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PubMedDate not supplied

Serum C3 complement concentrations correlate with liver function in patients with liver cirrhosis.

BACKGROUND/AIMS: The aim of this study was to investigate whether C3 and C4 serum complement concentrations have prognostic relevance for patients with liver cirrhosis. METHODOLOGY: Serum complement concentrations of C3 and C4 were measured in 69 patients with liver cirrhosis and correlated with the Child-Pugh score. RESULTS: C3 concentrations were 1.06+/-0.21 g/L in patients with Child-Pugh A liver cirrhosis and significantly lower in Child-Pugh B (0.78+/-0.24 g/L) and even lower Child-Pugh C (0.49+/-0.14 g/L) (p=0.006 B vs. A, p<0.001 C vs. B). Patients with consecutive hepatorenal syndrome (HRS) had the lowest C3 concentrations (0.44+/-0.05 g/L (Child-Pugh C +HRS) vs. 0.54+/-0.06g/dL (Child-Pugh C -HRS); p<0.05). C4 concentrations were 0.21+/-0.08 in Child-Pugh A and significantly lower in Child-Pugh B (0.11+/-0.04) and Child-Pugh C (0.09+/-0.04) patients (p<0.001). There was a negative correlation between C3 (r = -0.81, p<0.001) and C4 (r = -0.51, p<0.05) concentrations and the Child-Pugh score. CONCLUSIONS: Serum complement concentrations of C3 and C4 correlate negatively with the Child-Pugh score in patients with liver cirrhosis. C3 concentrations are lower in those Child-Pugh C cirrhosis patients with consecutive development of HRS.

Bacterial Infections↗
PubMed2025

Alcohol-induced KDM5B activation in hepatocytes drives pathogenic cell-cell communication, leading to loss of liver function.

BACKGROUND: Alcohol-associated liver disease (ALD) is a major cause of alcohol-associated mortality. Previously, we identified KDM5B as a sex-specific mediator of ALD development; however, the mechanism behind KDM5B-induced pathological changes is not established. METHODS: Kdm5b flox/flox female mice were fed a western diet and 20% alcohol in the drinking water for 8-16 weeks (WDA). To induce KO, mice received 2&#xd7;1011 genome copies of AAV8-CMV-Cre, AAV8-TBG-Cre, or AAV8-control. To test the role of myeloid C/EBP&#x3b2;, Cebpbfl/fl, or Cebpbfl/fl Lyz2-Cre mice were fed WDA for 16 weeks. RESULTS: We found that Kdm5b KO prevented alcohol-induced liver fibrosis and liver inflammation in female mice. These changes were in part mediated by hepatocyte-to-non-parenchymal cell communication changes. KDM5B in hepatocytes promoted pro-inflammatory and pro-fibrotic changes in liver macrophages, endothelial cells, and stellate cells. Moreover, KDM5B promoted alcohol-induced early increase in EpCAM-positive liver progenitors and loss of liver function at later time points of alcohol feeding. We found that loss of liver function was dependent on a hepatocyte-to-macrophage communication feedback loop. KDM5B in hepatocytes inhibited macrophage C/EBP&#x3b2; expression, which in turn resulted in loss of the mature KCs phenotype and prevented the ability of KCs to support hepatocyte differentiation, ultimately leading to loss of liver synthetic function. CONCLUSIONS: KDM5B activation in hepatocytes drives pathogenic cell-cell communication, leading to alcohol-induced loss of liver function in ALD.

Animals↗
PubMed1980

Aminopyrine N-demethylation: a prognostic test of liver function in patients with alcoholic liver disease.

To determine whether results of the aminopyrine breath test, an indirect measurement of functional hepatic microsomal mass, can be correlated with mortality and changes in clinical status and liver function, 51 hospitalized patients who had alcoholic hepatitis were studied prospectively for 3 wk. The aminopyrine breath test was performed weekly, and the results were compared with clinical features of liver disease and SGOT, SGPT, bilirubin, albumin, and prothrombin time. Only an aminopyrine breath test of > 1% of administered dose of 14C as 14CO2 correlated with 3-week survival (P = 0.0075). Only an increase of more than 100% in the aminopyrine breath test was associated with clinical improvement (P = 0.0036). For the 21 patients who had histologic confirmation of alcoholic liver disease, the aminopyrine breath test also correlated best with the degree of histologic severity. In this group of patients with alcoholic hepatitis the aminopyrine breath test predicted short-term survival, clinical improvement, and histologic severity more reliably than conventional liver function tests.

Adult↗
PubMed1989

Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases.

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range in healthy young subjects (age, 23-42 years) was 44-61 ml/100 g/min; in patients with grade I + II encephalopathy (mean +/- SEM) it was 32.8 +/- 3.6 ml/100 g/min in acute (n = 4; age, 28 +/- 8 years) and 37.0 +/- 3.3 ml/100 g/min in chronic liver patients (n = 10; age, 51 +/- 2 years). In grade III + IV encephalopathy it was 28.7 +/- 3.8 ml/100 g/min in acute (n = 8; age, 28 +/- 3 years) and 32.9 +/- 3.7 ml/100 g/min in chronic patients (n = 12; age, 49 +/- 3 years). CBF did not correlate with the liver function and was of no prognostic value. The liver function was markedly reduced in all the patients, without any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease.

Adult↗
PubMed1990

Use of quantitative liver function tests--caffeine clearance and galactose elimination capacity--after orthotopic liver transplantation.

To establish the potential value of quantitative tests of liver function following orthotopic liver transplantation (OLT), a total of 100 determinations of caffeine clearance (CafCl) and galactose elimination capacity (GEC) were made in ten OLT recipients early in the post-operative course (days 2, 4, 6, 8 and 12) and later when clinically stable (3-12 months). Values were compared with a reference range in six normal volunteers in whom it was shown that the standard doses of caffeine (125 mg) and galactose (0.5 g per kg body weight) could be given together without interference. In orthotopic liver transplantation recipients initial GEC and CafCl measurements showed no correlation with peri-operative blood loss, donor ischaemia time, initial bile flow or survival. Throughout the early post-operative period, there were wide inter- and intra-individual variations in both CafCl (17-fold range from 0.16 to 2.7 ml.min-1.kg-1) and GEC (2.4-fold range from 5.1 to 12 mg.min-1.kg-1), but the only correlation of test values with standard liver function tests results was between GEC and gamma-glutamyltranspeptidase. However, GEC values fell by 19% during periods of acute rejection and there was an inverse correlation of GEC with white cell count probably related to sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

[Effect of administration of Escherichia coli Nissle (Mutaflor) on intestinal colonisation, endo-toxemia, liver function and minimal hepatic encephalopathy in patients with liver cirrhosis].

The purpose of the study was to verify effects of Escherichia coli Nissle (Mutaflor) on intestinal colonisation, endotoxin levels, hepatic encephalopathy and liver function in patients with liver cirrhosis. The study involved 39 patients (22 taking Mutaflor and 17 taking placebo). Even though the number combination test showed extended reaction time in patients with described minimal hepatic encephalopathy the drop was not significant in the trend evaluation. However, the treated group displayed significant improvement of intestinal colonisation (p < 0.001) and a trend towards significant reduction of endotoxin levels on day 42 (p = 0.07) and improvement of liver function assessed with the Child-Pugh classification on days 42 and 84 (p = 0.06). Probiotic preparations can therefore represent a significant contribution to this group therapy.

Adult↗
PubMed2004

Abnormal liver function tests following bone marrow transplantation: aetiology and role of liver biopsy.

INTRODUCTION: Liver dysfunction is common in bone marrow transplant recipients. Common causes are graft-versus-host disease, drugs, veno-occlusive disease, sepsis and iron overload. We studied the prevalence and aetiology of abnormal liver function tests following bone marrow transplantation and the role of liver biopsy. METHODS: All allogeneic and autologous bone marrow transplantations undertaken in our institution over a 2-year period were studied. Subsequent liver function tests, the use and timing of liver biopsy and the final cause of liver dysfunction were determined in each case. RESULTS: We studied 121 patients (58 allogeneic, 63 autologous). Abnormal liver function tests were found in 52% of bone marrow transplant recipients (72% allogeneic and 33% autologous; P = 0.015). The most common causes of liver dysfunction were graft-versus-host disease, drugs and iron overload in the allogeneic group, and drugs and sepsis in the autologous group. Nineteen patients (16%; 18 allogeneic) underwent liver biopsy. The majority of liver biopsies were carried out in the late post-transplant period to exclude or confirm graft-versus-host disease, although only one case was confirmed. Sixteen of the 19 patients who underwent biopsy had significant hepatic iron overload, but no biopsy revealed evidence of fibrosis or cirrhosis. CONCLUSION: Liver dysfunction following bone marrow transplantation is common and most diagnoses can be ascertained without resorting to liver biopsy. In our series, hepatic iron overload was the most common finding in those who underwent liver biopsy.

Adult↗
PubMed1998

Evaluation of abnormal liver function in pregnancy.

Liver disease in pregnancy may present in a subtle or dramatic fashion. An approach using the pattern of liver function abnormalities, time of gestation, and constellation of symptoms will narrow the diagnostic possibilities. Diagnostic tests, including serology, ultrasonography of the hepatobiliary tree, and liver biopsy, can make a definitive diagnosis.

Biopsy↗
PubMed1994

[Evaluation of clinical usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging].

We studied 11C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection to 11C-MET, the increase in rate of radioactivity of 11C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates.

Carbon Radioisotopes↗
PubMed1996

Prognostic value of the monoethylglycinexylidide liver function test in assessing donor liver suitability.

BACKGROUND: Liver graft assessment prior to transplantation continues to be controversial. Various donor organ parameters must be evaluated to ensure that the transplanted organ will function and that the number of organs discarded will be minimized. Recent attempts to quantify liver function have utilized the metabolism of lidocaine to monoethylglycinexylidide (MEGX), and the MEGX test has been employed to evaluate the functional characteristics of donor livers prior to transplantation, with conflicting results. OBJECTIVE: To ascertain the role of quantitating the metabolic rate of lidocaine in predicting the results of liver transplantation. METHODS: Consecutive liver donors (N = 37) underwent quantitation of the amount of lidocaine converted to MEGX at 15 minutes. The donor patients were divided arbitrarily into efficient and poor lidocaine metabolizers, and the results of liver transplantation were evaluated. RESULTS: Patients who received livers that produced MEGX values of 80 ng/mL or less in 15 minutes had no definable alteration in transplantation outcome compared with patients who received livers that were more efficient lidocaine metabolizers. In a collected series, 46 patients who received livers that produced MEGX values of 80 ng/mL or less had a 1-month graft survival rate of 89% (41/46), while 74 patients who received livers that produced MEGX values greater than 80 ng/mL had a 1-month graft survival rate of 86% (64/74). CONCLUSIONS: The MEGX test had no practical utility in predicting liver graft functional status.

Humans↗
PubMed1980

Liver function tests in surgical infection and malnutrition.

Liver function tests were studied in chronically infected surgical patients, patients who recovered from infection, nonseptic malnourished patients and healthy control subjects. Liver function tests were abnormal in the septic patients but returned to normal values upon recovery from infection despite persistent loss of body weight. Malnourished, nonseptic patients similarly had normal liver function tests. These findings suggest that infection rather than accompanying malnutrition is the major cause of the abnormal liver function tests commonly observed in chronically septic surgical patients. Standard liver function tests may be helpful both in the diagnosis of occult intra-abdominal sepsis and also in indicating the efficacy of its treatment.

Alkaline Phosphatase↗
PubMed1980

Establishment of a fetal rat liver cell line that retains differentiated liver functions.

Fetal rat liver cells were transformed with a temperature-sensitive A mutant (tsA255) of simian virus 40. A CLONAL CELL LINE, RLA255-4, which was temperature sensitive in the maintenance of the transformed phenotype, was isolated. This cell line expressed the transformed phenotype (rapid growth, high cell density, overgrowth of normal cells, and cloning in soft agar) at the permissive temperature (33 degrees C) and the nontransformed phenotype (slower growth, lower saturation density, decreased efficiency of overgrowth of normal cells, and lower cloning efficiency in soft agar) at the restrictive temperature (40 degrees C). The tsA255-transformed cells expressed differentiated liver functions under controllable conditions. At the permissive temperature, they produced low levels of albumin and transferrin, whereas at the restrictive temperature the transformed phenotype was lost and the production of these hepatic proteins was greatly enhanced. RLA255-4 cells contained functional receptors for glucagon, as shown by the stimulation of intracellular cyclic AMP accumulation by glucagon. The response to glucagon was dose dependent (Kact = 5 x 10(-8) M) and could be demonstrated in cells grown at both permissive and restrictive temperatures after 7 days in culture (i.e., at a cell density of approximately 4 x 10(5) cells per cm2 or higher). Addition of cortisol to the culture medium enhanced the glucagon response selectively at the restrictive temperature.

Albumins↗
PubMed2002

Can quantitative tests of liver function discriminate between different etiologies of liver cirrhosis?

Studies comparing quantitative testing of liver function (QTLF) in large numbers of patients with defined etiology of cirrhosis are lacking. In all 316 patients with proven cirrhosis underwent QTLF, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol (SCI), and indocyanine green clearance (ICG). Values were correlated with the Child-Pugh classification (CP) and the etiology of liver cirrhosis. Fifty-five percent of the patients had alcoholic cirrhosis (ALC), 31% cirrhosis due to viral hepatitis (VIC), and 14% primary biliary cirrhosis (PBC). In all three groups there was a decrease of QTLF levels from CP grade A to C, which differed from normal values. QTLF was most compromised in patients with ALC and VIC compared to patients with PBC. In conclusion, QTLF in ALC and VIC patients was more reduced than in patients with PBC. This may be due to saturation of enzymes in ALC and ongoing inflammation in VIC.

Aged↗
PubMedDate not supplied

13C-breath tests in the study of mitochondrial liver function.

Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.

Breath Tests↗
PubMed1995

[Changes of liver function measured by 99mTc-GSA scintigraphy after hepatectomy].

In 14 patients with hepatic tumors, liver volume and liver function indices were studied by 99mTc-GSA liver scintigraphy before and after hepatectomy. The liver volume measured by 99mTc-GSA SPECT was significantly decreased after surgery in all 14 patients (p < 0.001). Postsurgically, 7 patients showed an increase of greater than 10% in the LU15 value, while 3 showed a decrease of 10% in the LU15 value, while 3 showed a decrease of 10%. Two patients showed a decrease of greater than 10% in the HH15 value after surgery. The changes in LU15 after surgery were inversely correlated with those in HH15. The present findings clarified that in several cases of surgically treated hepatic tumors, 99mTc-GSA indices of liver function generally thought to indicate the size of the functioning liver cell mass were distinctly improved after surgery in comparison with those before surgery, despite the postoperative decrease in the liver volume. Furthermore, the results of a 99mTc-GSA SPECT study separately measuring the volume of the unilateral hepatic lobe and its radioactivity uptake, indicated that regeneration of the functioning liver cells often occurred in the entire liver. 99mTc-GSA scintigraphy appears to be a valuable method for evaluating changes in both the liver volume and the liver function indices after hepatectomy.

Aged↗