[Effect of porto-systemic anastomosis on the liver function of patients suffering from liver cirrhosis. Clinical and statistical study].
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Liver injury has long been associated with occupational exposure to a wide variety of chemicals. The controversial data existing in relation to hepatotoxicity of organic solvents might be explained as a consequence of the different exposures or it may well be that the tests used for evaluating liver function might not be sensitive enough to detect any mild changes at an early stage. To study liver function during exposure to solvent mixtures, we determined serum bile acid (SBA) concentrations as compared with conventional liver function tests in a selected group of workers (n = 30) occupationally exposed to a mixture of organic solvents (mostly toluene, xylene, acetone, n-butylacetate, n-butanol, ethylacetate) and in a reference group (n = 20). The mean levels of liver enzyme activities and bilirubin concentrations in the two groups were similar, whereas mean SBA levels increased in the exposed group (8.0 +/- 6.0 mumol/l vs 2.8 +/- 1.4 mumol/l) and the difference as compared with the controls was significant (P less than 0.01). In 73% of the exposed workers, SBA levels were higher than 5.6 mumol/l (the cut-off value) as compared with 5% of the controls. These results demonstrate the higher sensitivity in detecting liver dysfunction achieved with the SBA test as compared with conventional hepatic function tests. As increased SBA concentrations are considered to reflect an impairment of anion transport across the liver, higher SBA levels in the group of workers exposed to organic solvents might be explained as a slight and early sign of liver dysfunction. Therefore, SBA determination in biological monitoring of workers exposed to potentially hepatotoxic chemicals might be proposed.
A novel, simple, clinically useful quantitative liver function test, called the galactose single point (GSP) method, was developed by measurement of galactose blood concentration 1 h after galactose was administered (0.5 g/kg). It was quickly infused intravenously in 55 normal healthy volunteers, 73 patients with chronic hepatitis (CH), 36 with cirrhosis and 41 with hepatocellular carcinoma (HCC). Patients with CH diagnosis were assessed by liver biopsy. Cirrhosis was diagnosed by histological examination or a chronic hepatitis history with esophageal varices or ascites, whereas HCC was diagnosed either histologically, or cytologically proved, or as implied in the 'one imagine study' being positive with AFP > 300 ng/dl. Highly significant galactose blood levels were observed between normal healthy volunteers and patients 50, 60 and 70 min after galactose was administered. Galactose elimination capacity (GEC), modified GEC (MGEC) and consecutive GSP tests were performed in 6 healthy volunteers for 2 days. 0.64-16.87% variation was observed for each subject. The significant differences (p < 0.001) in average GSP values were 247 +/- 18.1, 422 +/- 27.3, 629 +/- 42.8 and 579 +/- 43.6 micrograms/ml for normal healthy volunteers, CH, cirrhosis and HCC patients, respectively. Highly significant correlations (p < 0.001) were obtained among GSP, GEC and MGEC for all patients. Positive correlations were observed between GSP, GEC, MGEC and AST (serum aspartate aminotransferase), ALT (serum alanine aminotransferase), serum bilirubin, albumin, prothrombin time and r-globulin. According to results obtained from 202 normal healthy volunteers and patients, the GSP method may be a simple, clinically useful quantitative measurement of liver function for the determination of a patient's residual liver function, the prognosis of liver function for patients with cirrhosis, postoperational follow-up and, finally, the timing of a liver transplant.
Renal functional reserve capacity was evaluated in healthy controls, kidney transplant recipients and patients with impaired liver function by simultaneous measurements of periodic clearances of inulin, PAH and creatinine every 30 minutes before, during and after infusion of an amino acid (AA) solution. During AA infusion glomerular filtration rate rose in 10 healthy controls to about 35% above basal values (inulin clearance from 107 +/- 6 to 144 +/- 7 ml/min, p less than or equal to 0.0005), renal plasma flow increased by 27% (PAH clearance from 530 +/- 25 to 675 +/- 40 ml/min, p less than or equal to 0.002). 8 renal transplant recipients with good and stable renal function (creatinine clearance above 65 ml/min) showed no rise in GFR and RPF, as did 10 patients with severe impairment of liver function and normal basal kidney function (creatinine clearance above 100 ml/min). The lack of renal functional reserve in kidney transplant recipients might indicate a hyperfiltration of the transplanted kidney. This could affect the longtime prognosis of these patients. The liver seems to play a role in the mediation of the amino acid-induced rise of GFR, supporting the hypothesis of a putative liver hormone regulating GFR after protein ingestion or AA infusion.
Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo.
The effects of total and selective portasystemic shunting on hepatic haemodynamics and some aspects of liver function were studied in rats with dimethylnitrosamine-induced cirrhosis. Immediately following end-to-side portacaval shunting there were significant reductions in wedged hepatic venous pressure (WHVP) and liver blood flow. After side-to-side mesocaval shunting liver blood flow and wedged hepatic venous flow fell by approximately the same magnitude. Selective shunting (mesocaval 'H'-grafts and splenopancreaticocaval) preserved liver blood flow to a greater extent than total portasystemic shunting but had a less marked effect on WHVP. Furthermore, selective portasystemic shunting prevented liver atrophy and deterioration in liver function which was observed in rats following total portasystemic shunting. These results suggest that in the cirrhotic rat, selective portasystemic shunts which preserve functional liver blood flow and prevent liver atrophy and a deterioration in liver function do not produce such a marked decrease in WHVP as total shunts. Further studies in man are required to evaluate the relative advantages of total and selective portasystemic shunts.
The effects of propranolol on liver functions of healthy rats were studied administering daily doses of 1 mg/kg. Beta receptor blockade has been investigated in carbontetrachloride induced liver cirrhosis. Normal liver functions were unchanged with the exception of an increase in Glucos-6-Phosphatase. The severe cirrhotic injuries were counteracted or moderated when propranolol administration started the same day as CCl4 injection. The amount and function of mixed-function-monooxygenases were normalised. Carbohydrate and protein metabolism impairments were moderated. Serum triglyceride and HDL-cholesterin levels were however uninfluenced. The metabolic properties of propranolol seem to be advantageous in chronic liver impairments.
The effect of Saffan, a steroid anaesthetic, on the liver function of goats has been studied. Forty healthy animals were divided into 4 equal groups. The first 2 groups were given 2 and 4 mg Saffan/kg b. wt respectively. A mixture of Saffan (1 mg) and Xylazine (0.1 mg)/kg b. wt was given to the third group and Xylazine alone to the fourth group (0.1 mg/kg b. wt). Serum samples from all groups were analysed for glucose, total protein, total and direct bilirubin and the level of activity of transaminases. Administration of Saffan evoked more hyperglycemia than a mixture with Xylazine, or Xylazine alone. The hyperglycemic effect of both doses of Saffan (2 and 4 mg) was equivocal beyond 2 h. The effect then differed and glucose was increased 4-fold by 2 mg and 3-fold by 4 mg Saffan. Serum total protein, conjugated and total bilirubin, and GPT and GOT were not changed in the four experimental groups. This was good evidence of a normally functioning liver during the course of steroid anaesthesia administration in goats.
The influence of sex, age, and liver function on the androgenmetabolizing capacity of the liver was investigated. To that end, testosterone was administered orally to healthy men, women and prepubertal boys as well as to men with liver dysfunction. While normal men (n = 17) and men with fatty liver (n = 9) showed no rise in circulating plasma testosterone levels and only a slight increase in androstenedione, a steep increase in both steroids was observed in men with liver cirrhosis (n = 7). Unlike adult men, boys (n = 7) and women (n = 6) also showed elevated testosterone levels after oral administration of this steroid. It is concluded that the hepatic capacity to metabolize testosterone is influenced by sex, stage of development, and liver function. It seems possible that peripheral concentration of testosterone after its oral administration can serve as a clinical test for liver function.
The aim of this study was to determine whether liver function and portosystemic shunting are related to renal sodium retention in alcoholic liver disease. Twenty-three studies were performed; 10 patients had ascites. Liver function was assessed from the plasma elimination rates of antipyrine, caffeine and stable isotopes of cholic acid, the latter administered both orally [2,2,4,4-2H] and intravenously [24-13C]. Portosystemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Portosystemic shunt fraction was similar in patients with and without ascites (61% +/- 16% vs. 64% +/- 11%) and unrelated to urinary sodium excretion in patients with ascites (r = -0.145). Patients with ascites had significantly lower elimination rates of all administered compounds as compared with patients without ascites (antipyrine = 0.012 +/- 0.007 vs. 0.031 +/- 0.016/hr, p less than 0.001; caffeine = 0.014 +/- 0.013 vs. 0.061 +/- 0.041/hr, p less than 0.002; intravenous cholic acid = 1.355 +/- 0.442 vs. 2.284 +/- 0.885/hr, p = 0.005; orally administered cholic acid = 2.178 +/- 0.841 vs. 4.056 +/- 1.837/hr, p = 0.007). However, urinary sodium excretion in patients with ascites was not related to the elimination constants of these compounds (r = 0.360, 0.319, 0.067, -0.073, respectively). Ascites complicating alcoholic liver disease is associated with impaired liver function but not the extent of portosystemic shunting.
The hemodynamics during hemodilution occurred after hepatectomy for hepatocellular carcinoma with liver cirrhosis and its influences on the liver functions were studied. The hematocrit value gradually decreased about 10% until the 4th postoperative day owing to hemodilution after hepatectomy. While anemia progressed, cardiac index inversely increased. Under such a condition, oxygen consumption was maintained so that acidosis did not develop. Arterial blood ketone body ratio was also kept within a normal range except for a case whose hematocrit value decreased to 17.1%. Although the escaped hepatic enzymes such as GOT and GPT increased in the serum after hepatectomy, hemodilution was not responsible for their increase. While total bilirubin increased in the severe hemodiluted group, the increase was not due to hemodilution but caused by blood transfusion. The protein synthesis of the liver measured by rapid turnover protein levels in plasma was depressed after surgery, and this depression prolonged to the 14th postoperative day in the group whose hematocrit value decreased below 20%. These results suggest that it is better to keep hemodynamics without blood transfusion unless the hematocrit value decrease below 20%, and also better to maintain the hematocrit above 20% for liver regeneration after hepatectomy.
The liver is known to play a central part in carrying out the main phases of intermediate metabolism, in supplying the other organs and tissues with structure and energy substances. The investigations on the liver function of man in the process of organism adaptation to a variety of factors in northern regions are practically non-existent. This article has as its purpose a combined clinical and biochemical investigation of the main functions of the liver in people with various length of stay in extreme northern regions. The analysis of changes in the indices of the basic liver functions in practically healthy people during the process of adaptation to the extreme environmental conditions of the North show, that with a short-term adaptation these shifts were generally of a temporary character, whereas with a long-term adaptation of the newcomers there were relatively permanent changes in a number of indices.
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Liver function abnormalities are often found on routine chemical profiles. Abnormal test results are often false positive in asymptomatic patients. Repeat testing and confirmation that the liver is the source of the abnormality are the first steps of evaluation. A thorough history and physical examination may suggest reasons for the abnormalities. If no etiology for the abnormal test result is found, further testing is indicated.
The prognostic value of conventional renal and liver function tests was evaluated during surgical septicemia. Changes in renal function variables were associated with the development of septic shock. Creatinine clearance was the most sensitive variable in predicting the outcome of septic shock, but serum creatinine and urine output were also of some value in this respect. Significantly lower creatinine clearance and urine output values, as well as significantly higher serum creatinine concentrations, were thus observed during septic shock with fatal outcome compared to non-fatal septic shock. In septicemia not complicated with shock, the variables of renal function remained in the normal range irrespective of final outcome. Among the liver function tests, serum albumin and total protein concentration revealed significant differences in behaviour between survivors and patients dying with persistent septicemia. However, due to the small differences and considerable overlap observed between the two groups of patients during the first 2 weeks of septicemia, these two variables are of limited practical value as prognostic predictors. The other liver function tests gave no information as regards the outcome of septicemia in the present study.