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PubMed2001

The MEGX test: a tool for the real-time assessment of hepatic function.

The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) can complement established static liver function tests if prognostic information is of particular interest. Because of its ease of use and rapid turnaround, the MEGX test has found widespread application for realtime assessment of hepatic function in transplantation, critical care medicine, and various experimental models. Lidocaine is metabolized primarily by the liver cytochrome P450 system through sequential oxidative N-dealkylation, the major initial metabolite in humans being MEGX. Because of the relatively high extraction ratio of lidocaine, this liver function test depends not only on hepatic metabolic capacity but also on hepatic blood flow. For the determination of MEGX in serum, an immunoassay based on the fluorescence polarization immunoassay technique high-performance liquid chromatography and gas liquid chromatography methods have been described. Whereas high-performance liquid chromatography and gas liquid chromatography are specific for MEGX, the fluorescence polarization immunoassay also cross-reacts with 3-OH-MEGX. Although this is not a problem in humans, some species, such as the rat, produce significant amounts of this metabolite. The findings of most studies published so far suggest that the MEGX test is a useful tool that can improve our decision-making process with respect to the selection of transplant candidates. Patients with a MEGX 15- or 30-minute test value <10 microg/L have a particularly poor 1-year survival rate. Serial monitoring of liver graft recipients early after transplantation with the MEGX test may initially alert the clinician to a major change in liver function; if used with other tests, such as serum hyaluronic acid concentrations, it may become more discriminatory. In critically ill patients, several studies have shown that an initially rapid decrease in MEGX test values is associated with an enhanced risk for the development of multiple organ dysfunction syndrome and a poor outcome. Further, this decrease appears to be associated with an enhanced systemic inflammatory response. The MEGX test has potential for investigating the pathogenesis of multiple organ dysfunction syndrome with regard to early hepatic functional impairment in critically ill patients after polytrauma or sepsis.

Anesthetics, Local↗
PubMed1995

[Predictors of hepatic functional reserve in cirrhotic patients].

We have determined the interstitial ratio, hepatocyte numerical density on area (NA) by the method of Luzex-F Image Analyser, and the level of serum prealbumin (PA), choline esterase activity (ChE) by agarose immunodiffusion and ratemetry in control group (14 cases) and 25 cirrhotic patients undergoing pericardial devascularization. The results were compared with traditional hepatic function grade (Child's Grade). We found that NA, PA, and ChE are independently useful in evaluating the hepatic functional reserve in cirrhotic patients.

Adult↗
PubMed2003

Preoperative assessment of hepatic function: Utility of a new convenient two-compartment model analysis using galactosyl human serum albumin scintigraphy.

BACKGROUND AND AIM: Preoperative hepatic function was evaluated using technetium-99 m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin (Tc-GSA) and a scintillation camera to detect hepatic Tc-GSA uptake by the asialoglycoprotein receptor. METHODS: Sixty-two preoperative patients with liver cancer, including hepatocellular and cholangiocellular carcinomas, were studied, using two-parameter two-compartment model analysis. This model is simpler than either the three- or five-compartment model, both of which are accurate but which require complicated analysis and enormous calculation. The parameters k1 and k2 represented the transfer rate constant from the blood to the liver and from the liver to the blood, respectively. We calculated k1, k2, and k1/k2 from time-radioactivity curves of the heart and liver as well as VLmg, which represented the maximal amount of Tc-GSA in the liver. RESULTS: The results were compared to those of conventional liver function analysis using Tc-GSA (the index of blood clearance (HH15) and the receptor index (LHL15)) or indocyanine green (ICGR15). Both HH15 and LHL15 were significantly correlated with k1, k1/k2, and VLmg. In addition, they closely correlated with the results of ICGR15 and some serum hepatic function tests (aspartate aminotransferase, choline esterase, albumin, platelet). The pathological grading for liver cirrhosis also correlated with k1, k1/k2, and VLmg. From a clinical point of view, VLmg had a significant correlation with the Child-Pugh score. CONCLUSIONS: These results suggest that this new compartment analysis will be useful in evaluating liver function, as it is accurate, simple and convenient.

Adult↗
PubMedDate not supplied

Predetermining postoperative hepatic function for hepatectomies.

To perform major resections safely in liver cancer operations, we have developed a reliable preoperative method to estimate postoperative liver function. We first conducted a series of studies using dogs to determine the various correlations between the volume of the remaining liver and postresectional hepatic function. We calculated Indocyaningreen (ICG) plasma disappearance and retention rates 15 minutes after intravenous injection of ICG at 0.5 mg/kg and found a 1:1 ratio, thus: ICG(K) postop. = ICG(K) preop. x functional remaining rate. This was applicable in our study of dogs with normal livers; in clinical cases complicated by liver cirrhosis and cancer, however, the functional rate of the remaining liver cannot be calculated only by the volumetric ratio of the whole liver and the remaining part. In clinical cases it must also be calculated by using hepatic vein catheterization and by measuring the ICG extraction rate of each segment of the part to be resected and the part to remain. By using this segmental liver function test, the postoperative hepatic function can be estimated accurately before the operation, thus enabling the surgeon to perform major hepatectomies safely and efficiently.

Animals↗
PubMed1999

Perioperative hepatic functional risk assessed with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin liver scintigraphy in patients undergoing pancreaticoduodenectomy complicated by obstructive jaundice.

CONCLUSION: Liver scintigraphy with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) can be used to predict outcome of biliary drainage and hepatic function after pancreaticoduodenectomy in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. BACKGROUND: Preoperative obstructive jaundice has been reported as a crucial risk factor for serious postoperative complications in patients undergoing pancreaticoduodenectomy. The aim of the present study was to investigate whether Tc-GSA liver scintigraphy can assess hepatic functional risk in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. METHODS: Liver scintigraphy was performed before biliary drainage in 18 patients with obstructive jaundice. The maximum removal rate of Tc-GSA (GSA-Rmax; standard normal value > or = 0.60) was calculated. These patients underwent pancreaticoduodenectomy with wide lymphadenectomy. The efficacy of preoperative biliary drainage was assessed with the decrease in serum bilirubin concentration in the first week after biliary drainage. Postoperative liver function was assessed with the increase in serum bilirubin concentration, which was the difference between the immediate preoperative and maximal postoperative bilirubin concentrations. RESULTS: Serum bilirubin decreased more in the first week after biliary drainage in patients with GSA-Rmax > or = 0.60 (7.64 +/- 1.09 mg/Dl/wk) than in patients with GSA-Rmax < 0.60 (3.56 +/- 1.25 mg/DL/wk, p = 0.042). Postoperative bilirubin increased less in patients with GSA-Rmax > or = 0.60 (0.81 +/- 0.30 mg/dL) than in patients with GSA-Rmax < 0.60 (4.00 +/- 0.69 mg/DL, p = 0.0012). Multivariate analysis showed that GSA-Rmax significantly predicted the postoperative bilirubin increase (p = 0.020).

Adult↗
PubMedDate not supplied

Preoperative hyaluronic acid measurement to assess the hepatic functional reserve.

BACKGROUND/AIMS: With liver surgery, preoperative assessment of the hepatic functional reserve is important for estimating the extent of hepatectomy. Hyaluronic acid (HA) is specifically cleared and metabolized by endothelial cells in the liver. Its half-life time is 2-5 min and HA might be a sensitive liver function marker. We obtained data from 44 patients with liver tumor undergoing liver resection. METHODOLOGY: We studied 44 liver resected patients. Blood samples were obtained before surgery and HA levels and other liver function markers [type IV collagen (IV), procollagen-III-peptide (PIIIP), lecithin-cholesterol acyltransferase (LCAT), cholinesterase (ChE), albumin (Alb), platelets (Plt), prothrombin time (PT%)] levels in the samples were measured. We also performed indocyanine green retention test and calculate R15% (ICG). RESULTS: HA showed strong positive correlation with ICG, IV and PIIIP, negative correlation with LCAT, ChE, Alb, Plt and PT%. ICG was not correlated with ChE, Plt and PT%. The HA levels and ICG of the patients who had more than 2 segments of the liver resected were below 100 ng/mL and 20%, respectively. In the patients with obstructive jaundice HA levels of the 3 patients with obstructive jaundice who underwent bisegmentectomy were below 100 ng/mL. CONCLUSIONS: Our findings suggest that HA is a useful preoperative liver function test as well as ICGR15%. Preoperative HA levels <100 ng/mL and ICGR15% <20% might be helpful indicators for major liver resection. We also recommend that HA measurement for evaluating liver function in the patients with obstructive jaundice ICG is not helpful.

Adult↗
PubMedDate not supplied

Hepatic function immediately after hepatectomy as a significant risk factor for early recurrence in hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study was to clarify the significant risk factors as they relate to early recurrence after hepatectomy in cirrhotic patients with hepatocellular carcinoma (HCC). METHODOLOGY: We retrospectively investigated 42 cirrhotic patients undergoing hepatectomy for a single HCC. We compared the clinicopathologic features of 14 patients with early intrahepatic recurrence (recurrence was detected within 1 year after hepatic resection; Group 1) with 28 patients without recurrence or with late intrahepatic recurrence (recurrence was confirmed more than 1 year after hepatic resection; Group 2). RESULTS: There were no significant differences in the pre-operative and intra-operative clinical background data or pathological data between the 2 groups. Regarding recurrence pattern, although not significant, the incidence of intrahepatic metastasis in Group 1 (85.7%) was higher than in Group 2 (50.0%). Maximum values of total bilirubin and albumin within 7 days after hepatectomy for patients in Group 2 were significantly better than those in Group 1. Aspatate aminotransferase (AST) and alanine aminotransferase (ALT) immediately after hepatectomy in Group 1 were also higher than in Group 2, although statistically insignificant. The overall 1-year and 3-year survival rates between Group 1 versus Group 2 were 85.7% versus 100% (p < 0.01) and 57.2% versus 90.0% (p < 0.01), respectively. CONCLUSIONS: Hepatic functional damage immediately after hepatectomy is as significant risk factor for early intrahepatic recurrence in cirrhotic HCC. Careful perioperative management of hepatic function may therefore be important in preventing early recurrence and prolonging survival.

Alanine Transaminase↗
PubMed1987

Short-term and long-term changes in hepatic function in 60 patients with blunt liver injury.

We treated 60 patients with blunt liver injury over 14 years. According to Makiya's scale of severity, 22 of these lesions (37%) were of Type I, 23 (38%) of Type II, and 15 (25%) of Type III. The overall mortality rate was 23% (14 patients). Changes in hepatic function were studied in these patients. Transaminase levels showed abnormal elevations immediately after the injury but rapidly decreased to normal levels within about 40 days in both the patients who survived the injury and those who died. The alkaline phosphatase activity showed moderate gradual elevations with time, exceeding 20 K.A. units 10 days after the injury in those who died. The total bilirubin level increased to only about 4 mg/dl in those who survived but exceeded 8 mg/dl 10 days after the injury in about 80% of those who died. The total cholesterol level decreased below 100 mg/dl in those who died. In chloric cobalt reaction, the R-value shifted to the left in those who survived but to the right in those who died. Total plasma protein, which decreased to about 6.0 gm/dl immediately after the injury, gradually recovered in those who survived but further declined in those who died. Percentage of gamma-globulin increased but remained below 20% in those who survived but exceeded 20% within 10 days of injury in many of those who died. Hepatic functions 5 years after the injury were generally within the normal range.

Adolescent↗
PubMed1984

Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant.

To evaluate the potential role of taurine deficiency in the pathogenesis of parenteral nutrition-induced cholestasis, 20 premature (less than 34 weeks AGA) infants were randomized to receive parenteral nutrition with and without taurine (10.8 mg/kg/day) during the first 10 days of life. Birth weight, gestational age, and protein and caloric intake were similar in both groups. Plasma taurine levels and hepatic function were assessed before the study began (3 +/- 1 days of age), at 5 +/- 1 days of age, and at 9 +/- 1 days of age. Although plasma taurine levels were significantly greater at 5 +/- 1 and 9 +/- 1 days of age (p = 0.009) in the group receiving supplementation, no differential effect on hepatocellular function could be detected during this short period of time. A decrease in plasma ammonia (p = 0.001), alanine aminotransferase (ALT) (p = 0.036), gamma-glutamyltranspeptidase (GGTP) (p = 0.05), 5'-nucleotidase (5'N) (p = 0.001), and bile salt concentrations was noted in both groups, indicating the rapid maturation of hepatic function even in the presence of parenteral nutrition during the first 10 days of life.

Animals↗
PubMedDate not supplied

Effects of Fructus gardeniae extract on hepatic function.

This article discusses the effects of Fructus Gardeniae extract on hepatic function. Fructus Gardeniae extract manifested no hepatotoxic effects on rats, as shown by alkaline phosphatase, aspartate aminotransferase, and lactate dehydrogenase studies. Fructus Gardeniae extract failed to activate the UDP-glucuronyltransferase system; whereas in hyperbilirubinemic state the enzyme was activated, presumably by substrate induction. Fructus Gardeniae extract increased the activity of UDP-glucose dehydrogenase, which would result in an increase in availability of UDP-glucuronic acid intracellularly, BSP clearance study showed an unexpected impairment of hepatic uptake of the dye after extract treatment. The action mechanism involved in lowering of serum bilirubin level by Fructus Gardeniae extract may well be complex; it is probably acting on a locus other than glucuronyl transferase.

Alkaline Phosphatase↗
PubMed1986

[Effects of enflurane and halothane on hepatic function in biliary surgery].

The effects of two volatile anaesthetics on hepatic function are compared in 80 patients in hepato-biliary surgery. 40 patients were anaesthetized either with enflurane or halothane. This study is based on the variations of blood levels of gamma GT, bilirubin, SGOT SGPT, alkaline phosphatase, L.D.H. Samples were taken the day prior to the operation, one, two and five days afterwards. The results show an increase in the levels of BD, SGPT, LDH no 5, less important with enflurane than with halothane, and mainly in patients with preoperative hepatic abnormalities. Enflurane appears to be preferable in such cases.

Adult↗
PubMed2004

Study of hepatic function matching between Banna minipig inbred and humans.

As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig-to-human xenotransplantation due to its clear genetic background and minor interindividual differences. Previous studies of BMI have focused on immunological barriers between BMI and humans. However, a comparison of liver function between donor animals and humans is an essential premise for successful xenotransplantation. In this study, we investigated routine hepatic functions, protein electrophoresis, and drug metabolism to compare capacity of liver synthesis, metabolism, and drainage between BMI and humans. The results showed no significant differences in the concentrations of albumin and globulin synthesized in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI were higher than those in humans, and levels of total bilirubin and direct-reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16 times greater than that by humans, with a mean residual time of antipyrine in BMI, one-tenth of that in human. These findings suggested that BMI livers are similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have stronger functions compared with those of humans. No incompatibility was identified in hepatic function between BMI and humans.

Adult↗
PubMed1992

No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion.

One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.

Blood Proteins↗
PubMedDate not supplied

[Biochemical characteristics of hepatic functions in different clinical forms of chronic opisthorchiasis].

The main biochemical indices of hepatic functions (the activities of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, choline esterase and the concentrations of total bilirubin, cholesterol, and glucose) were studied in the sera of 256 patients with chronic opisthorchiasis. It was found that with diseases manifested in different clinical forms (cholangitis, cholecystitis, cholangiocholecystitis, cholangiohepatitis, cholecystitis in combination with pancreatitis), most study indices are within the normal ranges, but significantly differ from the means in a group of apparently healthy individuals. The findings suggest that such clinical forms of opisthorchiais as cholangiocholecystitis and cholangiohepatitis are characterized by manifestations of cytolysis and cholestasis, as cholecystitis is manifested by cytolysis, as cholecystitis in combination with pancreatitis, by cholestasis, and as cholangitis, by cholestasis and hepatic cell insufficiency. It is possible that further studies will provide evidence for how to correct detected disorders during pathogenetic therapy.

Adult↗
PubMedDate not supplied

Experimental evaluation of hepatic functional reserve using 111In colloid for clinical application.

We have postulated that reduced hepatic blood flow is the primary factor responsible for postoperative hepatic insufficiency, and have shown the usefulness of the hepatic blood flow index (KL) estimated by 198Au colloid. However, 198Au colloid has became unavailable due to its intense exposure activity. Therefore, we prepared 111In colloid as a substitute for 198Au colloid to evaluate hepatic functional reserve. In the present study, a 111In colloid was administered to rats to investigate the possibility of clinical application. First, liver cirrhosis was induced in rats using CCl4 Changes in KL and hepatic tissue blood flow were measured by hydrogen gas clearance (HL) after CCl4 injection, and was shown to correlates well with it. The correlation between KL and HL, together with normal and cirrhotic liver, was significant (r = 0.83, p < 0.01) Second, reticuloendothelial function was modulated with Zymosan A (stimulation) and Silica (suppression). The KL value remained unchanged in spite of the addition of an activator or suppressor to the reticuloendothelial system. Third, 30% and 70% hepatectomy models were studied according to the method of Higgins-Anderson. KL and HL was measured before and 1, 3 and 7 days after hepatectomy. KL and HL after 30% and 70% hepatectomy showed similar changes. These results indicate that the clearance of 111In colloid can be used clinically as an index of the hepatic blood flow.

Animals↗
PubMed1996

[Visual analysis of hepatic function by a scoring system using 99mTc-GSA].

To establish a simple hepatic function test, a five-point scoring system using 99mTc-galactosyl-human serum albumin (GSA) was applied to seventy-six patients with or suspected with hepatic dysfunction. Dynamic data at rest were obtained immediately and 30 minutes after intravenous bolus injection of 99mTc-GSA (185 MBq). Regions of interest (ROIs) were superimposed over the images of the liver and the entire heart. A visual analysis using a image taken 5 to 6 minutes after radiotracer injection was performed by the three observers blinded to the clinical information to assess their agreement or disagreement on the grading score. kappa-Test was used to evaluate the goodness of agreement. Three pairs in the first reading showed excellent interobserver agreement (0.92 mean kappa-value). Three pairs in the first and second reading also showed excellent intraobserver agreement (0.89 mean kappa-value). Data were also analyzed for correlations with heart/liver count ratio, ICG R15, LHL15, Alb, TB, PT, HPT and ZTT. There were good correlations between visual grading score and ICG R15 (Rs = 0.619, p < 0.0001) and between grading score and heart/liver count ratio (Rs = 0.866, p < 0.0001). Grading score was also correlated with LHL15, Alb, TB, PT, HPT and ZTT (Rs = -0.770; -0.580; 0.593; -0.544; -0.622; 0.518, p < 0.0001 for each). There was a significant difference between heart/liver count ratio and LHL15 in the Grade 4 and Grade 5 groups. In conclusion, the present data suggest that a five-point scoring system based on visual analysis using 99mTc-GSA uptake is a useful indicator for hepatic dysfunction in a clinical setting.

Aged↗
PubMedDate not supplied

Serum biochemical and histopathological changes related to the hepatic function in pigs following atrazine treatment.

Biochemical and histopathological parameters of the hepatic function were used to quantify the hepatotoxic effects of atrazine in female pigs (gilts) undergoing intensive breeding. Female pigs (cross-bred Swedish and German landrace) received 2 mg atrazine kg-1 body wt. in feed daily during 19 days of the oestrous cycle. The last treatment day corresponded to day -3 of the onset of the next expected oestrus. Blood samples were collected three times daily at 3-h intervals on the first four post-treatment days. Serum activities of gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) were determined. Serum activity of GGT was significantly increased throughout the four post-treatment days. In comparison with the control values, a slight but not significant decrease was observed in the serum activities of ALT, AST and AP. Histopathological examination of the liver of exposed pigs showed mild centrolobular parenchymatous degeneration. Interstitial connective tissue proliferation resulted in narrow and irregular bile canaliculi.

Alanine Transaminase↗