losartan-potassium and Liver-Diseases

Multiple and complex abnormalities of hemostasis are revealed by laboratory tests in such common diseases as cirrhosis and end-stage renal insufficiency. Because these abnormalities are associated with a bleeding tendency, a causal relationship is plausible. Accordingly, an array of transfusional and nontransfusional medications that improve or correct these abnormalities is used to prevent or stop hemorrhage. However, recent data indicate that the use of hemostatic drugs is scarcely justified mechanistically or clinically. In patients with uremia, the bleeding tendency (mainly expressed by gastrointestinal bleeding and hematoma formation at kidney biopsy) is reduced dramatically by the improvement of anemia obtained with the regular use of erythropoietin. In cirrhosis, the most severe and frequent hemorrhagic symptom (acute bleeding from esophageal varices) is not explained by abnormalities in such coagulation screening tests as the prothrombin and partial thromboplastin times, because formation of thrombin the final coagulation enzyme is rebalanced by low naturally occurring anticoagulant factors in plasma that compensate for the concomitant decrease of procoagulants. Rebalance also occurs for hyperfibrinolysis and platelet abnormalities. These findings are consistent with clinical observations that transfusional and nontransfusional hemostatic medications are of little value as adjuvants to control bleeding in advanced liver disease. Particularly in uremia, but also in cirrhosis, thrombosis is becoming a cogent problem.

Topics: Anemia; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Coagulants; Erythropoietin; Fibrosis; Hemorrhage; Hemostasis; Humans; Kidney Diseases; Liver Diseases; Partial Thromboplastin Time; Risk Factors; Uremia

In patients with liver disease, thrombocytopenia is a clinical feature that may represent an obstacle to invasive diagnostic or therapeutic procedures, chemotherapy, and anti-viral treatment. Stimulation of the bone marrow is the most promising therapeutic intervention for thrombocytopenia in patients with chronic liver disease. The description of thrombopoietin and its (de)regulation in patients with chronic liver disease have disclosed new treatment opportunities. Indeed, pharmacologic treatment options for thrombocytopenia can be divided into treatments targeted at the thrombopoietin receptor (synthetic thrombopoietins and thrombopoietin-mimetic agents), and use of cytokines with general thrombopoietic potential. Unfortunately, use of synthetic thrombopoietin was hampered by the development of neutralizing antibodies, and thrombopoietin mimetic agents have not yet entered clinical studies. Interleukin-11 proved to be useful in increasing platelet count in patients with chronic liver disease, although its use is limited by side-effects. Erythropoietin has shown promising results in improving thrombocytopenia in cirrhotic patients. In patients with chronic liver disease, safe and well-tolerated treatments aimed at improving thrombocytopenia are still lacking. Larger studies are needed to evaluate and better characterize the thrombopoietic potential of erythropoietin. Human studies with thrombopoietin-mimetic agents are eagerly awaited in order to assess both effectiveness and safety of these drugs.

Topics: Chronic Disease; Controlled Clinical Trials as Topic; Erythropoietin; Humans; Liver Diseases; Platelet Count; Receptors, Erythropoietin; Recombinant Proteins; Thrombocytopenia; Thrombopoietin

Topics: 2,3-Diphosphoglycerate; Bisphosphoglycerate Mutase; Erythropoiesis; Erythropoietin; Gene Expression Regulation; Hemoglobinopathies; Homeostasis; Humans; Hypoxia; Kidney Diseases; Liver Diseases; Neoplasms; Oxygen; Polycythemia; Polycythemia Vera

The liver plays an important role in the production of haemopoietic hormones. It acts as the primary site of synthesis of erythropoietin (EPO) in the fetal stage, and it is the predominant thrombopoietin (TPO)-producing organ for life. In contrast to that of EPO and other liver proteins, the hepatic synthesis of TPO is influenced little by external signals. Hepatocytes express the TPO gene in a constitutive way, i.e. irrespective of the level of platelets in blood. Megakaryocytes and platelets remove the hormone from blood by means of their high-affinity TPO receptors. Normally, the plasma level of TPO is relatively low ( approximately 10(-12) mol/l). However, in thrombocytopenic states due to marrow failure or bleeding, the concentration of circulating TPO may increase greatly. The simple feedback regulation by TPO and its target cells is efficient in maintaining constant platelet numbers in healthy people. Persisting thrombocytopenia develops only in severe liver or marrow failure. On the other hand, an increase in circulating TPO and interleukin 6 (IL-6) may cause reactive thrombocytosis in inflammatory diseases, including cancer. The indications for recombinant human thrombopoietin (rHuTPO) therapy and its impact on transfusion medicine are still under investigation.

Topics: Animals; Clinical Trials as Topic; Erythropoietin; Hematopoiesis; Hormone Replacement Therapy; Humans; Liver; Liver Diseases; Neoplasms; Recombinant Proteins; Thrombocytopenia; Thrombocytosis; Thrombopoietin

An erythrocytosis describes an increased peripheral blood packed cell volume (PCV) and is deemed to be absolute or apparent depending on whether or not the measured red cell mass (RCM) is above the reference range. This reference range must be related to the individual's height and weight to avoid erroneous interpretations using ml/kg total body weight expressions in obesity. Absolute erythrocytoses are divided into primary, where the erythropoietic compartment is intrinsically abnormal, secondary, where the erythropoietic compartment is normal but is responding to external pathological events leading to an increased erythropoietin drive, and idiopathic, where neither a primary nor a secondary erythrocytosis can be established. Both primary and secondary erythrocytoses have congenital and acquired forms. The only form of primary acquired erythrocytosis that has been defined is the clonal myeloproliferative disorder, polycythaemia vera (PV). Modified diagnostic markers for PV are proposed. Thrombocytoses can be classified into primary, where megakaryopoiesis is intrinsically abnormal, secondary, where megakaryopoiesis is normal but increased platelet production is a reaction to some other unrelated pathology, and finally idiopathic. This latter new group would be used for patients not satisfying the criteria for primary or secondary thrombocytoses, if these were more precise and rigidly used than currently is the case. While theoretically congenital and acquired forms of primary and secondary thrombocytoses might exist, only one cause of secondary congenital thrombocytosis has been established, and primary congenital thrombocytosis has not yet been precisely defined. Primary (essential) thrombocythaemia (PT) is one of the forms of primary acquired thrombocytoses. The diagnostic criteria of PT traditionally involve the exclusion of secondary thrombocytoses and other myeloproliferative disorders but marrow histology could hold a key positive diagnostic role if objective histological features of PT were agreed.

Topics: Anthropometry; Bone Marrow; Bone Marrow Diseases; Cells, Cultured; Diagnostic Imaging; Diagnostic Tests, Routine; Erythrocyte Volume; Erythroid Precursor Cells; Erythropoietin; Female; Hematocrit; Hemoglobinopathies; Humans; Hypoxia; Kidney Diseases; Liver Diseases; Male; Neoplasms; Polycythemia; Receptors, Erythropoietin; Thrombocytosis

Topics: Adult; Budd-Chiari Syndrome; Carcinoma, Hepatocellular; Erythropoiesis; Erythropoietin; Female; Humans; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Polycythemia

Topics: Animals; Central Nervous System Diseases; Erythropoiesis; Erythropoietin; Female; Genes, Regulator; Genital Diseases, Female; Hemodynamics; Humans; Hypertension; Hypoxia; Kidney; Kidney Diseases; Liver Diseases; Male; Polycythemia; Polycythemia Vera; Rats

To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM), in comparison with conventional steroid administration in a prospective randomized trial.. Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups: (1) A steroid group (STRD, n = 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2) An EPO1 group (n = 10) who received 30,000 U of Epo before the PM and at the end of surgery; and (3) An EPO2 group (n = 8) who received 60,000 U of Epo before the PM. Hemoglobin (Hb), hematocrit (Ht), aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), lactate, interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured before and just after (Day 0) surgery, and on postoperative days 1, 3, 7 and 14.. There were no increases in Hb and Ht in the EPO1 and EPO2 groups. AST was significantly lower in EPO1 than in STRD on Day 0 (P = 0.041), and lower in EPO1 than in STRD and EPO2 on Day 1 (P = 0.018). ALT was significantly lower in EPO1 than in STRD and EPO2 on Day 0 (P = 0.020) and Day 1 (P = 0.004). There were no significant inter-group differences in the levels of LDH and lactate. IL-6 was significantly lower in EPO1 than in STRD and EPO2 on Day 0 (P = 0.0036) and Day 1 (P = 0.0451). TNF-α was significantly lower in EPO1 than in STRD and EPO2 on Day 0 (P = 0.0006) and Day 1 (P < 0.0001). Furthermore, hospitalization was significantly shorter in EPO1 and EPO2 than in STRD.. Epo has greater potential than steroids to ameliorate IR/I after the PM. Epo at a dose of 30,000 U, administered before PM and just after surgery, yields better results.

Topics: Aged; Animals; Digestive System Surgical Procedures; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; L-Lactate Dehydrogenase; Lactic Acid; Length of Stay; Liver Diseases; Male; Middle Aged; Prospective Studies; Reperfusion Injury; Steroids; Tumor Necrosis Factor-alpha

Topics: Algorithms; Epoetin Alfa; Erythropoietin; Hematinics; Hemorrhage; Humans; Intraoperative Complications; Liver Diseases; Pancreatic Diseases; Recombinant Proteins

Preliminary studies suggest preemptive anti-HCV therapy in liver transplant recipients may enhance the rates of viral clearance, but the applicability and tolerability of preemptive therapy has not been evaluated in a contemporary cohort. In this randomized study, the safety and tolerability of preemptive standard (IFN) or pegylated (peg-IFN) interferon alfa-2b (3 MU thrice weekly or 1.5 microg/kg weekly), or IFN/peg-IFN plus ribavirin (600 mg increased to 1.0-1.2 g daily) was initiated 2-6 weeks post-transplantation and continued for a total of 48 weeks. Only 51 (41%) of 124 transplant recipients were eligible for preemptive treatment; eligible patients had lower model for end-stage liver disease (MELD) and Childs-Pugh scores pre-transplantation and were more frequently live donor transplant recipients than ineligible patients. Dose reductions and discontinuations were required in 85% and 37% of patients, respectively, and 27% experienced serious adverse events. Growth factor (GF) use (erythropoietin and GCSF) in the latter half of the study did not significantly affect the frequency of dose reductions. Only 15% of patients were able to achieve full-dose treatment during treatment. End-of-treatment and sustained virological responses were 13.6% and 9.1%, respectively, with most responders in the combination therapy group. We conclude that preemptive antiviral therapy is applicable to only a portion of transplant recipients, with 'sicker' patients less likely to be managed by this approach. Living donor liver transplant recipients were more frequently eligible for treatment than deceased donor recipients. Virological response rates are low, likely related to the poor tolerability of therapy and the lack of achievement of target drug doses. Future studies should focus on alternative dosing schedules with more aggressive use of adjuvant therapies, including GFs.

Topics: Adult; Aged; Antiviral Agents; Biopsy; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Growth Substances; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Interferons; Liver; Liver Diseases; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Polyethylene Glycols; Prednisone; Recombinant Proteins; Ribavirin; Tacrolimus; Time Factors

To investigate the possibility of correcting thrombocytopenia of chronic liver disease, 19 patients (6 male and 13 female) with long-term chronic liver disease and platelet count < or = 85,000/microliters were studied. Either a short-term course (7-20 days) of recombinant human erythropoietin, 4000 U daily SQ (12 patients) or placebo (7 patients) was administered. Treatment was interrupted if the platelets rose to > or = 100,000/microliters or if no significant increase was noted after 14 days. After treatment, platelets increased in the recombinant human erythropoietin group (from a baseline value of 70,000 +/- 11,184 to 101,250 +/- 37,625/microliters), while no difference was noted in the placebo group (70,714 +/- 9928 vs 70,000 +/- 10,231/microliters). The increase in the platelet count in the recombinant human erythropoietin group was significant, both compared to baseline values (paired Student's t-test, t = -3.80, p < 0.005) and to the results of treatment in the placebo group (unpaired Student's t-test, t = 2.71, p < 0.02). Eight out of 12 recombinant human erythropoietin-treated patients (66%) reached > or = 100,000/microliters platelets while four (33%) did not. In comparison to responders, non-responders had a significantly lower baseline platelet count (58,500 +/- 7937 vs 75,750 +/- 7498/microliters, t = -3.69, p = 0.004) and failed more frequently than responders to improve their haematocrit in response to recombinant human erythropoietin (Pearson chi 2 = 4.687, p = 0.03). When treatment was discontinued, the platelet count reverted to baseline in a few weeks. In conclusion, recombinant human erythropoietin treatment transiently corrected mild thrombocytopenia in patients with chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Platelets; Chronic Disease; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Liver Diseases; Male; Middle Aged; Recombinant Proteins; Thrombocytopenia

Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor in phase III development for the treatment of anaemia associated with chronic kidney disease. This study evaluated the effects of moderate hepatic impairment on roxadustat pharmacokinetics, pharmacodynamics and tolerability.. This was an open-label study in which eight subjects with moderate hepatic impairment (liver cirrhosis Child-Pugh score 7-9) and eight subjects with normal hepatic function (matched for body mass index, age and sex) received a single oral 100 mg roxadustat dose under fasted conditions. Blood samples were collected until 144 h post-dose in subjects with moderate hepatic impairment and until 96 h post-dose in subjects with normal hepatic function.. In subjects with moderate hepatic impairment, area under the concentration-time curve (AUC) from the time of drug administration to infinity (AUC∞) and observed maximum concentration (C max) were 23 % higher [geometric least-squares mean ratio (GMR) 123 %; 90 % CI 86.1-175] and 16 % lower (GMR 83.6 %; 90 % CI 67.5-104), respectively, than in subjects with normal hepatic function. Mean terminal half-life (t ½) appeared to be longer (17.7 vs. 12.8 h) in subjects with moderate hepatic impairment, however intersubject variability on apparent total systemic clearance after single oral dosing (CL/F), apparent volume of distribution at equilibrium after oral administration (V z/F) and t ½ was approximately twofold higher. Erythropoietin (EPO) baseline-corrected AUC from administration to the last measurable EPO concentration (AUCE,last) and maximum effect (E max) were 31 % (GMR 68.95 %; 90 % CI 29.29-162.29) and 48 % (GMR 52.29 %; 90 % CI 28.95-94.46) lower, respectively, than in subjects with normal hepatic function. The single oral roxadustat dose was generally well tolerated.. This study demonstrated the effect of moderate hepatic impairment on the pharmacokinetics and pharmacodynamics of roxadustat relative to subjects with normal hepatic function. These differences are not expected to be of clinical significance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Erythropoietin; Female; Glycine; Half-Life; Humans; Hypoxia-Inducible Factor 1; Isoquinolines; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prolyl-Hydroxylase Inhibitors; Young Adult

Some chronic hemodialysis (HD) patients can maintain normal hemoglobin levels without requiring erythropoiesis-stimulating agents (ESAs). However, the prevalence and the factors associated with this condition in Chinese chronic HD patients have not been reported. The aim of this study was to investigate clinical features, iron metabolism, and other characteristics to survey the prevalence rate and the related factors of this condition among Chinese chronic HD patients.. A total of 1,318 chronic HD patients participated in this study. The patients were classified into a non-ESA group (n = 11) and an ESA group (n = 1,307). The r-HuEPO-independent (non-ESA) HD patients were defined as having hemoglobin greater than 12 g/dl for more than 6 months without r-HuEPO injection, blood transfusion, or androgen therapy. Epidemiological and laboratory data were collected. Renal sonography was also performed on each patient to evaluate the formation of renal and liver cysts, and the number and size of the cysts were recorded.. Approximately 0.84 % of all HD patients were found to be r-HuEPO independent. The non-ESA group had a higher proportion of men (79.6 vs. 58.3 %), a longer duration of renal replacement therapy (RRT) (8.6 ± 6.1 vs. 5.1 ± 3.3 years), a higher prevalence of adult polycystic kidney disease (APKD) (46.3 vs. 9.7 %), a higher prevalence of hepatitis C virus (HCV) liver disease (26.2 vs. 3.2 %, P < 0.01), and had older patients (63.3 ± 13.6 vs. 49.6 ± 13.5 years). Endogenous erythropoietin levels in the non-ESA group were significantly higher than those in the ESA group (61.8 ± 27.1 vs. 29.3 ± 11.7 mU/ml). Non-ESA patients had a significantly higher number of renal (38.1 vs. 13.2 %) and hepatic cysts (9.3 vs. 1.9 %), which were also larger in size (2.9 ± 1.6 vs. 1.3 ± 0.3 cm) compared with those of patients in the ESA group. No significant difference in iron metabolism was found between two groups. In the multivariate Cox analysis, the independent predictor factors for the absence of anemia in these HD patients were the number of renal cysts >6 cysts (95 % CI 1.058-1.405; P = 0.00), endogenous erythropoietin levels (95 % CI 1.139-1.361; P = 0.05), HCV+ liver disease (95 % CI 1.129-1.316; P = 0.01), and time on RRT (95 % CI 1.019-1.263; P = 0.05).. To our knowledge, this study is the first to report on r-HuEPO independence among Chinese HD patients. The prevalence among Chinese chronic HD patients is significantly lower than that reported in the literature. Factors contributing to this condition are complex and multiple. The frequency of this condition is higher in men and in older patients with long-term RRT, in patients with HCV+ liver disease, and in APKD patients. This condition is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Topics: Adult; Age Factors; Aged; Anemia; China; Cross-Sectional Studies; Cysts; Erythropoietin; Female; Hematinics; Hemoglobins; Hepatitis C; Humans; Iron; Liver Diseases; Male; Middle Aged; Polycystic Kidney Diseases; Prevalence; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors; Ultrasonography

Ex vivo gene therapy is an interesting alternative to orthotopic liver transplantation (OLT) for treating metabolic liver diseases. In this study, we investigated its efficacy and biosafety in nonhuman primates. Hepatocytes isolated from liver lobectomy were transduced in suspension with a bicistronic liver-specific lentiviral vector and immediately autotransplanted (SLIT) into three cynomolgus monkeys. The vector encoded cynomolgus erythropoietin (EPO) and the conditional suicide gene herpes simplex virus-thymidine kinase (HSV-TK). Survival of transduced hepatocytes and vector dissemination were evaluated by detecting transgene expression and vector DNA. SLIT was safely performed within a day in all three subjects. Serum EPO and hematocrit rapidly increased post-SLIT and their values returned to baseline within about 1 month. Isoforms of EPO detected in monkeys' sera differed from the physiological renal EPO. In liver biopsies at months 8 and 15, we detected EPO protein, vector mRNA and DNA, demonstrating long-term survival and functionality of transplanted lentivirally transduced hepatocytes. Valganciclovir administration resulted in complete ablation of the transduced hepatocytes. We demonstrated the feasibility and biosafety of SLIT, and the long term (>1 year) functionality of lentivirally transduced hepatocytes in nonhuman primates. The HSV-TK/valganciclovir suicide strategy can increase the biosafety of liver gene therapy protocols by safely and completely ablating transduced hepatocytes on demand.

Topics: Animals; Antiviral Agents; Blotting, Western; Cell Line; Cells, Cultured; Erythropoietin; Ganciclovir; Genetic Therapy; Genetic Vectors; HeLa Cells; Hepatocytes; Humans; Lentivirus; Liver Diseases; Macaca fascicularis; Male; Polymerase Chain Reaction; Simplexvirus; Thymidine Kinase; Transduction, Genetic; Valganciclovir; Viral Proteins

The aim of the present study was to evaluate the role of erythropoietin (EPO) in liver and renal injury following hemorrhagic shock (HS) after inhibition of tyrosine kinase activity in rats... Forty-eight Sprague-Dawley rats were assigned to six groups: (I) HS alone; (II) HS followed by retransfusion; (III) EPO and genistein followed by HS; (IV) EPO and genistein followed by HS, followed by retransfusion; (V) HS followed by EPO and genistein; and (VI) HS followed by EPO and genistein, followed by retransfusion. HS was induced for 60 minutes after withdrawal of 30% of the calculated total blood volume of each rat from the left femoral artery. Blood and tissue samples (from the kidney and liver) were obtained 60 minutes after HS in Group I, III, and V; blood and tissue samples were obtained 60 minutes after retransfusion in Group II, IV, and VI. In Group III and IV, EPO was given 60 minutes before HS, and genistein 30 minutes before HS. In Group V and VI, EPO and genistein were given 30 minutes after HS.. Liver and renal injury were significantly attenuated with EPO and genistein administration.. These results suggest that EPO is effective in attenuating liver and renal injury in HS, even with inhibition of tyrosine kinase activity with genistein.

Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Erythropoietin; Genistein; Interleukin-2; Kidney; Kidney Diseases; Liver; Liver Diseases; Male; Protein-Tyrosine Kinases; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha

Iron overload presenting as exacerbation of hepatic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation has not been previously described. We report 6 patients with established hepatic GVHD in whom iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation, 77%) resulting from a lifetime median of 20 units of packed red blood cell transfusions was manifested by worsening of liver function. Liver biopsies performed in 4 patients confirmed severe iron overload and also hepatic GVHD. Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy resulted in normalization of liver function at a median of 7 months and of serum ferritin at a median of 11 months. Immunosuppressive therapy was successfully tapered in all 4 patients who completed the phlebotomy program, and this supported the impression that iron overload, rather than GVHD, was the principal cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76 months) from the transplantation and 25 months (range, 5-36 months) from ferritin normalization, all 4 patients require maintenance phlebotomy. We conclude that iron overload can mimic GVHD exacerbation, thus resulting in unnecessary continuation or intensification of immunosuppressive therapy for GVHD, and that maintenance phlebotomy is necessary after successful iron-reduction therapy.

Topics: Adult; Biopsy; Bone Marrow Transplantation; Combined Modality Therapy; Darbepoetin alfa; Diagnosis, Differential; Disease Progression; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Ferritins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Iron Overload; Liver Diseases; Male; Middle Aged; Pancreatic Diseases; Phlebotomy; Prospective Studies; Recombinant Proteins; Skin Diseases; Transferrin; Transplantation Conditioning; Transplantation, Homologous

Topics: Blood Transfusion; Child, Preschool; Erythropoietin; Female; Graft Survival; Hemodilution; Humans; Infant; Jehovah's Witnesses; Liver Diseases; Liver Transplantation; Living Donors; Male; Postoperative Care; Preoperative Care; Religion and Medicine; Treatment Outcome

Patients receiving maintenance hemodialysis (HD) present with hemostatic abnormalities, which may be aggravated by comorbid conditions, especially liver disease. The factors that influence plasma levels of thrombomodulin (TM), an initiator of the anticoagulant protein C pathway, and those of tissue factor (TF), which triggers the extrinsic coagulation pathway, were assessed. In 63 HD patients, TM and TF levels were higher than those in healthy controls. In bivariate analysis, TF positively correlated with TM, and both were directly associated with the presence of viral hepatitis B or C marker, serum liver enzymes, use of erythropoietin therapy, hemoglobin levels, and duration of HD therapy, and inversely correlated with body mass index. TF was also positively associated with plasma von Willebrand factor (vWF) antigen, and inversely associated with activated partial thromboplastin time. In multivariate analysis, increased vWF, alanine aminotransferase, and use of erythropoietin independently predicted both TF and TM levels. HD patients with vWF and ALT levels lower than middle, and not treated with erythropoietin had normal TF but increased TM concentrations compared with levels in healthy controls. Increased plasma levels of TM and TF in patients on maintenance HD are surrogates of vascular endothelial injury. Liver disease and use of erythropoietin treatment are also important determinants of these markers, and should be considered in further studies.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Case-Control Studies; Clinical Enzyme Tests; Cross-Sectional Studies; Endothelium, Vascular; Erythropoietin; Female; Hepatitis, Viral, Human; Humans; Liver Diseases; Male; Middle Aged; Prevalence; Renal Dialysis; Thrombomodulin; Thromboplastin; von Willebrand Factor

Liver dysfunction is a frequent complication that arises in the period following kidney transplantations, often resulting in death. We reported a case proving hemosiderosis as a cause of prolonged liver dysfunction after cadaveric kidney transplantation.. A 47-year-old man, who had been undergoing hemodialysis, was referred to our hospital on 2 November 1999. On the same day, cadaveric kidney transplantation was performed, and serum creatinine level reached a normal level within 2 weeks after surgery. However, serum transaminase gradually increased in the postoperative period. Serum ALT rose up to 116 IU/L on day 20 after the operation and 215 IU/L on day 30. Microscopic examination by needle biopsy revealed hemosiderosis of the liver. Recombinant human erythropoietin was administered and phlebotomy was performed. Liver function improved as a result.. Early histological diagnosis can be a useful marker in predicting the course of chronic liver disease.

Topics: Cadaver; Chronic Disease; Erythropoietin; Hemosiderosis; Humans; Kidney Transplantation; Liver Diseases; Male; Middle Aged; Recombinant Proteins

Topics: Chronic Disease; Erythropoietin; Humans; Liver Diseases; Recombinant Proteins; Thrombocytopenia

Topics: Erythropoietin; Humans; Liver Diseases; Recombinant Proteins; Thrombocytopenia

Topics: Erythropoietin; Hematocrit; Humans; Liver Cirrhosis; Liver Diseases

We measured serum erythropoietin (EPO) immunoenzymatically in 245 subjects (151 male, 94 female) to investigate the pathophysiology of its liberation in patients with liver disease. Twelve patients had acute hepatitis, 60 mild chronic liver disease (CLD), 50 cirrhosis (CIR), 43 hepatocellular carcinoma (HCC), 16 malignant extrahepatic disease, 32 benign extrahepatic disease (BEN); 32 subjects served as healthy controls. Higher EPO levels were found in all groups of patients as compared with controls (Bonferroni's test, P < 0.01); CIR and HCC had higher values than CLD and BEN (P < 0.01). By multiple regression analysis, EPO correlated with haematocrit, cholinesterase and C-reactive protein (F = 18.63, P < 0.0001). Thus, circulating EPO increases in patients with liver disease, particularly in its more advanced forms. Besides anaemia, both impairment of liver function (possibly via decreased EPO metabolism) and inflammation seem to play contributory roles in elevating serum EPO.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Erythropoietin; Female; Humans; Immunoenzyme Techniques; Liver Diseases; Male; Middle Aged; Radioimmunoassay

Topics: Adult; Aged; Anemia; Colony-Stimulating Factors; Endocrine System Diseases; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Infections; Liver Diseases; Male; Neoplasms; Rheumatic Diseases

Recently, a factor was discovered in the serum of hepatectomized animals which was capable of augmenting the hepatic erythropoietin response to hypoxia when injected into normal rats. This substance was localized in the liver via an in situ perfusion technique and was termed the hepatic erythropoietic factor (HEF). Patients with kidney disease, liver disease, and combined renal and hepatic disease were studied in this report. Detectable HEF levels were found in the plasma of patients with both liver and kidney disease and were highest in anephric patients with various liver diseases. However, HEF levels were negligible in normal humans or in patients manifesting renal disease with no hepatic involvement. The data suggest that HEF-induced hepatic erythropoietin synthesis may occur in humans as well as in animals.

Topics: Adult; Aged; Animals; Blood Proteins; Erythropoietin; Female; Humans; Kidney; Kidney Failure, Chronic; Liver; Liver Cirrhosis; Liver Diseases; Mice; Middle Aged; Rats

Topics: Androgens; Chronic Disease; Endocrine Glands; Erythropoietin; Estrogens; Female; Glucocorticoids; Gonadal Steroid Hormones; Humans; Liver Diseases; Male; Prolactin; Renin-Angiotensin System; Thyroid Hormones; Vitamin D

Topics: ABO Blood-Group System; Adolescent; Adult; Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Cell Count; Cell Differentiation; Cells, Cultured; Child; Erythropoietin; Female; Humans; Liver Diseases; Liver Function Tests; Male; Thymidine; Time Factors

Two mechanisms are felt to be responsible for the production of anemia in patients with chronic diseases. The first is failure to produce adequate amounts of erythropoietin (EP), and the second is failure to deliver iron to the bone marrow in amounts sufficient to support normal erythropoiesis. In order to evaluate these hypotheses we studied urine and serum EP levels and levels of 2,3-diphosphoglycerate in normal subjects, in patients with the anemia of chronic diseases, in patients with chronic liver disease, and in patients with a variety of other anemias. Based on the results, we propose first that insufficient production of EP is one of the major mechanisms responsible for anemia in patients with chronic diseases. Second, insufficient production of EP is, in part, responsible for anemia seen in patients with chronic liver disease. Third, serum and urine EP levels decrease with aging, and this correlates with the fall of hemoglobin levels seen in older normal subjects.

Topics: Aging; Anemia; Chronic Disease; Diphosphoglyceric Acids; Erythropoietin; Humans; Liver Diseases

Topics: Erythropoietin; Female; Hematocrit; Humans; Liver Diseases; Liver Neoplasms; Male; Polycythemia

Topics: Anemia; Animals; Biological Assay; Erythropoietin; Humans; Kidney Diseases; Liver Diseases; Rats

Topics: Adult; Anemia; Animals; Child; Erythropoietin; Fasting; Female; Hemoglobinometry; Humans; Hyperthyroidism; Iron Isotopes; Kidney Diseases; Leukemia; Liver Diseases; Rabbits; Rats; Staphylococcal Infections; Streptococcal Infections

Topics: Epoetin Alfa; Erythropoietin; Gout; Humans; Kidney Diseases; Liver Diseases; Neoplasms; Polycythemia Vera; Thyroid Diseases

Topics: Epoetin Alfa; Erythrocytes; Erythropoietin; Hypoxia; Liver Diseases; Plasma

Topics: Animals; Epoetin Alfa; Erythrocytes; Erythropoietin; Hypoxia; Liver Diseases; Oxygen; Plasma; Protein Binding