Serum Liver Enzyme Concentrations Research Articles

Histopathology of Acetaminophen-Induced Liver Changes: Role of Interleukin 1α and Tumor Necrosis Factor α

Administration of 500 mg/kg acetaminophen (APAP) to female B6C3F1 mice resulted in well-documented pathophysiological changes in the liver manifested as increased serum concentration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and serum sorbitol dehydrogenase), centrilobular congestion, and hepatocellular degeneration and necrosis. The role of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha), on the hepatotoxicity of APAP was examined at 4, 8, 12, and 24 hr following APAP administration. Neutralization of TNF-alpha or IL-1 alpha with specific antibodies partially prevented the hepatotoxic effects of APAP at the 4- and 8-hr time points. In addition, prior administration of anti-TNF-alpha antibodies shortened the recovery time following APAP treatment. While IL-1 receptor antagonist (IL-1ra) had only a modest protective effect against APAP-induced liver damage, as determined by serum enzyme release, IL-1ra had no effect on the degree of hepatic congestion or necrosis at any of the time points examined. On the other hand, administration of antibodies against IL-1ra exacerbated APAP-induced liver toxicity. These results suggest that TNF-alpha and IL-1 alpha play an important role in the degree of damage and recovery that the liver undergoes following APAP intoxication.

Elevated serum liver enzyme concentrations during ritodrine therapy.

Elevated serum liver enzyme concentrations during ritodrine therapy.

Response of growing swine to dietary exposure to pure fumonisin B1 during an eight-week period: growth and clinical parameters.

Consumption of corn or corn-based products contaminated with Fusarium moniliforme/fumonisins has been associated with a variety of animal and human diseases and is a major food/feed safety issue. This study focused on the clinical toxicity and performance parameters in growing swing exposed to low to moderate levels of pure fumonisin B1 (FB.) for 8 weeks. Male (castrated) and female pigs were fed diets containing 0,0.1,1.0, and 10 mg FB1/kg diet (ppm). Weight gains and feed consumption were measured weekly. Blood samples were collected throughout the study, and various clinical and hematological parameters were measured. Because fumonisins are potent inhibitors of sphingolipid biosynthesis, sphinganine and sphingosine concentrations were determined in the liver, lung, and kidney. Organ weights and carcass quality were measured at the end of the trial. In general, male pigs were more adversely affected by FB1 in the diet than females. The average daily gain for males decreased by 8% for pigs fed 1.0 ppm and by 11% at 10.0 ppm, when compared to the control (0 ppm). Males fed 0.1 ppm showed an erratic growth pattern during the first 5 weeks of the experiment. Feed consumption for the same animals was somewhat higher than that of the controls during each of the first 4 weeks but thereafter was 6-7% lower each week as compared to controls. Female pigs fed FB1-diets showed a general enhancement of feed consumption until week 4. Among clinical chemistry parameters, cholesterol increased in males for the 1.0 and 10.0 ppm diets as compared to controls after 2 weeks, while the levels in both sexes were elevated for the 1.0 ppm diet only by the end of the experiment. Serum liver enzyme concentrations were altered during week 2 only. Changes were observed in the weight of the pancreas and adrenals for male pigs fed FB1 diets as compared to controls. The free sphinganine to free sphingosine ratio (biomarker of exposure in FB1-consuming animals) increased in all three organs for the 10 ppm diet, regardless of sex. The study indicated that FB1 can cause different effects at each dose level, at concentrations as low as 0.1 ppm (showing erratic growth) followed by a reduced growth and biochemical abnormalities in blood (1.0 ppm) and sphingolipid alterations in tissues (10.0 ppm). Some of these effects occurred below the exposure level that caused alteration in sphingolipid metabolism.

Probable Ticlopidine-Induced Cholestatic Hepatitis

To report a case of probable ticlopidine-induced cholestatic hepatitis. A 76-year-old man with no known history of liver disease developed painless jaundice approximately 3 weeks after starting ticlopidine 250 mg bid. After ticlopidine was discontinued, the jaundice resolved and serum liver enzyme concentrations returned toward normal. A diagnosis of probable ticlopidine-induced cholestatic hepatitis was made. The patient was not rechallenged with ticlopidine. A literature search produced 6 case reports describing 7 patients in whom probable ticlopidine-induced cholestatic hepatitis had been diagnosed. Only 1 of these reports appeared in the North American literature. Jaundice developed within 1 to 3 months of starting ticlopidine at less than or equal to the recommended daily dose. In all cases, jaundice resolved and serum liver enzyme concentrations normalized over a period of months after drug discontinuation. Routine monitoring of serum liver enzyme concentrations is not recommended. However, patients should be instructed to watch for signs and symptoms of liver injury. Should they occur, patients should stop taking the ticlopidine and consult their physician immediately.

Hepatotoxicity of Saccharin

To the Editor: Saccharin is not known to alter liver function1–4. We report on a patient who had elevated serum concentrations of liver enzymes after the oral administration of three different drugs, of which saccharin was the only common constituent. Reexposure to pure saccharin supported its role in the pathogenesis of liver damage in this patient. A 70-year-old woman being evaluated for chronic fatigue was found to have increased levels of serum aspartate aminotransferase (306 U per liter), alanine aminotransferase (247 U per liter), γ-glutamyltransferase (1000 U per liter), and alkaline phosphatase (478 U per liter). The patient . . .

Effects of Acute Administration of Naltrexone on Cardiovascular Function, Body Temperature, Body Weight and Serum Concentrations of Liver Enzymes in Autistic Children

The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opiate receptor antagonist, on auscultated heart rate, systolic blood pressure and axillary body temperature were investigated before and about 1 h postdrug in 5 autistic children (4-12 years of age). In addition, an electrocardiogram was recorded on each child before and about 3 h after placebo or 2.0 mg/kg of naltrexone. Finally, the serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were measured 24 h following placebo or naltrexone administration. Naltrexone had no statistically significant effects on any of these measures in comparison with baseline or placebo levels. Thus, these data provide preliminary evidence for the safety of acute administration of naltrexone in children.

PROSPECTIVE STUDY OF LIVER FUNCTION IN CHILDREN FOLLOWING MULTIPLE HALOTHANE ANAESTHETICS AT SHORT INTERVALS

In the 4 years January 1981 to December 1984, 186 children received 1362 halothane anaesthetics. Twenty-five patients were anaesthetized with halothane at least 10 times in a year. No patient developed postoperative jaundice. Sixty-nine children were exposed to two halothane anaesthetics within 28 days on 149 occasions and serial estimations of serum liver enzyme concentrations were obtained. Minor increases in the concentrations of serum AST and ALT were recorded in 10.6% and 4.7% of patient entries, respectively. Postoperative GGT and SAP concentrations were increased in 2.7% of patient entries. Patients in whom enzyme values were increased before the first anaesthetic were no more likely than other subjects to develop further changes.

Immunization of zebu calves against Fasciola gigantica, using irradiated metacercariae.

The pathogenesis of unirradiated, 3 krad-irradiated and 20 krad-irradiated metacercarial infections was compared in zebu calves studied over a 10-week period. Calves exposed to 1000 unirradiated metacercariae (mc) became hypoalbuminaemic, and showed elevated serum concentrations of liver enzymes, whereas neither of the other groups was significantly affected. At slaughter, a mean of 332 flukes was recovered from the 0 krad group, while only 23% and 12% of this number were recovered from the 3 krad and and 20 krad groups, respectively. All the worms recovered from the 20 krad group were stunted, and found in biliary ductules, but a mean of 13% of the flukes recovered from the 3 krad group were large, and dwelling in main bile-ducts. Liver lesions typical of acute fascioliasis were present in the 0 krad group, but lesions in the other groups, and particularly the 20 krad group, were far less severe. Judged on clinico-pathological criteria, a single vaccination of calves with 1000 3 krad-irradiated mc induced partial resistance to a challenge with 1000 normal mc eight weeks later, but the reduction in worm recovery was not statistically significant. There was less evidence of protection when two vaccinating doses of 3 krad mc were given within four weeks, with challenge at week 8, and a single vaccination was ineffective against a challenge four weeks later. However, when the irradiation dose was increased to 20 krad, a hgh level of resistance (69% worm reduction) was induced by a single vaccination, given eight weeks before challenge, and liver pathology was strikingly reduced in the vaccinated animals.

Abnormal responses to morphine-neostigmine in patients with undefined biliary type pain.

The occurrence of pain and changes in serum concentrations of liver enzymes and amylase were investigated after challenge with intramuscular morphine (0.12 mg/kg) and neostigmine (0.012 mg/kg) in 25 control subjects and 80 patients with undefined biliary type pain, both with and without prior cholecystectomy. Peak enzyme concentrations were reached at four hours after the injection of morphine-neostigmine. When compared with controls, patients who had pain after cholecystectomy and a dilated bile duct and/or spontaneous changes in liver enzymes, had a higher frequency of drug induced pain and a higher frequency of rise (greater than 2 X N) in serum concentrations of aspartate aminotransferase (AST) and amylase; postcholecystectomy patients with pain but without bile duct dilatation, and patients with pain without prior cholecystectomy, had a higher frequency of drug induced pain but did not have a higher frequency of enzyme rise. Increases in liver enzymes after morphine-neostigmine were abolished by endoscopic sphincterotomy. Thirty three patients with a dilated bile duct and/or spontaneous changes in liver enzymes were also studied by endoscopic manometry of the sphincter of Oddi: similar frequencies of enzyme changes were observed in patients with normal manometry as in those with various manometric disorders. Increases in serum concentrations of liver enzymes after morphine-neostigmine may be explained by high biliary pressures resulting from an exaggerated motor response in the sphincter of Oddi.

Serum concentrations of vitamin D metabolites in untreated tuberculosis.

A prospective study of 50 consecutive patients presenting with tuberculosis has shown that patients have on average lower serum concentrations of 25-hydroxycholecalciferol (25-OHD) than healthy matched controls. No difference was shown in serum 1,25-(OH)2D, 24,25-(OH)2D, or parathyroid hormone. Uncorrected serum calcium was lower in the patient group but identical when correction concentrations were made for albumin. Serum liver enzyme concentrations were significantly higher in the patient population. Low serum vitamin D concentrations may be a consequence of disease. The possibility that low serum 25-OHD concentrations may predispose to tuberculosis infection cannot, however, be excluded. Prolonged treatment with isoniazid or rifampicin, both of which have been shown to reduce serum 25-OHD, may increase the risk of vitamin D deficiency and consequent osteomalacia in groups of patients most at risk, such as those of Indian subcontinental ethnic origin.

A clinical evaluation of safflower oil emulsion in total parenteral nutrition.

A new intravenous safflower oil emulsion (Liposyn, Abbott) was administered to 23 patients receiving total parenteral nutrition. In a prospective clinical trial, 500 ml of the 10% emulsion was administered each day for a minimum of 10 days. Plasma fatty acid estimations showed a rise in linoleic acid in 22 patients, and a fall in triene/tetraene ratio ( a guide to the presence of essential fatty acid deficiency), in 17 patients within four days of commencement of the infusion. Administration of Liposyn prevented the development of biochemical evidence of essential fatty acid deficiency. There were no clinical side effects attributable to the emulsion. Elevation of serum triglyceride and liver enzyme concentrations occurred in some patients.

The Neuroleptic Malignant Syndrome

The neuroleptic malignant syndrome (NMS) comprises hyperpyrexia, altered consciousness, muscular rigidity, and autonomic dysfunction. It is a rare idiosyncratic reaction to major tranquilizers, including the phenothiazines, butyrophenones, and thioxanthenes; haloperidol and fluphenazine enanthate or fluphenazine decanoate are the drugs most commonly incriminated. The syndrome occurs after therapeutic rather than toxic doses of neuroleptic drugs and is unrelated to the duration of therapy. The NMS is attributed to a disturbance of dopaminergic systems within the basal ganglia and hypothalamus. Associated laboratory abnormalities include leukocytosis, with elevated serum creatine phosphokinase (CPK) and liver enzyme concentrations. The NMS, which is known to some psychiatrists and neurologists but to few internists, probably is underdiagnosed; therefore, its true incidence is unknown. The NMS should be included in the differential diagnosis of any febrile patient with a history of neuroleptic treatment. Because the mortality of NMS is about 20%, early diagnosis and withdrawal of the neuroleptic drug therapy is crucial. Supportive treatment in a medical intensive care unit may be required.

Adverse effects of antituberculosis drugs.

Antituberculosis chemotherapeutic regimens do not often cause serious toxicity. When reactions do occur, they must be correctly and rapidly managed so that effective treatment is not unnecessarily interrupted or the patient exposed to the risk of acquired resistance. All the drugs can cause hypersensitivity reactions, particularly streptomycin, thiacetazone and paraaminosalicylic acid, but alternative drugs are readily available. However, if it is necessary to desensitise the patient, this can usually be achieved. Transient symptomless increases in serum liver enzyme concentrations are common during the early weeks of antituberculosis treatment, but these are not clinically important and must be distinguished from clinically evident hepatitis which may occur in up to approximately 1 % of patients. When hepatitis occurs, treatment should be interrupted until liver function tests are again normal. Treatment, even with the same drugs, can then usually be resumed uneventfully.

Amino acid incorporation into liver proteins during hemorrhagic shock in the dog.

Liver protein synthesis was studied with an in vitro method during and after 1 h of hemorrhagic shock in the dog. Protein synthesis was significantly decreased already 15 min after induction of hypovolemia and was about 50% of the initial value at the end of the shock period. 2 h following retransfusion, protein synthesis was normalized. Some of the underlying mechanisms leading to decreased protein synthesis in hemorrhagic shock are discussed. Serum concentrations of liver enzymes were unchanged during the shock period indicating that the liver metabolism may be affected without changes in parameters often used to evaluated liver function.

Liver enzyme concentrations as measure of possible infectivity in chronic asymptomatic carriers of hepatitis B.

Fifty-two British-born blood donors who were chronic carriers of hepatitis B surface antigen (HBsAg) were tested for the presence of hepatitis B e antigen (HBeAg) and antibody to HBeAg by an immunoradiometric assay. The presence of HBeAg was closely associated with a slight rise in serum liver enzyme concentrations, a high HBsAg titre, and male sex. We suggest that the finding of persistently raised serum liver enzyme concentrations in an asymptomatic HBsAg carrier might be useful as a likely indicator of HBeAg and high infectivity.