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PubMed1997

Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion.

The concept that leukocyte-endothelial cell adhesion (LECA) is a major determinant of the tissue injury elicited by ischemia/reperfusion (I/R) is largely based on studies employing adhesion molecule-specific monoclonal antibodies. The objective of this study was to assess the contribution of LECA to I/R injury using mutant mice (all on a C57B1 background) that are deficient in either intracellular adhesion molecule-1, P-selectin, or CD11/CD18. The accumulation of fluorescently labeled leukocytes and the number of nonperfused sinusoids in livers of control and adhesion molecule-deficient mice were monitored by intravital microscopy for 1 h after release of the occluded (for 15 min) superior mesenteric artery. Autofluorescence of pyridine nucleotide (NADH) was measured as an indicator of mitochondrial O2 consumption and redox status. The number of stationary leukocytes in the liver after gut I/R was significantly elevated compared with baseline values in C57B1 (control) mice. Autofluorescence of NADH was also significantly increased (indicating hypoxia) after I/R in these mice, especially in the pericentral region. Intercellular adhesion molecule-1-, CD11/CD18-, and P-selectin-deficient mice all exhibited a blunted leukosequestration response to I/R and smaller increments in nonperfused sinusoids, relative to C57B1 mice. All adhesion molecule-deficient mice also exhibited an attenuated increment in NADH autofluorescence in the pericentral region, relative to control mice. These results from adhesion molecule-deficient mice provide additional support for the view that LECA is an important determinant of the liver dysfunction induced by gut I/R.

Animals↗
PubMedDate not supplied

[Thyroid function tests in viral chronic hepatitis].

BACKGROUND: One hundred and twenty five patients with virus B or C chronic active hepatitis and postnecrotic cirrhosis and different degrees of liver dysfunction were studied. AIM: 1) To determine a thyroid hormonal profile; 2) to evaluate the prognostic value of these tests in relation to the progression of the disease and mortality; 3) compare these findings with Child-Pugh classification. PATIENTS AND METHODS: The patients were divided in four groups: a) 31 with chronic active hepatitis; b) 41 with postnecrotic cirrhosis Child A; c) 35 with postnecrotic cirrhosis Child B and d) 18 with postnecrotic cirrhosis Child C. The protocol comprised serum measurements of albumin and bilirrubin, estimates of prothrombin time and clinical evaluation of ascites and encephalopathy, measurement of total serum triiodothyronine, thyroxine, thyroid-stimulating hormone, free thyroxine, reverse triiosothyronine, calculated rT3/T3 index (IrT3) and thyrotropin-releasing hormone test. RESULTS: Total serum triiodothyromnine showed the most significant difference among the groups, gradually lower as the disease became more advanced (CAH: 149.2 +/- 42.3 ng/dL; PNC-A: 137.4 +/- 37.2 ng/dL; PNC-B: 88.0 +/- 28.4 ng/dL and PNC-C: 41.8 +/- 21.9 ng/dL). Low levels of T4 (4.5 +/- 2.0 micrograms/dL) and FT4 (0.7 +/- 0.4 ng/dL) and elevated levels of thyroid-stimulating hormone (7.2 +/- 11.5 microIU/mL), reverse triiosothyronine (60.8 +/- 52.1 ng/dL) and calculated rT3/T3 index (2.2 +/- 2.6) were more frequent in patients with postnecrotic cirrhosis Child C. Thyrotropin-releasing hormone test was normal in the majority of the patients. CONCLUSION: The present study shows a positive relationship between the low serum levels of T3 and elevated serum levels of rT3 and IrT3/T3 with the degree of hepatic dysfunction according to the Child-Pugh classification.

Hepatitis B, Chronic↗
PubMed2005

Type 2 diabetes mellitus complicated with smoldering myeloma and non-alcoholic steatohepatitis.

We report a 59-year-old woman with type 2 diabetes mellitus (DM) complicated with smoldering myeloma and non-alcoholic steatohepatitis. A diagnosis of smoldering myeloma was made on the basis of elevation of IgA, M-protein (type:IgA-lambda) and histological findings of bone marrow without bone lesion. As to liver dysfunction, anti-HBV, anti-HCV and a series of auto-immune antibody were negative. She had no alcohol drinking habit and histological findings showed pericellular fibrosis without fatty degeneration, suggesting liver cirrhosis due to non-alcoholic steatohepatitis (NASH). To date, there are no reports of cases with DM, NASH and myeloma. Particular attention may be necessary for these complications.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

[Disorder of liver functions in a schizophrenic patient after long-term risperidone treatment--case report].

We present a 51-year old man with an 18-year history of chronic paranoid schizophrenia. The last four years he was treated only with risperidone at a dose of 3 mg per day. He was admitted to hospital due to a psychotic decompensation. Jaundice and skin pruritus were also observed at admission. Laboratory tests revealed elevated liver enzymes. Cholestatic and viral hepatitis were excluded. Risperidone was changed to other antipsychotic drugs. After 7 weeks of treatment the patient was discharged with significant improvement of his mental condition. The liver function test results returned to normal values except for the slightly increased total bilirubin level. Regular liver monitoring was suggested. In this case liver dysfunction was possibly correlated with long-term risperidone therapy.

Antipsychotic Agents↗
PubMed1987

[Influence of pregnancy on HB virus carriers].

Liver function tests (GOT, GPT) were performed on 269 female HB virus carriers during pregnancy and puerperium with the following results: Pregnancy in HB virus carriers did not result in any deterioration in liver function, but was rather associated with its gradual normalization particularly in symptomatic carriers. At 1 month of puerperium, in contrast, the occurrence or rebound flare-up of hepatitis was frequently observed among the virus carriers, notably with overt liver dysfunction being seen in 43% of those positive for e antigen. Of 28 e antigen-positive carriers in whom a follow-up study was extended to the next pregnancy, 12 whose liver function was normal during puerperium had normal liver function during the next pregnancy and was positive for e antigen. In the other 16 carriers showing deteriorated liver function during puerperium, liver function during the next pregnancy was abnormal in 6 and normal in 10, with seroconversion and negativity for e antigen being observed in 2 and 4, respectively, of these 16. It is inferred that fluctuations in liver function and e antigen during pregnancy and puerperium might be consequent on increased secretion of corticoids during pregnancy.

Carrier State↗
PubMed1995

High-dose paclitaxel with granulocyte colony-stimulating factor in patients with advanced breast cancer refractory to anthracycline therapy: a European Cancer Center trial.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a novel cytostatic agent that has shown interesting antitumor activity in patients with advanced breast cancer. Depending on variable patient characteristics and amount and type of prior therapy, as well as the applied dose and schedule of paclitaxel, response rates have varied from 13% to 62%. However, optimal dose and schedule are still unknown. We studied a high-dose (250 to 300 mg/m2) 3-hour paclitaxel infusion schedule in a poor prognostic group of breast cancer patients who progressed or relapsed while taking anthracyclines. This regimen was given every 3 weeks. Twenty-one of the 36 patients studied had increased liver enzymes and 18 had documented liver metastases. The objective response rate was only 6%, but response rate by disease site indicated that soft tissue lesions responded in 30% of cases. For a better comparison with other reported data a uniform definition of "anthracycline refractory" is needed. Neuropathy, which was found to be dose limiting, and arthralgia/myalgia syndrome were the most frequently occurring toxicities. Both severe myelosuppression (and infections) and severe diarrhea and mucositis were reported more frequently in patients with liver dysfunction. As higher peak levels, increased areas under the concentration time curves, and longer times during which plasma concentrations were above the threshold level of 0.1 mumol/L were found in patients with elevated liver enzymes, a correlation with the observed toxicities is assumed. Further pharmacodynamic studies in such patients receiving a 3-hour infusion seem warranted.

Adult↗
PubMed1997

Hepatocyte growth factor in assessment of acute pancreatitis: comparison with C-reactive protein and interleukin-6.

Serum levels of hepatocyte growth factor (HGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were determined at the time of admission in 38 patients with acute pancreatitis. The clinical utility of HGF for the detection of severe pancreatitis and for predicting prognosis, bacterial infection (infected pancreatic necrosis or sepsis), and organ dysfunction (liver, kidney, and lung) during the clinical course of acute pancreatitis was compared with the clinical utility of CRP and IL-6 by analysis of receiver operator characteristic (ROC) curves. The optimum cutoff levels of HGF for severity, prognosis, infection, hepatic dysfunction, renal dysfunction, and respiratory dysfunction were 0.9, 1.1, 1.0, 1.1, 1.1, and 1.0 ng/ml, respectively. HGF was as useful as CRP and more useful than IL-6 for detection of severe pancreatitis and for predicting hepatic dysfunction. Moreover, HGF was more useful than CRP or IL-6 for predicting prognosis, renal dysfunction, and respiratory dysfunction. However, for predicting infection, CRP was more useful than HGF. These results suggest that serum HGF levels on admission may be a useful new clinical parameter for determining the prognosis of acute pancreatitis and that HGF may be closely related to the organ dysfunction of acute pancreatitis.

Acute Disease↗
PubMedDate not supplied

Acute fatty liver of pregnancy: a clinicopathologic study of 35 cases.

Acute fatty liver of pregnancy is a disease of the third trimester which is generally considered to be rare and to have a grave prognosis. This study found an optimistic outlook for patients with acute fatty liver of pregnancy due to early termination of the pregnancy as well as the recognition of milder cases. In prospectively followed women, a maternal mortality of 8% and a fetal mortality of 14% were observed. The disorder also appears to be more common than previously suspected and should be considered in all women with liver dysfunction in late pregnancy, even if they are anicteric. Histologically, the characteristic fine droplet steatosis usually produces distinct vacuolization in sections stained with hematoxylin-eosin. However, early in the course of the illness, liver cells have a ballooned appearance and the presence of lipid is masked. When accompanied by a significant necroinflammatory reaction, this stage may be difficult to distinguish from acute viral hepatitis. Whenever acute fatty liver of pregnancy is suspected, a small piece of the biopsy should be reserved for special stains to confirm the presence of lipid in frozen sections. Significant loss of hepatic parenchyma is a regular accompaniment of acute fatty liver of pregnancy and is due to hepatocytolysis, acidophilic degeneration and liver cell atrophy. Extramedullary hematopoiesis and giant mitochondria are often present; the latter change is probably an adaptive or degenerative response to an altered metabolic environment. Despite the frequent presence of signs and symptoms of toxemia in patients with acute fatty liver of pregnancy, no histologic overlap was observed, suggesting that they represent distinct etiologic entities.

Adipose Tissue↗
PubMed2000

A bleeding tendency as the first symptom of a choledochal cyst.

We report an 8-month-old male presenting with gingival hemorrhages and nasal bleeding as the first symptom of a choledochal cyst (CC). On physical examination, there was a large cystic mass in the right upper abdominal quadrant. Laboratory studies on admission revealed moderate liver dysfunction and a bleeding tendency due to vitamin K deficiency. After administration of 5 mg vitamin K the bleeding tendency disappeared. At laparotomy, a large CC 5 cm in diameter was found and the liver showed moderate cholestasis. The sudden onset of a bleeding tendency in infants with congenital liver or biliary-tract disease may suggest not only biliary atresia, but also CC.

Choledochal Cyst↗
PubMed2006

Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases.

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Adolescent↗
PubMed1989

Resting energy expenditure is increased in infants and children with extrahepatic biliary atresia.

To determine if liver dysfunction in children affects energy and macronutrient homeostasis, we performed 13 metabolic studies in 11 patients (age, 17.8 +/- 5.9 months [mean +/- SEM]) with extrahepatic biliary atresia (EHBA). Nutritional balance, indirect calorimetry, anthropometry, and biochemical liver function tests were utilised. Sixty-four percent of the energy losses were in the form of stool fat. Energy expenditure (68 kcal/kg/d) was 29% higher than normal (P less than 0.0025). Only one third of the metabolisable energy intake (37 kcal/kg/d) was stored in the body for new tissue synthesis. In spite of the bountiful protein intake for age, the increased protein oxidation (2g/kg/d) resulted in a virtually zero mean nitrogen balance. In addition, four patients oxidised endogenous protein as well. The respiratory quotient was 0.96, and did not change significantly between pre- and post-meal measurements, suggesting a predominant utilisation of carbohydrate for energy metabolism. Net lipid oxidation was severely diminished. We found that the higher the serum aspartate aminotransferase level (previously named SGOT), the lower the net fat oxidation, and the higher the conversion of glucose to fat. These data suggest that markedly increased energy expenditure contributes to the malnutrition of patients with EHBA. We characterised for the first time how severe liver disease in infants and children affects carbohydrate, fat, and protein metabolism, thus inducing protein-energy malnutrition.

Basal Metabolism↗
PubMed1998

Terbinafine hepatotoxicity: case report and review of the literature.

We report a patient who developed significant liver dysfunction following therapy with terbinafine. At the end of a 3 1/2-wk course of terbinafine, he developed progressive jaundice and pruritus. His serum bilirubin peaked at 30.9 mg/dl 3 wk after discontinuing terbinafine. A liver biopsy revealed mild to moderate mixed cellular infiltrate in the portal tracts, and hepatocellular and canicular cholestasis. His liver tests normalized 100 days after stopping terbinafine.

Adult↗
PubMed1996

Serum levels of endothelial injury markers creatine kinase-BB and soluble thrombomodulin during human liver transplantation.

Endothelial damage within the sinusoids of the liver probably plays a key role in primary liver dysfunction following transplantation. The aim of this work was to study the serum levels of two potential markers of endothelial damage, creatine kinase-BB and soluble thrombomodulin, during human graft revascularization. Thirteen human liver grafts were preserved in UW solution (mean time: 13.8 h). Creatine kinase-BB and transaminase activities and soluble thrombomodulin levels were measured: 1) in effluent and 2) in serum samples sequentially collected before revascularization, then during the first 120 min of revascularization and first post-operative week. No correlation was observed between serum values (peak) and effluent values. In serum, pre-operative creatine kinase-BB activities were correlated with soluble thrombomodulin levels (p = 0.01). Both increased significantly during the first minutes of the revascularization, then decreased markedly. In contrast, AST activity was maximal at day 1. This detectable and early release of creatine kinase-BB and soluble thrombomodulin in blood is in keeping with the early occurence of endothelial damage. Together with previous data, these findings suggest that serum determination of these two markers may be a useful tool in the assessment of endothelial injury in liver transplantation.

Alanine Transaminase↗
PubMed2003

A case of manganese induced parkinsonism in hereditary haemorrhagic telangiectasia.

A 44 year old right handed woman complained of difficulty in moving. She and her relatives had skin telangiectasia or recurrent epistaxis. On neurological examination, she had a mask-like facies and bradykinesia in both extremities. Laboratory examinations showed iron deficiency anaemia and mild liver dysfunction with raised serum manganese. On T1 weighted cranial magnetic resonance imaging there were hyperintense areas in the globus pallidus bilaterally, suggesting manganese deposition. Abdominal angiography confirmed multiple portal-systemic shunts in the liver, and a needle biopsy of the liver showed diffuse dilatation of the sinusoids with fatty change. Levodopa did not improve the bradykinesia. This appears to be a case of hereditary haemorrhagic telangiectasia with manganese induced parkinsonism, which may be a new type of neurological disorder in such patients.

Adult↗
PubMed1987

Amsacrine evaluation.

Amsacrine, an antineoplastic agent currently undergoing clinical trials in the U.S., has been shown to be active against adult and pediatric leukemias, Hodgkin's disease, and non-Hodgkin's lymphomas. Amsacrine is highly bound to plasma proteins and is eliminated primarily via hepatic metabolism. Severe hepatic dysfunction will result in a decreased excretion rate of the drug. The primary side effect is a dose-related suppression of bone marrow function. Other reported toxic effects include mucositis, nausea, vomiting, cardiotoxicity, liver dysfunction, and alopecia. Despite these negative effects, amsacrine appears to have a role in the combination therapy of acute leukemias.

Adult↗
PubMedDate not supplied

Liver function tests in patients of pulmonary tuberculosis using four different drug regimens.

BACKGROUND: Chemotherapy is the basic approach to clinical tuberculosis control. Antituberculous therapy causes derangement of hepatic functions revealed by disturbed liver function tests. The incidence of side effects may vary depending upon a number of factors. The primary purpose of this study was to determine the relative and absolute hepatotoxicity of different antituberculous drug regimens in Pakistani population where majority of the tuberculous patients belong to poor socioeconomic status. METHODS: One hundred patients between 30 to 70 years of age with newly diagnosed pulmonary tuberculosis were selected and divided into four groups on the basis of different drug regimens. Blood and urine tests of these patients were made. Liver function tests were performed before therapy and then after one, two, three, six and nine months of treatment. RESULTS & CONCLUSIONS: Antituberculous therapy causes derangement of hepatic function to a variable extent in patients of four different antituberculous drug regimens under study. Drug combination of Streptomycin, Isoniazid and Myambutol seem to be best tolerated of all the four regimens. Monitoring of the liver function in patients on antituberculous therapy indicated that liver dysfunction most frequently occurs during first three months of therapy. There is a tendency for enzyme values to return to normal inspite of continuous treatment. The mechanism underlying this adaptation to injury to the liver is unknown. Biochemical tests in the patients presenting with jaundice yielded the pattern of acute hepatocellular necrosis with high transaminases and moderately elevated Alkaline Phosphatase. None of the patients had hepatitis associated antigen in their serum.

Adult↗
PubMedDate not supplied

Microwave coagulation therapy for unresectable hepatocellular carcinoma.

BACKGROUND/AIMS: Surgical resection is not always feasible for patients with hepatocellular carcinoma. We used microwave coagulation therapy (MCT) as an alternative to resection and evaluated its efficacy. METHODOLOGY: Twenty-four patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy by laparotomy (n=18), laparoscopy (n=4), or thoracoscopy (n=2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 11 patients, 2 nodules were treated in 7, 3 nodules were treated in 3, 6 nodules were treated in 1, and 7 nodules were treated in 2. Tumor size ranged from 10 to 50 mm. Liver function was analyzed at the time of initial MCT and at treatment for recurrence. Patient outcomes were studied. RESULTS: Two patients died postoperatively after initial MCT. Other patients showed rapid recovery without hepatic dysfunction. Liver function just before MCT was equivalent to that measured just before treatment for recurrence. One patient developed local recurrence at the margin of the treated tumor. Recurrent nodules in different segments were detected in 15 patients. Transcatheter arterial embolization was performed in 13 recurrences, percutaneous ethanol injection therapy was performed in 1 recurrence, and MCT was performed in 1 recurrence. The 3-year cancer-free survival rate was 9.9%, and the 3-year cumulative survival rate was 83.9%. CONCLUSIONS: Because MCT is indicated for hepatocellular carcinoma patients with advanced liver cirrhosis, intrahepatic recurrences are frequent. Since, liver function is preserved after MCT, however, locoregional therapy can be selected when intrahepatic recurrence is detected, thus improving patient survival rate.

Adult↗
PubMed1991

Tetracycline-induced pancreatitis.

Tetracycline has long been implicated as a causative agent in acute pancreatitis. Early reports of acute pancreatitis after tetracycline administration were associated with liver dysfunction attributed to the drug's ability to induce fatty degeneration of this organ. At present, few data are available to suggest that tetracycline-induced pancreatitis may occur in the absence of overt liver failure. We report here, the third and fourth cases of acute pancreatitis after the administration of oral tetracycline in patients without evidence of liver abnormalities. A review of the relevant literature is presented.

Acute Disease↗