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PubMed1989

Role of the standard 'liver function tests' in current clinical practice.

A prerequisite of current therapy in liver disease is precise diagnosis. The rapid increase in the number of tests available--immunological, virological, histological and radiological--testifies to this, and reflects the inadequacy of the 'standard' liver function tests (LFTs). The LFTs are, however, in contrast to these more sophisticated tests, observer independent and despite their lack of specificity, several characteristic patterns of abnormality can be recognised which direct the physician to the most appropriate definitive investigation. The cheapness and non-invasive nature of the LFTs makes them particularly appropriate for monitoring the course of liver diseases once the diagnosis has been established and this, together with screening for hepatotoxicity of newly developed drugs, is now their main role. A second generation of liver function tests based on the capacity of the liver to eliminate various test compounds may come closer to offering a true estimate of liver function. More accurate methods of measuring the various bilirubin fractions, particularly bilirubin conjugates may also become available in the near future and provide more sensitive tests of liver dysfunction.

Humans↗

PubMed1985

A possible beneficial effect of metronidazole in reducing TPN-associated liver function derangements.

Cholestasis and fatty infiltration of the liver are common complications of total parenteral nutrition (TPN). Following a recent suggestion that TPN-associated liver function derangements may be related to intestinal overgrowth of anaerobic bacteria, the effect of metronidazole on hepatic dysfunction during TPN in rats was investigated. After 5 days of TPN with either amino acids and glucose or amino acids with glucose and fat, all groups exhibited a mild weight gain, positive nitrogen balance, increased liver weight, increased liver:body weight ratio, increased levels of liver enzymes, and increased hepatic lipid content. The administration of metronidazole at 15 mg/kg/day significantly decreased the hepatic lipid content from 0.077 g fat/g liver for controls to 0.053 g fat/g liver. The efficacy of metronidazole in reducing hepatic fat accumulation during nutritionally effective and adequate TPN in rats suggests the possible involvement of anaerobic bacterial flora of the intestinal tract, at least in part, in the pathogenesis of TPN-associated liver function derangements. However, the various biochemical and morphological expressions of these changes and the discrepancy between unchanged liver weight, liver:body weight ratio, liver enzymes, and the improved hepatic fat content suggest multifactorial mechanisms for TPN-related liver damage.

Amino Acids↗

PubMed1983

Assessment of liver function by the aminopyrine breath test.

The aminopyrine breath-test (ABT) has been proposed as a non-invasive quantitative test of liver function and reserve. To evaluate its usefulness, we compared the ABT with standard liver function tests, Child's classification of liver disease and ICG clearance, as means of assessing liver function in 30 patients with cirrhosis. The cumulative output of 14CO2 in breath during the 6 h following [14C]aminopyrine administration was significantly decreased in the cirrhotic group as compared with control subjects. The severity of liver dysfunction, as assessed by Child's classification, was associated with a progressive and statistically significant impairment of the ABT. There was a good correlation between the ABT and ICG systemic clearance (r = 0.770, P less than 0.001) and also between the ABT and ICG intrinsic clearance (r = 0.885, P less than 0.001), a measure which is independent of hepatic blood flow variations. These results further strengthen the concept that the ABT is a simple non-invasive method to assess quantitatively liver function and reserve, and could be useful in following the evolution of patients with liver disease.

Adult↗

PubMed1976

[Liver function in hormonal contraception].

Numerous interactions between hormonal contraceptives and liver function have been described. Changed laboratory results do not represent obligatory pathologic conditions or hepatotoxi effects. Some of these changed results are transient, suggesting that liver cells are capable of adaptation. The use of oral contraceptives is contraindicated in the following liver diseases: - recurrent intrahepatic cholestasis (recurrent jaundice of pregnancy, Dubin-Johnson syndrome, Rotor syndrome); - acute disturbances of liver function. In general it is recommended that hormonal contraceptives should not be used by patients with biliary cirrhosis although some authors have stated that chronic disturbances of liver function did not appear to be aggravated by these agents. Impairment of carbohydrate and lipid metabolism needs careful control of the laboratory tests concerned. Due to its low frequency the increased risk of gallstones does not necessitate the withdrawal of the medication. Up to now the interrelationship between the use of contraceptive steroids and the induction of hepatic tumours has not been proven.

5-Aminolevulinate Synthetase↗

PubMed1978

14C-D-galactose breath test for evaluation of liver function in patients with chronic liver disease.

D-Galactose metabolism and demethylation of aminopyrine by healthy controls and patients with chronic active hepatitis (CAH) and cirrhosis (Ci), were assessed by a breath analysis technique measuring 14CO2 exhalation after oral ingestion of 14C-D-galactose or 14C-aminopyrine. Patients with CAH and Ci exhibited decreased 14CO2-exhalation rates following 14C-D-galactose or 14C-aminopyrine. D-Galactose oxidation capacity of the liver can be assessed by a breath analysis technique in analogy to the demethylating function for aminopyrine. The ordinary oral D-galactose tolerance test seems, however, superior in comparison to the 14C-D-galactose tolerance test, in discriminating between healthy controls and patients with chronic liver disease.

Administration, Oral↗

PubMed1984

Acute doxorubicin toxicity. Relationship to pretreatment liver function, response, and pharmacokinetics in patients with acute nonlymphocytic leukemia.

To determine if there is a relationship between development of acute doxorubicin toxicity, pretreatment liver function studies, and response, 64 acute nonlymphocytic leukemia patients undergoing induction chemotherapy with doxorubicin and cytosine arabinoside were evaluated. No statistically significant correlation could be found between the development of acute toxicity (mucositis) and the number or type of abnormal pretreatment liver functions. Patients receiving full doses of doxorubicin with mild hepatic dysfunction as determined by bromsulphalein (BSP) retention and serum liver function studies had the same incidence of toxicity and complete response rate as those with normal hepatic function. There was no significant difference between duration of response (P = 0.41) or survival (P = 0.17) between the two groups. Ten patients receiving a decreased dose of doxorubicin due to hepatic dysfunction had the same complete response rate but a lower incidence of toxicity as patients receiving full doxorubicin dose. Pharmacokinetic data from fluorescence plasma assays suggest no difference among patients with normal or mildly abnormal liver function studies receiving full doxorubicin doses. The results suggest that leukemia patients with mild hepatic dysfunction receiving a combination of full-dose doxorubicin and cytosine arabinoside for acute leukemia will have the same plasma pharmacokinetics, incidence of toxicity, and complete response rate as those with normal hepatic function. Reduction of doxorubicin dose in patients with abnormal liver function tests results in lower plasma concentrations, less toxicity, and the same response rate, but may also yield a shorter duration of response and survival.

Adolescent↗

PubMed1987

Liver function abnormalities in chronic heart failure. Influence of systemic hemodynamics.

To characterize the incidence and severity of liver function abnormalities in patients with congestive heart failure, we analyzed systemic hemodynamics and biochemical profiles in 133 patients with stable chronic congestive heart failure, secondary to a dilated cardiomyopathy. The patients were divided into three groups, based on the severity of the reduction in cardiac index (CI). The mean values of all liver function tests in groups 1 (n = 43; CI greater than or equal to 2.0 L/min/m2) and 2 (n = 48; CI greater than 1.5 and less than 2.0 L/min/m2) were essentially normal, except for minimally elevated alkaline phosphatase levels and slightly decreased albumin levels in both groups, and slight increases in levels of gamma-glutamyl transpeptidase and total bilirubin in group 2. In contrast, group 3 patients (n = 42; CI less than or equal to 1.5 L/min/m2) had the most severe heart failure, as assessed by the lowest CI and highest cardiac filling pressures, and significantly higher levels of aspartate aminotransferase (65 +/- 82 U/L), alanine aminotransferase (77 +/- 102 U/L), lactate dehydrogenase (282 +/- 91 U/L), and total bilirubin (29 +/- 14 mumol/L [1.7 +/- 0.8 mg/dL]). The percentage of patients in group 3 with these abnormalities ranged between 27% and 80%. Although linear regression analysis showed that the elevations in right atrial and pulmonary wedge pressures, and the decreases in CI, were significantly correlated with liver function abnormalities, the correlation coefficients were small. Thus, liver function abnormalities remain common in patients with congestive heart failure but are generally small in magnitude and not associated with clinically apparent hepatic disease. It is likely that reduced forward flow and passive backward congestion are both contributing factors in the pathogenesis of these biochemical abnormalities, although nonhemodynamic factors may also be important.

Adult↗

PubMed1990

Liver function assessment by drug metabolism.

Liver function can be assessed by administering an exogenous substance to quantify changes in hepatic blood flow, uptake, biotransformation, and excretion. Characterization of drug half-life, clearance, and product formation rates are possible methods for measuring hepatic efficiency. Allopurinol and caffeine have been used to measure metabolite formation followed by renal elimination of both parent substance and metabolite. Sorbitol, a substance with high intrinsic clearance, can reflect liver blood flow, while trimethadione, a low-extraction drug, has been used to measure liver enzyme capacity. Metabolites from lidocaine, methacetin, and aminopyrine have been measured in serum, urine, and breath tests. Salivary clearance measurements of caffeine and antipyrine are reported as suitable for routine use. Genetic diversity of isoenzymes and the many metabolic processes used by hepatocytes make it extremely difficult to quantify functional changes with one substance. Combinations of model substrates have been suggested to assess the many hepatic processes.

Acetamides↗

PubMed1987

The effects of liver directed radiotherapy and chemotherapy on liver function tests and hematological parameters in patients with surgically resected colon cancer: findings from the Gastrointestinal Tumor Study Group.

The effects on liver function tests of liver-directed radiation (RT) and systemic chemotherapy (CT) were examined at 6 months after initiation of treatment on two Gastrointestinal Tumor Study Group protocols. Data from patients on protocol GI 6175 (adjuvant CT or no adjuvant therapy) were used to evaluate the effect of CT alone, and data from patients on protocol GI 6179 (adjuvant CT plus liver directed RT or no adjuvant therapy) were used to evaluate the combined effects of CT and RT. Finally, data from patients on GI 6179 who received less than protocol specified RT doses were used to determine whether minor differences in dose are detectable via liver function tests. In 40 patients receiving CT, the serum level of alkaline phosphatase was not significantly increased (p = 0.14) compared to that of control patients whereas the level of serum glutamate oxoloacetate transaminase was significantly elevated (p = 0.03). In 31 patients receiving both CT and RT, both alkaline phosphatase and SGOT were significantly elevated (both p = 0.03). In addition, in 19 patients who received less than full RT doses, the changes in dose were not detectable from those patients who received full dose (all p greater than 0.10). In summary, CT alone may elevate hepatocellular enzymes, whereas a combination of CT and liver-directed RT is associated with a significant increase in both SGOT and alkaline phosphatase. Small alterations in the dose of volume of RT are not detectable by liver function test variations.

Alkaline Phosphatase↗

PubMed1991

Caffeine clearance by enzyme multiplied immunoassay technique: a simple, inexpensive, and useful indicator of liver function.

The clinical value and sensitivity of serum caffeine clearance measurement has been evaluated as an indicator of hepatic disease. After a 17 hour caffeine exclusion period, 300 mg of caffeine citrate was administered orally to the study subjects. Serum samples were taken four and 16 hours later. Serum caffeine concentrations were measured using an enzyme multiplied immunoassay technique (EMIT) and a clearance value derived. Conventional liver function tests were measured at the same time. A total of 103 subjects attending the medical unit in a district general hospital were studied. Twenty one had alcoholic liver disease, 11 non-alcoholic cirrhosis, nine non-cirrhotic liver disease, 21 suspected liver disease, six hepatic tumours, and 35 were hospital and normal control subjects. Caffeine clearance values were lowest in subjects with alcoholic liver disease (median 0.19 ml/min/kg, range 0.04-0.61 ml/min/kg) and significantly reduced in all subjects with liver disease (median 0.32 ml/min/kg, range 0.04-2.68 ml/min/kg) compared with control subjects (median 1.27 ml/min/kg, p less than 0.001). In subjects with suspected liver disease subsequently shown to have another explanation for abnormal liver function test results, caffeine clearance values were normal (median 1.31 ml/min/kg, range 0.23-2.64 ml/min/kg) and significantly different, p less than 0.001, from those of subjects with liver disease. Serum albumen values were not different for these latter two groups. Using a cut off value of 0.86 ml/min/kg, caffeine clearance measurement was 100% sensitive for alcoholic liver disease and 89% sensitive for all liver disease. The respective sensitivities for conventional liver function test measurement were 76% and 83%. In the suspected liver disease group, caffeine clearance was abnormal in only 24%, conventional liver function tests were abnormal in 95%. The respective specificities for caffeine clearance and liver function test measurement in control subjects were 93% and 100%. Caffeine clearance determined by EMIT is a simple inexpensive hepatic metabolic function test. This study indicates that it is a more sensitive indicator of structural liver disease than conventional liver function tests, especially for alcoholic liver disease. The test could be widely introduced as a useful, repeatable assessment of hepatic function.

Adult↗

PubMed1988

[Comparison of quantitative liver function tests to clinical, laboratory chemical and biopsy findings in patients with liver diseases].

Quantitative liver function tests (QLFT), e.g. 1) galactose elimination capacity (GEK) and 2) fractional indocyanine-green elimination constant k (ICG) were performed in patients with various liver diseases. Retrospectively the results of QLFT were compared to clinical, histological and laboratory findings which are known to reflect severity of liver disease. Patients showing clinical symptoms like ascites and/or encephalopathy demonstrated lower values for GEK and ICG. In addition similar data were obtained for those patients who showed histological evidence of cirrhosis. When dividing up the group of cirrhotics according to PUGH's classification, correspondingly lower results of QLFT were observed between different PUGH classes, however, due to a substantial overlap an individual classification could not be achieved by QLFT. Compared to routine laboratory tests which might estimate hepatic functional impairment the following correlations were found: GEK to albumin: r = 0.47, p < 0.01, to Quick: r = 0.44, p < 0.001, to bilirubin: r = -0.23, p < 0.05, ICG to albumin: r = 0.45, p < 0.01, to Quick: r = 0.53, p < 0.001, to bilirubin: r = -0.42, p < 0.001. No correlation could be demonstrated to transaminase activity. The results obtained support the view that QLFT are capable of estimating hepatic function, however, compared to conventional characteristics of advanced liver disease only moderate correlations were detected. A superiority of quantitative liver function tests could not be detected.

Adult↗

PubMed1975

Liver morphology and liver function before and after intestinal shunt operation for obesity.

Liver biopsy and liver function tests were performed in 17 obese patients before and 14 months after intestinal shunt operation for obesity. In another 20 patients liver biopsy was performed postoperative only, in 12 patients preoperatively only. Steatosis was present in 85 per cent. of the patients before the operation. After the operation steatosis decreased in half the patients and increased in the other half. In patients with biopsy twice postoperatively there was a significant trend of decreasing steatosis up to 56 months after the operation. No patient developed cirrhosis during the time of observation. Within the first postoperative year there was a substantial and significant increase in serum alanine-aminotransferase and a minor increase in alkaline phosphatases and BSP. There was no correlation between the rate of weight loss and the change in steatosis or liver function.

Adolescent↗

PubMed1982

Prognosis of hepatitis B virus surface antigen carriers in relation to routine liver function tests: a prospective study.

The employees of the Japan National Railways Co. working in the Tokyo area, comprising 98% men over the age of 40 yr, were examined for hepatitis B virus seromarkers and routine liver function tests (serum glutamic oxaloacetic transaminase, alkaline phosphatase, and zinc turbidity test) and were followed for 5 yr. The examinees included 202 hepatitis B surface antigen carriers, 502 positive for hepatitis B surface antibody, and 2426 negative for both. We found that the frequency of continuously abnormal liver function test was higher in hepatitis B surface antigen carriers compared with noncarriers. Of the 202 carriers, 4 (1.98%) died from hepatocellular carcinoma with or without cirrhosis, whereas in 2928 noncarriers only 2 (0.07%) died from liver diseases unrelated to hepatitis B virus, the difference being 28.3-fold. Three of the 4 who died from hepatocellular carcinoma initially had normal liver function tests. Mortality in carriers with initially normal liver function tests was 44.5 times higher than that in noncarriers with normal tests. Thus, asymptomatic carriers carry a high risk of dying from chronic liver disease. Routine liver function tests appear of limited value in predicting prognosis.

Adult↗

PubMed1978

Liver function and lactate metabolism in the ill surgical patient.

Liver function and lactate metabolism were investigated in non-shocked, severely ill surgical patients. Fasting venous blood lactate concentration was increased and plasma liver function tests were abnormal in ill patients compared with controls. Ill patients were glucose-intolerant and blood lactate changes following intravenous glucose infusion were similar in both ill and control patients. Blood lactate half-life was increased in ill patients following a sodium L-lactate infusion, suggesting that the increased fasting lactate concentration may have been due to decreased hepatic removal rather than to increased peripheral production of lactate.

Aged↗

PubMed1989

Acute abdominal pain: the value of liver function tests in suspected cholelithiasis.

Over a 4-year period, prospective data were collected on 311 patients with suspected acute cholecystitis. By identifying the diversity of conditions which can masquerade as acute cholecystitis, we have examined the role of biochemical liver function tests in the diagnosis and management of these patients. The initial clinical diagnosis of acute cholecystitis was confirmed in 229 patients (73.6%). Of those patients on whom liver function tests were performed, 76.3% (206/270) were confirmed to have cholecystitis and 69.9% (144/206) of these had some evidence of liver dysfunction. In the group of patients (64/270) with other diagnoses on whom liver function tests were performed, significantly fewer (57.8%, 37/64) had abnormal liver function tests (P less than 0.05). This is of little clinical value since normal liver function does not exclude cholecystitis (predictive value of negative test = 30.3%). In proven cases of cholecystitis, there was a significantly increased incidence of liver dysfunction when ductal calculi were present. Using the information obtained from this study, an investigative protocol is proposed which may substantially reduce the rate of misdiagnosis of patients with abdominal pain suggestive of cholelithiasis.

Abdomen, Acute↗

PubMed1988

Effects of conjugated equine oestrogens with and without the addition of cyclical norgestrel on serum and urine electrolytes, and the biochemical indices of bone metabolism and liver function.

Serum and urine electrolytes, and biochemical indices of bone metabolism and liver function were measured in 51 post-menopausal women treated with two hormone replacement therapy regimens for 24 wk. Twenty-six of the women were treated continuously with conjugated equine oestrogens (0.625 mg/day) and the remainder were treated as above with the addition of norgestrel (0.15 mg/day) during the last 12 days of each 28-day cycle. Both treatment regimens affected electrolytes in a similar manner. The most consistent effect was a reduction in serum sodium levels and a reduction in urinary sodium/creatinine ratios. The combined regimen appeared to have a greater effect on sodium reabsorption. Both regimens decreased all the biochemical indices of bone metabolism measured, viz serum calcium (corrected for albumin), phosphate and alkaline phosphatase and urinary calcium/creatinine and hydroxyproline/creatinine ratios. The preparations used decreased the parameters by similar amounts over the 24 wk indicating that both were equally effective in reducing bone turnover. The data suggested, however, that the combined regimen had a more profound effect on bone metabolism during the early phase of treatment. The two treatment regimens had broadly the same effects on the biochemical indices of liver function, reducing albumin levels and all the liver enzymes. Judging by these indices neither regimen had a deleterious effect on liver function. We conclude that the two hormone replacement regimens have similar effects on the biochemical indices measured, but there are subtle differences between the two treatments which merit further research.

Bone and Bones↗

PubMed1984

Hepatitis, epidemiology and liver function in hemophiliacs in Sweden.

The epidemiology of viral hepatitis and liver function were studied in a retrospective survey of 69 patients with moderate and severe hemophilia A and B, and with severe von Willebrand's disease. Forty-nine patients were on prophylactic self-therapy and 20 on episodic treatment by medical personnel. Serologic markers of viral hepatitis (HBsAg, anti-HBs, anti-HBc, anti-HAV, and in some cases HBeAg and anti-HBe) and liver function tests (ASAT, ALAT, IgG) were followed for up to 12 years. There was a history of clinical hepatitis in 19%, and 96% showed some serologic evidence of exposure to hepatitis B virus. Only one patient was a HBsAg carrier. The prevalence of elevated ASAT and/or ALAT was 65% and the incidence 96%. In 68% of the patients there had been a transaminase elevation for more than 6 months. The clinical picture, serologic markers or liver function tests showed no significant difference between the types of hemophilia, amounts and modes of therapy, or age groups. The chronic hepatitis seen in our hemophiliacs seemed to be a slowly or non-progressive disease.

Adolescent↗

PubMedDate not supplied

New methods for assessing liver function in infants and children.

Assessment of liver function in infants and children has traditionally relied on static indices of hepatic structure, cellular integrity, or function and are often based on the release of substances from damaged tissues. There has been a rapid development of dynamic tests based on the measurement of substances metabolized or cleared from blood by the liver. These tests, which have been touted to offer a more precise quantitative estimation of hepatic functional capacity, include the measurement of serum bile acids and the hepatic metabolism of xenobiotic compounds such as caffeine and lidocaine. Serum bile acid measurements appear to be reliable indicators of enterohepatic circulation and may be useful in screening for liver disease. It has been observed that caffeine metabolism is decreased in patients with various forms of liver disease in correlating with disease status. Caffeine has the advantage of being well tolerated when administered orally; the saliva level parallels the serum concentration, making a non-invasive test feasible. Lidocaine is metabolized by oxidative de-ethylation to monoethylglycinexylide (MEGX); analysis of MEGX by common laboratory instrumentation makes rapid evaluation of liver function possible. The MEGX values correlated were with pretransplant liver disease assessment. These tests are currently being evaluated at other centers and, if the initial studies are repeated, they offer the hope for reliable dynamic tests of hepatic function.

Adult↗