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Influence of liver dysfunction on volume of putaminal hemorrhage.

We studied the relations of age, sex, hypertension, alcohol consumption, liver dysfunction, and thrombocyte count to the volume of the hematoma in 141 patients with spontaneous putaminal hemorrhage. Hematomas were significantly larger in men, regular alcohol consumers, those with liver dysfunction, and those with low platelet counts. Our findings reflect the fact that almost all of the alcohol consumers were men, most of them had liver disorders, and the volume of hematoma in such patients was relatively large.

Adult↗

[A case of elderly-onset systemic lupus erythematosus (SLE) complicated with severe liver dysfunction and pancytopenia due to myelofibrosis].

A 67-year-old woman was admitted to our hospital with a fever. She had been experiencing arthralgia for about one month. On admission, she had a fever of 38.5 degrees C, was anemic and was experiencing tenderness in the joints of both hands, elbows and feet. Laboratory data revealed proteinuria, urinary cylinders, pancytopenia (WBC 900/mm3, Hb 9.5 g/dl, Plt 7.8 x 10(4)/mm3), liver dysfunction (GOT 414 IU/l, GPT 140 IU/l), and hyper-gamma globulinemia. Antibiotics and granulocyte-colony stimulating factor were administered intravenously. Bone marrow aspiration was unsuccessful, but a bone marrow biopsy revealed bone marrow fibrosis. Immunological examinations were positive for antinuclear antibodies, anti-deoxyribonucleic acid (DNA) antibodies, anti-double stranded anti- DNA antibodies, as well as a decreased level of serum complement and an increased level of serum immune complexes. Tests for viral antigens and antibodies known to cause hepatitis were negative. Based on these findings, a diagnosis of SLE accompanied by liver dysfunction and bone marrow fibrosis was made. Steroid pulse therapy was initiated, but her liver function deteriorated on the first day of steroid therapy, and she died three days later. SLE accompanied by myelofibrosis is extremely rare, and only 17 and cases have been reported to date. Among these reports, the present case is the second oldest subject and the first SLE patient to suffer from both myelofibrosis and severe liver dysfunction.

Aged↗

Doppler study of hepatic vein in cirrhotic patients: correlation with liver dysfunction and hepatic hemodynamics.

AIM: To elucidate the significance of Doppler measurements of hepatic vein in cirrhotic patients and to correlate with liver dysfunction and hepatic hemodynamics. METHODS: One hundred patients with liver cirrhosis and 60 non-cirrhotic controls were studied. Doppler waveforms were obtained from right hepatic vein and flow velocity measured during quiet respiration. Doppler measurements were also obtained from portal trunk, right portal vein and proper hepatic artery. RESULTS: Hepatic vein waveforms were classified into three classical patterns. Flat waveform was uncommon. Mean hepatic vein velocity was significantly higher in cirrhotic patients (12.7 +/- 6.4 vs 5.1 +/- 2.1 and 6.2 +/- 3.2 cm/s; P<0.0001). The poorer the grade of cirrhosis, the higher was the mean velocity. Maximum forward velocity was never greater than 40 cm/s in controls. Degree of ascites was found to be highly correlated with mean velocity. "Very highq group (>=20 cm/s) presented clinically with moderate to massive ascites. Correlations between right portal flow and mean velocity was significant (P<0.0001, r = 0.687). CONCLUSION: Doppler waveforms of hepatic vein, which is independent of liver dysfunction, should be obtained during normal respiration. Mean hepatic vein velocity reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of liver cirrhosis.

Aged↗

Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin.

OBJECTIVE: Coumarin, used in the treatment of chronic venous diseases, is mainly metabolized to non-toxic 7-hydroxy-coumarin by CYP2A6. At least, 3 variant alleles, CYP2A6*2, CYP2A6*3 and CYP2A6*4A, have been shown to encode catalytically defective proteins. Sporadic elevation of liver enzymes has been reported on the chronic administration ofcoumarin. We sought to determine if susceptibility to coumarin-associated liver dysfunction is genetically determined by polymorphism in CYP2A6 and impairment of the 7-hydroxylation ofcoumarin. Additionally, we were interested in the effect of polymorphism on smoking because of the predominant role of CYP2A6 in the metabolism of nicotine. METHODS: The investigation was performed prospectively within a randomized double-blind clinical trial of the coumarin-containing drug SB-LOT (90 mg coumarin + 540 mg troxerutin/d) vs. placebo in 231 German patients with chronic venous insufficiency. Monitoring of the hepatic status involved regular measurements of liver function during the 16-week treatment. Genotyping of CYP2A6 was carried out by means of PCR and confirmed by DNA sequencing analysis. RESULTS: The allelic frequencies of the variant CYP2A6*2 and CYP2A6*3 alleles were 0.023 and 0.014, respectively. There was no significant difference in the incidence of liver dysfunction between heterozygotes with CYP2A6*2, CYP2A6*3 and wild-type homozygotes. CYP2A6 polymorphism had no significant effect on smoking behavior. CONCLUSION: No evidence was obtained that the studied polymorphism in CYP2A6 is a determinant of the coumarin-associated liver dysfunction.

Adult↗

Light chain deposition disease with liver dysfunction.

Light and transmission electron microscopic study as well as immunohistochemical investigation were performed on three cases of light chain deposition disease (LCDD) with severe liver dysfunction. In two cases, the amount of light chain deposits in the liver was moderate and did not correlate with the severity of clinical and biological symptoms. Ultrastructural study demonstrated a collagenization of the Disse's space, with basement membrane-like material in association with light chain deposits. Immunohistochemical investigation showed a marked increase of collagen types I, III, and IV, as well as fibronectin and laminin in perisinusoidal space. This study suggests that collagenization of the Disse's space has a minor role in liver dysfunction. The analogy between kidney and liver lesions in diabetes and in LCDD is stressed, but the mechanism of this abnormal accumulation of matrix proteins remains unknown.

Aged↗

Serum retinyl esters are not associated with biochemical markers of liver dysfunction in adult participants in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994.

BACKGROUND: Serum retinyl ester concentrations are elevated in hypervitaminosis A. It was suggested that retinyl esters >10% of total serum vitamin A indicate potential hypervitaminosis, but this cutoff was derived from small clinical samples that may not be representative of the general population. OBJECTIVE: We sought to examine the distribution of serum retinyl ester concentrations and associations between retinyl ester concentrations and biochemical markers of liver dysfunction in a nationally representative sample. DESIGN: We assessed the associations between serum retinyl ester concentrations and 5 biochemical indexes of liver dysfunction by using multivariate linear and multiple logistic regression techniques and controlling for age, sex, use of supplements containing vitamin A, alcohol consumption, smoking status, and use of exogenous estrogens in 6547 adults aged > or =18 y in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994. RESULTS: Thirty-seven percent of the sample had serum retinyl ester concentrations >10% of total serum vitamin A and 10% of the sample had serum retinyl esters >15% of total vitamin A. We found no associations between serum retinyl ester concentrations and 1) concentrations of any biochemical variable (multiple linear regression) or 2) risk of having biochemical variables above the reference range (multiple logistic regression). We did not find a serum retinyl ester value with statistically significant sensitivity and specificity for predicting increases in biochemical indexes of liver dysfunction. CONCLUSIONS: The prevalence of serum retinyl ester concentrations >10% of the total vitamin A concentration in the NHANES III sample was substantially higher than expected but elevated retinyl ester concentrations were not associated with abnormal liver function.

Adult↗

[Recovery from pancytopenia and liver dysfunction after administration of thiamazole for hyperthyroidism].

A 45-year-old woman was referred to our hospital because of hyperthyroidism complicated by atrial fibrillation and heart failure. Laboratory data revealed pancytopenia, with a white blood cell count of 2,600/microliter, red blood cell count of 330 x 10(4)/microliter, and platelet count of 6.2 x 10(4)/microliter. The patient had normal transaminase levels, but tests for hepaplastin and cholinesterase showed values of 34% and 1.4 U/ml, respectively, indicating liver dysfunction. There was also decreased excretion of indocyanine green. After initiation of treatment with 30 mg thiamazole and 20 mg propranolol daily, the patient's thyroid function normalized and the other abnormal laboratory findings such as pancytopenia and liver dysfunction also disappeared. Pancytopenia is a rare complication of hyperthyroidism. In this case, various laboratory abnormalities were normalized by antithyroid therapy alone, indicating that the hyperthyroidism itself was closely related to the pathogenesis of pancytopenia and liver dysfunction.

Antithyroid Agents↗

Effect of acute experimental liver dysfunction on the pharmacodynamics of heptabarbital in rats.

The present study aimed to investigate whether the pharmacodynamics of a lipophilic barbiturate, heptabarbital, is altered by liver dysfunction. Heptabarbital was slowly infused i.v., to rats with liver necrosis induced by carbon-tetrachloride, until the rats lost their righting reflex. The concentrations of the drug in serum, brain and CSF were determined in both the diseased animals and solvent-treated controls. Although the concentrations of heptabarbital in the CSF, serum and brain were not significantly different between controls and diseased rats, the total heptabarbital dose required to induce sleep was markedly lower in the diseased animals. Accordingly, the pharmacodynamics of heptabarbital is unaffected in experimental liver dysfunction in rats.

Acute Disease↗

The effects of dopamine infusion during operation on the postoperative liver dysfunction.

Dopamine improves renal function and renal blood flow by increasing cardiac output but its effect to ameriolate postoperative liver dysfunction has not yet been defined. Effect of 3-5 microg.kg(-1).min(-1) dopamine was studied in 22 patients who had total gastrectomy (dopamine group), and was compared with 22 patients who underwent the same operation and without dopamine infusion (control group). Liver function was evaluated from serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) values. Although postoperative SGOT and SGPT values in both groups were increased significantly higher than the preoperative values, the increases in SGOT (40 +/- 14 IU) and SGPT (32 +/- 15 IU) values in the dopamine group were significantly less than those in the control group (67 +/- 27 IU, 43 +/- 19 IU) ( P < 0.05, P < 0.01).In conclusion, these results suggested that this observation might be explained by amelioration of the postoperative liver dysfunction by infusion of dopamine. Dopamine infusion at a small dose during upper abdominal surgery is beneficial for liver function.

Journal Article↗

Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion.

Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of sinusoidal perfusion and decrease of erythrocyte flux, indicating the decisive role of microvascular perfusion failure for the manifestation of hepatic tissue damage and liver dysfunction.

Alanine Transaminase↗

Persistent liver dysfunction among workers at a vinyl chloride monomer polymerization plant.

Thirteen workers with persistent abnormalities in one or more liver function tests (LFT) at a vinyl chloride monomer (VCM) polymerization plant were investigated. Twelve workers were found to have VCM-induced liver dysfunction based on circumstantial evidence. They were employed between 1971 and 1982 when the VCM levels ranged from 1 to 21 p.p.m. After 1982 when the environmental VCM levels were controlled to below 1 p.p.m., no cases of VCM-induced liver dysfunction were detected. In most cases, glutamic pyruvic transaminase was the earliest parameter to be raised. The second most common parameter is serum gamma glutamyl transpeptidase. The latent period ranged from 1 to 13 years. An improvement in their LFT results was shown by 83.3 per cent of workers within 6 months to 2 years after removal from further VCM exposure. For workers who returned to VCM work, their LFT became abnormal again. Liver scans showed hepato and/or splenomegaly in most cases. Liver biopsies on 9 workers were reported as 'non-specific fatty changes' of varying degrees. These observations highlight the need for continual vigilance with environmental monitoring and medical surveillance of VCM-exposed workers.

Adult↗

Anthracycline doses in patients with liver dysfunction: do UK oncologists follow current recommendations?

The question of whether UK oncologists follow current anthracycline dose modifications when treating patients with liver dysfunction was addressed through a questionnaire. Oncologists were asked the dose of doxorubicin or epirubicin they would prescribe for a woman with breast cancer and liver metastases who had one of four different patterns of abnormal liver chemistry. In each case, the median dose of anthracycline that would have been prescribed was close to that currently recommended. There was, however, wide variation in the dose that oncologists said they would prescribe, some avoiding an anthracycline altogether, whereas others would give full-dose treatment. Medical oncologists would prescribe a significantly lower dose of anthracycline than clinical oncologists for a patient with the most severely disturbed liver tests. Overall, medical oncologists were also significantly more likely to prescribe epirubicin. These results show the need for new, widely accepted anthracycline dose modifications for patients with liver dysfunction.

Antibiotics, Antineoplastic↗

The influence of liver dysfunction on the pharmacokinetics of carprofen.

The pharmacokinetics of the investigational agent carprofen were examined in 12 patients with liver dysfunction (hepatic cirrhosis) and in six normal volunteers following single 100-mg oral administration of carprofen. In addition, three patients with acute hepatitis received a single 100-mg dose during the acute phase of the disease, and two of these patients received the same dose after they had convalesced. The pharmacokinetic parameters and urinary excretion data did not differ significantly (P greater than 0.05) between patients with hepatic cirrhosis and healthy volunteers. The mean +/- SD area under plasma concentration-time curve and apparent oral plasma clearance values were 57.8 +/- 11.7 micrograms X h/mL and 30.0 +/- 6.3 mL/min, respectively, in patients and 52.4 +/- 11.3 micrograms X h/mL and 33.1 +/- 7.2 mL/min in normals. The respective harmonic mean elimination half-lives were 10.5 and 9.4 hours. The 0-24 hour urinary recovery of intact drug and the glucuronide conjugate were 7.0 +/- 4.9% and 28.9 +/- 11.0%, respectively, in patients compared to 5.5 +/- 7.1% and 20.1 +/- 12.3% in normal subjects. The results of this study showed that liver dysfunction (hepatic cirrhosis) had no effect on the pharmacokinetic profile of carprofen. In the two patients with acute hepatitis who completed the study, the results suggest that the apparent oral clearance of carprofen may increase during the acute phase of the disease.

Adult↗

[Captopril-induced liver dysfunction].

Captopril is widely used for congestive heart failure and arterial hypertension. Its main side effects are cough, neutropenia, and renal injury. Liver dysfunction has rarely been described. We present a 71-year-old man with an acute myocardial infarction who developed high fever and progressive disturbance of liver function tests, hepatocellular and cholestatic, after beginning captopril. When other, more likely causes for his condition were ruled out, captopril was discontinued and the fever and liver dysfunction then quickly resolved. We recommend periodic laboratory follow-up in patients treated with angiotensin-converting enzyme inhibitors.

Aged↗

Liver dysfunction in severe ovarian hyperstimulation syndrome.

We report the case of a 32-year-old woman suffering from severe liver dysfunction in the course of ovarian hyperstimulation syndrome (OHSS). Complications occurred after successful fertilization subsequent to ovarian stimulation with human menopausal gonadotropin followed by ovulation induction with human chorionic gonadotropin. Because of nausea, vomiting, abdominal distention and enlarged ovaries on an ultrasound examination, she was admitted on the diagnosis of OHSS. During the course of hospitalization severe hepatic injury developed. An increase of more than 100-fold in blood aminotransferase activity was observed. Applied treatment resulted in gradual reduction of ovarian size and resolution of ascites, as well as pleural and pericardial effusions. The patient was discharged from hospital after 46 days. Follow-up examinations at the 13th and 32nd weeks of gestation did not reveal any abnormalities. Pregnancy developed without complications and the woman went into spontaneous labor, giving birth to a viable child at 38 weeks' gestation. Taking into account the above case and previously published reports, the issue of liver dysfunction may have a great impact on the understanding both the pathology and the treatment of OHSS.

Adult↗

Rib fractures in chronic alcoholic men: Relationship with feeding habits, social problems, malnutrition, bone alterations, and liver dysfunction.

Rib fractures are common in alcoholics. This high prevalence might be due to ethanol-associated malnutrition, bone disease, liver dysfunction, or the peculiar lifestyle of the alcoholic with frequent trauma and altercations. In this study we try to discern the role of these factors on rib fracture (assessed on a plain thoracic X-ray film) in 81 consecutive alcoholic patients, 25 of them cirrhotics. Serum albumin, prothrombin aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin growth factor 1, 1,25-dihydroxyvitamin D, parathyroid hormone, estradiol, free testosterone, and corticosterone were measured, and the patients also underwent assessment of bone mineral density by a HOLOGIC QDR-2000 bone densitometer (Waltham, MA, USA). Body mass index, triceps skinfold, and brachial perimeter were also determined, and the patients and their families were asked about tobacco consumption, social and familial links, consumption of ethanol by other members of the family, kind of job, and feeding habits. Forty-two male nondrinker sanitary workers of similar age served as controls. Forty of the 81 patients showed rib fractures. There was a statistically significant association between rib fractures and disruption of social and familial links, irregular feeding habits (in bars or pubs, not at home), ethanol consumption by close relatives, and intensity of tobacco consumption, but not between rib fractures and liver function tests, nutritional parameters, or bone mineral density, besides a nearly significant trend (p = .053) with the presence of osteopenia at the femoral neck. Patients with major withdrawal symptoms at admission also presented more frequent rib fractures. We conclude that rib fractures in alcoholics are related to the peculiar lifestyle of these patients rather than to bone alterations, liver dysfunction, or nutritional status.

Absorptiometry, Photon↗

Idiopathic portal hypertension associated with high serum titer of autoantibodies and liver dysfunction.

Idiopathic portal hypertension (IPH) is a condition marked by unexplained portal hypertension. Although a number of immunological abnormalities occur in patients with IPH, liver function is usually normal. We experienced an unusual case of IPH in a 49-year-old woman, who had pronounced splenomegaly. Laboratory data revealed pancytopenia, hypergammaglobulinemia, and liver dysfunction. Antinuclear antibodies were positive, with high titer at 1280 dilutions of sera. LE cell phenomena were also positive. Histological examination of biopsied liver showed only mild changes, but portal venous pressure was markedly elevated, at 38 cm H2O. This case was thus characterized by both a high serum titer of autoantibodies and liver dysfunction.

Autoantibodies↗