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Liver function tests.

For optimal timing of liver transplantation and for the evaluation of new pharmacotherapeutic options, objective modalities for estimating the liver's functional reserve and prognosis in an individual patient are highly desirable. In the past a number of tests and several scoring systems have been proposed and validated to varying degrees for this purpose. The issues still to be clarified include: (1) any observed prognostic value of individual quantitative function tests and of scoring systems must be validated in independent, large enough and well defined patient populations; (2) it must be prospectively defined which (serially performed) quantitative test(s) add(s) prognostic information for the individual patient to the survival estimates defined by the more universally available scores and in which disease state(s); and (3) existing scoring systems must be validated, or new ones developed, that allow follow-up data to be used in order to adapt the original prognosis estimate to the evolution of the disease, e.g. during therapy.

Humans↗

Investigation of the patient with abnormal liver function tests.

About one-half of patients with ulcerative colitis develop abnormal liver function tests at some time during the course of the illness. This should prompt an investigation for primary sclerosing cholangitis and other common hepatobiliary diseases. Primary sclerosing cholangitis occurs in 2-10% of patients with ulcerative colitis. The diagnosis of primary sclerosing cholangitis is most often made by endoscopic retrograde cholangiography. Liver histopathology is often inconclusive but magnetic resonance cholangiography shows promise as a useful non-invasive diagnostic tool. Cholangiocarcinoma complicates 20-40% of patients with end-stage primary sclerosing cholangitis and is now one of the most common causes of death in patients with ulcerative colitis. Distinction between benign and malignant strictures can be difficult and is best done with a combination of clinical suspicion, repeated imaging for mass lesions, cholangiography, and endoscopic brushings and/or biopsies. Dominant lesions of the common bile duct or common hepatic duct produce progressive jaundice and liver damage. Early treatment may improve prognosis. Single strictures can be dilated endoscopically. If the stricture is more complicated and extends into the intrahepatic ducts or there is suspicion of cholangiocarcinoma, surgical resection may be more appropriate. Liver transplantation should be considered in end-stage disease.

Bile Duct Diseases↗

Comparison of the metabolic effects of two hormonal contraceptive methods: an oral formulation and a vaginal ring. I. Carbohydrate metabolism and liver function.

A prospective, long-term study was undertaken to compare the metabolic effects of a contraceptive vaginal ring releasing levonorgestrel (about 290 microgram per day) and estradiol (about 180 microgram per day) and a combined oral contraceptive containing 30 microgram ethinylestradiol and 150 microgram levonorgestrel in two groups of women (n = 22 and 20, respectively). An intravenous glucose tolerance test, including determination of the insulin response to glucose, and liver function tests were performed. Both the glucose tolerance and fasting values of glucose were unaltered. The early insulin response to glucose increased by 50 percent in the contraceptive ring roup after one year of treatment, but not in the oral contraceptive group. All other insulin values were unchanged. All liver function values remained within the normal range in all subjects. There was a small significant decrease in alkaline phosphatases in both groups, which is in contrast to the effects of the early combined pills, which could cause an elevation. It is concluded that neither of these two contraceptive methods, the effects of which are predominantly gestagenic, seems to cause impairment of glucose tolerance or hepatic function.

Blood Glucose↗

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy volunteers (median and 95% CI for differences: -5.4% [-19.9% to 2.0%] and -19.4% [-45.6% to 0.4%]). Conservatively, a dose adjustment of dexketoprofen trometamol in patients with impaired hepatic function is recommended.

Administration, Oral↗

Stone or stricture as a cause of extrahepatic cholestasis--do liver function tests predict the diagnosis?

BACKGROUND: Cholestasis, roughly divided into intrahepatic and extrahepatic forms, is a clinical challenge. Extrahepatic cholestasis, characterized by dilated bile ducts, is caused by either a bile duct stone or stricture, with stricture most often related to a malignancy. The aim of the present study was to analyze the value of common liver function tests in separating patients with malignant bile duct strictures from those with stones. METHODS: All consecutive patients admitted for endoscopic retrograde cholangiopancreatography (ERCP) were included in the study population if a bile duct stricture related to a malignancy was found by ERCP (n=103) or if a bile duct stone was successfully extracted during ERCP, thus confirming the diagnosis of a stone (n=109). Plasma alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase and bilirubin values were determined in the morning before ERCP. RESULTS: Plasma bilirubin (p<0.001), alkaline phosphatase (p<0.001) and alanine aminotransferase (p=0.040) levels were significantly higher in patients with malignant bile duct strictures than in those with bile duct stones. In addition, gamma-glutamyltransferase levels seemed to be higher in patients with malignant strictures than in those with stones, although the difference did not reach statistical significance (p=0.053). In receiver operating characteristic analyses, bilirubin proved to be the best laboratory test in differentiating patients (p=0.001 vs. alkaline phosphatase, p<0.001 vs. alanine aminotransferase and p<0.001 vs. gamma-glutamyltransferase). With a plasma bilirubin cutoff value of 145 micromol/L, four out of five patients were categorized correctly. CONCLUSIONS: Plasma bilirubin seems to be the best liver function test in distinguishing patients with malignant bile duct strictures from those with bile duct stones. This routine test should receive more attention in clinical decision-making than has previously been given.

Adult↗

Liver function and pharmacokinetics of molsidomine and its metabolite 3-morpholinosydnonimine in healthy volunteers.

Plasma levels of N-carboxy-3-morpholinosydnonimine ethyl ester (molsidomine, Corvaton) and its pharmacologically active metabolite 3-morpholinosydnonimine (SIN-1) were measured in six healthy male and female volunteers after single intravenous and oral dosing of 4 mg molsidomine. Additionally indocyanine green and phenazone (antipyrine) clearances were determined to estimate hepatic blood flow and metabolic liver function in each subject. The pharmacokinetic parameters of molsidomine were similar to already published data in healthy volunteers and patients. The plasma level of SIN-1 formed was always lower than the molsidomine level but obviously reflects the corresponding molsidomine concentration time course in plasma. Indocyanine green plasma clearance was reduced by 15%. after intravenous dosing of 4 mg molsidomine. There was no clear-cut relationship between the plasma clearances of molsidomine and phenazone in these subjects with normal metabolic liver function.

Adult↗

Effect of hepatitis C virus coinfection on liver function of patients infected with HIV.

AIMS: Both the human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) share similar routes for their transmission, encouraging the possibility of a coinfection with the two viruses in some individuals. We wanted to find out the prevalence of HCV in patients infected with the HIV virus. METHODS: We tested 57 HIV positive patients for anti-HCV antibodies. Liver functions tests, ultrasound abdomen and upper gastrointestinal endoscopy were carried out in the anti-HCV positive patients. RESULTS: Coinfection with HCV was seen in 5.3% of patients. Of these 2 had acquired the infections through blood transfusions and one through heterosexual contact. One patient had cirrhosis with portal hypertension and one had raised alkaline phosphatase as the only abnormality on liver function tests. CONCLUSIONS: Because HCV is more infectious by the parenteral route, the incidence of coinfection is lower in our population possibly due to the fact that majority of our HIV positive patients acquire infection through heterosexual contact.

Adult↗

N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study.

OBJECTIVE: In septic shock, decreased splanchnic blood flow is reported, despite adequate systemic hemodynamics. Aacetylcysteine (NAC) was found to increase hepatosplanchnic blood flow in experimental settings. In septic shock patients, NAC improved the clearance of indocyanine green and the relationship of systemic oxygen consumption to oxygen demand. We investigated the influence of NAC on liver blood flow, hepatosplanchnic oxygen transport-related variables, and liver function during early septic shock. DESIGN: Prospective, randomized, double-blind study. SETTING: Septic shock patients admitted to an interdisciplinary surgical intensive care unit. PATIENTS: We examined 60 septic shock patients within 24 hrs after onset of sepsis. They were conventionally resuscitated with volume and inotropes and were in stable condition. A gastric tonometer was inserted into the stomach and a catheter into the hepatic vein. Microsomal liver function was assessed by using the plasma appearance of monoethylglycinexylidide (MEGX). INTERVENTIONS: Subjects randomly received either a bolus of 150 mg/kg iv NAC over 15 mins and a subsequent continuous infusion of 12.5 mg/kg/hr NAC over 90 mins (n = 30) or placebo (n = 30). MEASUREMENTS AND MAIN RESULTS: Measurements were performed before (baseline) and 60 mins after beginning the infusion (infusion). After NAC, a significant increase in absolute liver blood flow index (2.7 vs. 3.3 L/min/m2; p = .01) and cardiac index (5.0 vs. 5.7 L/min/m2; p = .02) was observed. Fractional liver blood flow index (cardiac index-related liver blood flow index) did not change. The difference between arterial and gastric mucosal carbon dioxide tension decreased (p = .05) and MEGX increased (p = .04). Liver blood flow index and MEGX correlated significantly (r(s) = .57; p < or = .01). CONCLUSIONS: After NAC treatment, hepatosplanchnic flow and function improved and may, therefore, suggest enhanced nutritive blood flow. The increase of liver blood flow index was not caused by redistribution to the hepatosplanchnic area, but by an increase of cardiac index. Because of its correlation with liver blood flow index, MEGX may be helpful in identifying patients who benefit from NAC treatment in early septic shock.

Acetylcysteine↗

Liver biopsy and liver function tests in 28 consecutive long-term alcoholics.

Liver cirrhosis was not found by needle biopsy performed on 28 consecutive male alcoholics of "skid-row" type, but 14 had fatty degeneration and 14 normal histology of the liver. Hypoalbuminemia was the most consistent finding. The combined galactose tolerance test could not predict fatty degeneration. There was no correlation between the laboratory tests used to assess liver function and the degree of fatty degeneration.

Adult↗

Rapid improvement of liver function in a patient with HIV and hepatitis B coinfection treated with lamivudine and tenofovir.

Since the introduction of HAART, the clinical importance of hepatitis virus infection and its complications in human immunodeficiency virus (HIV)-infected persons have continuously grown. Coinfection with hepatitis B virus (HBV) and HIV is one of the leading causes of morbidity and mortality. To date, neither the optimal time point for initiation of anti-HBV therapy nor the best therapeutic approach has been clearly defined. We report the case of a 22-year-old African woman infected with HBV- and HIV-1 coinfection and severe impairment of liver function. HAART including lamivudine and tenofovir was started. Three weeks later, the patient achieved not only a restoration of her clinical situation and liver function, but she also demonstrated a complete suppression of both viruses. This impressive clinical course might be explained by the application of antiviral combination therapy including lamivudine and tenofovir. Tenofovir has shown a higher activity against HBV than other drugs. In addition, combination therapy for chronic hepatitis B might be more effective than monotherapy. Future studies need to clarify the value of combination treatment for patients with chronic hepatitis B.

Adenine↗

High serum carotenoids are inversely associated with serum gamma-glutamyltransferase in alcohol drinkers within normal liver function.

BACKGROUND: Many studies have reported that the consumption of alcohol induces the generation of free radicals. Moreover, recent studies suggest that serum gamma-glutamyltransferase (gamma-GTP) within its normal range might be an early marker of oxidative stress. In this study, we tested the hypothesis that serum antioxidant carotenoids would be inversely associated with serum gamma-GTP in alcohol drinkers within normal liver function. METHODS: A total of 266 Japanese men who had received health examination in 2003 participated in the study. The associations of serum gamma-GTP and serum-carotenoid concentrations stratified by alcohol intake levels were evaluated cross-sectionally. The participants were divided into three groups according to their ethanol intake level (non-drinker, less than 1 g/day; light drinker, 1-25 g/day; and moderate and heavy drinkers, 25+ g/day). The multivariate-adjusted geometric means of the serum gamma-GTP concentrations in each tertile of the serum-carotenoid concentrations were calculated after adjustment for ethanol intake, age, body mass index, total cholesterol, triacylglycerols, current tobacco use, and habitual exercise. RESULTS: The serum gamma-GTP concentrations were significantly high in accordance with the ethanol intake level. In moderate and heavy drinkers, the multivariate-adjusted geometric means of serum gamma-GTP concentrations were significantly low in accordance with the tertiles of the serum lycopene, alpha-carotene, beta-carotene, and beta-cryptoxanthin concentrations. CONCLUSIONS: The serum antioxidant carotenoids were inversely associated with alcohol-induced increases of serum gamma-GTP in moderate and heavy drinkers within normal liver function.

Adult↗

[Effects of intraarterial infusion chemotherapy on liver function in patients with hepatocellular carcinoma].

Periodic infusion chemotherapy from the reservoir implanted by direct arterial puncture (Seldinger method) was performed in 21 cases of hepatocellular carcinoma. The effectiveness of treatment in terms of efficacy and liver function in about 12 patients who survived more than 6 months was investigated. Owing to the progressive liver atrophy and liver dysfunction with ascites, some cases had to delay infusion treatment. Thus, it is necessary to check liver function regularly.

Adult↗

Liver function test abnormalities and pruritus in a patient treated with atorvastatin: case report and review of the literature.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) are associated with elevated transaminase levels in 1-3% of patients. Therapy with these drugs requires monitoring of alanine aminotransferase (ALT) levels because animal studies and premarketing clinical trials showed signs of hepatotoxicity that were primarily minor elevations of ALT. Nevertheless, postmarketing experience suggests that hepatotoxicity is rare, and that elevated ALT levels are reversible with continued therapy and probably are related to cholesterol lowering. Based on the low occurrence of ALT elevations and the lack of clinical evidence of hepatotoxicity, some clinicians are calling for a change in the current practice of monitoring liver function tests. We report, however, the case of a 71-year-old woman who was receiving atorvastatin and experienced elevated transaminase levels on two occasions, and developed pruritus on rechallenge with the drug. Thus, clinicians should be aware of asymptomatic elevations in liver function tests in patients receiving atorvastatin who do not have known risk factors for liver damage.

Administration, Oral↗

Liver function tests and lidocaine metabolism (MEGX test) during i.v. CMF therapy in breast cancer.

The measurement of monoethylglycinexylidide (MEGX test) is considered a sensitive method for the evaluation of hepatic metabolic capacity. The multidrug chemotherapy CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/ m2, 5-fluorouracil 600 mg/m2) is widely used in breast cancer patients but very few clinical studies have investigated its possible liver toxicity. We have prospectively evaluated the possible acute liver toxicity after a cycle (i.e. two courses) of CMF by means of the measurement of standard liver function tests and of MEGX, i.e. the main lidocaine (Lid) metabolite after the i.v. injection of Lid. Consecutive patients (n = 15), aged 43-68 years, were radically operated on because of M0 primary breast cancer and candidates for adjuvant CMF because of nodal axillary involvement (pN1) were studied. Tests were performed before the first (given at day 1) and 48 h after the second course (given at day 8) of an i.v. CMF regimen to be repeated every 28 days. Full blood count, serum ALT, AST, gamma-GT, alkaline phosphatase and albumin were measured with standard methods. To investigate the appearance of MEGX, blood samples were taken before, and 5, 10, 15, 20, 25, 30 and 60 min after i.v. Lid injection. MEGX serum concentration was measured by means of a fluorescent polarization immunoassay. We found no significant variation between pre- and post-CMF standard liver function tests with the exception of ALT levels, which, however, decreased (mean 48%, p < 0.05). The MEGX serum concentration was significantly increased over the sampling time period and the 42% mean rise was statistically significant (p < 0.001). Moreover, the post-CMF increase of circulating MEGX was steeper than the basal pre-CMF values. The slopes relating to the curves of MEGX formation over the first 20 min were 3.30 and 2.24, respectively (p < 0.001). In conclusion, no hepatic acute toxicity was observed during the CMF chemotherapy. Further studies are required to understand the meaning of the unexpected MEGX rise.

Adult↗