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Perioperative real-time monitoring of indocyanine green clearance by pulse spectrophotometry predicts remnant liver functional reserve in resection of hepatocellular carcinoma.

BACKGROUND: There is no standard method for predicting remnant liver functional reserve after hepatectomy or for monitoring it in real time. METHODS: Indocyanine green (ICG) clearance (K) was measured non-invasively and instantaneously using pulse spectrophotometry before surgery, during inflow occlusion and after hepatectomy in 75 patients who underwent anatomical liver resection for hepatocellular carcinoma (HCC). RESULTS: Eight patients (11 per cent) suffered liver failure and one (1 per cent) died in hospital. An estimated remnant K value of 0.090 per min was the cut-off value for liver failure. In a logistic regression model, the estimated remnant K (0.090 per min; P = 0.022) and age (65 years; P = 0.025) were significant predictors of postoperative liver failure. There was a correlation between the estimated and measured post-hepatectomy K, and between the inflow occlusion K and measured post-hepatectomy K (P < 0.001). The cut-off value of less than 0.090 per min for the estimated remnant K resulted in 88 per cent sensitivity and 82 per cent specificity for predicting liver failure. CONCLUSION: Perioperative real-time monitoring of ICG-K is useful for evaluating the remnant liver functional reserve before, during and after liver resection for HCC. The estimated remnant K is a significant predictor of liver failure.

Aged↗

An expert system for the evaluation of liver functional assessment.

The paper describes an expert system for the assessment of the liver function. Since the system must act as an intelligent assistant for a general physician, a major emphasis has been laid upon its interactive capabilities. In particular, the user can ask the system how a given conclusion has been reached (explanation facilities) and can alter the normal operation flow. In the design of the system, the different significance and availability of the clinical data and the laboratory tests have been taken into account: The investigations about a given patient start from the clinical data, and only when there is some evidence of hepatopathy are the results of some laboratory tests requested. The final result of the investigations consists of the assessment of the liver function in terms of four aspects (biosynthesis, cholestasis, cytolysis, reactivity), each of which is assigned a linguistic value describing its impairment degree. The techniques adopted in the system are based on Artificial Intelligence methodologies augmented with linguistic terms handled according to the fuzzy set theory.

Diagnosis, Computer-Assisted↗

Value of ultrasound and liver function tests in determining the need for endoscopic retrograde cholangiopancreatography in unexplained abdominal pain.

The value of serum liver function tests and abdominal ultrasound as screening tests of the need for endoscopic retrograde cholangiopancreatography (ERCP) was determined in patients with unexplained abdominal pain without associated jaundice. In 1989 and 1990 1005 ERCPs were undertaken, of which 138 (14%) were for this indication. The duct or ducts of interest were delineated by ERCP in 95% of patients. The lesions found were bile duct stones in 10 patients, chronic pancreatitis in five, pancreatic carcinoma in one, peptic ulcer or duodenitis in four. A satisfactory ultrasound examination had been performed in 94% of patients. For chronic pancreatitis, its sensitivity was 60% and specificity 95%. For choledocholithiasis, the ultrasonic detection of duct dilatation or stones had a sensitivity of 90% and specificity of 86%. Of the liver function tests, the alkaline phosphatase was more sensitive (67%) than the transaminases (44%) in indicating the presence of bile duct stones and had a high specificity (95%). None of the 10 patients with duct stones had normal ultrasound and normal alkaline phosphatase. Thus it was found that demonstration of a normal common bile duct by abdominal ultrasound and normal serum alkaline phosphatase together have 100% specificity in excluding bile duct stones. Using such knowledge over the two year period of this study would have spared 36 patients the need for ERCP.

Abdominal Pain↗

[Assessment of liver function using indocyanine green (Ujoviridin) during normal pregnancy, during labor and in puerperium].

Indocyaningreen (ICG) was given for the characterize of the excretion function of the liver during the course of normal pregnancy, sub partu and post partum. Studies were performed in 168 primi- and multigravidas with normal medical and obstetric histories (mean age of 23,5 years). 0,5 mg ICG/kg body mass were injected intravenously as a bolus. 18 healthy nonpregnant women served as controls (mean age of 24,2 years). In the I. and II. trimester of pregnancy the elimination of ICG was not decreased in comparison to the controls (3,64 +/- 0,86). The increased retention of ICG in the 40th week of pregnancy (4,67 +/- 0,41) and during labor (7,02 +/- 2,32) are caused through the physiological alterations of pregnancy. No placental transfer of the dye could be detected by simultaneous measurement of ICG in the maternal and fetal cord blood. During the post partum period the elimination of ICG will be normal. ICG is recommend instead of Bromsulfaleine (BSP) for the estimation of excretion function of the liver during pregnancy and childbed.

Adolescent↗

The diagnostic necessity of liver biopsy in drug abusers with normal liver function tests.

Forty-six of sixty-one drug abusers admitted for detoxification had liver biopsies. Nineteen biopsied patients had normal liver function tests. Of these, two had chronic active hepatitis; nine had chronic persistent hepatitis; six including three with fatty changes, had minor changes, and only two had normal liver histology. Chronic active hepatitis was found only in those with persistent HBS antigenaemia. Chronic persistent hepatitis was found in four patients who were negative HBS antigen and antibody, and in four patients who had cleared HBSAg. In parenteral drug abusers with normal liver function tests the absence of persistent HBS antigenaemia does not rule out chronic liver disease: liver biopsy is necessary for accurate assessment of liver status.

Biopsy↗

Liver function alterations in synthetic leather workers exposed to dimethylformamide.

A cross-sectional study of the prevalence of chronic liver function alterations was performed in 75 workers employed in a synthetic leather factory, exposed to dimethylformamide (DMF) air concentrations below threshold limit values (30 mg/m3). Biological monitoring among workers revealed acceptable urine levels of monomethylformamide (NMF) on average, but the very wide range indicated that occasional overexposure was possible. The worker survey showed a high percentage of disulfiram-like symptoms (50%) and liver function abnormalities (22.7%), compared with a demographically similar group of unexposed workers. Covariance analysis (ANCOVA) revealed that enzyme levels were significantly higher in exposed workers than in controls after data were corrected for age, alcohol consumption, body mass index, and cholesterol levels. The authors conclude that DMF can cause liver diseases even if air TLVs are respected, because accidental contact with liquid DMF can significantly increase DMF uptake. In this situation, air monitoring is no longer sufficient to evaluate worker exposure.

Adult↗

13C-methacetin and 13C-galactose breath tests can assess restricted liver function even in early stages of primary biliary cirrhosis.

OBJECTIVE: The 13C-methacetin breath test quantitatively evaluates cytochrome P450-dependent liver function. The 13C-galactose breath test non-invasively measures the galactose oxidation capacity of the liver. The aim of this study was to find out whether these breath tests are sensitive parameters also in non-cirrhotic patients with primary biliary cirrhosis. MATERIAL AND METHODS: Nineteen patients with early-stage primary biliary cirrhosis (no cirrhotic alterations in the liver biopsy, Ludwig stage I-III) and 20 healthy controls underwent the 13C-methacetin and 13C-galactose breath tests. RESULTS: Patients with primary biliary cirrhosis metabolized less 13C-methacetin than controls (cumulative recovery within 30 min 7.5+/-2.4% versus 14.0+/-2.6%; p < 0.001). When a cut-off > 9.8% was used for the cumulative recovery after 30 min, the methacetin breath test reached 84.2% sensitivity and 95.0 specificity. In the 13C-galactose breath test, the percentage recovery at 60 min in patients was 3.1+/-1.3%/h, and 6.3+/-1.1%/h in controls (p < 0.001). Using a cut-off > 4.7%/h, the galactose breath test reached 89.5% sensitivity and 95.0 specificity. CONCLUSIONS: In non-cirrhotic, early-stage, primary biliary cirrhosis the 13C-methacetin breath test and the 13C-galactose breath test reliably indicate decreased liver function. The 13C-galactose breath test can also predict the histological score.

Acetamides↗

Plasma amino acids in cirrhosis and after liver transplantation: influence of liver function, hepatic hemodynamics and circulating hormones.

Liver cirrhosis is characterized by substantial changes in amino acid (AA) metabolism, resulting in a deranged plasma AA profile. To investigate the effect of liver transplantation (OLT), we studied arterial AA profiles in 52 patients with advanced cirrhosis, 16 stable patients over 6 months after OLT and 48 controls. Changes in AA levels were correlated with portal pressure (hepatic venous pressure gradient), functional hepatic blood flow (indocyanine green extraction) and circulating hormone levels (catecholamines, insulin, C-peptide). Fourteen of 18 measured AA were significantly altered in cirrhosis and 11 of 18 remained abnormal after OLT compared with controls. Aromatic AA (AAA) and methionine were elevated in cirrhosis (p < 0.001 each), increasing with disease stage, and normalized after OLT. Branched chain AA (BCAA) levels were decreased in cirrhosis (p < 0.001) and were unrelated to disease stage. After OLT, BCAA levels remained subnormal (p < 0.01), although higher than in cirrhosis (p < 0.001). AAA levels increased with decreasing functional hepatic blood flow (r = -0.67; p < 0.001) and increasing portal pressure (r = 0.59; p < 0.001). BCAA levels decreased with increasing catecholamine (r = - 0.54, p < 0.001) and insulin levels (r = - 0.40, p = 0.001). We conclude that despite normal liver function, AA metabolism is only partially normalized after OLT. AAA levels mainly determined by hepatic metabolic function and functional liver blood flow return to normal, while BCAA levels remain subnormal, indicating persistent changes in muscular AA metabolism after OLT.

Adult↗

Liver function in protein-energy malnutrition measured by cinnamic acid tolerance and benzoic acid tolerance: effect of carnitine supplementation.

1. Rats fed on a protein-depleted diet for 8 weeks were repleted for 5 weeks on high-protein (HP), high-protein + 20 g DL-carnitine/kg (HP + C), or low-protein + 20 g DL-carnitine/kg (LP + C) diets. At 4 and 8 weeks of depletion, and 1 and 5 weeks of repletion, rats from each treatment group were given a benzoic acid tolerance test (BATT) or a cinnamic acid tolerance test (CATT) as a measure of liver function. 2. BATT and CATT measured the molar percentage of a test dose (1 mmol/kg body-weight) of benzoic acid or cinnamic acid excreted in the urine as hippuric acid within 24 h. Liver weight, liver lipid levels, and carnitine concentration in plasma and liver were also measured following liver-function testing. 3. BATT and CATT were severely impaired in protein-depleted rats, but returned rapidly to control levels following protein refeeding. Correlations of BATT and CATT with liver lipid concentration were high (r -0.49 and -0.62 respectively), and both tests show promise as clinical tests for liver function in protein-energy malnutrition. 4. Carnitine supplementation was required to return liver carnitine concentration of protein-depleted rats to control levels during repletion, but was not associated with accelerated reduction in liver fat concentration in protein-repleted rats.

Animals↗

The quantitative liver function as measured by the galactose elimination capacity. II. Prognostic value and changes during disease in patients with cirrhosis.

The quantitative liver function, measured by the galactose elimination capacity (GEC), was determined repeatedly in 44 patients with cirrhosis during the course of the disease. After a median observation period of 57 months (range 28-85) 17 had died from liver insufficiency. GEC was found to be of prognostic value, as classification of the patient series on the basis of the median value of two extreme prognostic groups indicated that the survival of patients with GEC greater than 1.37 mmol . min-1 at entry was significantly larger than of patients with GEC below that value (p less than 0.05). The prognostic values of serum albumin and prothrombin were of the same order of magnitude. At repeated examinations during the course of the disease, the survivors always had higher GEC values than those who died from liver insufficiency. Among those who survived and those who died there were patients with both increasing and decreasing GEC values, but no significant changes were observed within the groups. The individual changes in GEC can result from changes in the balance between liver cell necrosis and regeneration, but the possibility cannot be excluded that changes are due to methodological problems in the determination of the quantitative liver function as measured by GEC.

Adult↗

Liver function in patients with vitamin K deficiency in infancy.

Liver chemistry was studied in fifteen patients with vitamin K deficiency in infancy (VKDI). All except 2 were exclusively breast fed and 4 of the 15 infants had received intramuscular vitamin K prophylaxis. A high incidence of hepatic dysfunction was found during long term follow-up in patients with VKDI. Abnormal aminotransferase was noted either at the time of onset (n = 6) or during the ensuing few weeks (n = 6). Cholestasis was documented in six cases at onset and another two in a later period. Most cases had increased serum alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), or bile acid levels regardless of hepatic enzymes and bilirubin levels. The abnormal enzymes returned to normal after 5 weeks to 23 months. This study demonstrates a close relationship between hepatic dysfunction and VKDI. Liver function impairment other than cholestasis may play some role in the pathogenesis of VKDI, but the cause of hepatic dysfunction can not be defined. Follow-up of liver chemistry is recommended in patients with VKDI. Parenteral vitamin K prophylaxis at birth may not give sustained protection against VKDI, especially in those with underlying liver disease.

Female↗

The thymol turbidity test and determination of serum cholesterol : two tests to abandon in the routine evaluation of liver function.

The thymol turbidity test (Macglan's test) and the determination of serum cholesterol are still performed routinely as liver function tests in many laboratories. In this report, we have employed quantitative methods in order to evaluate the real usefulness of these two parameters. In a first step, the value of the thymol test and of cholesterol determination for the discrimination of the 13 most frequent hepato-biliary diseases was studied by analysis of variance, and compared to that of the following tests : serum bilirubin, serum glutamic pyruvic transaminase, serum alkaline phosphatase serum protein electrophoresis and prothrombin time. It was found that of all these parameters, the thymol test and cholesterol measurement had the lowest discriminatory powers. In a second step, the consequences of the suppression of the two tests were examined by linear discrimination analysis, which was done for all the possible pairs of diseases. It appeared that in each case, the loss of information due to the elimination of the thymol test or of cholesterol determination was nil or negligible. We conclude therefore that the thymol turbidity test and determination of serum cholesterol should be abandoned as routine tests of liver function.

Cholesterol↗

The limitation of liver function tests in metastatic carcinoid tumors.

To evaluate the utility of liver function tests (LFT) as indicators of metastatic carcinoid tumors, a retrospective study was performed. The LFT results of 17 patients with carcinoid tumors metastatic to the liver were compared with 17 patients with other malignant tumors. In the noncarcinoid group, 82.4% of the patients had elevated alkaline phosphatase (AP) or gamma glutamyl transpeptidase (GGTP), whereas only 28.6% of carcinoid patients had abnormal enzymes. The medians of all LFT values were significantly higher in noncarcinoid patients than in the carcinoid group, except for glutamic pyruvic transaminase (SGPT). Our data indicate that LFT are helpful in screening for liver metastases in patients with noncarcinoid tumors, but are unreliable in carcinoid tumors. Imaging tests should be used to rule out liver metastases in carcinoid tumors, irrespective of LFT results.

Carcinoid Tumor↗

Comparison of the effects between ursodeoxycholic and chenodeoxycholic acids on liver function and structure and bile acid composition in the Rhesus Monkey.

The hepatotoxic potential of the cholelitholytic bile acids, chenodeoxycholic (chenic), and ursodeoxycholic acids, was compared in the rhesus monkey. A placebo-controlled treatment trial with 40 and 120 mg/kg/day doses of chenic acid and ursodeoxycholic acid, respectively, was conducted in 20 animals. Both chenic and ursodeoxycholic acids induced comparable abnormalities of liver function and structure. Liver biopsies, performed before and after 6 mo of treatment, showed the development of distinct light microscopic changes, including inflammation, fibrosis, and ductular proliferation in the portal fields as well as lobular rearrangement with formation of septa and regenerative nodules. Electron microscopy confirmed light microscopy, but showed no specific changes of cell organelles. Light microscopic examination of the kidneys, lungs, heart, intestine, and brain in 10 monkeys, which were sacrificed after 6 mo of controlled bile acid treatment, showed no abnormalities. Biliary lithocholic acid, all of which was unsulfated, increased several-fold to comparable levels in the bile acid-treated groups. Follow-up studies 6 mo after termination of bile acid treatment showed normalization of liver function tests and of bile acid composition as well as a considerable improvement of the histologic abnormalities. However, the restitution of normal liver structure was incomplete, with fibrosis and mild inflammation persisting in the portal fields. Our studies show that, in this primate species, chenic and ursodeoxycholic acids have comparable hepatotoxic effects, which are associated with similar increases of unsulfated lithocholic acid in bile.

Animals↗

[Multiple organ failure after severe trauma: predictable by the MEGX liver function test?].

The prognostic value of a dynamic liver-function test, based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting multiple organ failure (MOF) was prospectively investigated in 28 critically ill patients after multiple trauma. The MEGX test and conventional static liver tests (bilirubin, aspartate aminotransferase, glutamate dehydrogenase and factor V) were performed on days 1, 3, 5, and 7 after trauma and patients were classified by a modified MOF score into a group without (n = 18) and a group with the MOF syndrome (n = 9). All patients who subsequently developed MOF, however, displayed a sharp decrease in their MEGX values between days 1 and 3.

Alanine Transaminase↗

A monoclonal antibody-based enzyme-linked immunosorbent assay of glycolithocholic acid sulfate in human urine for liver function test.

Urinary levels of sulfated metabolites of lithocholic acid (LCA) are expected to be a useful index of liver function. Thus, a sensitive, specific, and feasible enzyme-linked immunosorbent assay (ELISA) of these sulfated LCA metabolites (LCA-Suls) should be established. A newly generated monoclonal antibody specific to glycolithocholic acid sulfate (glycine-amidated LCA-Sul (GLCA-Sul)) was immobilized on microtiter plates via a second antibody. A urine specimen and an alkaline phosphatase-labeled antigen were added to the plate, which was then incubated at room temperature for 3h. After this competitive reaction, bound enzyme activity was measured colorimetrically using p-nitrophenyl phosphate as a substrate. The detection limit for GLCA-Sul was 0.4 pg/assay. Nonamidated LCA-Sul and taurine-conjugated LCA-Sul showed 40 and 11% cross-reactivities, respectively, while 3-sulfates of cholic acid (CA; 0.02%), chenodeoxycholic acid (CDCA; 0.63%), and deoxycholic acid (DCA; 2.2%) exhibited very low cross-reactivities. Applicability of the ELISA system to clinical samples was well validated by parallelism, recovery test, and intra/inter-assay variance. Enzymatic deconjugation with bile acids sulfatase resulted in dramatically decreased urinary levels, supporting the specificity of the ELISA toward GLCA-Sul. The mean GLCA-Sul levels in early morning urine from healthy volunteers were 314 ng/mg Ucre (males: n=16) and 507 ng/mg Ucre (females: n=9). Patients with liver diseases, including chronic hepatitis (CH) and liver cirrhosis (LC) exhibited significantly higher values (mean 5222 ng/mg Ucre: n=21). The present 'monoclonal ELISA' is predicted to be useful as a novel noninvasive diagnostic tool for liver function and hepatobiliary diseases.

Animals↗

Circadian rhythms of body temperature and liver function in fed and food-deprived goats.

Daily rhythms of body core temperature and liver function were recorded in goats maintained under various schedules of lighting and feeding. Concentration of urea in the blood was used as an index of digestion-driven hepatic activity, whereas concentration of cholesterol served as an index of autonomous hepatic activity. Body temperature exhibited robust circadian rhythmicity in the presence and absence of a light-dark cycle and/or a feeding regime. The rhythm was more responsive to shifts in feeding time than to shifts in the light-dark cycle. Urea concentration in the blood exhibited daily rhythmicity only in the presence of a daily feeding regime and, therefore, was driven by ingestive and digestive processes. The rhythm of cholesterol concentration persisted in the presence or absence of a light-dark cycle and/or a feeding regime, except when the feeding time was shifted under constant light. However, the cholesterol rhythm did not respond either to shifts in the light-dark cycle or, more importantly, to shifts in feeding time. Thus, based on this index of hepatic function, the liver cannot be identified as the site of the putative food-entrainable pacemaker.

Activity Cycles↗