyprogesterone.

The effect of high-dose medroxyprogesterone acetate (MPA, 250 mg intramuscularly for six days) on hepatic drug-metabolism and liver function was investigated in eleven females with endometrial carcinoma. Antipyrine plasma clearance, an index of hepatic drug-metabolizing ability, improved significantly during this treatment, and the serum total bilirubin level was lowered, whereas other liver function tests, including alkaline phosphatase, and albumin values in the serum, remained unchanged. The results demonstrate that therapy with MPA has an inducing effect on hepatic enzyme activity and antipyrine metabolism. The findings may be of importance when prescribing drugs for females receiving large doses of MPA.

Adult↗

Pharmacokinetics of diazepam in disordered liver function.

The plasma elimination curves of diazepam following intravenous administration of 10 mg were studied in nine patients with cirrhosis of the liver and four patients without liver disease. The data were analyzed according to a two compartment model. The mean biological half-life (T/2) of diazepam was increased five-fold in patients with cirrhosis compared to the controls (164 hours vs. 32.1 hours). The plasma clearance of diazepam could be correlated neither with a quantitative measure of liver function, as estimated by galactose elimination capacity, nor to semiquantitative measures of liver function, such as serum albumin and prothrombin. It is suggested that the plasma clearance of diazepam is an inaccurate index of its rate of hepatic metabolism due to the complex kinetics of the drug.

Adult↗

Prevalence of hepatitis B and C seromarkers and abnormal liver function tests among hemophiliacs in Guilan (northern province of Iran).

BACKGROUND: The aim of this study was to determine the seroprevalence of hepatitis B and C viruses and abnormal liver function tests among hemophiliacs in Guilan province, Iran. MATERIAL/METHODS: Patients registered with Guilan Hemophilia Society (GHS) were enrolled in this study, and evaluated for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab) and liver function tests. RESULTS: One hundred and one patients (100 males, 1 female, mean age 19.7 years, range 3-71 years) from 110 registered hemophiliacs were enrolled in this study. 29 patients (28.7%) had elevated Alanine aminotransferase (ALT), 27 (26.7%) and 72 (71.3%) were positive for HBsAg and HCV-Ab, respectively. Seropositivity for HCV-Ab correlated with the duration of treatment with clotting factor until 1997 (P=0.01). There was also an inverse correlation between factor VIII & IX activity and seropositivity for HCV-Ab (P<0.001) and HBsAg (P<0.04). HCV-Ab was more likely to be positive among those received lyophilized factor VIII and cryoprecipitate than lyophilized factor VIII alone (P<0.01). In addition HCV-Ab seropositivity was more common among those received factor IX concentrate and fresh frozen plasma (FFP) than those received only FFP (P<0.01). CONCLUSIONS: Based upon our finding, prevalence of HBsAg positive cases in Guilan province was higher than other studies. Although frequency of HCV-Ab was similar to other studies, frequency of increased ALT was less. Upon the results emerged from this study, we recommend that all hemophiliacs should be vaccinated against HBV and should have regular program for checking HCV.

Adolescent↗

[Bile acid concentration in serum after a test meal in hepatobiliary diseases. A comparison with quantitative liver function tests].

The concentration of bile acids in serum was measured by an enzymatic-fluorometric method under fasting conditions and 2 hours after a standardized meal in 26 patients with chronic liver disease (chronic hepatitis, liver cirrhosis, primary biliary cirrhosis) and compared with other tests of liver function. Postprandial bile acids and transaminases were false negative in only 12% and are thus the most sensitive tests after the BSP-retention test (3% false negative results). In comparison, fasting bile acids proved to be a relatively insensitive screening test for liver disease (38% false negative results). Postprandial bile acids were more closely correlated with BSP retention and BSP disappearance rate constant (Ki) than fasting bile acids. In view of these findings postprandial serum bile acid concentrations should be preferred to fasting bile acid concentrations in screening for liver disease and monitoring liver function.

Adult↗

[Use of breath analysis in diagnosis of liver function (author's transl)].

Breath tests with analysis of 14CO2 after oral ingestion of 14C-labeled substrates (14C-aminopyrin. 14C-diazepam, 14C-phenacetin, 14C-D-galactose) have been used as quantitative liver function tests. Their diagnostic value is discussed. Breath tests are non-invasive, cheap, easy to perform often without assistance and allow to assess a function of the liver (drug metabolizable function) which is not accessible by other simple analysis techniques. Decreased demethylation of 14C-aminopyrine, 14C-phenacetin, 14C-diazepam is present in chronic liver disease, whereas increased demethylation correlating with chemically determined drug elimination capacity is observed in patients on drugs which induce the capacity of the drug metabolizing enzyme system of the liver.

Aminopyrine↗

Effects on the hemostatic system and liver function in relation to Implanon and Norplant. A prospective randomized clinical trial.

In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase.

Adult↗

Effects of occupational and nonoccupational factors on liver function tests in workers exposed to solvent mixtures.

A total of 368 workers from six paint-manufacturing factories participated in this study. The workers were classified according to type of exposure: direct, intermittent, and no exposure. The workers' liver-function tests were influenced greatly by gender, hepatitis B, alcohol consumption, and body mass index. Both the serum concentration and the odds of abnormality of total serum bile acids were elevated among the directly exposed group. The authors concluded that analysis of covariance should take into account occupational and nonoccupational factors on liver-function tests to avoid any errors. Total serum bile acids also indicated liver dysfunction from solvent exposure.

Adolescent↗

Restoration of liver function and portosystemic pressure gradient after TIPSS and late TIPSS occlusion.

TIPSS (transjugular intrahepatic portosystemic shunt) may be indicated to control bleeding from esophageal and gastric varicose veins, to reduce ascites, and to treat patients with Budd-Chiari syndrome and veno-occlusive disease. Numerous measures to improve the safety and methodology of the procedure have helped to increase the technical and clinical success. Follow-up of TIPSS patients has revealed shunt stenosis to occur more often in patients with preserved liver function (Child A, Child B). In addition, the extent of liver cirrhosis is the main factor that determines prognosis in the long term. Little is known about the effects of TIPSS with respect to portosystemic hemodynamics. This report deals with a cirrhotic patient who stopped drinking 7 months prior to admission. He received TIPSS to control ascites and recurrent esophageal bleeding. Two years later remarkable hypertrophy of the left liver lobe and shunt occlusion was observed. The portosystemic pressure gradient dropped from 24 mmHg before TIPSS to 11 mmHg and remained stable after shunt occlusion. The Child's B cirrhosis prior to TIPSS turned into Child's A cirrhosis and remained stable during the follow-up period of 32 months. This indicates that liver function of TIPSS patients may recover due to hypertrophy of the remaining non-cirrhotic liver tissue. In addition the hepatic hemodynamics may return to normal. In conclusion, TIPSS cannot cure cirrhosis but its progress may be halted if the cause can be removed. This may result in a normal portosystemic gradient, leading consequently to shunt occlusion.

Adult↗

Liver function test abnormalities in early Lyme disease.

OBJECTIVE: Lyme disease is a widespread, tick-borne, spirochetal infection with multiple organ system involvement Hepatic dysfunction has not been emphasized in the literature. We report clinical findings and laboratory abnormalities in 73 patients with the pathognomonic erythema migrans rash early in the course of the illness. DESIGN: Case series. SETTING: Offices of family physicians in private practice and the model offices of a family practice residency program in the lower Connecticut River valley, an area to which Lyme disease is endemic. PATIENTS: Thirty-seven female and 36 male patients with erythema migrans who had not yet been treated with antimicrobial agents. MAIN OUTCOME MEASURE: Liver function tests. RESULTS: Twenty patients (27%) had liver function abnormalities. Elevation of gamma-glutamyltransferase was the most common finding. Only seven patients (9%) had a positive titer in response to the enzyme-linked immunosorbent assay for Lyme disease. Other laboratory and clinical findings are described. CONCLUSION: Subclinical hepatitis is a common finding in early Lyme disease.

Adolescent↗

Quantitative liver functions after 70% hepatectomy.

Following 70% hepatectomy on rats the galactose elimination capacity, taken as a measure of the cytosolic liver function, was reduced from 2.55 +/- 0.48 to 1.27 +/- 0.19 (mean +/- SEM) mumol/min. Six hours later it was restored to control values. The prothrombin index, representing the function of the endoplasmic reticulum, was reduced from 1.13 +/- 0.02 to 0.34 +/- 0.02 (arbitrary units) after 12 h, and it was restored after 96 h. The rapid normalization of the initial fall in the capacity to metabolize galactose reflects a two- to three-fold increase of the galactose metabolizing capacity of the remaining liver. This study demonstrates that liver functions are dissociated in time following 70% hepatectomy in the rat, and that the galactose elimination capacity is restored before regeneration can compensate for the loss in liver cell mass.

Animals↗

Correlation of donor nutritional status with sinusoidal lining cell viability and liver function in the rat.

We have demonstrated that the sinusoidal lining cell injury sustained by rat liver allografts during hypothermic storage is a critical determinant of graft viability. The present study was designed to examine the effect of donor nutritional status on hepatic microcirculation and graft function. Rat livers from four nutritional groups (group I, fasted; group II, fed; group III, intraperitoneal glucose; and group IV, fed plus intraperitoneal glucose) were excised and stored for 24 hr in Marshall's isotonic citrate solution. Then the livers were perfused under anoxic conditions with trypan blue. The percentage of nonviable SLC in each group was 26.7 +/- 8.1, 24.9 +/- 7.9, 17.6 +/- 6.9, and 5.9 +/- 1.9 in groups I, II, III, and IV respectively; i.e., there was a significant improvement in SLC viability with nutritional repletion in group IV. Electron microscopy was performed on livers from groups I and IV following 30-hr preservation in University of Wisconsin solution and after 16-hr preservation in Marshall's isotonic citrate solution. Biopsies were taken at the end of storage and after 1 hr of reperfusion at 37 degrees C. At the end of preservation group IV livers contained glycogen and had much more normal liver ultrastructure than group I livers. After reperfusion there was partial recovery of normal SLC morphology in both groups and depletion of glycogen in group IV. Liver function was studied on the isolated perfused rat liver system at 37 degrees C following 30-hr storage in UW solution. Transaminase release into the perfusate was significantly lower in nutritionally repleted livers than in livers from fasted animals. A significant reduction in perfusate platelet count occurred only in livers from fasted animals. The results show that nutritional repletion can reduce the injury of cold preservation to both hepatocytes and endothelial cells and improve liver function in the postpreservation period.

Alanine Transaminase↗

[Nuclear medicine for evaluation of liver functions].

The clinical usefulness of colloid liver scintigraphy to detect space occupying lesions in the liver has been reduced by X-ray CT and ultrasonography. However, scintigraphic examinations have potentials for characteristic diagnosis of liver tumors, such as 99mTc RBC SPECT for hepatic hemangioma, 99mTc PMT for positive imaging of hepatocellular carcinoma and its extrahepatic metastasis, and radioimmunoscintigraphy for metastatic tumors. Moreover, prediction of the prognosis and monitoring therapeutic effect to liver cancer can be made by the use of nuclear medicine techniques. Recently, 99mTc galactosyl serum albumin (GSA), a newly developed radiotracer to evaluate hepatocyte function, has become commercially available. Quantitative parameters of liver functions can be obtained by analysis of time-activity curve in blood and liver after 99mTc-GSA administration. In several cases, 99mTc-GSA study showed intrahepatic unevenness of function, which could not be depicted by other imaging examinations. Positron emission tomography (PET) with 18F-fluoro-2-deoxy glucose (FDG) is useful to detect malignant tumors in the liver. Since PET can provide absolutely quantitative data in better resolution, it is expected that regional true metabolic functions in the liver may be able to be quantitatively evaluated with PET in near future.

Carcinoma, Hepatocellular↗

Liver function tests and low-dose estrogen oral contraceptives.

Twenty healthy female volunteers were treated with 35 microgram ethinyl estradiol and 0.4 mg norethindrone for a two-month period of time. Liver function tests (serum SGOT, SGPT, LDH, alkaline phosphatase, total bilirubin, total protein, albumin and prothrombin times) were measured at baseline and control prior to treatment, and at one and two months of therapy. There was a 1.25% incidence of abnormalities in the 320 tests conducted during therapy. During the first month of therapy, there was a 1.9% incidence of abnormal tests. 0.625% incidence of abnormal tests was seen in the second month of treatment. A 5% incidence of abnormalities (single episodes in each parameter) was seen in SGPT, LDH, total bilirubin and prothrombin time levels during the two-month period. This was well below the 10-30% incidence of abnormalities reported with 50-100 microgram of estrogen-containing birth control pills in previous studies. There seems to be little effect on liver function tests with use of estrogen preparations containing 35 microgram ethinyl estradiol.

Adult↗

Wernicke's encephalopathy in hyperemesis gravidarum: association with abnormal liver function.

A 27-year-old woman developed Wernicke's encephalopathy in the 18th week of her pregnancy after 11 weeks of vomiting accompanied by weight loss of 21 kg and moderately abnormal liver function tests. The patient recovered after thiamine therapy but the fetus was lost. Review of the literature published during the last 25 years revealed an additional 14 cases of Wernicke's encephalopathy complicating hyperemesis gravidarum. All patients vomited for at least 4 weeks. Six of the 15 patients (40%) had aspartate aminotransferase values > 100 U/l, much higher than the rate reported in previous series of patients with hyperemesis gravidarum (7%). This suggests the need for parenteral thiamine supplementation in patients with severe hyperemesis gravidarum lasting more than 3 weeks, especially those with abnormal liver function, and supports the hypothesis that the hepatic abnormality plays a pathogenetic role in the development of Wernicke's encephalopathy in hyperemesis gravidarum.

Adult↗

Short-term effects of branched-chain amino acids on liver function tests in cirrhotic patients.

A randomized study was conducted in 29 ambulatory cirrhotic patients to determine the short-term effects of branched-chain amino acids (BCAA) on nutritional status, biochemical liver function tests and caffeine clearance. Each patient received a 4-week period of isonitrogenous and isocaloric regimens, either a standardized diet contained 40 g protein with supplementation of BCAA 150 g daily (group I) or only a standardized diet contained 80 g protein daily (group II). At the end of treatment, only group I showed significant improvements in transaminase levels as well as the caffeine clearance test compared with those of the pre-treatment levels. Nonetheless, significant improvements in nutritional parameters and additional liver function tests were not yet detected. We conclude that the short-term nutritional supplementation of BCAA is well tolerated and leads to improvement in hepatic metabolic capacity assessed by the caffeine clearance test.

Adult↗

[Evaluation of liver function in carbon tetrachloride-damaged rabbits by dynamic SPECT: comparison of 99mTc-GSA and 99mTc-Sn colloid].

Technetium-99m-DTPA-galactosyl human serum albumin (99mTc-GSA) is a new ligand that binds specifically to asialoglycoprotein receptors in hepatocytes. We performed liver dynamic SPECT using 99mTc-GSA and 99mTc-Sn colloid in nine normal control rabbits and 17 chronically CCI4-damaged rabbits (total 29 examinations), and also performed liver function tests (ICGR15, Alb, etc). Using the obtained dynamic SPECT data, we analyzed the liver kinetics of 99mTc-Sn colloid using a one-compartment model (hepatic blood flow [K]) and 99mTc-GSA using a two-compartment model (hepatic blood flow and receptor binding [K1], catabolism [K2]). As the CCl4-treated period increased, K1 decreased most significantly. K1 showed the most significant statistical correlation with the results of liver function tests, ICGR15 (p < 0.0001), Alb, PT, HP, Bil and GPT. Further, only K1 showed a correlation with the hepatic fibrosis of the HAI score. From the present results, liver dynamic SPECT using 99mTc-GSA may be said to provide a novel method for the evaluation of hepatic functional reserve.

Animals↗