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Comparison of postoperative hepatic function after laparoscopic versus open gastric bypass.

BACKGROUND: Pneumoperitoneum has been shown to reduce hepatic portal blood flow and alter postoperative hepatic transaminases. This study evaluated the changes in hepatic function after laparoscopic and open gastric bypass (GBP). METHODS: Thirty-six morbidly obese patients were randomly assigned to undergo either laparoscopic (n = 18) or open (n = 18) GBP. Liver function tests--total bilirubin (T Bil), gamma GT (GGT), albumin, alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT)--and creatine kinase levels were obtained preoperatively and at 1, 24, 48, and 72 hours postoperatively. RESULTS: The two groups were similar in age, sex, and body mass index. Albumin and ALP levels decreased while T Bil and GGT levels remained unchanged from baseline in both groups without significant difference between the two groups. After laparoscopic GBP, ALT and AST transiently increased by sixfold and returned to near baseline levels at 72 hours. After open GBP, ALT and AST transiently increased by fivefold to eightfold and returned to near baseline levels by 72 hours. Creatine kinase level was significantly lower after laparoscopic GBP than after open GBP at 48 and 72 hours postoperatively. There was no postoperative liver failure or mortality in either group. CONCLUSIONS: Laparoscopic GBP resulted in transient postoperative elevation of hepatic transaminase (ALT, AST) but did not adversely alter hepatic function to any greater extent than open GBP. Creatine kinase levels were lower after laparoscopic GBP reflecting its lesser degree of abdominal wall trauma.

Adult↗

Characterization of the human liver vasopressin receptor. Profound differences between human and rat vasopressin-receptor-mediated responses suggest only a minor role for vasopressin in regulating human hepatic function.

The [Arg8]vasopressin (AVP) receptor expressed by human hepatocytes was characterized, and compared with the rat hepatic V1a vasopressin receptor subtype. In addition to determining the pharmacological profile of the human receptor, the cellular responses to AVP were measured in human and rat hepatocytes by assaying glycogen phosphorylase alpha activity and DNA synthesis. Marked differences were observed between human and rat hepatocytes regarding vasopressin receptors and the intracellular consequences of stimulation by AVP. Data presented in this paper demonstrate the following, (i) Vasopressin V1a receptors are present in low abundance on human hepatocytes. (ii) Species differences exist between human and rat V1a receptors with respect to the affinity of some selective antagonists. (iii) AVP-stimulated glycogen phosphorylase a activation in human hepatocytes was approx. 5% of that observed in rat cells. (iv) In contrast with rat hepatocytes, DNA synthesis in human cells in culture was not stimulated by AVP. It is concluded that vasopressin plays only a minor role in the regulation of human hepatic function. Furthermore, conclusions drawn from observations made with AVP and its analogues on rat hepatic function cannot be directly extrapolated to the human situation.

Animals↗

Hepatic functional reserve in patients with obstructive jaundice: an assessment by the redox tolerance test.

PURPOSE: Hepatic mitochondrial response to oral glucose load (redox tolerance test) was evaluated as an indicator of hepatic functional reserve of patients with obstructive jaundice. PATIENTS AND METHODS: The redox tolerance test was performed in 29 patients with obstructive jaundice before percutaneous transhepatic biliary drainage and 2 weeks after the procedure. RESULTS: The redox tolerance index (RTI) before drainage was not related to conventional parameters other than albumin, but was significantly associated with bilirubin half-life (P < 0.01). Of 19 patients with an RTI > or = 0.5 before drainage, all maintained similar values after drainage and experienced satisfactory clinical courses, even after major surgery. Of 10 patients with an RTI < 0.5 before drainage, 5 showed improvement and 5 deteriorated after drainage. Four of the latter 5 died within 60 days after drainage. The hospital mortality was significantly greater in patients with initial RTI < 0.5 than in patients with RTI > or = 0.5 (P < 0.01). CONCLUSION: The redox tolerance test is useful for evaluating hepatic functional reserve and prognosis in patients with obstructive jaundice.

Adult↗

Hepatic function and portal hemodynamics in patients with liver cirrhosis.

We investigated the distribution of portal blood flow per kilogram of body weight (PBF/BW) in 112 healthy volunteers and 90 patients with liver cirrhosis using an ultrasonic Doppler duplex system. The PBF/BW in healthy volunteers showed a log-normal distribution, while the distribution was irregular and showed two peaks in patients with cirrhosis. This irregular distribution was thought to reflect their complex physiopathological state. We next analyzed the relationship between PBF/BW and the data from hepatic function tests (serum albumin, total bilirubin, indocyanine green 15-min retention rate, and indocyanine green plasma disappearance rate) in 48 patients with liver cirrhosis. The patients were divided into four groups according to their portal blood flow: group A with a hepatofugal or stagnant portal blood flow, group B with a hepatopetal PBF/BW of less than 12 ml/min/kg, group C with a hepatopetal PBF/BW of 12 or more but less than 20 ml/min/kg, and group D with a hepatopetal PBF/BW of 20 ml/min/kg or more. Among patients with cirrhosis, group A showed the worst results in hepatic function tests, group D the second worst, and group C the best. The effective hepatic blood flow was thought to have decreased because of the development of extrahepatic portosystemic shunts in the patients in groups A and B, whereas it decreased because of the development of intrahepatic shunts in patients in group D. The results of hepatic function tests deteriorated as a consequence of the decrease in the effective hepatic blood flow.

Adult↗

Compromised hepatic function in dogs treated with anticonvulsant drugs.

Hepatic function tests were performed on 48 dogs that had been given primidone, phenytoin, or a combination of anticonvulsant drugs for 6 months or longer. Except for histories of seizures, 44 of the dogs were healthy at the time the tests were performed. Abnormal test results were observed most frequently in dogs given only primidone and in dogs given combinations of anticonvulsant drugs. The test results that were abnormal most often were those for alanine transaminase and alkaline phosphatase activities, and sulfobromophthalein excretion. The dosage of anticonvulsant drug was found to modify certain test results. Statistically significant positive correlations were found between the dosage of primidone and serum alanine transaminase activity and between the dosage of phenytoin and serum alkaline phosphatase activity. Four of the dogs were examined because of signs of weakness and anorexia and 2 also had ascites. Three of the 4 dogs were euthanatized 2 to 49 days after admission with clinical signs compatible with hepatic failure, and cirrhosis of the liver was confirmed at necropsy. The fourth dog died at home and was not necropsied. Four of the remaining 44 dogs that apparently were healthy at the time of examination had abnormalities in hepatic biochemical test results that were comparable with those in the 4 dogs with clinical illness. We concluded that, although results of hepatic biochemical tests frequently may be abnormal in dogs given anticonvulsant drugs long-term, severe hepatic injury is observed less often.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of octreotide on morphological hepatic regeneration and hepatic functional recovery after a two-thirds hepatectomy in rats.

BACKGROUND/AIMS: The aim of this study was to clarify the effect of octreotide on either morphological hepatic regeneration or hepatic function after a two-thirds hepatectomy in rats. METHODOLOGY: The rats were separated into two groups as follows: group 1 received 100 microg of octreotide acetate subcutaneously every 6 hours from 24 hours before hepatic resection until sacrifice; group 2 received 0.9% saline solution instead of octreotide as a control. Morphological hepatic regeneration, protein synthesis and mitochondrial function were all studied. RESULTS: The regenerative rate in liver volume and the BrdU labeling index in group 1 were significantly lower than those in group 2. The levels of glutamic acid dehydrogenase were significantly lower in group 1 than those in group 2 at 24 (64.2+/-14.6 and 77.8+/-8.3 IU/l, respectively), 36 (46.1+/-14.4 and 60.6+/-5.9 IU/l, respectively) and 48 hours (39.7+/-13.7 and 51.0+/-11.8 IU/l, respectively) after hepatectomy. At 24 hours after hepatectomy, the levels of arterial ketone body ratio was higher in group 1 than in group 2 (0.67+/-0.05 and 0.51+/-0.07, respectively), and the energy charge of the liver was also higher in group 1 than in group 2 (0.662+/-0.031 and 0.605+/-0.053, respectively). CONCLUSIONS: Our results suggest that morphological hepatic regeneration is not necessarily synchronized with hepatic functional recovery. In addition, hepatic functional recovery was preserved by keeping the energy metabolism in hepatocytes, even when the use of octreotide suppressed morphological hepatic regeneration.

Animals↗

[Reevaluation of protective effects of alprostadil on hepatic function in patients undergoing hepatectomy].

BACKGROUND: The protective effect of alprostadil (PGE1), used during hepatectomy, on hepatic function has not been clearly proven. We reevaluated this effect by measuring serum alpha-glutathione S-transferase (aGST), which detects liver injury sensitively. METHOD: Thirty hepatocellular carcinoma patients scheduled for hepatectomy were randomly assigned to control (n=12) and PGE1 (n=10) groups. In the latter group, PGE1 was administered intravenously at a rate of 0.05 microg x kg(-1) x min(-1) during surgery. For measuring alphaGST, arterial blood samples were obtained before anesthesia, following laparotomy, and immediately, 2, 4, and 6 hrs after liver resection. RESULTS: The alphaGST concentrations after liver resection were significantly higher, while mean arterial pressures were significantly lower in the PGE1 group. CONCLUSIONS: Our findings suggest that PGE1 medication during hepatectomy cannot protect hepatic function during and after liver resection.

Aged↗

[Serum and urinary inorganic fluoride concentrations with renal and hepatic functions after repeated sevoflurane anesthesia].

The purpose of this study is to examine changes in serum and urinary inorganic fluoride (F) concentrations with their effects on renal and hepatic functions after repeated sevoflurane anesthesia with relatively short time interval. Eight patients received sevoflurane anesthesia twice within 7 days for gynecological surgery. Serum and urine F levels before induction, 0.5 and 1 hour after induction, and 0.5 hour after anesthesia were compared between first and second anesthesia. There were no significant differences in serum and urine F concentrations at the same point between first and second anesthesia. Two obese patients exhibited peak concentrations greater than 50 mumol.l-1 of F. Laboratory findings of renal function remained stable throughout 2 operations, whereas hepatic function deteriorated in the two obese patients after the first anesthesia, and resolved within 14 days after the second anesthesia. In conclusion, it is suggested that the second exposure to sevoflurane within 7 day interval does not alter the sevoflurane metabolism. However, obesity may contribute to a rise in serum inorganic fluoride after repeated sevoflurane anesthesia.

Adult↗

Hepatic function and indocyanine green clearance during and after prolonged anaesthesia with propofol.

We have studied the effects of propofol on hepatic function and clearance of indocyanine green (ICG) in 13 consecutive patients undergoing prolonged plastic and reconstructive surgery. Hepatic function was assessed using serum concentrations of liver-specific glutathione-S-transferase (GST). There were no significant changes in GST activity or plasma clearance of ICG throughout the study.

Adult↗

[Usefulness of 99mTc-GSA scintigraphy for estimation of residual hepatic functions and postoperative changes of HH15 and LHL15].

We investigated the usefulness of 99mTc-GSA scintigraphy for estimation of residual hepatic functions and postoperative changes of HH15 and LHL15. 99mTc-GSA scintigraphy was performed on 61 patients and following points were studied: 1) correlation between HH15-LHL15 and conventional liver function tests, 2) correlation between HH15-LHL15 and the Child classification, 3) relations of preoperative HH15 and LHL15 to postoperative complications after hepatectomy, 4) early changes of HH15 and LHL15 after hepatectomy, 5) changes of HH15 and LHL15 1 year after hepatectomy, and 6) changes of HH15 and LHL15 1 year after Hassab's operation. Results were as follows. 1) There were significant relations between preoperative HH15 and ICGR15 and Alb. There were significant relations between preoperative LHL15 and ICGR15, T-Bil, Alb, HPT and ChE. 2) There were significant relations between preoperative HH15-LHL15 and the Child classification. 3) In Hr2 group, preoperative LHL15 of patients who contracted postoperative complications had been significantly lower than that of those who did not. 4) There were no early changes of HH15 and LHL15 after hepatectomy. 5) HH15 and LHL15 were significantly improved 1 year after hepatectomy. 6) HH15 were significantly improved 1 year after Hassab's operation. We concluded that 99mTc-GSA scintigraphy is useful for estimation of residual liver function tests and for investigation of changes after surgery from viewpoints different from conventional hepatic function tests.

Adult↗

Risk factors before hepatectomy, hepatic function after hepatectomy and computed tomographic changes as indicators of mortality from hepatic failure.

The mortality rate from hepatic failure after extensive resection should be negligible in the presence of normal results from preoperative liver function tests in patients without pre-existing hepatitis and cirrhosis. Despite conventionally acceptable results from preoperative hepatic function tests in 56 patients undergoing extensive hepatic resection for tumours (47 metastatic, six hepatomas and three adenomas), however, five patients died of hepatic failure. Among the many preoperative and intraoperative risk factors studied, the important factors in the group with hepatic failure were very high levels of serum alkaline phosphatase (p less than 0.05) in the presence of normal levels of bilirubin and large tumor, preoperative administration of chemotherapy, the presence of hepatomas rather than metastatic carcinoma (p = 0.083) and intraoperative blood loss of greater than 5,000 milliliters (p = 0.03). The patients receiving preoperative chemotherapy or those with hepatoma showed a minimal rise of alkaline phosphatase (p less than 0.03) and a minimal regeneration of liver on computed tomographic (CT) scan after hepatic resection. In the group with hepatic failure, a consistent postoperative pattern of increasing bilirubin with normal or subnormal alkaline phosphatase levels corresponded with lack of regeneration of liver on repeated CT scans. Conversely, the pattern of decreasing bilirubin with reciprocal increase in alkaline phosphatase corresponded with hepatic regeneration on CT scan in the group of survivors. Thus, we observe that alkaline phosphatase is a good indicator of hepatic regeneration in the absence of jaundice in patients after hepatectomy. To avoid postoperative hepatic failure, we recommend more discriminant tests than conventional hepatic function tests in patients with large tumors associated with high alkaline phosphatase levels, preoperative chemotherapy and hepatoma even without pre-existing cirrhosis or hepatitis.

Adult↗

Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations.

We analyzed retrospectively the relationship between coagulation profile, and either hepatic function or hemodynamics, in patients who had undergone a Fontan-type procedure, comparing them, first, with a control group of 12 patients without significant hemodynamic abnormality, and, second, with a group of 14 patients who had not undergone a Fontan procedure, but whose mean right atrial pressure exceeded 8 mmHg. Follow-up catheterization had been performed in all 30 patients submitted to the Fontan-type operation. Prothrombin time, and factor XIII, were significantly lower in those who had undergone the Fontan procedure than in the other groups. Those submitted to the Fontan operation also had lower levels of protein C than controls, and their levels of plasminogen were lower than the patients with high right atrial pressure. Both aspartate aminotransferase and alanine aminotransferase were higher in those undergoing the Fontan procedure than in the other groups, while gamma-glutamyltranspeptidase in these patients was higher than in the control group. Mean right atrial pressure was highest in those undergoing the Fontan procedure, while cardiac index was lowest. Prothrombin time was correlated to some extent with aspartate aminotransferase, mean right atrial pressure, and cardiac index. Protein C correlated with both aspartate aminotransferase and mean right atrial pressure, while factor XIII correlated with alanine aminotransferase, mean right atrial pressure, and cardiac index. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase, parameters of hepatic function, correlated significantly with mean right atrial pressure. In those who had undergone the Fontan procedure, decreased synthesis of pro-and anti-coagulant factors is a risk factor for both thrombosis and bleeding. Abnormal hemodynamics, in the absence of a right sided pumping chamber, may predispose to subclinical hepatic dysfunction, leading to selective disturbances of protein synthesis.

Adolescent↗

Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function.

Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Clp), volume of distribution (Vd), and elimination half-life (t1/2 beta) of VP16 were, respectively, 22.8 +/- 1.0 (SE) ml/min/m2, 11.4 +/- 0.8 liters/m2, and 5.6 +/- 0.4 h. In patients with renal insufficiency Clp was 12.8 +/- 1.1 ml/min/m2, Vd was 20.8 +/- 4.9 liters/m2, and t1/2 beta was 19.2 +/- 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Clp and creatinine clearance. In 12 of 15 patients with abnormal liver tests Clp, Vd, and t1/2 beta were, respectively, 27.9 +/- 2.7 ml/min/m2, 12.4 +/- 1.5 liters/m2, and 5.4 +/- 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t1/2 beta values were similar (5.1, 4.4, and 5.1 h) whereas Clp values (320, 87, and 96 ml/min/m2) and Vd values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 Vd and Clp values found in a subset of patients with liver impairment require further elucidation.

Adult↗

Comparison of quantitative methods to assess hepatic function: Pugh's classification, indocyanine green, antipyrine, and dextromethorphan.

STUDY OBJECTIVES: To compare three quantitative metabolic markers used to assess hepatic function, indocyanine green (ICG), a high-extraction marker; antipyrine, a low-extraction marker; and dextromethorphan, a P-450IID6 marker, with the clinically used Pugh's classification. DESIGN: Comparison of 12 healthy controls with 12 age- and sex-matched patients with different degrees of liver disease. SETTING: Research center in a university-affiliated teaching hospital. PATIENTS: The 12 patients had different degrees of liver disease: 4 mild (Pugh's score 6 or 7); 4 moderate (Pugh's score 8 or 9); and 4 severe (Pugh's score > or = 10). Each level had an equal number of men and women subjects. MEASUREMENTS AND MAIN RESULTS: Clearance of ICG detected mild alterations in hepatic function as efficiently as it did for moderate and severe impairment, but it lacked the specificity to distinguish among the classification groups. In contrast, antipyrine was effective in identifying moderate and severe hepatic impairment; however, its clearance was not reduced in mild liver disease. Pugh's classification appears to be a clinically useful method of assessing the global degree of hepatic impairment in patients with chronic disease, and there was a significant correlation between it and antipyrine clearance (r = 0.67, p = 0.0003) and ICG clearance (r = 0.86, p = 0.0001). Four of eight patients with a Pugh's score greater than 8 had a dextromethorphan metabolic ratio expression reflective of a poor metabolizer phenotype based on 0- to 4-hour urine collection, but only two of those eight patients were classified as poor metabolizers based on 4- to 12-hour urine collection. These percentages of poor metabolizers are substantially higher than for historical controls (8.5-10.4%) and most likely reflect a decrease in the P-450IID6 functional ability with progression of liver disease. However, due to small sample size and lack of knowledge of the patients' genotypes, these data are only suggestive. CONCLUSION: Pugh's classification appears to be a reliable indicator of the degree of chronic liver disease and could be employed as a drug development research classification tool; however, it does not replace quantitative metabolic markers, especially isozyme-specific markers.

Adult↗

Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation.

BACKGROUND: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation. METHODS: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days. RESULTS: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT. CONCLUSION: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.

Adenosine↗

Hepatic function in previously exposed thorium refinery workers as compared to normal controls from the health and nutrition survey.

The effect of thorium exposure on hepatic function was investigated in 275 former workers of a thorium refinery. Body burden of radioactivity from the decay chain of thorium was measured as 212Bi and 220Rn in the exhaled breath. Asparate aminotransferase, globulin and total bilirubin in sera were found to be associated with body burden of radioactivity at high levels of significance. Thorium-exposed workers were also compared with a population of white males from the Health and Nutrition Survey conducted by the National Center for Health Statistics from 1971 to 1975. The results showed the means of aspartate aminotransferase alkaline phosphatase to be significantly higher (P = 0.0001) in the thorium-exposed workers when corrected for age, alcohol use and weight. The changes observed in liver function may be compatible with a toxic effect of thorium or daughter products on hepatocytes. The correlation of some hepatic function tests with body burden of radioactivity suggests a radiation effect of thorium although a chemical toxic effect cannot be ruled out and further investigation of chemical toxicity of rare earths are indicated.

Adult↗

An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function.

AIM: The aim of this study was to evaluate the pharmacokinetic profile of donepezil HCl (5 mg) in patients with impaired hepatic function, following the administration of single oral doses. METHODS: This was an open-label, non-randomized study comparing the pharmacokinetic profile of donepezil in male volunteers with chronic compensated cirrhosis of the liver (n = 10) to that in healthy age- and sex-matched controls (n = 10). Each subject received a single 5 mg oral dose of donepezil. Blood samples for pharmacokinetic analyses were taken at specified intervals up to 120-h post-dose. Concentrations of donepezil in plasma were determined by HPLC with UV detection. RESULTS: No statistically significant differences in donepezil pharmacokinetics were observed between hepatically impaired patients and normal subjects, with the exception of Cmax. The hepatically impaired patients showed a statistically significant, but not clinically significant, higher mean Cmax value of 6.6 ng ml(-1) compared with the control group, which had a mean Cmax value of 4.8 ng ml(-1) (P=(0.022). This represented an increase of 37.5%. The observed changes in AUC values were smaller and not statistically different. The AUC(0-120) and AUC(0-infinity) were 7% and 21% larger in the hepatically impaired patients than in the normal subjects, respectively, although clearance and volume of distribution were almost identical in the two groups. The t1/2 increased by 20%, but this change was also not statistically significant. Donepezil was equally well tolerated by all subjects. CONCLUSIONS: This study demonstrates that compromised hepatic function does not produce clinically significant changes in the pharmacokinetics of donepezil following single-dose administration. These results suggest that the administration of donepezil to patients with hepatic disease in clinical practice should not require any dosing modifications.

Administration, Oral↗

[Impact of anthelminthic therapy for opisthorchiasis on the biochemical parameters of hepatic function].

A response of a complex of biochemical parameters of hepatic function to therapeutic exposures was studied at different stages of development of Opisthorchis invasion. The activity of AST, ALT, GGT, GGT, AP, AM, and CE and the concentration of bilirubin, cholesterol, and glucose in the sera from 232 patients with acute or chronic opisthorchiasis were studied. Their study was conducted in several steps: before treatment, after a course of pathogenetic therapy, 1-3 days after antihelminthic therapy with bilthricide and azinox, in early (following 1-3 months) and late (following more than 6 months) residual periods. Pathogenetic therapy was found to alleviate an acute inflammatory process in the liver, but without eliminating cholestasis completely. Antihelminthic therapy improved the results of hepatic tests in different periods after treatment for acute or chronic opisthorchiasis in relation to the rate of compensation of structural lesions. By and large, after pathogenetic and antihelminthic therapy for opisthorchiasis the parameters characterizing the cytolytic syndrome became more rapidly than those that reflect the biliary system. However, there was no complete recovery of impaired hepatic and pancreatic functions throughout the follow-up.

Alanine Transaminase↗