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Experimental study of the evaluation of liver function on the opposite side during portacaval anastomosis and ligation of the left portal branch.

BACKGROUND: Hepatocellular carcinoma is likely to accompany liver cirrhosis in which the portal pressure increases with portasystemic shunt. When portal tumor thrombus is present in the primary bifurcation, blood flow differs between the thrombolic lobe and the non-thrombolic lobe. In those cases, it is difficult to evaluate exactly residual liver function by conventional test. Therefore, the following studies were performed. MATERIALS AND METHODS: Adult mongrel dogs are divided into a control group (C group), group undergoing ligation of the left portal branch (PL group), group undergoing portacaval anastomosis (PCS group) and group undergoing both ligation of the left portal branch and portacaval anastomosis (PL+PCSgroup)(n=5). ICG-R15 and MEGX15 in peripheral venous blood and right hepatic venous blood were determined. Mitochondrial metabolic capacity (adenosine triphosphate level, energy charge) was measured by high-performance liquid chromatography using liver biopsied specimens. RESULTS: The MEGX ratio (right hepatic venous blood MEGX15/peripheral venous blood MEGX 15) positively correlated with energy charge in the right hepatic lobe. CONCLUSIONS: In evaluating liver function of the right hepatic lobe during portacaval shunt and the left portal branch ligation, the MEGX ratio may sensitively reflect the mitochondrial function.

Animals↗

Splanchnic and renal extraction of circulating type III procollagen aminoterminal propeptide in patients with normal liver function and in patients with alcoholic cirrhosis.

Splanchnic and renal extraction of circulating aminoterminal propeptide of type III procollagen and related antigens were studied in 12 patients with normal liver function and in 19 patients with alcoholic cirrhosis during catheterization. Type III procollagen peptide in serum was measured in two assays: the Type III Procollagen Peptide Radioimmunoassay Kit, a new assay that selectively determines the intact propeptide (and larger type III propeptide-holding antigens) and the Type III procollagen Fab assay that measures both the intact propeptide and the smaller fragments that quantitatively dominate in serum. A significant decrease in the concentration of the intact propeptide between the artery and the hepatic vein was found in the group with normal liver function (p less than 0.01) and in patients with cirrhosis (p less than 0.01). In patients with cirrhosis, however, the splanchnic extraction ratio of the intact propeptide (median = 0.04, range = -0.03 to 0.16) was significantly lower than in patients with normal liver function (median = 0.17, range = 0.05 to 0.36, p less than 0.01). The concentration of the intact propeptide in the hepatic vein was positively correlated to hepatic pressure (n = 18, r = 0.51, p less than 0.05) and inversely correlated to indocyanine green clearance (n = 15, r = -0.61, p less than 0.05). No splanchnic extraction could be demonstrated in the Type III propeptide Fab assay. A significant renal extraction was found in the Fab assay, but not in Type III Procollagen Peptide Radioimmunoassay Kit.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

[Liver function in undisturbed pregnancy].

In order to evaluate liver function during pregnancy the enzyme activities of GPT, GOT, GLDH, LDH, AP, LAP, gamma-GT and CHE were determined in 272 healthy pregnant women from the 16th week of gestation up to term. The normal range of GPT, GOT, GLDH, LDH, gamma-GT and CHE did not differ significantly from those in non-pregnant women. Increases in AP and LAP are conditioned by placental synthesis. The functional reserves of a healthy liver obviously suffice to compensate for increased demands during pregnancy. Increases in enzyme aktivities during pregnancy are not physiologic - except for increases in AP and LAP.

Alanine Transaminase↗

Effect of subdermal levonorgestrel contraceptive implants, Norplant, on liver functions.

Forty-seven normal health women were studied longitudinally for changes in liver functions during the use of the levonorgestrel contraceptive implant system, NORPLANT. Samples were collected before insertion of the implants and after one, three and six months of use. The enzymes studied were the transaminases (SGOT and SGPT), alkaline phosphatase and gamma-glutamyl transferase. Serum bilirubin and bile acid levels were also measured. The protein synthetic function of the liver was tested by estimation of total proteins, albumin, transferrin, hemopexin, ceruloplasmin and haptoglobin. The three main immunoglobulins, G, M and A, were also measured. There were no significant changes in the liver enzymes after NORPLANT use. Serum bilirubin and bile acid concentrations showed rises in the first month of use which ameliorated in subsequent months. Serum albumin was transiently increased during the first and third months. Ceruloplasmin decreased significantly at the sixth month. The concentrations of total serum proteins and the other individual proteins showed no significant change. The results point to safety of NORPLANT implant use, as regards hepatic functions.

Adult↗

Elevated urokinase-type plasminogen activator plasma levels are associated with deterioration of liver function but not with hepatocellular carcinoma.

We measured urokinase-type plasminogen activator (u-PA) plasma levels in patients with various chronic liver diseases, including hepatocellular carcinoma (HCC), also measuring these levels in healthy volunteers. Plasma u-PA levels in the group of patients with decompensated liver cirrhosis (mean modified Pugh score of 14 points) were markedly elevated and significantly higher than those in the patients with decompensated liver cirrhosis with HCC (modified Pugh score of 10 points), those with compensated liver cirrhosis with HCC, and those with compensated liver cirrhosis. Patients in all these three latter groups had moderately and significantly elevated u-PA levels compared to levels in the chronic hepatitis group and the healthy volunteers, but the levels were not significantly different from each other. There was no relationship between u-PA plasma level and the type of HCC tumor invasion or number or size of tumors. Significant correlations were found between u-PA plasma levels and the results of seven different liver function tests in three groups without associated HCC; u-PA antigen and prothrombin time (%), hepaplastin test (%), serum cholinesterase, serum albumin, serum total cholesterol, and indocyanine green clearance correlated negatively, while u-PA antigen and serum total bilirubin correlated positively. These results suggest that plasma u-PA is associated with deterioration of liver function but not with HCC invasion.

Carcinoma, Hepatocellular↗

Disturbances of liver function of long acting neuroleptic drugs.

In a study in 97 patients on the occurrence of disturbances of liver functions by use of long acting neuroleptic drugs (fluphenazine decanoate, flupenthixol decanoate and fluspirilene) no indications were found that these agents, even in relatively high dosages, are hepatotoxic. Furthermore, in 40% of the patients slight disturbances were found, which nevertheless, were not specific in nature, and mostly concerned the turbidity tests. In spite of these findings a regular control (for instances, once a year) of the liver functions in patients with long acting neuroleptic drugs seems to be called for.

Adolescent↗

Disulfiram use in patients with abnormal liver function test results.

BACKGROUND: Concern about the precipitation of severe hepatitis by disulfiram often causes clinicians to avoid using this effective treatment in patients who have elevated baseline transaminase levels, even though no empirical evidence has so far shown severe hepatotoxicity to be related to such laboratory abnormalities. This study examines the effects of disulfiram in alcohol-dependent patients with elevated liver function test results and/or serologic evidence of hepatitis C virus (HCV) infection. METHOD: Hepatitis serologies and baseline transaminase levels were obtained for 57 male alcoholics starting treatment with disulfiram. Sequential liver function test results were obtained for up to 12 weeks while subjects took disulfiram. RESULTS: Although subjects with elevated baseline transaminase levels and serologic evidence of HCV infection were the most likely to evidence marked elevations in transaminase levels while taking disulfiram, most subjects took disulfiram without other adverse consequences. In only 1 subject did elevations appear directly related to disulfiram. CONCLUSION: Monitoring of liver function test results is warranted for patients taking disulfiram and permits most patients with moderately elevated transaminase levels to take it safely.

Adult↗

Allopurinol kinetics in humans as a means to assess liver function: comparison of different models.

To describe the mechanisms involved in allopurinol kinetics after intravenous injection in humans, a number of alternative computer-based biodynamic models were designed. Distribution processes were described with two-compartment as well as with three-compartment kinetics for both allopurinol and its metabolite oxipurinol. These two major physiological alternatives were combined with biochemical models assuming either competitive or tight-binding-complex inhibition kinetics. The four resulting basic models were evaluated (and successively improved) using sets of plasma allopurinol and oxipurinol concentration curves, measured after intravenous injection in healthy subjects and in patients with different degrees of liver function. A three-compartment model with tight-binding-complex inhibition was selected and used to analyze the 35 loading tests performed. One of the parameters estimated in this way, the fractional rate constant for transport of allopurinol from the central compartment to the metabolically active (liver) compartment (kA31), turned out to be a powerful discriminative parameter between a group of healthy subjects, a group of patients with slightly to moderately reduced overall liver function, and a group with severely reduced overall liver function [kA31(min-1) = 0.136 +/- 0.042 (mean +/- SD, n = 13), 0.072 +/- 0.024 (n = 13), and 0.025 +/- 0.015 (n = 8), respectively].

Allopurinol↗

Estimation of remnant liver function before hepatectomy by means of technetium-99m-diethylenetriamine-pentaacetic acid galactosyl human albumin.

To improve the results of hepatectomy in cirrhotic patients, the likely reserve function of the liver was evaluated before surgery. Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m-diethylene triamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is a newly developed analog ligand to ASPG-R. The probable functional reserve of the remnant liver after hepatectomy was estimated preoperatively as the hepatic binding protein (HBP) concentration specific for ASGP-R on the hepatocellular membrane of the remnant liver. This estimate was based on the effective liver volume rate, obtained by the uptake of 99mTc-GSA. In all, 3 normal volunteers, 3 patients with chronic hepatitis (CH), 9 patients with liver cirrhosis (LC), 2 patients with hepatic cystadenoma, 3 patients with hepatocellular carcinoma (HCC) associated with CH, and 21 HCC patients with LC were studied. The mean value +/- SD obtained for HBP in normal volunteers (three cases) and in patients with mild (four cases), moderate (two cases), and severe liver damage (five cases) were 0.74 +/- 0.03 microM, 0.43 +/- 0.042 microM, 0.31 +/- 0.05 microM, and 0.20 +/- 0.05 microM, respectively. Most of the cases in which the preoperative HBP of the remnant liver was above 0.22 microM had a good postoperative course irrespective of the type of hepatectomy. On the other hand, in subjects with a remnant liver HBP of between 0.22 and 0.11 microM, postoperative severe liver dysfunction occurred in about 50% of cases. In all cases with a remnant liver HBP below 0.1 microM, the prognosis was very poor, indicating that hepatectomy should be avoided. The HBP concentration detected by the 99mTc-GSA study is a very sensitive indicator of changes in the hepatic functional reserve, and the HBP value for the functional reserve of the remnant liver is extremely useful for estimating the liver function before and after hepatectomy.

Adult↗

Effects of verapamil on hepatic and systemic hemodynamics and liver function in patients with cirrhosis and portal hypertension.

The effects of verapamil on hepatic and systemic hemodynamics and on liver function were investigated in 10 patients with portal hypertension due to advanced micronodular cirrhosis to verify whether, as it has been suggested, this calcium channel blocker may improve liver function and reduce portal pressure in these patients. The oral administration of 100 mg of verapamil caused systemic vasodilation, evidenced by a significant reduction in mean arterial pressure (-8.1 +/- 7.6%, p less than 0.025) and systemic vascular resistance (-12.5 +/- 9.5%, p less than 0.001), and increased heart rate (+13.9 +/- 10.4%, p less than 0.01). However, no beneficial effect was noted on portal pressure evaluated by hepatic vein catheterization (baseline 19.8 +/- 4.0, verapamil 20.2 +/- 3.6 mmHg, NS), hepatic blood flow (1.45 +/- 0.64 vs. 1.47 +/- 0.62 liters per min, NS) and hepatic vascular resistance (1.314 +/- 611 vs. 1,266 +/- 513 dyn per sec per cm-5, NS). Similarly, no change was observed in portal blood flow, measured in six patients by pulsed Doppler flowmeter (0.94 +/- 0.30 vs. 0.89 +/- 0.35 liter per min, NS). In addition, verapamil did not increase the hepatic intrinsic clearance of these patients (0.20 +/- 0.07 vs. 0.19 +/- 0.06 liter per min, NS). This study suggests that verapamil is of no beneficial effect in patients with advanced cirrhosis of the liver.

Adult↗

Pre-operative endoscopic ultrasonography can optimise the management of patients undergoing laparoscopic cholecystectomy with abnormal liver function tests as the sole risk factor for choledocholithiasis: a prospective study.

BACKGROUND: Pre-operative endosonography has been proposed as a cost-effective procedure in the management of patients who undergo laparoscopic cholecystectomy having an intermediate risk of common bile duct stones. We prospectively evaluated the impact of pre-operative endosonography on the management of patients facing laparoscopic cholecystectomy with abnormal liver function tests as the sole risk factor for choledocolithiasis. METHODS: Among 587 consecutive patients scheduled for laparoscopic cholecystectomy, 47 (8%) patients having one or more abnormal liver function tests but a normal appearance of common bile duct at abdominal ultrasound, underwent pre-operative endosonography. In patients with endosonography-detected common bile duct stones, a pre-operative endoscopic retrograde cholangiography was performed, or an intra-operative endoscopic retrograde cholangiography was scheduled. In all endosonography-negative patients, an intra-operative trans-cystic cholangiography was performed. RESULTS: Endosonography detected common bile duct stones in nine patients (19%) but only in five of them stones were radiologically confirmed (PPV 0.55). Endosonography-detected stones were confirmed in four of four (100%) patients in whom cholangiography was performed within 1 week, but only in one of five (20%) patients in whom radiology was further delayed (P < 0.05). In three of four cases (75%), stones detected at endosonography but not confirmed at X-rays, were smaller than 2.0 mm. Among 38 patients with negative endosonography, common bile duct stones were found in two patients (NPV 0.95), whereas unplanned endoscopic stone extraction was needed only in one patient (NPV 0.97). CONCLUSIONS: Pre-operative endosonography can spare unnecessary pre-operative endoscopic retrograde cholangiography as well as inappropriate scheduling of intra-operative endoscopic retrograde cholangiography in patients undergoing laparoscopic cholecystectomy with abnormal liver function tests. To maximise the impact of endosonography on the management of these patients, the procedure should be performed immediately before laparoscopic cholecystectomy.

Cholangiopancreatography, Endoscopic Retrograde↗

A quasi-experimental study on the effect of upper gastrointestinal surgery on liver function tests.

BACKGROUND/AIMS: To determine the effect of upper gastrointestinal (UGI) surgery on liver function tests, a study was performed at Loghman Hakim Hospital, Tehran, Iran. METHODOLOGY: In this quasi-experimental study, 60 patients undergoing UGI operations were compared to 20 patients with extra-abdominal surgery. In each case, after obtaining a thorough past medical history and physical exam, 5 ml of fasting venous blood was drawn pre-operatively on the morning of the operation, and liver function tests (LFTs), namely serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH), were measured. The three tests were repeated on the morning of days 2 and 4, post-operatively. Other intra- and post-operative parameters were also recorded. Finally, the results were analyzed in all 80 cases using the Student's t-test, Yate's corrected chi-square and Pearson's coefficient of correlation. RESULTS: The operations performed in the case group were biliary tract operations (75%), surgery on the esophagus and stomach (18.3%) and liver and pancreas operations (6.7%). The control operations consisted of head and neck surgery (45%), breast and thorax operations (35%) and prostate and testes surgery (20%). The mean duration of general anesthesia in the cases and controls was 3.62 and 3.58 hours, respectively, with no statistically significant difference. The SGOT level increased 54% in the study cases on day 2, which significantly differed with the 9% increase in the controls (p<0.05). In the cases studied, SGPT increased 65% on day 2 and 50% on day 4, with a significant difference compared to the 2% decrease and 2% increase on days 2 and 4 in the controls (p<0.005 and p<0.02, respectively). LDH levels also increased 17% on day 2 in the case group with a significant difference compared to the 8% increase in controls (p<0.05). CONCLUSIONS: An increase in the levels of SGOT, SGPT and LDH in the first 4 days following UGI surgery is a common problem which seems to be due to local trauma to the liver rather than the effect of other factors such as anesthetic drugs, the duration of surgery, blood transfusions, hypotension and other underlying conditions.

Alanine Transaminase↗

Serum glutathione S-transferase B1 activity as an index of liver function in cystic fibrosis.

AIMS: To evaluate serum glutathione S-transferase B1 (GST B1), a highly sensitive test of hepatocellular function, as a means of identifying liver disease in patients with cystic fibrosis (CF). METHODS: The presence of liver disease was sought over a three year period in 60 children with CF, using a combination of clinical assessment, ultrasound examination, conventional biochemical tests of liver function (LFTs), and measurement of GST B1. RESULTS: Reference ranges for serum GST B1 were established in a paediatric control population. The 95% value (4.55 micrograms/l) was similar to the upper limit of normal previously derived in adults. Mean (SE) serum GST B1 activities were higher in the CF population (9.0 (1.14) micrograms/l) than in age matched controls (2.4 (0.15) micrograms/l). Ten patients with CF showed clinical signs of liver dysfunction. All but one had a serum GST B1 > 4.55 micrograms/l. Twelve other patients had elevated LFTs without clinically evident liver dysfunction, six had abnormal ultrasound scans and two showed both of these anomalies. Thirty patients with CF had neither biochemical, ultrasonographic nor clinical signs of liver disease. On review three years later, clinically important liver disease was reaffirmed in eight of the 10 index cases and had become apparent in a further eight, all of whom had elevated GST B1 activities. Five (36%) of the patients with elevated LFTs and two (33%) with isolated ultrasound changes continued to show these abnormalities. CONCLUSIONS: The limitations of conventional LFTs and ultrasound scans were evident from this study. The results suggest that elevated GST B1 activities may be a better predictor of hepatic dysfunction in CF than conventional LFTs.

Adolescent↗

MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study.

BACKGROUND: Indices for predicting survival are essential for assessing prognosis and assigning priority for liver transplantation in patients with liver cirrhosis. The model for end stage liver disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. However, this model has not been validated beyond its original setting. AIM: To evaluate the short and medium term survival prognosis of a European series of cirrhotic patients by means of MELD compared with the Child-Pugh score. We also assessed correlations between the MELD scoring system and the degree of impairment of liver function, as evaluated by the monoethylglycinexylidide (MEGX) test. PATIENTS AND METHODS: We retrospectively evaluated survival of a cohort of 129 cirrhotic patients with a follow up period of at least one year. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. All patients had undergone a MEGX test. Multivariate analysis was performed on all variables to identify the parameters independently associated with one year and six month survival. MELD values were correlated with both Child-Pugh scores and MEGX test results. RESULTS: Thirty one patients died within the first year of follow up. Child-Pugh and MELD scores, and MEGX serum levels were significantly different among patients who survived and those who died. Serum creatinine, international normalised ratio, and MEGX(60) were independently associated with six month mortality while the same variables and the presence of ascites were associated with one year mortality. MELD scores showed significant correlations with both MEGX values and Child-Pugh scores. CONCLUSIONS: In a European series of cirrhotic patients the MELD score is an excellent predictor of both short and medium term survival, and performs at least as well as the Child-Pugh score. An increase in MELD score is associated with a decrease in residual liver function.

Adult↗

[Changes in the liver function of workers exposed to petroleum products].

The function of the liver is examined in 120 workers (at 52 controls) in biological purification of the waters in a petrochemical plant, exposed to above the norm concentrations of strong hepatotropic chemical substances: benzene, toluene, styrene, aldehydes, ketones, mercaptans, acrylonitrile, octanole, butanol. etc. The established hyperenzymia, hyperlipaemia and significant reduction of glutathione in certain per cent of the workers (from 7 to 31% at different indices) points out an effect of the above mentioned toxic substances on the enzymic, lipidic and detoxic function of the liver. This proves the presence of certain potential risk for those working in this production and especially workers engaged in repair and technology process.

Air Pollutants, Occupational↗

Inhibition of drug metabolism by cimetidine in man: dependence on pretreatment microsomal liver function.

The effect of cimetidine on hepatic microsomal drug metabolism was studied in six patients with normal liver and eleven patients with chronic liver disease using the aminopyrine breath test. Before administration of cimetidine, the elimination rate constant of 14CO2 from breath (Kb) was 28.3 +/- SD 1.3%/h in patients with normal liver and 13.5 +/- 7.7%/h in patients with liver disease (P less than 0.001). After 7 days of cimetidine therapy (1 g/day) Kb decreased to 23.3 +/- 5.2%/h (19.0 +/- 13.8% decrease; P less than 0.05) and 7.4 +/- 5.8%/h (50.5 +/- 14.4% decrease; P less than 0.001), respectively. Plasma levels of cimetidine were not significantly different (1.05 +/- 0.14% micrograms/ml v. 0.88 +/- 0.41; P greater than 0.05). The findings indicate that therapeutic doses of cimetidine lead to an inhibition of drug metabolism which is more pronounced in patients with impaired liver function than in liver normals. Therefore, patients with chronic liver disease may be at increased risk with respect to interactions between cimetidine and other drugs which are demethylated by the liver.

Aged↗