losartan-potassium and Hepatitis-C

Anemia is the most common complication of inflammatory bowel disease (IBD). Control and inadequate treatment leads to a worse quality of life and increased morbidity and hospitalization. Blood loss, and to a lesser extent, malabsorption of iron are the main causes of iron deficiency in IBD. There is also a variable component of anemia related to chronic inflammation. The anemia of chronic renal failure has been treated for many years with recombinant human erythropoietin (rHuEPO), which significantly improves quality of life and survival. Subsequently, rHuEPO has been used progressively in other conditions that occur with anemia of chronic processes such as cancer, rheumatoid arthritis or IBD, and anemia associated with the treatment of hepatitis C virus. Erythropoietic agents complete the range of available therapeutic options for treatment of anemia associated with IBD, which begins by treating the basis of the inflammatory disease, along with intravenous iron therapy as first choice. In cases of resistance to treatment with iron, combined therapy with erythropoietic agents aims to achieve near-normal levels of hemoglobin/hematocrit (11-12 g/dL). New formulations of intravenous iron (iron carboxymaltose) and the new generation of erythropoietic agents (darbepoetin and continuous erythropoietin receptor activator) will allow better dosing with the same efficacy and safety.

Topics: Anemia; Erythropoiesis; Erythropoietin; Hematinics; Hepatitis C; Humans; Inflammatory Bowel Diseases; Ribavirin

To review the hematologic adverse effects of hepatitis C virus (HCV) therapy and adjuvant treatment with epoetin alfa and granulocyte colony-stimulating factor (ie, filgrastim).. Medical literature indexed in MEDLINE (1966-January 2007) and EMBASE (1980-January 2007) was searched, and published conference abstracts were reviewed.. Peer-reviewed articles and relevant conference abstracts regarding the use of epoetin alfa and granulocyte colony-stimulating factor were reviewed.. Ribavirin induces a dose-dependent hemolytic anemia. Studies using epoetin alfa 40 000 units subcutaneously once weekly have demonstrated efficacy in maintaining hemoglobin, ribavirin dose, and quality of life scores, but clear benefit shown with sustained virologic response (SVR) is lacking. The hemoglobin threshold for initiation of epoetin alfa used in studies may not adequately reflect values used in clinical practice. Treatment-related neutropenia is caused primarily by interferon or peginterferon. Few studies have investigated the impact of granulocyte or granulocyte-macrophage colony-stimulating factor derivatives on neutropenia. Results of dose maintenance evaluation vary, and studies reporting data on SVR showed no effect from growth factor therapy. The frequency of bacterial infections was not reported.. The role and benefit of hematopoietic growth factors in HCV therapy have not been conclusively determined to date. However, the possibility of a benefit to individual patients seen on an outpatient basis remains, and an individualized treatment approach is recommended.

Topics: Anemia; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hepatitis C; Humans; Interferons; MEDLINE; Neutropenia; Recombinant Proteins; Ribavirin

Recombinant human erythropoietin (rHuEpo) has become the most widely used cytokine in the world. Following the success of its use in patients with end-stage renal disease, the usefulness of rHuEpo to ameliorate other anemias was assessed, including pediatric patients and newborn infants. The treatment or prevention of anemia of prematurity with rHuEpo resulted in a significant reduction in the number of transfusions and donor exposure. A clear definition of which premature babies must receive therapy needs yet to be established. Other indications in neonatal period include hyporegenerative and hemolytic anemias. With the exception of chronic renal failure, in older children the efficacy of rHuEpo has not been evaluated as in adults. While an impressive amount of studies were carried out during the last years in adult patients with cancer-related or HIV-infection-related anemias, allowing to establish clear conclusions on its efficacy, only a few trials with small number of patients have been reported in children. Up to date, results in pediatric patients suggest that rHuEpo therapy is as useful as in adult patients, but prospective, randomized trials including large number of patients are essential to achieve definitive conclusions. Results of studies designed to evaluate the efficacy of rHuEpo for sustaining an adequate dose of ribavirin in patients receiving treatment for hepatitis C are encouraging. The potential for use of the non-hematopoietic effects of rHuEpo in newborn infants is a novel and exciting issue. The role of rHuEpo as a tissue protective factor for central nervous system and intestinal mucosa is under exhaustive investigation.

Topics: Adult; Anemia; Anemia, Neonatal; Child; Child, Preschool; Erythropoietin; Hepatitis C; HIV Infections; Humans; Infant; Infant, Newborn; Infant, Postmature; Neoplasms; Recombinant Proteins; Renal Dialysis; Renal Insufficiency

Today, combination antiviral therapy with pegylated interferon-alpha and ribavirin (RBV) allows many patients infected with hepatitis C virus (HCV) to achieve a sustained virological response, which is equivalent to cure. Data also support the clinical benefit of combination antiviral therapy in patients coinfected with HCV and HIV, and in patients who have received a liver transplant. Antiviral therapy with pegylated interferon-alpha and RBV is, however, associated with a high incidence and significant magnitude of anemia. This anemia may have several mechanisms, including bone marrow suppression and hemolysis. In addition, patients coinfected with HIV may have both pre-existing and RBV-associated anemia. Management of anemia in patients with HCV through RBV dose reduction or treatment discontinuation may compromise the effectiveness of treatment, because studies have demonstrated that treatment adherence or maintenance of antiviral therapy dose is an important predictor of sustained virological response. Anemia associated with combination antiviral therapy in patients with HCV is frequently associated with an inadequate or blunted endogenous erythropoietin response. Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEpo) to manage anemia in these patients, with the objective of maintaining the RBV dose, but clinical standards are lacking. The present article reviews the data relevant to the use of rHuEpo in this patient population and proposes a set of clinical practice standards to assist clinicians in selecting patients for rHuEpo and in implementing rHuEpo therapy effectively.

Topics: Algorithms; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Quality of Life; Recombinant Proteins; Ribavirin

In the United States, about 2.7 million people are chronically infected with the hepatitis C virus, accounting for nearly 1.8% of the population. The current standard of therapy is a combination of pegylated interferon products and ribavirin. A common adverse effect associated with this therapy is anemia, which is frequently referred to as mixed anemia because of the synergistic contribution of the interferons and ribavirin. The effect of ribavirin on the development of anemia is considered greater than that of interferon. The current standard of practice for treating this adverse effect is reduction of the dosages of both drugs, at prespecified hemoglobin levels. However, recent findings underscore the importance of maintaining adequate dosages of interferon and ribavirin, which may be crucial in achieving an early virologic response and a sustained virologic response in treating patients with hepatitis C infection. Treatment with epoetin alfa for this mixed anemia significantly improved hemoglobin levels and quality of life, and enabled adequate dosages of ribavirin to be maintained. Future studies should address several issues: when to start epoetin alfa treatment, the duration of treatment, the drug's optimal dosage, its effects on end-of-treatment and sustained virologic response rates, and a cost analyses.

Topics: Anemia, Hemolytic; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Health Care Costs; Hepatitis C; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin; Risk Factors

Anemia is a significant adverse effect of current hepatitis C treatment and may be a particular problem for HIV-infected patients, in whom there is a high prevalence of disease- or drug-related anemia at baseline. Hepatitis C treatment-induced anemia in HIV-HCV-coinfected patients can lead to ribavirin dose reduction or premature discontinuation of hepatitis C therapy, limiting sustained virologic response rates. Mean decreases in hemoglobin levels during hepatitis C treatment appear to be less in HIV-HCV-coinfected patients than in HCV-monoinfected patients, but any decrease in hemoglobin level may be more of a problem for coinfected patients. Thus, close monitoring of the hemoglobin level and appropriate management of the anemia that may develop in HIV-infected patients during hepatitis C therapy is essential.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Hepatitis C; HIV Infections; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).

Topics: Anemia, Hemolytic; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Recombinant Proteins; Ribavirin

The strategy to prevent hepatitis C virus (HCV) transmission to hemodialysed patients includes the screening of blood donors, the use of erythropoietin and the actual, strict application of Universal Precautions. In particular, articles should not be shared between patients, gloves changed and handwashing performed systematically after caring for a patient. The isolation of anti HCV (+) hemodialysed patients is not warranted. The prevention of HCV transmission to staff members relies mainly on the prevention of accidental needlestick injuries.

Topics: Blood Donors; Erythropoietin; Hepatitis C; Humans; Infection Control; Needlestick Injuries; Occupational Diseases; Renal Dialysis; Universal Precautions

Topics: Anti-Bacterial Agents; Australia; Biotechnology; Cost-Benefit Analysis; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hepatitis C; Humans; Insulin; Pulmonary Surfactants; Recombinant Proteins; Technology, Pharmaceutical; Tissue Plasminogen Activator; Viral Hepatitis Vaccines

Relapse of hepatitis C virus infection after liver transplantation is universal. Standard-of-care (SOC) treatment for relapse offers less satisfactory treatment response than in nontransplanted patients. Tolerance for treatment is suboptimal and withdrawals owing to adverse events induced by treatment frequent. To improve tolerance for SOC, and ribavirin (RBV) in particular, concentration-guided RBV dosing calculated by a formula taking renal function and weight into consideration was utilized. A serum RBV concentration of 10 μm was set as the goal. All patients were given maintenance darbepoetin therapy from 2 weeks prior to initiation of treatment. In total, 21 patients with a mean age of 52 (range 25-64) years were included. The mean RBV concentration at week 4 was 10.2 and 7.36 μm in genotype 1/4 and non-1/4 patients, respectively, and 11.7 and 9.42 at week 12. The mean haemoglobin drop was 25 g/L vs 21 g/L in the genotype 1/4 and non-1/4 group, respectively, a nonsignificant difference. With this treatment approach, 80-90% of patients could be kept adherent to treatment. Sustained viral response was achieved 8/16 (50%) with low-grade fibrosis (fibrosis stage ≤ 2) vs in none of five patients with advanced fibrosis (Fibrosis stage 3 and 4), P < 0.05. We conclude that a treatment algorithm utilizing concentration-guided RBV dosing during darbepoetin maintenance therapy substantially improves tolerance and allows high adherence to a SOC treatment schedule, and that therapy needs to be initiated before advanced fibrosis is developed.

Topics: Adult; Aged; Darbepoetin alfa; Drug Monitoring; Drug Therapy, Combination; Erythropoietin; Female; Hepatitis C; Humans; Interferon-alpha; Liver Transplantation; Male; Medication Adherence; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Recurrence; Ribavirin; RNA, Viral; Treatment Outcome; Viral Load

Darbepoetin alfa is used to treat renal anemia; however, little information is available concerning its use during the posttransplant period, especially in HCV-positive patients treated with ribavirin for active hepatitis C.. This study investigated the efficacy and safety of using darbepoetin alfa in this population during a 6-month treatment period. All anemic patients were HCV/RNA-positive, treated with ribavirin, and had impaired renal function. Patients (n=7) who had not been treated previously with recombinant human erythropoietin (rHuEPO) were placed in "group no rHuEPO." Patients previously with recombinant human erythropoietin (n=16; "group rHuEPO") were switched to darbepoetin alfa according to the European summary of product characteristics.. Seventy-three percent of the patients were men. The mean creatinine clearance at baseline was 58.7 -/+ 21.5 mL/min. All patients received an immunosuppressive treatment. Although mean hemoglobin levels remained stable in group no rHuEPO and increased in group rHuEPO, the difference was not statistically significant. Also, the median darbepoetin-alfa-weighted dose in group no rHuEPO increased while it remained stable in group rHuEPO, as did the median daily dosage of ribavirin; however, these differences were not statistically significant. Creatinine levels and creatinine clearance levels remained stable throughout the study. No significant medical events related to the treatment were reported during the study.. Darbepoetin alfa was found to be efficient and well tolerated in correcting renal anemia in transplant recipients treated with ribavirin for active hepatitis C.

Topics: Anemia; Antiviral Agents; Chronic Disease; Creatinine; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Hepacivirus; Hepatitis C; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Liver Transplantation; Male; Pilot Projects; Postoperative Care; Prospective Studies; Retrospective Studies; Ribavirin; RNA, Viral; Treatment Outcome

Recurrence of hepatitis C virus (HCV) infection is a relevant problem of liver transplantation programs. We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients.. Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n = 54) were randomized to no treatment (group A, n = 27) or peginterferon alfa-2b/ribavirin for 48 weeks (group B, n = 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n = 27). All patients (n = 81) underwent a liver biopsy at baseline and after follow-up; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients.. Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed > or =1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P = .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P = .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] =3.7, 95% confidence interval [CI] 1.3 to 10, P = .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P = .01; respectively).. Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Biopsy; Darbepoetin alfa; Disease Progression; Dose-Response Relationship, Drug; Erythropoietin; Female; Hematinics; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Liver; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Polyethylene Glycols; Portal Pressure; Recombinant Proteins; Ribavirin; Secondary Prevention

HIV/hepatitis C virus (HCV)-coinfected individuals have accelerated liver disease, increased drug toxicities, and modest responses to peginterferon and ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation are limiting factors to HCV treatment in the coinfected patient. This study aimed to identify predictors for the need of filgrastim and darbepoetin to manage hematologic toxicities so as to maintain patients on full doses of study drugs for the duration of study. The primary study was a single-center, open-label, prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the first month, fortnightly until week 8, then monthly from week 12 to 48. Filgrastim was initiated when absolute neutrophil count (ANC) fell below 750 cells/mm(3) and darbepoetin was used when hemoglobin dropped to less than 10 g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30 (66.6%) of patients required hematopoeitic growth factors, 15 (50%) received filgrastim, and 12 (40%) received darbepoetin. Seven (23.3%) required both. Baseline ANC of less than 2250 cells per millimeter and negative rate of change of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and darbepoetin use, respectively. Supplemental growth factors were associated with substantial increase in overall cost for HCV treatment. Larger clinical trials will be needed to address the cost effectiveness of supplemental growth factor use in the HIV/HCV-coinfected patients.

Topics: Adult; Antiviral Agents; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin

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

Topics: Adolescent; Adult; Aged; Anemia; Antiviral Agents; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hepatitis C; HIV Infections; Humans; Interferons; Male; Middle Aged; Quality of Life; Recombinant Proteins; Ribavirin

Hepatitis C virus (HCV) infection is the most common indication for liver transplantation (LTx) in the United States. Ribavirin with pegylated interferon is the only treatment option for HCV recurrence in post-LTx patients. In clinical practice, for more than 50% of patients, ribavirin dose needs to be modified.. The aim of this study was to examine the role of ribavirin level and its relevance in the management of post-LTx patients in terms of renal dysfunction, efficacy, toxicity, and potential drug interactions.. Thirty-four blood samples were available from 22 post-LTx patients. Ribavirin concentrations in plasma (all samples) and whole blood concentrations (16 samples) were examined. The dose of ribavirin ranged from 400 mg/d to 1000 mg/d, but concentrations were normalized to 800 mg/d.. There was a wide variation in plasma concentration of ribavirin, ranging from 1.8 to 122.1 mg/mL. The concentrations were similar in whole blood and plasma. Dose-normalized concentration with creatinine clearance below 70 mL/min were significantly higher when compared with creatinine clearance above 70 mL/min (P = .015). Eleven patients required erythropoietin; their mean ribavirin dosage was higher but mean ribavirin concentration was lower compared to the 11 patients who did not require erythropoietin factor. There was no difference in mean ribavirin concentration in patients who cleared the virus (n = 7) compared and who did not clear the virus (n = 9). Three patients were on nucleoside reverse transcriptase inhibitors (NRTI) had significantly higher concentration (mean 87.1 microg/mL) compared to those who did not receive NRTI (mean 34.4 microg/mL, P = .00). Ribavirin concentration in plasma and whole blood were similar, with a wide variation. Patients with impaired renal function and those who were on NRTI had significantly higher concentrations of ribavirin. The ribavirin concentrations did not predict either the clearance of HCV RNA or the need for erythropoitin factor.

Topics: Adult; Aged; Antiviral Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hepatitis C; Humans; Liver Transplantation; Male; Middle Aged; Recombinant Proteins; Recurrence; Ribavirin

Combination therapy with interferon alpha (IFN-alpha) and ribavirin (RBV) or pegylated IFN-alpha (PEG-IFN-alpha)/RBV for chronic hepatitis C virus (HCV) infection often causes anemia, prompting RBV dose reduction/discontinuation. This study assessed whether epoetin alfa could maintain RBV dose, improve quality of life (QOL), and increase hemoglobin (Hb) in anemic HCV-infected patients.. HCV-infected patients (n = 185) on combination therapy who developed anemia (Hb < or = 12 g/dL) were randomized into a U. S. multicenter, placebo-controlled, clinical trial of epoetin alfa, 40,000 U subcutaneously, once weekly vs. matching placebo. The study design used an 8-week, double-blind phase (DBP) followed by an 8-week, open-label phase (OLP), in which placebo patients were crossed over to epoetin alfa.. At the end of the DBP, RBV doses were maintained in 88% of patients receiving epoetin alfa vs. 60% of patients receiving placebo (P < 0.001). Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment (LASA) and on 7 of the 8 domains of the Short Form-36, version 2 (SF-36v2). Mean Hb increased by 2.2 +/- 1.3 g/dL (epoetin alfa) and by 0.1 +/- 1.0 g/dL (placebo) in the DBP (P < 0.001). Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP. Epoetin alfa was well tolerated; the most common adverse effects were headache and nausea.. Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy.

Topics: Adult; Aged; Anemia; Antiviral Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hepatitis C; Humans; Interferon-alpha; Liver; Liver Function Tests; Male; Middle Aged; Quality of Life; Recombinant Proteins; Ribavirin; Viral Load

Haemodialysed patients are highly exposed to different virus infections namely hepatitis B (HBV) and C (HCV). Recently it was shown, that the use of recombinant human erythropoietin (rHuEPO) in haemodialysed patients with chronic renal failure (CRF) stimulates not only erythropoesis but also increases--in an indirect or direct manner--the humoral and cell--mediated immune defense. The aim of the present study was to determine the prevalence of HBV and HCV infection in haemodialysed patients with CRF and renal anaemia treated either with rHuEPO or with allogenic blood transfusions only. 32 patients with CRF and renal anaemia (haematocrit value below 28%) were included in this study at the early stage of the dialysis therapy (0 to 6 months from the first haemodialysis session). All patients were randomly allocated into two groups. The first one consisted of 15 haemodialysed patients treated with rHuEPO, the second group composed of 17 occasionally treated with blood transfusions (No-EPO group). In patients of both groups the following parameters were examined before (0) and after 3, 6, 9, 12 months of monitoring number of units blood transfused, hemoglobin concentration, serum levels of ferritin. Before the study (0) and after 6 and 12 months presence of antigen HBs (AgHBs), antibodies anti-HBc, anti-HBs, anti-HCV, DNA HBV and RNA HCV were examined. Before the study markers of HBV infection (DNA HBV and/or AgHBs and/or anti-HBc) were found in 46.7% of patients in EPO group and in 52.9% of patients in NO-EPO group respectively (NS). After six months of the study markers of HBV infection were present in 60% of patients in EPO group and in 76.5% of patients in No-EPO group (NS). After 12 months of dialysotherapy HBV infection markers were found in 66.7% patients in EPO group and in 76.5% of patients in No-EPO group (NS). Significantly higher prevalence of HBV infections were found after 6 and 12 months respectively in No-EPO group in comparison to the prestudy period (p < 0.05). At the beginning of the study markers of HCV infection (RNA HCV and/or anti-HCV) were present in 26.7% of patients in EPO group compared to 35.3% of patients in No-EPO group (NS). After 6 months of therapy markers of HCV infection were found in 26.7% of patients in EPO group and in 64.7% of patients in No-EPO group (p < 0.05). After 12 months of treatment markers of HCV infections were present in 40% of patients in EPO group and 76.5% of patients in No-EPO group (p < 0.05).ln patients. Treatment of renal anaemia with rHuEPO contributes to the significant decrease in prevalence of HCV infection. Decrease of prevalence of HCV infection in haemodialysed patients with chronic renal failure treated with rHuEPO seems to be predominantly a result of the complete cessation of allogenic blood transfusion. Blood transfusions seem not to be the main cause of HBV transmission in haemodialysed patients.

Topics: Adult; Anemia; Erythropoietin; Female; Hepatitis B; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Time; Uremia

We are presenting 20 patients with hepatitis C, who developed anemia on interferon alpha-2b/ribavirin treatment and were treated with recombinant human c alpha. Median age was 43 years (range 25-72). Four patients received previous treatment. Interferon-alpha-2b was given at six million units three times a week to 10 patients and at three million units three times a week to five patients. PEG-interferon-alpha-2b (80-120 mug/week) was given to five patients. The dose of ribavirin was 800-1200 mg/day (19 patients) and 200 mg/day (one patient with renal failure). Duration of an interferon/ribavirin treatment was 6-12 months. Baseline median hemoglobin was 13.3 g/dl (range 12.2-15.8); median hemoglobin nadir: 9.8 g/dl (range 8.4-11.2). On erythropoietin, the hemoglobin increased to median 11.7 g/dl (range 9.6-12.8). The ribavirin dose had been decreased to 800 mg in four patients, to 600 mg in four patients, to 400 mg in one patient. Thirteen patients responded to interferon/ribavirin treatment, six patients (all genotype 1) did not. Of the 13 initial responders 11 had sustained response, one still under treatment and two patients relapsed. In conclusion, in our patients with chronic hepatitis C treated with interferon/ribavirin combination therapy, erythropoietin was beneficial in the treatment of ribavirin-induced anemia.

Topics: Adenosine Triphosphate; Anemia; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Glutathione; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Recombinant Proteins; Reticulocyte Count; Ribavirin

The influence of hepatitis B (HBV) and hepatitis C virus (HCV) infection on blood hemoglobin (Hb) and serum erythropoietin (Epo) and interleukin-6 (IL-6) concentrations was studied in 48 anemic patients on regular hemodialysis. They were grouped as follows: (I) 19 patients whose Hb values improved after infection (Hb > 85 g/L), (II) 10 patients with persisting anemia after infection (Hb < 75 g/L), and, without hepatitis virus markers (III) 8 patients with Hb > 85 g/L and (IV) 11 patients with Hb < 75 g/L. Serum immunoreactive Epo levels were significantly higher in group I (34.4+/-47.1 U/L) than in the other groups (II, 10.8+/-6.0; III, 7.9+/-3.2; IV, 8.4+/-4.3). Serum IL-6 was higher in group I than group III (7.7+/-7.8 pg/ml vs. 3.6+/-2.4; p = 0.05) but similar to the other groups. Hb levels in group I were maximal at the time of serum alanine aminotransferase normalization. Red cell production increases as a result of elevated circulating Epo during hepatic regeneration after HBV or HCV infection.

Topics: Anemia; Erythropoietin; Female; Hemoglobins; Hepatitis B; Hepatitis C; Humans; Interleukin-6; Linear Models; Male; Middle Aged; Renal Dialysis

Anemia is a complication of interferon-containing hepatitis C treatments. We characterized effects of interferon-based therapy on hepcidin and erythropoietin (EPO) production, iron metabolism, hemolysis, and hematopoiesis. Standard hemopoiesis [reticulocyte hemoglobin (Hb), reticulocyte production index (RPI), free Hb, and haptoglobin], iron biochemistry, hepcidin, and EPO levels were measured in 10 subjects over 12 weeks. There was a rapid decline in Hb during treatment, from a mean pretreatment (t = 0 weeks) Hb of 158.6 to 125.2 g/L at week 4 (P = 0.003) and 122.8 g/L at week 12 (P = 0.005). Paradoxically, the RPI (a measure of bone marrow responsiveness to EPO) decreased on initiation of hepatitis C virus treatment from 0.78% to 0.53% (P = 0.04). Despite worsening anemia, there was no significant increase in EPO levels. Hepcidin levels increased to >20 nM in 3 subjects from 5.8 to 27.5 nM (P = 0.009) compared with 9.6 to 12.3 nM (P = 0.5) for the remainder of subjects. Hepcidin levels peaked at week 1 before returning to baseline levels at week 4. Subjects who responded with a rise in serum hepcidin levels to >20 nM had a significantly greater drop in Hb (27.2 g/L, P = 0.008) and reticulocyte Hb (-1.4 g/L, P = 0.013) compared with the subjects who did not exhibit any change in hepcidin production. In conclusion, 30% of subjects treated with interferon exhibited significant transient increase in serum hepcidin levels, which was associated with more extreme anemia and decreased iron availability as evidenced by decreased reticulocyte Hb. In addition, there was a failure to upregulate EPO production in response to anemia and hemolysis ( https://clinicaltrials.gov trial NCT01726400).

Topics: Adult; Anemia; Bone Marrow; Dose-Response Relationship, Drug; Erythropoietin; Female; Genotype; Hepatitis C; Hepcidins; Humans; Interferons; Iron; Male; Middle Aged

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

Antibody-mediated pure red cell aplasia (PRCA) has been primarily observed in patients with chronic kidney disease treated with an erythropoiesis-stimulating agent (ESA); only a few anecdotal cases have been reported in other patient populations. We searched the Amgen Global Safety Adverse Event Database and identified 14 patients with hepatitis C who developed severe anemia, anti-erythropoietin antibodies, and bone marrow biopsy-proven PRCA, while receiving interferon therapy (with or without ribavirin) and an ESA. During the follow-up period and after ESA treatment stopped, 11 patients no longer required transfusions and 3 did. Analysis of antibody isotypes showed that, contrary to reports of patients with chronic kidney disease, immunoglobulin G1 was the predominant isotype rather than immunoglobulin G4 (immunoglobulin G4 was detected in only 1 of 6 patients). Epitope mapping showed the anti-erythropoietin antibodies bound domains required for receptor binding. Therefore, the potential benefits of ESA therapy must be weighed against the risk for PRCA in patients with hepatitis C who are receiving treatment with interferon and ribavirin.

Topics: Adult; Aged; Antibodies; Antiviral Agents; Epitope Mapping; Erythropoietin; Hematinics; Hepatitis C; Humans; Immunoglobulin G; Middle Aged; Red-Cell Aplasia, Pure

HCV infection is related to hepatic disease and mixed cryoglobulinaemia (MC). Renal involvement is reported in one third of cryoglobulinaemic patients. The combination of HCV related MC with renal involvement has been associated with poor survival and identified as Hepatitis C Virus Risk Syndrome (HCV RS). Here we describe antiviral treatment and management of side effects (anaemia and neutropenia) with RHuEpo and G CSF in a rare case of HCV RS.

Topics: Anemia; Antiviral Agents; Cryoglobulinemia; Drug Therapy, Combination; Erythropoietin; Glomerulonephritis, Membranoproliferative; Granulocyte Colony-Stimulating Factor; Hepatitis C; Humans; Interferons; Liver Cirrhosis; Male; Middle Aged; Neutropenia; Recombinant Proteins; Ribavirin; Risk Factors; Treatment Outcome

Topics: Anemia; Diabetes Mellitus, Type 2; Erythropoietin; Female; Glycated Hemoglobin; Hepatitis C; Humans; Insulin Glargine; Insulin, Long-Acting; Interferon-alpha; Metformin; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin

A small number of hemodialysis (HD) patients have normal hemoglobin (Hb) levels without the need for erythropoiesis-stimulating agents (ESAs). The factors associated with this condition have been little studied. The objective of this prospective study was to determine these factors in a prevalent population of HD patients.. All patients who had normal Hb levels and who had not received ESAs in the last 6 months (non-ESA group) were included. Epidemiological and laboratory data were collected and we performed an abdominal ultrasound to assess hepatic and renal cysts. This group was compared to a control group of 205 prevalent HD patients on ESA therapy (control group).. We included 45 patients (16% from the whole group) in the non-ESA group. In this group, there was a higher proportion of men (76.5 vs. 61%), patients were younger (61.1 ± 14.7 vs. 67.5 ± 15.2 years), had a longer duration of renal replacement therapy (RRT) (9.4 ± 8.3 vs. 5.3 ± 5.8 years) and had a higher prevalence of adult polycystic kidney disease (APKD) and hepatitis C virus (HCV) liver disease (42.2 vs. 10.2%), p < 0.01. In the non-ESA group, HCV+ patients had a lower prevalence of APKD (2.2 vs. 38.4%) and hepatic cysts (2.2 vs. 19.2%), but significantly higher endogenous erythropoietin levels (55.8 ± 37.1 vs. 30.9 ± 38.4 mU/ml). No significant differences in anemia, iron metabolism, insulin, IGF-1 and renin were found between non-ESA and control groups. Non-ESA patients had a significantly higher number of renal (90.6 vs. 36.5%) and hepatic cysts (12.5 vs. 3.4%), and these were also larger in size (3.3 ± 2.4 vs. 1.5 ± 0.8 cm). In the multivariate Cox analysis, independent predictor factors for absence of anemia in HD patients were number of renal cysts >10 cysts (95% CI 1.058-1.405; p = 0.00), HCV+ liver disease (95% CI 1.147-1.511; p = 0.05) and time on RRT (95% CI 1.002-1.121; p = 0.05).. The absence of anemia in HD patients is not infrequent. Its frequency is higher in men and younger patients with long-term RRT, in patients with HCV+ liver disease and in APKD. It is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Cysts; Erythropoietin; Female; Hematinics; Hepacivirus; Hepatitis C; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Polycystic Kidney, Autosomal Dominant; Prevalence; Prospective Studies; Renal Dialysis; Spleen; Ultrasonography

Topics: Anemia; Erythropoietin; Female; Hepatitis C; Humans; Kidney; Kidney Failure, Chronic; Male; Polycystic Kidney, Autosomal Dominant; Renal Dialysis

Patients with hepatitis C recurrence after liver transplantation represent a clinical challenge. Antiviral treatment in transplant patients has usually poor tolerability and limited efficacy, with a mean sustained virological response (SVR) of 30%. Our pilot study was aimed at evaluating whether 8-week ribavirin pre-treatment could increase either adherence or antiviral effect of a 48-week combination therapy.. Ribavirin pre-treatment (8 weeks) was started with 600 mg daily and increased to 10.4 mg/kg/day. After pre-treatment, 1.5 μg/kg/week pegylated interferon-α2b was added for 48 additional weeks of combination therapy. Blood count, liver function tests and plasma HCV-RNA were examined monthly. Ribavirin plasma concentrations were determined by HPLC.. Thirteen patients (mean age 53±2 years, 11 males) were treated: eight were HCV genotype 1/4; five were genotype 2/3. The median baseline HCV RNA level was 6.5 log(10) (range 5.84-7.42 log(10)). During ribavirin pre-treatment the median HCV RNA levels decreased significantly (5.7 log(10) ; P=0.023). During combination therapy 6/13 (46%) patients exhibited a rapid virological response (RVR) and 10/13 (77%) patients a complete early virological response, two were non-responders. A decline of 0.5 log(10) HCV RNA during pre-treatment predicted RVR. SVR occurred in six patients (46%): four were genotype 2/3. Stable ribavirin dose reduction was required in only two patients (15%) in whom transient interferon reduction was also required.. This proof-of-concept study indicates that ribavirin pre-treatment increased the tolerability of the antiviral treatment, and improved its efficacy in liver transplant patients. Moreover, the degree of HCV RNA decline during pre-treatment allowed one to predict on-treatment response.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hepatitis C; Humans; Interferons; Liver Transplantation; Male; Middle Aged; Pilot Projects; Premedication; Recurrence; Ribavirin; Treatment Outcome; Viral Load

We sought to expose the possible effect of hepatitis C virus (HCV) infection on oxidative stress indicators, nutritional status, and erythropoietin (rHuEPO) requirements in maintenance hemodialysis (MHD) patients. A total of 111 MHD patients (69 males, 42 females; mean age 51.3 +/- 13.0 years; MHD duration 78.5 +/- 52.1 months) and 46 healthy controls were enrolled in the study. We excluded patients with hepatitis B infection or malignancy. Indicators for oxidative status were studied in plasma samples obtained at the beginning of a clinically stable MHD session. Measurements were performed for plasma superoxide dismutase, glutathione peroxidase (antioxidative agents), and malonyldialdehyde (MDA; oxidative agent) by spectrophotometric methods. All patients were analyzed for the presence of anti-HCV; positive patients were also evaluated for the presence of HCV RNA. MHD patients were divided into three groups according to HCV infection status: group I (anti-HCV-positive, HCV-RNA-negative; n = 22); group II (anti-HCV-positive, HCV-RNA-positive; n = 22), and group III (anti-HCV-negative; n = 67). According to the analyses, MHD patients showed higher plasma oxidative stress indicators and lower antioxidative indicator levels compared to controls (P < .0001). MHD patients also displayed lower albumin and higher C-reactive protein (CRP) levels compared to controls (P < .0001). Antioxidant levels were decreased significantly from group I to III (P < .0001). MDA levels significantly increased from group I to III (P < 0.01). HCV-RNA-positive patients showed lowest albumin and highest CRP levels and rHuEPO requirements. Although alanine transferase (ALT) levels were in the normal range, group II patients had significantly higher ALT levels than the other groups (P < .01). In conclusion, we observed negative effects of active HCV infection on oxidative stress and rHuEPO requirements. In contrast, we detected that clinically inactive HCV infection was associated with reduced oxidative stress and rHuEPO requirements compared with active HCV infection and HCV-negative patients.

Topics: Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Blood Urea Nitrogen; C-Reactive Protein; Erythropoietin; Female; Glutathione Peroxidase; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Status; Oxidative Stress; Renal Dialysis; Superoxide Dismutase

There are different approaches for treating recurrent hepatitis C viral infection after a liver transplant. However, sustained virologic response is achieved in < 40% of infected allografts. We examined sustained virologic response improvement using a prolonged course of peginterferon and aggressive use of ribavirin.. From October 1998 to May 2008, 24 patients (13 male, 11 female; mean age at transplant, 49.4 +/- 7.7 years) received a prolonged course of peginterferon and ribavirin (range, 48-180 weeks). The mean interval from liver transplant to hepatitis C antiviral therapy was 26.6 +/- 27.8 months. Patients began weight-based standard dosages of peginterferon and ribavirin. In case of hemolysis, patients were treated with Epogen, with and without blood transfusions.. Fourteen patients (58.3%) had an end of treatment response, and 8 patients (33.3%) maintained sustained virologic response after the first course of therapy. Of 10 patients who did not respond to the first course, 6 received an extended course of antiviral therapy after a mean of 15 +/- 4.6 weeks from completion of first course. Five of these 6 patients achieved end of treatment response and maintained a sustained virologic response, resulting in an overall end of treatment response in 17 patients and a sustained virologic response in 13 patients. Twenty-two patients experienced hemolysis and were treated with Epogen. Fifteen patients received blood transfusions. Ribavirin dosage was reduced in 12 patients, and peginterferon dosage was reduced in 2 patients.. Aggressive use of ribavirin and prolonged course of peginterferon provided sustained virologic response in 54.1% of liver transplant recipients with recurrent hepatitis C virus-infection. More prospective studies are warranted to evaluate the benefit of this approach fully.

Topics: Adult; Antiviral Agents; Blood Transfusion; Drug Administration Schedule; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Genotype; Hematinics; Hemolysis; Hepacivirus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Male; Middle Aged; Pennsylvania; Polyethylene Glycols; Recombinant Proteins; Recurrence; Retrospective Studies; Ribavirin; RNA, Viral; Time Factors; Treatment Outcome; Viral Load

Topics: Antiviral Agents; Cerebrovascular Circulation; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Female; Headache Disorders, Primary; Hematinics; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Middle Aged; Recombinant Proteins; Vasoconstriction

Hepatitis C virus infection is common among patients undergoing hemodialysis, and HD patients are at high risk for infection with such virus. Recently, some studies and case reports indicated attenuated anemia in HD patients with HCV infection, and they previously considered this to be related to increased erythropoietin production after hepatic stimulation by chronic infection with hepatitis virus.. The aim of our study is to investigate whether HCV-positive HD patients have higher hemoglobin (Hb) and hematocrit (HCT) values compared to HCV-negative patients.. We retrospectively studied 83 chronic HD patients from Prince Salman Center for Kidney Disease, and monthly samples were collected between July 2007 and July 2008. The HCV status was determined by anti-HCV antibodies and confirmed with RNA polymerase chain reaction (PCR). Those with a history of blood transfusion or massive blood loss during the last six months were excluded from the study.. Thirty-three percent of our patients tested positive for anti-HCV antibody (51.8% were male). The mean age for HCV-positive group was 54.92 +/- 15.61 years, while it was 51.01 +/- 14.81 years for the HCV-negative group (p = 0.27). Mean Hb in the HCV-positive group was 11.18 +/- 1.41 gm/dL compared to 10.87 +/- 1.29 gm/dL for the HCV-negative group (p = 0.05). Mean HTC values for the HCV-positive group was 34.4 +/- 3.9, compared to 32.41 +/- 3.41 for the HCV-negative group 12 months after starting hemodialysis. Eighty-one patients (27 HCV-positive and 54 HCV-negative) received erythropoietin (EPO) therapy. Seventy-two patients (25 HCV-positive and 47 HCV-negative) received IV iron (p = 0.28). Mean erythropoietin dose was (114.83 +/- 84.92 IU/kg/week) for HCV-positive compared to (122.2 +/- 91.46 IU/kg/week) for HCV-negative group (p = 0.74). Liver function tests were normal except for higher bilirubin level in the HCV-positive group, 7.74 +/- 4.03 Umol/L compared to 5.47 +/- 3.71 Umol/L in the HCV-negative group (p = 0.01).. Our study showed that ESRD patients on HD with HCV infection have higher Hb and HCT levels compared with HCV-negative patients.

Topics: Adult; Aged; Chi-Square Distribution; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Hemoglobins; Hepacivirus; Hepatitis C; Humans; Infusions, Intravenous; Iron Compounds; Kidney Failure, Chronic; Male; Middle Aged; Polymerase Chain Reaction; Prevalence; Probability; Recombinant Proteins; Renal Dialysis; Retrospective Studies; RNA, Viral; Treatment Outcome

Although the incidence of (myelodysplastic syndrome (MDS)) is higher among heart and lung transplant recipients than the general population, the same has not been shown in liver transplant (OLT) patients. We present the second known case of MDS after OLT. Case reports of MDS in OLT were identified using PubMed. Patient data were gathered from the patient and the medical record. A 54-year-old Caucasian man underwent OLT in 2003 and again in 2004 for hepatitis C-related cirrhosis. In 2007, the patient developed weakness, malaise, and shortness of breath. Laboratory studies revealed pancytopenia. Bone marrow biopsy showed MDS, with refractory anemia and excess blasts-1. The patient underwent chemotherapy and reduction in immunosuppression without a clinical response. Our experience suggested that MDS, although rare, should be considered in the differential diagnosis of pancytopenia after OLT. Once diagnosed, immunosuppression reduction, chemotherapy, and even stem cell transplantation may be the appropriate treatment in selected candidates.

Topics: Anemia; Antiviral Agents; Erythropoietin; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Myelodysplastic Syndromes; Polyethylene Glycols; Recombinant Proteins; Recurrence; Reoperation

Hepatitis C (HCV) infection is commonly seen in dialysis patients, but its long-term deleterious effects in these patients are unknown. We evaluated the effect of HCV infection on anemia in our hemodialysis population. This retrospective case control study was carried out from January 1999 to February 2007. The HCV positive patients were assessed for a 12-month period by quarterly lab results for the prevalence of anemia, iron stores, dialysis adequacy, and alanine aminotranferase levels. Their requirements of erythropoietin (EPO) and intravenous (IV) iron were assessed during these months of clinical stability. A control group of age-matched, race-matched, and gender-matched hemodialysis patients with no history of HCV was similarly assessed for anemia, iron stores, and EPO and IV-iron requirements. Twenty-two HCV-positive patients were included for comparison analysis with 44 control patients for 1:2 matching. The mean EPO requirement for the hepatitis group was 17,307 +/- 14,708 U/month in comparison with the control group, which required 49,134 +/- 49,375 U/month (p value <0.01). The mean dose of IV-iron was 120 +/- 143 mg/month for hepatitis patients and 163 +/- 112 mg/month in the control group (p=0.07). The patients with HCV have lower requirement of exogenous EPO replacement compared with their age-matched, gender-matched, and race-matched dialysis counterparts. The IV-iron requirement was not significantly different between the 2 groups but had a suggestive lower trend in the hepatitis group. This needs to be further studied in larger trials.

Topics: Adult; Aged; Anemia; Case-Control Studies; Cohort Studies; Erythropoietin; Female; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Middle Aged; Patient Selection; Polycystic Kidney, Autosomal Dominant; Renal Dialysis; Retrospective Studies

This study investigated prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients.. A cross-sectional analysis was performed on registry data for 2,746 chronic (>6 months) hemodialysis patients aged 25-84. Data collection included years of dialysis, hours of dialysis/wk, disease causing hemodialysis, body mass index (BMI), erythropoietin (EPO) treatment, hemoglobin, markers of viral hepatitis, serum albumin, calcium, and phosphorus.. Prevalence was 88.7% for anemia (hemoglobin <11 g/100 mL and EPO treatment at any Hb level), 39.4% for uncontrolled anemia (hemoglobin<11 g/100 mL). Gender, years of dialysis, hereditary cystic kidney disease (HCKD), and low BMI (<24 kg/m2) were independent correlates of anemia (P<0.001). Gender, HCKD, low BMI, serum albumin and calcium were independent correlates of uncontrolled anemia (P<0.05). An interaction was found between age (not correlated with anemia and uncontrolled anemia) and the association of gender with uncontrolled anemia (P<0.05). EPO doses were higher in patients with high prevalence of uncontrolled anemia than in patients with low prevalence (i.e., women vs men, other diseases vs HCKD, low vs not-low BMI, P<0.01). Gender, years of dialysis, HCKD, BMI, serum albumin, and calcium were independent correlates of the hemoglobin/EPO dose ratio in patients on EPO treatment (P<0.05).. Anemia and uncontrolled anemia are more frequent in hemodialysis patients with shortterm dialysis, diseases other than HCKD, low BMI, and female gender. Gender effect was lower in elderly patients. Uncontrolled anemia was also associated with low serum albumin and calcium, suggesting that these parameters are indices of EPO resistance.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Body Mass Index; Calcium; Cross-Sectional Studies; Erythropoietin; Female; Hematinics; Hemoglobins; Hepatitis B; Hepatitis C; Humans; Italy; Kidney Diseases, Cystic; Male; Middle Aged; Phosphorus; Prevalence; Registries; Renal Dialysis; Serum Albumin; Sex Factors; Time Factors

Ribavirin-induced anemia (RIA) is a common adverse effect of chronic hepatitis C treatment. Studies have shown that the use of epoetin decreases the need for ribavirin dose reduction or discontinuation. The primary objective was to calculate the incremental cost of treating hepatitis C in those without versus with RIA, using either the strategy of ribavirin dose reduction/discontinuation or epoetin. The secondary objective was to calculate the incremental cost of using epoetin versus no epoetin to treat RIA, per ribavirin dose reduction/discontinuation averted.. Estimates from the literature and decision-analytic techniques were used to model treatment patterns and estimate the cost of managing RIA in genotype 1, 2, and 3 subjects. Sensitivity analyses were used to address uncertainty.. Clinically significant RIA, a reduction in hemoglobin of > or = 2 g/dL (1.2 mmol/L), developed in 72% of patients in observational studies. The incremental cost of treating chronic hepatitis C decreased when employing the strategy of ribavirindose reduction/discontinuation to treat RIA, and increased by 5.7% (genotype 1) or 34.4% (genotype 2 or 3), when using epoetin. Using one-way sensitivity analyses, the cost of using epoetin per ribavirin dose reduction/discontinuation averted was $39,579-$52,023. Generalizability may be limited to settings in which a similar proportion of patients develop RIA.. The proportional cost of treating hepatitis C when using epoetin to treat RIA is significant in genotype 2 or 3 patients. The cost of using epoetin per ribavirin dose reduction/discontinuation averted is substantial in patients with genotypes 1, 2, or 3; and varies with the probability of response to epoetin. These findings suggest that additional studies are warranted that will determine the effect of epoetin on treatment outcomes and its role as supportive therapy in patients with RIA.

Topics: Algorithms; Anemia; Antiviral Agents; Cohort Studies; Cost-Benefit Analysis; Erythropoietin; Genotype; Health Care Costs; Health Resources; Hepatitis C; Humans; Models, Theoretical; Recombinant Proteins; Ribavirin; Treatment Outcome

After liver transplantation, reinfection of the newly engrafted liver with hepatitis C virus is essentially universal in patients who are viremic at the time of transplantation. Treatment with interferon preparations with or without ribavirin is recommended in patients with marked histologic injury; however, hematologic toxicity associated with therapy has been reported, which is usually treated with growth factor support, including erythropoietin analogues. We present the first reported case of anti-erythropoietin antibody-mediated pure red cell aplasia arising in the setting of hepatitis C virus therapy in a patient who underwent living donor liver transplantation.

Topics: Anemia; Antibodies; Antiviral Agents; Epoetin Alfa; Erythropoietin; Graft Rejection; Hematinics; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Polyethylene Glycols; Prednisone; Recombinant Proteins; Red-Cell Aplasia, Pure; Ribavirin; Secondary Prevention; Tacrolimus

Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEPO) to manage anemia in PEG-IFN/RBV treated patients, with the objective of maintaining the RBV dose, but currently no official guidelines exist. Actually, rHuEPO exact utilizable dose in PEG-IFN/RBV treated patients is not known. We describe the case of a patient with severe ribavirin-induced anemia.

Topics: Alanine Transaminase; Anemia; Antiviral Agents; Aspartate Aminotransferases; Erythropoietin; Female; Hematocrit; Hemoglobins; Hepatitis C; Humans; Middle Aged; Recombinant Proteins; Ribavirin

Hepatitis C recurs on grafts after liver transplantation and cirrhosis develops more rapidly than in patients without transplants. It is thus essential to develop effective antiviral treatments for these patients. Prolonged virologic response rate after treatment by pegylated interferon and ribavirin of recurrent HVC is limited, because so many patients stop or reduce the treatment because, in particular, of profound anemia. Administration of erythropoietin can enable these patients to continue treatment and thus improve viral eradication.. We report three cases where antiviral treatment continued although the clinical data would, in the absence of erythropoietin, have led us to interrupt it and where prolonged virologic response was obtained.. These data suggest that the onset of anemia largely explains the failure of previous trials, although response to treatment is at least as good as in non-transplanted patients, despite immunosuppressive treatment.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Hepatitis C; Humans; Immunocompromised Host; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Male; Middle Aged; Multicenter Studies as Topic; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Ribavirin; Treatment Outcome; Viral Load

Topics: Antiviral Agents; Chemotherapy, Adjuvant; Erythropoietin; Hepacivirus; Hepatitis C; Humans; Interferons; Recombinant Proteins; Ribavirin

Although the current standard of care for controlling anaemia and neutropenia during anti-viral therapy for hepatitis C is to use dose reduction of ribavirin and pegylated interferon, respectively, erythropoietin and granulocyte colony-stimulating factor are now being advocated as alternatives to dose reduction.. To determine the cost-effectiveness of erythropoietin and granulocyte colony-stimulating factor as an alternative to anti-viral dose reduction during antihepatitis C therapy.. Decision analysis was used to assess cost-effectiveness by estimating the cost of using a growth factor per quality-adjusted life-year gained.. Under baseline assumptions, the cost per quality-adjusted life-year of using growth factors ranged from 16,247 US dollars for genotype 1 with neutropenia to 145,468 US dollars for genotype 2/3 patients with anaemia. These findings are sensitive to the relationship between dose reduction and sustained virological response.. Based upon our findings and the varying strength of the evidence for a relationship between dose reduction and sustained virological response: granulocyte colony-stimulating factor may be cost-effective for genotype 1 patients; erythropoietin is probably not cost-effective for genotype 2/3 patients; no conclusion can be reached regarding the cost-effectiveness of erythropoietin for genotype 1 patients or granulocyte colony-stimulating factor for genotype 2/3 patients. Randomized trials are needed to firmly establish the relationship between dose reduction and sustained virological response.

Topics: Antiviral Agents; Cost-Benefit Analysis; Decision Support Techniques; Erythropoietin; Genotype; Granulocyte Colony-Stimulating Factor; Hepatitis C; Humans; Treatment Outcome

Iron supplementation is the cornerstone of anaemia management in haemodialysis (HD) patients. However, efficacy and safety of intravenous (IV) iron therapy in hepatitis C virus (HCV)-positive HD patients is yet to be elucidated.. Sixty-six maintenance HD patients with suboptimal response to recombinant human erythropoietin (rh-EPO) were administered IV iron. Each patient received 100 mg/session IV iron sucrose for ten consecutive HD sessions and then the dose was decreased to 50-100 mg weekly or biweekly. Patients were followed for haemoglobin (Hb), ferritin, rh-EPO dose requirements, transaminase levels, and adverse drug reactions.. Baseline demographic and clinical characteristics, as well as Hb, ferritin, transaminase levels, rh-EPO and iron doses were similar between HCV-positive (n = 32) and HCV-negative patients (n = 29). After 5 months of follow-up, a significant increase in ferritin and Hb levels and decrease in rh-EPO doses were observed in both groups. The incidence of adverse drug reactions was not associated with HCV serology. Significant elevation in both alanine and aspartate aminotransferase levels were detected in HCV-positive patients.. This study has shown that IV iron administration reverses suboptimal response to rh-EPO administration in HD patients regardless of HCV serology. There is however subtle increase of transaminase levels in HCV-positive patients. Further studies are warranted to reveal the impact of variation in serum transaminase levels during IV iron administration in HCV-positive HD patients.

Topics: Adult; Alanine Transaminase; Anemia; Aspartate Aminotransferases; Cohort Studies; Erythropoietin; Female; Hepatitis C; Humans; Injections, Intravenous; Iron; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

The total number of end-stage renal disease patients treated by renal replacement therapy increased from 1584 on 31 December 2002 to 1661 on 31 December 2003 (4.9% increase). Of these patients, 70.5% were treated by hemodialysis, 7.0% by peritoneal dialysis and 22.5% had a functioning renal graft. The patients were treated at 18 dialysis centers and one transplant center. The number of prevalent patients treated by renal replacement therapy per million of the population (p.m.p.) was 846 at the end of 2003. The number of incident (new) patients in 2003 was 131 p.m.p. The gross mortality rate of dialysis patients was stable through the years of the study and reached 11.8% in 2003. 57.6% of new patients starting hemodialysis were > or = 65 years old and 23.2% were diabetics. Epoetin therapy was prescribed to 89.8% of dialysis patients. The number of patients positive for hepatitis B or hepatitis C viruses is stable and low (3.1% of all dialysis patients).

Topics: Age Factors; Aged; Diabetes Complications; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis B; Hepatitis C; Humans; Incidence; Kidney Failure, Chronic; Kidney Transplantation; Peritoneal Dialysis; Prevalence; Recombinant Proteins; Renal Dialysis; Renal Replacement Therapy; Slovenia

Current therapy for the treatment of hepatitis C virus (HCV) infection is standard interferon (IFN) or pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). Hematologic side effects (neutropenia, thrombocytopenia, anemia) are a major reason for dose reduction of anti-HCV therapy. Because treatment adherence and maintenance of IFN or PEG-IFN and RBV doses have been shown to be important in achieving a sustained virologic response, appropriate management of hematologic side effects might play a substantial role in optimizing treatment outcomes. Neutropenia and thrombocytopenia are usually managed by IFN or PEG-IFN dose reduction; the role of hematopoietic growth factors to ameliorate these side effects needs further evaluation, but some studies suggest granulocyte colony-stimulating factor (G-CSF) may be useful in the management of IFN/PEG-IFN-associated neutropenia. Anemia is primarily due to RBV-induced hemolytic anemia, but IFN/PEG-IFN also suppresses bone marrow erythroid precursors. Treatment-induced anemia has usually been managed by RBV dose reduction or discontinuation. However, recent studies suggest that epoetin alfa can increase hemoglobin levels and facilitate maintenance of RBV dosage in patients with chronic hepatitis C who became anemic during standard combination therapy. Results of a randomized, randomized, double-blind, placebo-controlled trial suggest that epoetin alfa therapy can maintain RBV dosage, increase hemoglobin levels, and improve quality of life in this population. In patients who have chronic hepatitis C who experience hematologic toxicities during standard therapy, the use of hematopoietic growth factors such as epoetin alfa might have the potential to improve treatment adherence rates and allow optimal doses of IFN or PEG-IFN and RBV to be maintained, thereby leading to improved treatment outcomes.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Thrombocytopenia

Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.

Topics: Anemia; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; Epoetin Alfa; Erythropoietin; Forecasting; Hepatitis C; HIV Infections; Humans; Quality of Life; Recombinant Proteins

Anemia is a common complication during interferon-ribavirin therapy for hepatitis C. While normally a fall in hematocrit in results in an exponential compensatory rise in erythropoietin, such that the correlation between hematocrit and erythropoietin is sharply negative, the erythropoietin response during interferon-ribavirin combination therapy is not known.. We measured the hematocrit and erythropoietin levels before and after about 4 weeks of interferon-ribavirin therapy for hepatitis C (n = 43), and compared their relation to the normal human response to anemia.. The hematocrit fell from an average pre-treatment level of 43.7 +/- 3.7% to 36.9 +/- 5 (P < 0.0001). The erythropoietin level rose from 14.5 +/- 15.1 to 58.5 +/- 94.1 units/L (P < 0.0001), indicating there was an adequate stimulus for erythropoietin release. The rise of erythropoietin was severely impaired in relation to the normal human response to a fall in hematocrit. Using the normal human response to anemia as the population line, for our population there was a significant difference in the slope of hematocrit (x) versus log10 erythropoietin (y) (-8.7 vs. -3.098 respectively, P < 0.001) and y-intercept (4.609 vs. 2.753 respectively, P < 0.001). The Bonferroni adjusted "p" value was derived to be <0.002. There was an approximate 2 log10 reduction in maximal achievable erythropoietin level in subjects exposed to interferon-ribavirin combination.. There is a subnormal rise of erythropoietin after interferon-ribavirin combination therapy for hepatitis C.

Topics: Adult; Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Female; Hematocrit; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Hepatitis C; HIV Infections; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin

Hepatitis C virus (HCV) recurrence is a serious problem after orthotopic liver transplantation (OLT). The role of ribavirin as a single agent to treat recurrent HCV is controversial. Our aim was to evaluate the correlation between alanine aminotransferase (ALT) levels and histological findings in OLT recipients treated with ribavirin monotherapy for recurrent HCV. The mean [+/- standard error (SE)] age of 11 patients was 50.1 (SE +/- 8.6) years. The estimated mean dose and duration of ribavirin treatment (+/- SE) was 661.5 (+/- 52.5) mg and 20.4 (+/- 1.7) months, respectively. Five patients required either dose reduction or erythropoietin. We found a significant decrease of mean (+/- SE) ALT value from 246 +/- 44.8 U/L to 109.4 +/- 49.1 U/L (p = 0.002) in patients treated with ribavirin. However, there was also significant worsening of interface activity (p = 0.03) and fibrosis (p = 0.02). No significant association was found between ALT values and (i) stage of hepatic fibrosis, (ii) interface activity, (iii) lobular activity and (iv) HCV RNA values. Our results suggest that HCV disease can progress despite a significant decrease in ALT values. ALT values are inadequate markers of the ribavirin monotherapy and can lead to erroneous conclusions of efficacy.

Topics: Adult; Aged; Alanine Transaminase; Antiviral Agents; Erythropoietin; Female; Fibrosis; Hepacivirus; Hepatitis C; Humans; Liver Transplantation; Male; Middle Aged; Recurrence; Ribavirin; Time Factors

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Topics: Anemia; Central Nervous System Diseases; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Although the natural history of vaccination-induced hepatitis B virus (HBV) antibodies (Abs) is becoming clearer, little is known about naturally acquired immunity. Some assume that these patients never lose their Abs.. To document the natural history of HBV immunity, we prospectively followed up all naturally immune patients initiating hemodialysis (HD) therapy at St Michael's Hospital (Toronto, Canada). Patients presenting with Ab to hepatitis B surface antigen (HBsAb) who had no history of vaccination had a core Ab level measured to confirm natural immunity. When HBsAb titer decreased to less than 10 IU/L, patients were administered a single dose of 40 microg of Engerix B vaccine (Smith Kline Beecham Pharma Inc, Oakville, Ontario, Canada) intramuscularly as a booster dose.. We identified 29 patients beginning HD therapy with natural immunity. Nine patients (30%) subsequently lost immunity (defined as Ab titer decreasing to < 10 IU/L) during follow-up. They were older and had a lower Ab titer at initiation of HD therapy. Four of 5 patients with a low response to the booster dose were 75 years or older. Two patients with a low peak Ab titer after the booster dose again had their Ab titer decrease to less than 10 IU/L after 6 and 10 months. Both patients were switched to intradermal vaccination. All other patients were still immune after a median of 26 months.. Individuals who are naturally immune against HBV may experience a decrease in Ab titer. Their responses to booster vaccinations varied widely. It is possible that elderly patients with natural immunity require closer surveillance. We provide recommendations for surveillance in these patients.

Topics: Aged; Erythropoietin; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis C; Humans; Immunity, Innate; Immunization, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Population Surveillance; Renal Dialysis; Smoking; Transfusion Reaction; Vaccination

Some case reports indicated that red cell status increased after hepatitis C viral infection. The aim of study was to define the influence of hepatitis C infection (HCV) on red cell status in hemodialyzed patients.. A total of 49 (21 anti-HCV-positive and 28 anti-HCV-negative) patients with ESRD were included in this study. Exclusion criteria were blood transfusion and massive blood loss in the last 6 months preceding the study. None of the patients used any drug containing aluminum.. The prevalence of anti-HCV antibody was 42.8%. Mean age was 51.6 +/- 14.3 in anti-HCV (+) group and 50.4 +/- 17.0 in anti-HCV (-) group. There was no statistically significant difference between the ages of the 2 groups. Mean duration time of hemodialysis was significantly longer in patients with anti-HCV antibody (+) group (54.9 +/- 34.2 months) compared to anti-HCV-negative group (12.5 +/- 9.0 months) (p < 0.001). Mean hemoglobin (Hb) and hematocrit (Htc) levels were significantly higher in anti-HCV-positive patients than in anti-HCV-negative patients (Hb: 10.4 +/- 1.8 g/dl, Htc: 30.5 +/- 5.5% vs Hb: 8.8 +/- 1.7 g/dl, Htc: 26.1 +/- 5.3%) (for Hb p < 0.005, for Htc p < 0.007). There was no significant difference regarding the usage ofrHuEPO between the 2 study groups (57.1% in anti-HCV antibody (+)/59.3% in anti-HCV antibody (-)) (p > 0.05). All patients not receiving rHuEPO did so because of economical reasons. Serum AST and ALT levels were significantly higher in the anti-HCV antibody-positive group compared with the anti-HCV antibody-negative group. (AST p < 0.04, ALT p < 0.04).. Anti-HCV antibody-positive ESRD patients have higher hemoglobin and hematocrit levels compared to HCV-negative patients.

Topics: Chi-Square Distribution; Erythropoietin; Female; Hematocrit; Hemoglobins; Hepatitis C; Hepatitis C Antibodies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Recombinant Proteins; Renal Dialysis; Statistics, Nonparametric

Topics: Adenine; Antiretroviral Therapy, Highly Active; Dideoxynucleosides; Drug Administration Schedule; Drug Combinations; Drug Resistance, Microbial; Drug Therapy; Epoetin Alfa; Erythropoietin; Hepatitis C; HIV Infections; Humans; Lamivudine; Organophosphonates; Organophosphorus Compounds; Recombinant Proteins; Saquinavir; Tenofovir; Zidovudine

Hepatitis C virus (HCV) is currently the most common etiology for liver transplantation (LTx) in the United States. A significant number of patients develop recurrent HCV after LTx. Although there is no completely satisfactory treatment for recurrent HCV, a combination of interferon-alpha (INF) and ribavirin remains the most widely used. Ribavirin is eliminated through the kidneys and tends to accumulate in the presence of renal dysfunction. The primary side effect of ribavirin is hemolysis. The goal of the present study was to correlate the incidence of hemolysis with renal function in LTx patients with recurrent HCV who were being treated with ribavirin. The incidence of hemolysis and the renal function were examined in 72 liver transplant patients (58 male and 14 female patients) with recurrent HCV receiving INF (3 million units, three times per week) and ribavirin (initial dose of 400 mg twice daily). Patients were grouped according to the decrease in the percentage of hematocrit after the introduction of ribavirin, with their baseline serum creatinine and creatinine clearance calculated using the Cockcroft-Gault formula. The decrease in the percentage of hematocrit after ribavirin treatment was also examined with respect to creatinine clearance as a continuous variable. In addition, for purposes of presentation, patients were analyzed in three groups: creatinine clearance of >/= 70 mL/min (group A), creatinine clearance < 70 mL/min and >/= 40 mL/min (group B), and creatinine clearance < 40 mL/min (group C). Forty-five (62.5%) patients experienced a decrease in hematocrit (Hct) >/=15% after starting INF and ribavirin. The mean serum creatinine was 1.3 +/- 0.5 mg/dL (median, 1.3) in this group, and the mean calculated creatinine clearance was 71 +/- 29 mL/min (median, 66.47). In the 27 patients who did not show a significant decrease (< 15%) in hematocrit, the mean serum creatinine was 1.1 +/- 0.3 mg/dL (median, 1.0) and the mean creatinine clearance was 95 +/- 39 (median, 96) mL/min (P =.018). On continuous variable of calculated creatinine clearance, there was a trend in the decrease in hematocrit after ribavirin treatment compared with pretreatment (P =.09). However, the rate of hemolysis was significantly different in group A (53.7%), group B (70.8%), and group C (100%) (P =.042). Patients on INF and ribavirin therapy who experienced hemolysis had significantly higher serum creatinine levels and lower creatinine clearances compared with those who d

Topics: Adult; Antiviral Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Female; Hemolysis; Hepatitis C; Humans; Interferon-alpha; Kidney; Liver; Liver Transplantation; Male; Middle Aged; Retrospective Studies; Ribavirin

The thrombopoietic status of patients with uremia remains unclear. This issue was addressed with particular reference to marrow megakaryocytopoiesis and endogenous thrombopoietin (TPO) levels. A study was conducted in 114 patients on hemodialysis, 43 patients on continuous ambulatory peritoneal dialysis, and 48 age-matched controls. Reticulated platelets, a marker of marrow megakaryocytopoiesis, were measured by flow cytometry. Serum TPO levels, platelet-associated IgG (PAIgG) levels, and hepatitis C virus (HCV) antibody titers were also measured by enzyme-linked immunosorbent assay. Circulating and reticulated platelet counts were significantly lower in the patients on dialysis than in the controls. Thrombocytopenia (less than 150 x 10(9)/L) was most frequent in the HCV-positive hemodialysis patients, who had a higher incidences and higher PAIgG titers. The following results were obtained in the HCV-negative dialysis patients: (1) platelet counts chronologically decreased with years on hemodialysis; (2) platelet counts were associated with the reticulated platelet counts; (3) serum TPO levels were significantly elevated in the dialysis patients, responding to the decrease of reticulated platelets; (4) hematocrits had a positive correlation with serum TPO levels, and serum TPO levels were significantly higher in the patients on hemodialysis who did not require recombinant human erythropoietin therapy than in the other patients. In conclusion, thrombocytopenia is a frequent finding in patients on dialysis. The failure of megakaryocyte production could be the principal cause of the platelet reduction, and the peripheral destruction and sequestration of platelets may be concomitantly involved. Elevation of serum TPO may in part serve as an aid to erythropoiesis in dialysis patients.

Topics: Adult; Anemia; Antigens, Human Platelet; Autoantibodies; Blood Platelets; Bone Marrow; Erythropoietin; Flow Cytometry; Hematocrit; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Immunoglobulin G; Kidney Failure, Chronic; Megakaryocytes; Middle Aged; Platelet Count; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombopoietin

Chronic hepatitis C virus (HCV) infection is quite prevalent in long-term hemodialysis (HD) patients. Patients who are candidates for renal transplantation might be treated, before grafting, with interferon-alpha (IFN-alpha). Among 39 HCV-positive long-term HD patients treated with IFN-alpha, we observed three cases of reversible posterior leukoencephalopathy syndrome (PLES). PLES included headaches in three patients, confusion in three patients, cortical blindness in two patients, visual hallucinations in one patient, seizures in three patients, and respiratory distress in one patient in a context of fluid overload and severe hypertension in all cases. The three patients were receiving IFN-alpha and recombinant erythropoietin therapies simultaneously for de novo anemia. Contrast-enhanced computed tomography scan or magnetic resonance imaging showed low-density areas in the occipital lobes (in three patients), frontal lobes (in one patient), and temporal lobes (in one patient). After withdrawal of IFN-alpha and recombinant erythropoietin therapies, hemodiafiltration, and symptomatic treatment of seizures and hypertension, PLES was reversible within 1 week in one patient, 10 days in one patient, and 2 months in the third patient. Our case reports show the occurrence of reversible PLES in HCV-positive long-term HD patients treated with IFN-alpha. Physicians caring for HCV-positive long-term HD patients treated with IFN-alpha need to be particularly cautious when these patients receive simultaneously recombinant erythropoietin and when IFN-alpha therapy induces a weight loss, which indicates a reduction in dry weight.

Topics: Adult; Anemia; Brain Diseases; Comorbidity; Erythropoietin; Hepatitis C; Humans; Hypertension; Interleukin-1; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Syndrome

We describe a complete cytogenetic response to interferon-alpha in a patient with chronic myelogenous leukemia undergoing chronic hemodialysis. Although IFN-alpha therapy has been applied to patients with chronic hepatitis C receiving hemodialysis, the pharmacokinetics of IFN-alpha in patients with poor renal function still remain unclear. In the present patient, the serum IFN-alpha concentration remained high even 48 hours after injection (42.9 IU/ml), and IFN-alpha was almost completely removed by hemodialysis (< 6 UI/ml). The patient was treated with IFN-alpha (3 x 10(6) IU, three times a week), and cytogenetic disappearance (0%) of the Ph-positive clone was confirmed 31 months after the start of therapy. Recombinant human erythropoietin (Epo) was used to treat anemia due to renal failure and IFN-alpha therapy. The anemia was controllable with Epo, and no adverse effect was observed.

Topics: Anemia; Erythropoietin; Hepatitis C; Humans; Interferon-alpha; Kidney Failure, Chronic; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Philadelphia Chromosome; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to evade the detrimental effects of anemia during radiotherapy, but the economic consequences of selecting either intervention are not well defined. The RBC transfusion needs during chemoradiotherapy for cervix cancer were quantified to allow comparison of RBC transfusion costs with the projected cost of EPO in this setting.. For patients receiving pelvic radiotherapy, weekly cisplatin, and brachytherapy, the RBC units transfused during treatment were tallied. RBC transfusion costs per unit included the blood itself, laboratory fees, and expected value (risk multiplied by cost) of transfusion-related viral illness. EPO costs included the drug itself and supplemental RBC transfusions when hemoglobin was not adequately maintained. An EPO dosage based on reported usage in cervix cancer patients was applied.. Transfusions were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at least 1 U of RBC before or during treatment, most commonly after the fifth week. A total of 37 U was given during treatment, for an average of 3.1 U/patient. The sum total of the projected average transfusion-related costs was $990, compared with the total projected EPO-related costs of $3869.. Because no proven clinical advantage has been documented for EPO compared with RBC transfusions to maintain hemoglobin during cervix cancer treatment, for most patients, transfusions are an appropriate and appealingly less expensive option.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Brachytherapy; Cisplatin; Costs and Cost Analysis; Erythrocyte Transfusion; Erythropoietin; Female; Hepatitis B; Hepatitis C; HIV Infections; Humans; Middle Aged; Probability; Radiation-Sensitizing Agents; Retrospective Studies; Uterine Cervical Neoplasms

Topics: Adult; Dose-Response Relationship, Drug; Erythropoietin; Female; Hepacivirus; Hepatitis C; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors

Prevention of exposure to allogeneic blood transfusion during surgery is an important financial issue when recombinant human erythropoietin (rHuEPO) is used in addition to preoperative blood donation.. The aim of this study was to carry out a cost-effectiveness analysis of the use of rHuEPO in preoperative blood donation in orthopedic surgery. The study, based on a decision tree analysis of the use of rHuEPO, was conducted from the perspective of the French health care system. The efficacy criterion was the number of hepatitis C infections prevented. The decision tree analysis was constructed as follows: the residual risk of hepatitis C infection was 8.26 per million units transfused, and the chance node was defined according to the number of units transfused.. With the use of rHuEPO in preoperative blood donation, 0.30562 cases of hepatitis C infection per 100,000 patients were prevented. The incremental cost of one prevented hepatitis C infection amounted to $888,000,000 (US).. Despite the limitations of our model, the cost-effectiveness ratio was so large that variations only slightly modified the size of the result. From the societal perspective, it was not cost-effective to add rHuEPO to preoperative blood donation.

Topics: Blood Donors; Blood Transfusion, Autologous; Combined Modality Therapy; Cost-Benefit Analysis; Erythropoietin; Hepatitis C; Humans; Preoperative Care; Recombinant Proteins; Sensitivity and Specificity

Recombinant human erythropoietin (rHuEPO) has been advocated for the treatment of anaemia in patients submitted to cancer chemotherapy. We used decision analysis to compare the cost-effectiveness of rHuEPO supplemented with red blood cell (RBC) transfusions with conventional treatment with RBC transfusions alone. At baseline, we analysed the use of rHuEPO as secondary prophylaxis according to effectiveness estimates from a community-based oncology study. In order to reduce the probability of transfusions from 21.9% to 10.4%, and the number of RBC units per patient per month from 0.55 to 0.29, 150 units kg(-1) s.c. rHuEPO three times per week for 4 months resulted in an incremental cost of $189,652 per quality-adjusted life year (QALY). In patients treated with cisplatin-containing chemotherapy, rHuEPO added $190,142 per QALY. In a hypothetical scenario of a transfusion pattern that maintained the same haemoglobin level of rHuEPO-responsive patients, the marginal cost of rHuEPO was always greater than $100,000 per QALY. Results were stable with regard to variations in the probability of blood-borne infections, quality of life of responding patients and cancer-related mortality. The additional cost could be lowered to less than $100,000 per QALY by saving 4.5 RBC units over 4 months for any patient treated. In conclusion, according to current use, rHuEPO is not cost-effective in the treatment of chemotherapy-induced anaemia. More tailored utilization of the drug and better consideration of predictive response indicators may lead to an effective, blood-sparing alternative.

Topics: Aged; Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Decision Support Techniques; Erythropoietin; Hepatitis C; Humans; Quality-Adjusted Life Years; Recombinant Proteins; Transfusion Reaction

Hepatitis B vaccine is effective in producing protection against hepatitis B virus (HBV) infection in hemodialysis (HD) patients, but the antibody response is variable. To identify those factors implicated in the vaccine response, in a prospective study over a 24-month period, we vaccinated 80 seronegative patients on HD (group A) and monitored clinical, biochemical, and immunologic parameters. The protective immunity acquired by vaccination was compared with that developed through HBV infection in 22 age-matched HD patients (group B). The anti-HBs antibody-seronegative patients followed a four-dose vaccination schedule (0, 1, 2, and 6 months) with 40 microg DNA-recombinant hepatitis B vaccine. One month after vaccination, 77.5% of the patients had seroconverted, and 72.5% achieved high antibody response, whereas 22.5% were nonresponders. Patients aged younger than 40 years seroconverted 100%; those aged 40 to 60 years, 75% (P < 0.01); and patients older than 60 years, 74% (P < 0.001). No differences between responders and nonresponders concerning sex, time on HD, HD dose, nutritional status, hemoglobin level, HD membrane, iPTH level, calcitriol treatment, or number of transfusions during vaccination were found. The presence of other factors, such as recombinant human erythropoietin (rHuEPO) therapy or hepatitis C virus (HCV) infection, did not significantly influence antibody responses to hepatitis B immunization. A greater frequency of DR3 (53.8% v 25.7%, P < 0.05), DR7 (53.8% v 18.6%, P < 0.01), and DQ2 (76.9% v 44.1%, P < 0.05), and a lesser frequency of A2 (7.7% v 37.2%, P < 0.05) were found in nonresponders compared with responders. Eighteen months after vaccination, the analysis showed similar antibody titers but lower seroconversion rates in group A as compared with group B. In conclusion, unresponsiveness to hepatitis B vaccine in HD patients was related to factors such as older age, the presence of DR3, DR7, and DQ2, and the absence of A2 alleles. Although the seroprotection produced by the vaccine was less than that achieved through natural HBV infection, our protocol of vaccination was sufficiently immunogenic and provided lasting protection.

Topics: Adult; Erythropoietin; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Vaccines; Hepatitis C; HLA Antigens; Humans; Lymphocyte Subsets; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Topics: Adult; Aged; Erythropoietin; Female; Hepatitis B Antibodies; Hepatitis B Vaccines; Hepatitis C; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Vaccines, Synthetic

HCV infection is a major complication among patients undergoing dialysis therapy throughout the world. In the years prior to the use of human recombinant erythropoietin (rHuEpo), patients undergoing haemodialysis were subjected to an excessive iron load as a consequence of frequent blood transfusions. Recent data in the non-dialysis population have shown a positive correlation between iron deposits and the severity of HCV hepatitis and between iron deposition and an impaired response to interferon therapy.. One hundred and five haemodialysis patients were studied. Every patient was screened for HCV infection by ELISA II and HCV RNA. Serum biochemistries were analysed by SMAC20. Ferritin was measured by radioimmunoassay.. The aminotransferase levels for the HCV positive (n = 39) and negative patients (n = 66) were below the normal levels for the general population. The mean values of aminotransferases and plasma ferritin were, however, higher in the HCV-positive patients than in the HCV-negative patients. A positive correlation between aminotransferases and plasma ferritin was evident in HCV-positive patients, which was absent in the HCV-negative individuals. The histological severity of liver disease (n = 7) was, however, not statistically related with the levels of either ferritin or aminotransferases.. HCV infection is a relevant variable when estimating iron deposits by measuring plasma ferritin. Accordingly, a misinterpretation of the actual amount of iron deposits may occur in HCV-positive patients, which should be taken into account at the time of planning their iron reposition therapy. On the other hand, the level of iron deposits might have a significant role in the evolution of HCV-related liver disease.

Topics: Aged; Alanine Transaminase; Aspartate Aminotransferases; Erythropoietin; Female; Ferritins; Hepatitis C; Humans; Interferon-alpha; Iron; Kidney Failure, Chronic; Liver; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Topics: Anemia, Refractory; Blood Transfusion; Chronic Disease; Combined Modality Therapy; Erythropoietin; Hepatitis C; Humans; Male; Middle Aged; Pancytopenia; Recombinant Proteins; Recurrence; Remission Induction; Splenectomy

Hepatitis C virus infection in chronic hemodialysis patients is associated with several unresolved problems. We report a 85 years old female patient in chronic hemodialysis and treated with erythropoietin, that during the course of an Herpes zoster, presented severe malaise, weight loss and muscle weakness. Two weeks later, a slight rise in serum transaminases was detected. The patient had negative antibodies for HIV and hepatitis C virus and negative hepatitis B surface antigen. A PCR test was positive for serum hepatitis C virus RNA. The patient's condition deteriorated and she died 7 days after admission. Erythropoietin administration, whose immunosuppressive effect has been reported previously, could have influenced the dismal outcome of this patient.

Topics: Aged; Aged, 80 and over; Erythropoietin; Female; Follow-Up Studies; Hepatitis C; Herpes Zoster; Humans; Renal Dialysis; Renal Insufficiency; Transfusion Reaction; Viremia

Topics: Adult; Blood Cell Count; Chronic Disease; Combined Modality Therapy; Drug Therapy, Combination; Erythropoietin; Hemoglobins; Hepatitis C; Humans; Interferon-alpha; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Hepatitis B remains a significant risk to patients receiving chronic hemodialysis. Hepatitis B vaccines are effective in providing protection against this infection. However, the minimum antibody level necessary to guarantee an efficacious protection is not clear. Little is known about the effect of this vaccine in persons treated with erythropoietin (EPO) and in patients with hepatitis C virus (HCV) infection. We have studied 36 chronic hemodialysis patients; 17 of them receiving EPO and 9 were diagnosed as having HCV infection. Effective immunity (antibody titer higher than 100 mIU/ml) was observed in 61.1% of the participants and was not influenced by EPO administration, but the effective immunization rate was lower in HCV infected patients (33.3% vs. 70.3%, p < 0.05). These results suggest the possibility that HCV infection may modify the effectiveness of hepatitis B vaccine.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Erythropoietin; Female; Hepatitis B; Hepatitis B Vaccines; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Vaccination

Topics: Anemia; Erythropoietin; Female; Hemoglobins; Hepatitis C; Hepatitis, Chronic; Humans; Middle Aged; Nephrectomy; Renal Dialysis; Uremia

Topics: Aged; Drug Interactions; Erythropoietin; Hematocrit; Hepatitis C; Humans; Interferon-alpha; Kidney Neoplasms; Male; Renal Dialysis; Uremia