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PubMed1982

Effect of chronic alcohol administration on liver morphology and on brush border membrane enzymes after jejunoileal bypass operation in rat.

To determine whether jejunoileal bypass operation and alcohol administration exerted a synergistic effect on the activities of brush border membrane enzymes and on liver morphology, adult rats where submitted either to sham operation or to jejunoileal bypass operation. 2 weeks after operation the rats received a 15% solution of ethanol during a period of 4 weeks, controls received water. In the sham-operated rats, alcohol provoked stimulation of the disaccharidase activities in the proximal jejunum but had no effect on these activities in the ileum. Bypass operation alone induced a significant increase in sucrase activity in the functioning ileum but had no effect on the jejunal disaccharidase activities. Alcohol administered after bypass provoked a further increase in ileal brush border sucrase activity. The increase of the brush border enzyme specific activities in the excluded loop resulted from the important protein loss observed in this segment. Alcohol alone or bypass operation by itself had little effect on liver morphology. In contrast, when associated they induced extensive accumulation of fat droplets in the hepatocytes. Since alcohol is frequently associated with the diet in man, alcohol should be considered as an important contributing factor to intestinal enzyme adaptation and liver dysfunction after jejunoileal bypass operation.

Aminopeptidases↗

PubMed1996

Toxic hepatitis: a rare complication associated with the use of ritodrine during pregnancy.

OBJECTIVES: To evaluate the incidence of toxic hepatitis associated with the use of ritodrine in pregnancy. DESIGN: A prospective study. SETTING: A large teaching hospital in Barcelona, Spain. PATIENTS: One hundred and twenty-three consecutive pregnant women, 101 singleton and 22 multiple pregnancies, receiving intravenous ritodrine with normal transaminase levels prior to the initiation of therapy. MEASUREMENTS: Serum glutamic pyruvic transaminase (SGPT) and glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (PA), direct and total bilirubin. RESULTS: In two (l.9%) of 101 singleton and two (9.1%) of 22 multiple pregnancies, elevation of SGOT and SGPT levels was detected. PA, GGT, and bilirubin were normal in all women studied. Other causes of hepatitis were ruled out, and no other signs of liver impairment were found in these women. Transaminase levels recovered rapidly in all cases after discontinuation of therapy. CONCLUSION: Elevation of liver enzymes is a rare complication of ritodrine. Discontinuation of therapy does not appear to be indicated as long as other signs of liver dysfunction are not present and tocolytic treatment is required.

Adult↗

PubMed2001

Interleukin 18 levels reflect the severity of acute pancreatitis.

The serum interleukin 18 (IL-18) levels were significantly increased in cases of acute pancreatitis, corresponding to the severity of the disease. The IL-18 levels were also significantly correlated with the serum tumor necrosis factor alpha (TNF-alpha) and bilirubin levels. The possible involvement of IL-18 in the development of liver dysfunction in acute pancreatitis is suggested.

Acute Disease↗

PubMed1990

Hepatic granulomas--an experience over the last 8 years.

Twenty cases of hepatic granulomas seen in the Department of Medicine over the period of 8 years from 1981-1988 were reviewed. Prolonged fever and jaundice were the commoner presentations. While the aetiology was varied, patients with tuberculosis and idiopathic causes formed the major groups. There were also 2 rare causes, one due to cytomegalovirus infection and the other a result of allopurinol hypersensitivity. The idiopathic group of cases fared well but those with tuberculosis did badly and 2 out of 6 died. The absence of pulmonary involvement and the high incidence of jaundice and liver dysfunction in the patients with tuberculosis were the other striking features.

Granuloma↗

PubMed2003

Ganciclovir nucleotides accumulate in mitochondria of rat liver cells expressing the herpes simplex virus thymidine kinase gene.

BACKGROUND: Ganciclovir exhibits broad-spectrum activity against DNA viruses such as cytomegaloviruses, herpes simplex viruses, varicella-zoster virus, Epstein-Barr virus and human herpes virus-6. Ganciclovir is widely applied for anti-herpetic treatment, cytomegalovirus prophylaxis after organ transplantation, and, more recently, in experimental gene therapy to eradicate cycling cells that express the herpes simplex virus thymidine kinase gene. Although ganciclovir supposedly acts as a chain terminator, there is compelling evidence demonstrating the presence of ganciclovir, but not of acyclovir, incorporated internally into DNA, leaving the precise mechanism by which ganciclovir inhibits DNA synthesis enigmatic. METHODS: To study the potential involvement of mitochondria in the ganciclovir nucleotide cytotoxicity, we used adenovirus-mediated gene transfer to express herpes simplex virus thymidine kinase in rat liver and administered ganciclovir 2 days post-infection. The integrity and function of mitochondria in the rat liver cells were evaluated by several techniques. In addition, we analyzed the nucleotide pools in cellular extracts and in isolated mitochondria. RESULTS: We show that ganciclovir nucleotides are abundantly present in the mitochondria of rat livers that express the HSVtk gene. Already 48 h after administration, 10-30% of the total mitochondrial nucleotide pool consists of ganciclovir nucleotides. Their presence is correlated with a lower amount of mitochondrial DNA, a reduced mitochondrial-membrane potential, morphological abnormalities, and liver dysfunction. CONCLUSIONS: These data provide evidence for the involvement of mitochondria in the hepatotoxicity of the HStk/ganciclovir combination. This may explain the toxicity of the HSVtk/gancilovir combination in some metabolically active but non-proliferating cells, such as liver cells. This toxicity limits the applicability of this enzyme/prodrug combination.

Adenoviridae↗

PubMed1984

A phase I toxicity study of human rDNA interferon in patients with solid tumours.

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.

Blood↗

PubMed2004

Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.

BACKGROUND: Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage. METHODS: Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide. RESULTS: Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide. CONCLUSION: Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.

Animals↗

PubMed2003

Liver metabolism in CRF.

Alteration in liver function are not typically present in patients with uremic syndrome, but varying degrees of liver dysfunction were observed in animals with experimental uremia and, to a lesser degree, in patients with chronic renal failure. This article summarizes the data obtained during the last 2 decades on protein, carbohydrate, and lipid metabolism by the liver in uremia and molecular aspects of regulation of lipids and protein synthesis. Particular attention is given to the role of cytosolic calcium ([Ca(2+)](i)) regulation and calcium signal transduction in hepatocytes in chronic renal failure. It is proposed that the parathyroid hormone (PTH)-mediated increase in the [Ca(2+)](i) of hepatocytes in chronic renal failure is a major signal for the downregulation of hepatic receptors for PTH-PTHrP, vasopressin and angiotensin II as well as as hepatic lipase. It is possible that the mRNA of other hormone receptors and various proteins of the liver cells are affected similarly by the elevated basal levels of [Ca(2+)](i) in CRF.

Animals↗

PubMed2003

Estimation of fractional liver uptake and blood retention of 99mTc-DTPA-galactosyl human serum albumin: an application of a simple graphical method to dynamic SPECT.

The objective of this study was to investigate clinical utility of a graphical method for estimating liver uptake and blood retention of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA; DTPA is diethylenetriaminepentaacetic acid) using dynamic single photon emission computed tomography (SPECT) data. When considering the kinetics of 99mTc-GSA, if it is assumed that (1) 99mTc-GSA distributes only between blood and liver, and (2) no metabolism of 99mTc-GSA occurs during the observation period, a plot of liver counts versus cardiac blood pool counts should, theoretically, be a straight line. From the slope and y intercept of a regression line, coefficients for converting count based liver and blood pool data to the per cent injected dose (%ID) can be calculated. The applicability of this method was tested on dynamic SPECT data from 30 patients with liver dysfunction. To validate this method, plasma concentrations (%ID/ml plasma) at 6, 15 and 30 min after the injection were estimated by this method and compared with the measured ones. To investigate the clinical significance of the per cent liver uptake, the value obtained by this method was compared with the results of conventional liver function tests, including serum albumin, the hepaplastin test, prothrombin time and indocyanine green clearance. In every data set, a plot of liver counts to cardiac blood pool counts was fitted well by a straight line (P<0.00001). Estimated plasma concentrations by this method showed good correlation with the measured ones at 6, 15 and 30 min after the injection (r=0.748, 0.838, 0.875, respectively; P<0.0001). The liver uptake determined by this method showed good correlation with the results of conventional hepatic function tests (P<0.002). The graphical method could provide an accurate estimate of %ID of 99mTc-GSA in blood without the need for blood sampling. The liver uptake determined by this method could be a simple but useful quantitative indicator of hepatic function.

Adult↗

PubMed1992

[A case of recurrent liver tumor from gastric cancer responding remarkably to hepatic arterial infusion of large doses of mitomycin C and 5-fluorouracil].

A 69-year-old man underwent subtotal gastrectomy for gastric cancer in 1989. He was diagnosed with recurrent liver tumors at 9 months after the operation. Mitomycin C and 5-Fluorouracil were infused repeatedly into hepatic artery, at total doses of 170 mg and 15 g, respectively. Metastatic tumors disappeared in liver by this therapy. There were no side effects such as liver dysfunction, bone marrow suppression and anorexia in spite of the large amount of anti-cancerous agents. This case suggested that hepatic arterial infusion of a large amount of anti-cancerous agents is a good method for liver metastasis from gastric cancer.

Aged↗

PubMed2002

Chronic renal dysfunction late after liver transplantation.

With the increasing success of liver transplantation, more patients are developing late complications such as renal dysfunction. The goal of the current study was to assess the prevalence of renal dysfunction years after liver transplantation and to identify patients at risk for the development of this complication. Of the 527 liver transplantations performed at our institution between April 1990 and October 1998, 353 had pretransplantation and posttransplantation glomerular filtration rate (GFR) determinations by iothalamate clearance. From this entire group, 198 patients had actual 4-year follow-up and 52 had actual 6-year follow-up. In addition, 191 of these patients had intensive follow-up with GFR measurements pretransplantation and at 1 and 3 years posttransplantation (complete follow-up group). All patients received either tacrolimus- or cyclosporine-based immunosuppression. The overall mean GFR levels in both of these groups was acceptable and was not different in cyclosporine- versus tacrolimus-based immunosuppressive regimens. Renal dysfunction was progressive, with 27.5% of patients in the intensive group having a GFR < 40 mL/min/body surface area 5 years after transplantation. GFR pretransplantation did not correlate well with late renal function; however, GFR at 1 year identified patients with subsequent renal dysfunction. The cumulative incidence of renal failure for the entire group was 6.25% at 7 years and 10% at 10 years. Renal dysfunction is a major late complication after liver transplantation. The GFR at 1 year correlates best with late renal function. Patients with a low GFR at 1 year (< 40 mL/min/BSA) are a high-risk group that might benefit from early therapeutic interventions aimed at preventing subsequent renal failure.

Chronic Disease↗

PubMed1983

Normal liver function. A basis for understanding hepatic disease.

The physiology of the liver involves metabolism, excretion, and body defense. Within the context of metabolism, the liver is the site of a multitude of biochemical reactions essential to the human organism; included are synthesis, degradation, interconversion, storage, and biotransformation. A working knowledge of the relationship between structure and function and of hepatic processes under normal conditions is essential for understanding the derangements observed in clinical diseases affecting the liver. Our overview of hepatic physiology highlights some of these facets of normal hepatic anatomy and function of special relevance to the physician confronting liver dysfunction and its varied clinical consequences.

Amino Acids↗

PubMed2006

Acute liver failure induced by green tea extracts: case report and review of the literature.

In industrialized countries, over-the-counter dietary supplements have become popular in preventing and treating an expanding list of medical conditions. Although most commercially available supplements have not been rigorously tested for safety and efficacy, they have found an enlarging market because they are considered natural. Oral supplements containing green tea extract have been marketed as effective for weight loss and to prevent and cure some solid tumors. Although there is little scientific evidence of the effectiveness of green tea extracts to improve the quality of health of regular consumers, there is an increasing body of medical literature supporting the hypothesis that they can cause serious side effects. Our experience adds to previous reports of acute liver toxicity observed in individuals consuming supplements containing green tea extract. We highlight the importance of obtaining a detailed history of dietary supplement consumption when evaluating a patient presenting with acute liver dysfunction.

Adult↗

PubMedDate not supplied

Radioimmunoassay of urinary 3 beta-hydroxy-5-cholenoyl glycine in hepatobiliary disease.

A radioimmunoassay for 3 beta-hydroxy-5-cholenoyl glycine in human urine has been developed. The antiserum was elicited with the antigen in which the steroid hapten is linked to a bovine serum albumin through the C-19 position. The [125I]-tyrosine derivative of the hapten was used as radioligand. The standard curves were linear ranging from 10 to 320 ng/mL. The cross-reactivities with other bile acids were not detectable and below 0.3% with cholesterol. Sample preparation includes extraction of 3 beta-hydroxy-5-cholenoyl glycine from urine and solvolysis of the sulfates--main form present in urine. Urinary excretion of 3 beta-hydroxy-5-cholenoyl glycine was 0.373 +/- 0.133 mumol/day in healthy adults. Urinary excretion of 3 beta-hydroxy-5-cholenoyl glycine increased in chronic liver dysfunction, hepatoma and obstructive jaundice in this order.

Adult↗

PubMed1987

Multi-component analysis of urine of dogs with liver diseases by high-performance liquid chromatography.

Components of the urine of normal dogs and dogs with liver diseases were analysed by high-performance liquid chromatography (HPLC) using a macroreticular anion-exchange resin with UV detection. The dogs with liver diseases were experimentally prepared by either Eck fistula by portal-caval anastomosis, dimethylnitrosamine-induced liver failure or total hepatectomy by operation. Eighteen chromatographic peaks were numbered and the cross-correlation coefficient of the intensities of every pair of peaks was computed. There were high correlations between several pairs of peaks according to the types and degrees of the hepatic failures, whereas no significant correlation was observed for the peak pairs of normal urine samples. The results showed that HPLC analysis of urine is useful in the diagnosis of the physiological state in liver dysfunction.

Animals↗

PubMed2001

Hepatocellular carcinoma arising in non-alcoholic steatohepatitis.

The incidence and significance of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH) has not been previously evaluated in detail. We recently experienced a case of NASH with multicentric HCC in a female patient. At the age of 58 years, the patient was diagnosed with non-insulin-dependent diabetes mellitus, treated by insulin therapy. The patient did not drink alcohol. She was negative for all serological markers of hepatitis B and C virus infection. Because of liver dysfunction, a needle biopsy was performed at the age of 62 years, and pathological findings, such as fatty change, Mallory's body, nuclear glycogen and pericellular fibrosis, suggested a diagnosis of NASH. Subsequently, four nodules were detected in the liver by imaging. Liver biopsies were performed from each nodule. One nodule was pathologically diagnosed as a pseudolymphoma, while three other nodules were moderately differentiated HCC (10 years after the diagnosis of non-alcoholic steatohepatitis), well-differentiated HCC (11 years later) and dysplastic nodule (11 years later), suggesting multicentric occurrence of HCC. This case suggests that HCC could be a late complication of NASH.

Biopsy, Needle↗

PubMed2001

Higher hematocrit improves liver blood flow and metabolism during cardiopulmonary bypass in piglets.

OBJECTIVES: Hemodilution has been applied conventionally during cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) to counteract the increase in viscosity and deleterious rheological effects caused by hypothermia. However, liver dysfunction after low-flow bypass and DHCA is common, and little is known about the effects of hematocrit (Hct). The purpose of the present study is to evaluate the impact of two hemodilution priming protocols used clinically on liver perfusion and metabolism. MATERIALS AND METHODS: Ten piglets were randomized into 2 groups. One group (n = 5) had a crystalloid prime resulting in an Hct of about 15 % (low hematocrit; group L), the other (n = 5) a total-blood prime (Hct = 25 %; high hematocrit; group H). All animals underwent 70 min cooling at full flow (150 ml/kg/min), 30 min of low flow (50 ml/kg/min) at 15 degrees C followed by 45 min of DHCA and 75 min of rewarming at full flow. Liver blood flow (LBF) was assessed at the beginning of CPB at 34 degrees C, at the end of cooling at 15 degrees C, at the end of low flow, 5 min after the start of warming, and at the end of rewarming at 34 degrees C by injections of radioactive microspheres. Liver function was evaluated at the same time using the MEGX test, which measures the metabolism of lidocaine. RESULTS: LBF was insignificantly reduced during cooling, decreased during low flow (p = 0.001), and increased again after DHCA with the highest flow at the end of rewarming. LBF tended to be lower at all times in group L (p = 0.096). The liver lidocaine metabolic rate did not significantly decrease during cooling and low flow, but was increased at the end of rewarming (p = 0.01); the metabolism was higher in group H (p = 0.025). Multiregression analysis revealed liver blood flow (p = 0.003) and hematocrit (p < 0.001) as independent determinants of the liver lidocaine metabolism; arterial blood pressure and temperature did not have significant influence in this model. CONCLUSION: Hemodilution results in a tendency towards reduced liver blood flow during CPB; much worse is the resulting impaired liver metabolism, independent of reduced blood flow and pressure. Avoidance of low hematocrit during CPB may be a useful adjunct to preserve liver function in patients undergoing cardiac surgery with long duration CPB and DHCA.

Animals↗

PubMed2006

Liver transplantation for liver rupture due to light chain deposition disease: a case report.

Light chain deposition disease (LCDD) is a rare pathologic condition distinct from amyloidosis. Amyloidosis is most often characterized by overproduction of lambda light chains, while kappa chains are overproduced in LCDD. In contrast to amyloid deposits, those of LCDD do not stain with Congo red and have a granular ultrastructure. LCDD primarily affects the kidney; clinically significant liver dysfunction is less common and less severe than renal disease. We describe a case of kappa chain deposition disease in a patient with plasma cell dyscrasia and platelet pool storage defect, which produced massive hepatomegaly and rupture of the liver leading to orthotopic liver transplantation. The liver weighed 6800 g and showed severe atrophy due to massive deposition of light chains. In this case, the deposits were composed of unbranched fibrils, which measured 12 to 20 nm in width, did not possess a hollow core, and were arranged randomly rather than in structured arrays.

Adult↗