[Liver function & liver therapy in endogenous psychoses].
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Liver function during continuous subcutaneous deferoxamine therapy was investigated in 29 patients with homozygotic beta-thalassaemia. Average duration of treatment was 26 months (range 8-51 months). A decrease in haemosiderosis and an improvement in liver function was observed in 27 patients: Mean liver density, determined by computed tomography, decreased from 98 to 84 HU, mean serum ferritin concentration fell from 8028 to 3661 ng/ml, mean serum GOT activity from 44 to 13 U/l and GPT from 51 to 16 U/l. Mean cholinesterase activity, reflecting the improved synthetic activity of the liver, increased from 4063 to 4530 U/l.
Liver functions in patients with liver disease can be estimated by caffeine clearance. Our data, however, demonstrate the additional influence of factors other than liver disease on the caffeine test. Smoking enhances caffeine clearance in both healthy volunteers and patients with severe hepatic disorders, whereas co-medication with mexiletine strongly inhibits caffeine elimination.
The liver function results from the interaction of anatomical, histological and biochemical aspects. Thus the concept of functioning liver mass must be related to the many biological aspects involved in the process under evaluation, and its measure can be viewed as a virtual parameter averaging the liver function. In the present review the functioning liver mass has been categorized with respect to the many aspects involved (biochemical transformations, membrane transports and passive intraluminal transports) and their interactions (intracellular, transcellular, transacinar and flow-dependent). Parameters reflecting the functioning liver mass (whether static or dynamic) have been considered with respect to the experimental conditions and characterized according to the type of estimate they provide (capacity or activity). Methods for evaluating the functioning liver mass have been presented and discussed, and a protocol has been proposed for clinical applications, based on the association of the galactose elimination capacity measuring the metabolic mass with the hepatic clearance of D-sorbitol evaluating the functional hepatic plasma flow.
Accidental or intentional chloroform poisoning is rare, but a few such cases have been reported in literature. We report here a successful management of acute chloroform toxicity in a 33-year-old white female who attempted suicide by injecting one half milliliter of chloroform, followed by drinking half a cup the next morning. Plasma chloroform levels, measured by headspace gas chromatography declined rapidly. Sequential measurement of biomarkers in serum for liver cell necrosis, liver function, and liver regeneration indicated the presence of initial liver damage followed by recovery. These results suggest that in addition to biomarkers for liver cell necrosis, serial determinations of markers for liver regeneration provide objective evidence for recovery from chloroform poisoning and possibly other hepatotoxins.
Serum glycocholic acid (SGC) was measured by radioimmunoassay in 277 samples from 122 children with hepatobiliary disorders and from 23 healthy age-matched controls. In patients with hepatobiliary disease the SGC was more frequently abnormal (83%) than values for serum albumin (7%), prothrombin time (17%), bilirubin (22%), alkaline phosphatase (45%), aspartate transaminase (57%) and gammaglutamyl transpeptidase (63%). The cumulative frequency of abnormality of these six tests was equal to that of SGC alone. Serum glycocholic acid concentrations were raised in 13 patients in whom all other tests of liver function were normal. Two of these had clinical and histological evidence of liver disease, while four had biopsy-proven hepatic fibrosis or cirrhosis, and two of three with chronic active hepatitis in remission subsequently relapsed. Four patients have as yet, no other clinical or biochemical evidence of continuing liver disease. Serum glycocholic acid was normal in seven children with abnormal aspartate transaminase or gammaglutamyl transpeptidase in whom there is strong suspicion of significant hepatic disease. A wide range of values of SGC was found with marked overlap between the values found in the different disease entities studied. The SGC value was related to the serum concentration of aspartate transaminase and gammaglutamyl transpeptidase but not to other tests of liver function. Serum glycocholic acid concentration was considered in relation to the severity of histological abnormality in 25 percutaneous liver biopsies. The extent of the rise in SGC was related to the presence or degree of histological severity of oedema in the portal tracts, disruption of the limiting plate, parenchymal fibrosis and hepatocellular necrosis but not to other histological features. The very high incidence of abnormal SGC values found in this study does suggest that in an ordinary inpatient and outpatient service SGC determination is a practical and sensitive indicator of the presence of significant liver disease but for its comprehensive identification aspartate transaminase and gammaglutamyl transpeptidase must also be determined.
BACKGROUND: Portal tract eosinophil infiltration and an increase in the blood eosinophil count (EOS) have been shown to be specific markers of liver allograft rejection. The graft eosinophil infiltration is associated with the local release of eosinophil cationic protein. Therefore, serum eosinophil cationic protein concentration (ECP) is a potential marker for acute allograft rejection. We investigated the chronological relationship among and diagnostic value of serial changes in EOS, ECP, and liver function tests (LFTs) following liver transplantation. METHODS: EOS, ECP, serum alpha-glutathione S-transferase concentration, and conventional LFTs were measured in serial samples collected over the first 3 postoperative months following 58 liver transplants. The diagnostic potential of each test, alone or in combination, was reviewed over the entire follow-up period. RESULTS: EOS and ECP increased at a median period of 3.5 and 4 days, respectively, before the diagnosis of acute rejection, and this increase was significantly earlier than the corresponding changes in LFTs (P<0.05). There was a significant correlation between the day of the first increase in EOS and alpha-glutathione S-transferase (rs=0.535; P=0.009) and EOS and alanine transaminase (rs=0.629; P=0.004). The optimum combination of tests for the diagnosis of acute rejection was an increase in both EOS and GST with a predictive efficiency of 84%. CONCLUSIONS: Increases in EOS and ECP are early indicators of acute liver allograft rejection and precede evidence of hepatocellular damage. However, an increase in ECP was also frequently associated with infection. Therefore, we recommend the regular monitoring of EOS in conjunction with routine LFTs after liver transplantation as an aid to the early diagnosis of acute rejection.
We developed a method for the rapid successive cultures of adult rat mature hepatocytes on plastic dishes while avoiding viral transformation or co-culture with other cell lines. This method also allows for culturing adult human mature hepatocytes up to the secondary culture. These can be expected to provide a good source for hepatocyte autotransplantation, and, combined with the previously reported methods for the transplantation of hepatocytes into the spleen, a promising option for the support of liver function after liver resection for cancer without the need for immunosuppressive agents.
The hepatic metabolism of lidocaine to monoethyl-glycinexylidide (MEGX) is the basis of a dynamic test of liver function. To understand its potential value in liver transplantation, the latter has been considered in the following three separate stages: pretransplantation assessment of potential candidates, potential liver donors, and the transplant recipient. In pretransplantation patients, data support its role in assessing risk of morbidity and mortality. In assessment of the liver transplant donor, there are differences concerning apparent usefulness, and these must be resolved. In the liver transplant recipient, serial measurements are useful to measure real-time hepatic metabolic activity. Low MEGX values reflect the clinical condition of the patient, and the importance of entirely assessing the patient, not just noting the test result, is paramount. This review has considered the role of the MEGX test in liver transplantation.
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Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the various metabolic pathways and functions forms the basis for the efficient adaptation of liver metabolism to the different nutritional requirements of the whole organism in different metabolic states. The present review summarizes current knowledge about this heterogeneity, its development and determination, as well as about its significance for the understanding of all aspects of liver function and pathology, especially of intermediary metabolism, biotransformation of drugs and zonal toxicity of hepatotoxins.
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Early functioning of the transplanted liver is of crucial importance to the recipient. This function may be assessed by measuring the disposition of substances that are mainly eliminated via the liver. None of the agents currently used is ideal for this purpose. Measurement of mono-ethyleneglycinexylidide (MEGX) formation from lignocaine is useful and has been widely used in liver transplantation to assess liver graft function. MEGX formation can be affected by the use of drugs that influence liver perfusion or interfere with the CYP450 enzyme system. Indocyanine green clearance is a convenient method but both blood flow and hepatocellular function affect the test results. Tests of caffeine clearance, galactose elimination capacity and antipyrine clearance all require time-consuming, technically cumbersome and expensive serial blood sampling. The aminopyrine breath test is non-invasive, but gastric emptying and the patient's physical state affect results. The potential hazard of exposure to radioactive compounds limits the wide clinical use of both aminopyrine and erythromycin breath tests. Monitoring the rate of recovery from neuromuscular blockade induced by vecuronium and rocuronium can provide valuable information on liver function.
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