Disturbed Liver Function Research Articles

Anästhesiologische und intensivmedizinische Aspekte der schweren Präeklampsie mit HELLP-Syndrom

From 1984 to 1988 22 patients with preeclampsia and HELLP syndrome were treated in our ICU. The HELLP syndrome is defined as preeclampsia complicated by thrombocytopenia, hemolysis and disturbed liver function. 3 patients developed a severe DIC with consumption of hemostatic potential. One patient died in multiorgan failure having a consumption coagulopathy, liver rupture and renal failure. To prevent severe hemostatic complications, it is essential to start therapy of DIC as soon as possible by inhibition of the activated coagulation system. Bleeding caused by blood coagulation disorders can occur spontaneously and during operative treatment. Epidural or spinal anaesthesia should be avoided in patients with HELLP syndrome. Because of severe complications such as respiratory failure, diffuse bleeding caused by DIC and progressive deterioration of the renal and liver function in most of the cases, patients with HELLP syndrome require a close cooperation between obstetrics and anesthesist.

Acute sodium valproate intoxication: Occurrence of renal failure and treatment with haemoperfusion-haemodialysis

In a child who probably received an overdose of sodium valproate, progressive coma, intermittent tonic-clonic seizures and anuria developed. Laboratory investigations revealed coagulopathy, and anaemia and mildly disturbed liver function. Progressive renal insufficiency, probably due to rhabdomyolysis and myoglobulinuria, occurred later. Treatment consisted of supportive measures, combined haemoperfusion and haemodialysis and IV thiopentone. Clinical and biochemical normalisation was observed after 11 days.

Alpha-fetoprotein-lectin binding as a marker of tumour activity or liver damage

To establish whether alpha-fetoprotein (AFP) produced in the early post-treatment phase of a patient with a germ cell tumour of the testis or the ovary originates from the tumour or is due to an underlying disturbance in liver function, the binding of AFP to concanavalin A (Con A) was investigated as a discriminative variable. A two-step assay is described that can distinguish the type of AFP produced at levels as low as 10 ng/ml. A Con A-binding ratio of 12–43% was found in the patients with disseminated germ cell tumours and in patients with AFP-positive gastrointestinal carcinomas. AFP from the liver gives ratios below 10%.

Transient liver function disturbances after the intraperitoneal use of 32% dextran 70 as adhesion prophylaxis in infertility surgery

In 1982 the adhesion study group showed that intraperitoneal administration of 32% dextran 70 in women who underwent infertility surgery, reduced the risk of postoperative adhesions occuring. Owing to the fact that at our department liver function disturbances seem to occur very frequently after the administration of 32% dextran 70, we have conducted a retrospective study to examine this possible side-effect

Aetiology and Pathophysiology of Chronic Liver Disorders

The aetiology of chronic liver disease covers a wide range of congenital or acquired abnormalities of the hepatocellular biochemical network. Although our knowledge has considerably increased in recent years, the aetiology of chronic liver disease often remains obscure. Acquired irreversible disturbances of normal liver function can be mediated by hepatotrophic viruses, chemicals, chronic oxygen depletion, or interference with the immune system. Considerable progress has been made in the detection and characterisation of hepatitis B, C, and D viruses as causative agents of chronic active hepatitis. Alcohol abuse remains the predominant cause of chronic liver disease in the Western world. The targets of autoantibodies used to diagnose autoimmune diseases of the liver and primary biliary cirrhosis continue to be biochemically defined. Their significance for the aetiology of the disease, however, remains to be established. Nonparenchymal cells play an important role in the sequence of events following hepatocellular injury and ultimately leading to liver cirrhosis. They release vasoactive compounds, cytokines, and other important mediators, and participate in the modulation of the extracellular matrix that is characteristic of liver fibrosis and cirrhosis. The biochemical basis of liver cell necrosis remains poorly defined. In spite of recent progress, and the detection of some new pathogenic principles that help in the understanding of the complications of chronic liver disease such as portal hypertension, oesophagogastric variceal bleeding, portosystemic encephalopathy, ascites, and other metabolic disturbances, many questions concerning the aetiology and pathophysiology of chronic liver disease and its complications remain to be answered.

Halothane and Hepatitis

Despite early controversy, it is now recognised that halothane anaesthesia may be followed by abnormalities of liver function. The resulting hepatitis may take 1 of 2 forms: in type I, there is a minor degree of disturbance of liver function shown by increased serum transaminases or glutathione-S-transferase in up to 25 to 30% of patients; subsequent re-exposure to halothane is not necessarily associated with evidence of liver damage. In contrast, type II hepatitis is often associated with massive liver cell necrosis, frequently leading to fulminant hepatic failure. This type of liver damage has clinical, serological and immunological features compatible with an immune-mediated idiosyncratic reaction. The incidence is low (between 1 in 3500 and 1 in 35,000 anaesthetic procedures), but the mechanism of halothane hepatitis remains uncertain: there have been extensive animal models showing that halothane has a direct hepatotoxic potential, although the relevance of this to the human patient is not yet clear. Prevention of halothane hepatitis may be difficult, and the only clear way of reducing the incidence is to avoid re-exposure to halothane in those patients who have had a previous adverse reaction to the drug, demonstrated either by unexplained pyrexia or by jaundice. Halothane should also be avoided in those patients where there is a family history of sensitisation to the drug. In such cases, halothane-free equipment should be used, and exposure to other volatile non-halogenated anaesthetics should be avoided.

肝硬変症に見出だされたＴｎ‐ｐｏｌｙａｇｇｌｕｔｉｎａｔｉｏｎの一例

A case of Tn-polyagglutination was reported. The patient, 60-year-old man, had pancytopenia and chronic liver function disturbances. His blood cells were polyagglutinable due to Tn-activation. The true blood group of the patient was B, but his cells had an acquired A-like specificity. In addition to the reactions of his red cells with various lectins, the nature of Tn antigen was analysed, using SDSPAGE, flow cytometry and Western blotting. Western blot study revealed that monoclonal anti-Tn reacted with α2, αδ, and β sialoglycoproteins.

A case of temporal arteritis with intrahepatic arterial involvement

We report a case of temporal arteritis associated with anicteric cholestasis. Serial sections of a transthoracic needle biopsy of the liver revealed giant-cell arteritis in medium-sized hepatic arteries and cholangitis in adjacent bile ducts. The literature reveals that similar pathologic features have only exceptionally been observed in liver biopsies. These lesions may account for liver function disturbances commonly seen in temporal arteritis or polymyalgia rheumatica.

Phase II Study of Recombinant Interferon Alpha-2A and Vinblastine in Advanced Renal Cell Carcinoma

A total of 66 patients with advanced renal cell cancer received a combination of recombinant interferon alpha-2a (18 times 106 units subcutaneously 3 times weekly) and vinblastine (0.1mg. per kg. intravenously every 3 weeks). Four patients were ineligible and 6 were inevaluable for response but evaluable for toxicity. There were no complete and 9 partial responses among the 56 evaluable patients, for a response rate of 16 per cent. Median duration of response was 26 weeks, with a range of 8 to 50 weeks. Responses were observed predominantly in patients with lung and soft tissue metastases. Patients who had undergone nephrectomy did not show a better response rate than those who had not.Almost all patients had a flu-like syndrome, fatigue and anorexia. Other side effects included leukopenia, nausea, vomiting, liver function disturbances and neurotoxicity. Most of the side effects were World Health Organization grade 1 or 2; no grade 4 toxicity was observed.Antibodies against interferon developed in 6 patients during the course of treatment. However, there was no relationship between the appearance of antibodies and disease progression. The combination of recombinant interferon alpha-2a and vinblastine has modest but definite activity in patients with advanced renal cell carcinoma, although the role of vinblastine is unclear.

Autonomic Neuropathy and Chronic Liver Disease

Autonomic neuropathy has been reported in association with alcoholic cirrhosis but there is no information on its occurrence in non-alcoholic liver disease. We have examined autonomic function in 64 patients with biopsy-proven liver disease (22 with alcoholic liver disease and 42 with non-alcoholic liver disease) together with 29 age-matched controls. Forty-five per cent of patients with alcoholic liver disease and 43 per cent with non-alcoholic liver disease showed evidence of parasympathetic damage; 11 per cent of patients with alcoholic liver disease and 12 per cent with non-alcoholic liver disease had sympathetic damage. Forty-five per cent of patients with alcoholic liver disease and 22 per cent with non-alcoholic liver disease had peripheral neuropathy on clinical examination. Sixty-eight per cent of those with peripheral neuropathy also had autonomic neuropathy. This study confirms that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggests that the neurological defect may be secondary to the disturbed liver function. The implications of these observations with regard to prognosis of chronic liver disease are discussed.

Systemic therapy with fumaric acid derivates: New possibilities in the treatment of psoriasis

For the past two decades fumaric acid (FA) therapy has become an increasingly popular treatment in Western Europe for psoriasis. FA therapy originally was developed by Schweckendiek and subsequently standardized, by Schäfer. Schäfer's fumaric acid compound therapy (FACT) consists of the oral intake of dimethylfumaric acid ester (DMFAE) and several salts of monoethylfurnaric acid ester (MEFAE) in combination with topical fumaric acid therapy (1% to 3% MEFAE in an ointment or FA in bathing oils) and a diet. Schäfer claimed excellent results in a large number of patients. Preliminary studies by German dermatologists, however, revealed contradictory therapeutic results and serious side effects, and FA treatment was soon abandoned by dermatologists. To assess, the value of FA therapy we conducted an open pilot study of 36 patients in which FACT therapy appeared to be rather effective. Thereafter, several controlled studies with MEFAE sodium in two different dosages versus placebo, and DMFAE versus placebo, were done. The results indicated that MEFAE sodium in dosages up to 240 mg daily was ineffective, whereas daily dosages of 720 mg resulted in a significant decrease in scaling and itching but did not affect extension of the eruption, DMFAE, 240 mg daily, produced a significant amelioration and prevented extension. Side effects of FA treatment were nausea, diarrhea, general malaise, and severe stomachache. Mild disturbances of liver and kidney function during treatment were observed with the 720 mg dosage of MEFAE and with the 240 mg dosage of DMFAE. Moreover, a relative lymphopenia with a selective decrease of suppressor T lymphocytes occurred in about 50% of the patients treated with DMFAE. Although oral therapy with FA derivatives has to be considered experimental, it may be a new possibility in the systemic treatment of psoriasis.

Plasminogen Activators and Plasminogen Activator Inhibitors in Liver Deficiencies Caused by Chronic Alcoholism or Infectious Hepatitis

Plasma concentrations of tissue-type plasminogen activator (t-PA), urokinase (u-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 were studied in 53 patients with liver deficiency caused by chronic alcoholism (n = 40), viral hepatitis (n = 10) or malignant disease of the liver (n = 3) and compared to that of a control group (n = 20) of healthy subjects. u-PA and PAI-1 levels were significantly increased in all patients with chronic alcoholism, whereas high t-PA was only observed in combination with disturbed liver function tests or with liver cirrhosis (two and six-fold above control values, respectively). A good correlation was observed between t-PA and gamma glutamyl transferase (r = 0.615; p less than 0.001). In patients with infectious hepatitis or with malignant disease of the liver t-PA was normal whereas u-PA and PAI-1 were increased. PAI-2 levels were close to or below the detection limit (15 ng/ml) in the control group and in most patients. However, in two patients with alcohol induced cirrhosis PAI-2 levels were approximately 45 ng/ml and in one patient with hepatocarcinoma even 66 ng/ml. Thus, in liver disease, marked elevations of t-PA, u-PA and PAI-1 levels may occur, with increased PAI-1 as an early marker of liver defects and t-PA a marker of severe liver defects.

Risk factors for type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913.

This report presents data on antecedents of Type 2 (non-insulin-dependent) diabetes mellitus in a homogeneous sample of randomly selected 54-year-old men from an urban Swedish population with a diabetes incidence of 6.1% during 13.5 years of follow-up. The increased risk leading to diabetes for those in the top quintile compared to the lowest quintile of the distribution of statistically significant risk factors were: body mass index = 21.7, triglycerides = 13.5, waist-to-hip circumference ratio = 9.6, diastolic blood pressure = 6.7, uric acid = 5.8, glutamic pyruvic transaminase = 3.9, bilirubin = 3.2, blood glucose = 2.7, lactate = 2.4 and glutamic oxaloacetic transaminase = 2.0. Those with a positive family history of diabetes had 2.4-fold higher risk for developing diabetes than those without such a history. In a multivariate analysis glutamic pyruvic transaminase, blood glucose, body mass index, bilirubin, systolic blood pressure, uric acid and a family history of diabetes were all significantly associated with the development of diabetes. Our study demonstrates the great importance of adiposity and body fat distribution for the risk of diabetes. A number of established risk factors for coronary heart disease are risk factors for diabetes as well. Disturbed liver function and increased levels of lactate are early risk factors for diabetes - presumably indicators of the presence of impaired glucose tolerance and/or hyperinsulinaemia.

Clinical and endocrine effects of cyproterone acetate in postmenopausal patients with advanced breast cancer

A phase II study with cyproterone acetate (CPA) was done as the primary treatment in female breast cancer patients. Twenty-three patients, mean age 64 years, range 52–75 years, were entered and treated with CPA 400 mg daily. Twenty patients were evaluable and responses were sparse. There was one partial and one complete remission, 17 patients were stable and one patient progressed within 3 months. Side-effects were frequent: five patients complained of nausea, three had severe weight loss, one suffered from depression and seven showed disturbed liver function tests. Six patients had to stop treatment for side-effects, while two other patients were taken off treatment because they developed an acute necrotizing hepatitis. The hepatitis recovered after drug withdrawal in both patients. The serum levels of CPA, cortisol, androstenedione, DHAS, LH, FSH and prolactin were measured during CPA treatment. The levels of cortisol and androstenedione did not change, while LH, FSH and DHAS were suppressed. The DHAS showed an inverse relation to serum CPA concentrations. The prolactin levels rose uniformly. The therapeutic effect of CPA in postmenopausal patients with advanced breast cancer is disappointing, and inferior to that of other progestins. Side-effects are frequent, possibly as a result of the high dosage used in this study. The hormonal changes are different from those of other progestins, which may explain the different efficacies.

Samtidige EKG-forandringer, Ieverpåvirkning og vaegtstigning under behandling med klozapin

Lublin H, Kistrup K. Samtidige EKG-forandringer, leverpavirkning og vaegtstigning under behandling med klozapin.A 32-year-old man simultaneously developed electrocardiographic (ECG) changes, disturbed liver function and weight increase (18 kg) during clozapine treatment. The connection with clozapine treatment was established through reappearance of the reactions to repeated exposure. The ECG changes disappeared soon after treatment withdrawal, and the changes in the liver function normalized slowly during the subsequent months. The pathophysiology and clinical importance of the ECG changes during neuroleptic treatment are still not clear, so any ECG changes have to be evaluated individually to determine the potential clinical impact and to minimize the risk for the patient.Clozapine, ECG changes, Liver function, Weight gain

Euvolemic cirrhotic dogs in sodium balance maintain normal systemic hemodynamics

Dogs with chronic biliary cirrhosis and portal hypertension commonly develop plasma volume expansion, urinary sodium retention, ascites, and perturbed systemic hemodynamics, i.e., a rise in cardiac output and a fall in peripheral vascular resistance. Our laboratory has previously demonstrated that creating a side-side portacaval anastomosis in such animals, and so venting hepatoportal pressure, will prevent sodium retention and ascites formation and will maintain the animals euvolemic. In the present study, in four cirrhotic dogs with such an anastomosis, observations made at 12 weeks postbiliary duct ligation, and in the presence of grossly disturbed liver function and morphology, failed to demonstrate any change from control conditions in arterial blood pressure, cardiac output, or peripheral vascular resistance. We conclude that venting hepatoportal pressure in cirrhotic dogs with markedly disturbed liver function prevents the advent of a hyperdynamic circulation, possibly by preventing volume expansion.

Measles Epidemic in Young Adults

Between February and June 1985, 40 military personnel were hospitalized because of measles. Diagnosis in all patients was entirely clinical, and serologic investigations were noncontributory. A transient disturbance in liver function occurred in 70% of patients, and its extent correlated with duration of fever and disease complications. Spontaneously resolving, measles-specific hypocalcemia, which was not associated with hepatic dysfunction, was noted in about one third of the patients. All these patients were asymptomatic, except one patient who developed tetany. The pathophysiologic basis for the hypocalcemia is still unknown. The disease course in three previously immunized patients was benign and uncomplicated.

Influence of renal and hepatic function on pharmacodynamics and pharmacokinetics of non-depolarizing muscle relaxants.

Liver and kidney function disturbances influence the pharmacodynamic and pharmacokinetic behaviour of drugs. Because of the differences in metabolism and excretion between the various muscle relaxants, liver and kidney disturbances do influence their pharmacodynamics and pharmacokinetics to a different extent. A description of the changes is given for the most frequently used non-depolarizing muscle relaxants. It is related to the practical clinical implications of the difference in the pharmacokinetics.

The relationship between disturbed liver function, iron and markers of hepatitis B virus infection in british children with beta thalassaemia

The relationship between disturbed liver function, iron and markers of hepatitis B virus infection in british children with beta thalassaemia

Ｗｉｎ４０６８０（Ａｍｒｉｎｏｎｅ）の臨床第１相試験 １回静注法

A phase I study of Win 40680 Amrinone, 5-amino-3, 4'-bipyridin-6 (1H)-one, a new non-glycosidic and non-adrenergic cardiotonic agent, by intravenous bolus injection was carried out on 12 healthy Japanese volunteers to examine the drug's safety, pharmacodynamics and pharmacokinetics.Subjective complaints, objective findings, and laboratory data were collected before and after intravenous administration of Win 40680 at doses of 0.25mg/kg, 0.50mg/1.0mg/kg and 2.0 mg/kg.Burning pain at the injection site was noticed at high doses (high concentrations), but eliminated by lowering the concentration. Facial flushing, dizziness, and nausea also appeared in some subjects, but these effects were transient and mild and rapidly disappeared spontaneously.Elevation of systolic blood pressure, reduction of diastolic blood pressure, and increase in heart rate were noted just after bolus injection and each change returned to the baseline in approximately one or two hours. Continuous ECG recording for 12 hours following the bolus injection revealed no arrhythmia. No serious side effects attributable to the drug such as thrombocytopenia or liver function disturbance were observed in hematological, blood biochemical and coagulation examinations or urinalysis except for transient lowering of the level of serum potassium and inhibition of platelet aggregation.It was concluded that Win 40680 (Amrinone) could be administered intravenously quite safely without serious side effects except for influence to serum potassium level and platelet aggregation and would be applicable to the clinical stage.