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Danazol Increases Platelet Counts in Thrombocytopenia Patients with Chronic Hepatitis C or Cirrhosis
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By Maria Bishop
http://www.docguide.com
BOSTON, MA -- November 5, 2007 -- Patients receiving the standard treatment of pegylated interferon alfa 2a plus ribavirin for chronic hepatitis C virus (HCV) may become thrombocytopenic, but are able to achieve increased platelet counts through danazol therapy, according to research presented here at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
This is the first report of using a novel alternative treatment for thrombocytopenia in this difficult patient population, noted lead author, Guillermo Cabrera-Alvarez, MD, Gastroenterology and Liver Department, Internal Medicine Division, Regional General Hospital - Family Medicine Unit #1, Mexican Social Security Institute, Cuernavaca, Morelos, Mexico.
Dr. Cabrera-Alvarez and colleagues conducted an open-label clinical trial of 41 danazol-naive patients with chronic HCV (90% with cirrhosis of the liver), who had developed thrombocytopenia as a result of treatment with pegylated interferon alga 2a plus ribavirin. The treatment group (n = 26, 20 female) received danazol at 300-600 mg/day until the end of the HCV therapy. Fifteen control subjects (9 females) were matched for baseline platelet count, presence of cirrhosis, age, sex, and HCV genotype, but were not considered thrombocytopenic.
The mean baseline platelet count for treated patients was 75,300 ± 11,502, which was increased at the end of the study to 123,900 ± 30,411 (P =.0063) in the 23 patients available for evaluation (20 females).
Of those 23 danazol-treated patients, 4 were considered non-responders, 7 were mild responders, and 12 were considered to have had a good response. Efficacy was evaluated as the capacity to increase platelet counts until the end of the treatment period.
In the control group (non-thrombocytopenic), the mean platelet count went from 238,953.3 ± 141,962.9 at baseline to 174,200 ± 91,643 at end of treatment (P =.9246).
Only two danazol-treated patients developed reversible cholestasis, noted Dr. Cabrera-Alvarez. No other patients presented with side effects.
"We believe that maybe [the mechanism of action] involves impairment of macrophage-mediated clearance of antibody-coated platelets via decreased Fc receptor expression, as in autoimmune thrombocytopenia," said Dr. Cabrera-Alvarez. Danazol has been used successfully to treat patients with autoimmune thrombocytopenia.
Danazol is a derivative of the synthetic steroid ethisterone, a modified testoterone. This drug decreases the follicle-stimulating hormone and luteinizing hormone. Liver function must be monitored on a periodic basis in patients receiving long-term therapy with danazol, as it is metabolised by the liver.
[Presentation title: Danazol Increases the Platelets Count in Thrombo-Cytopenic Patients with Chronic Hepatitis C and Liver Cirrhosis Treated With Peg-Interferon Alfa 2a and Ribavirin. Abstract 260]
ABSTRACT
Danazol Increases the Platelets Count in Thrombo-Cytopenic Patients with Chronic Hepatitis C and Liver Cirrhosis Treated With Peg-Interferon Alfa 2a and Ribavirin.
G. Cabrera-Alvarez1; L. Canedo-Dorantes2; J. Reyes-Esparza3; L. Rodriguez-Fragoso3; N. Mendez-Sanchez5; A. Burguete4; V. Madrid-Marina4
1. Gastroenterology, IMSS, Cuernavaca, Morelos, Mexico.
2. Faculty of Medicine, Postgraduate Division, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Morelos, Mexico.
3. Faculty of Pharmacology, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Morelos, Mexico.
4. Chronic Infections and Cancer Division, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Morelos, Mexico.
5. Liver Unit, Medica Sur Clinic & Foundation, Mexico city, México, Mexico.
Background and Aim: Chronic hepatitis C (HCV) infection has been associated with the development of several extrahepatic alterations, including thrombocytopenia. Currently it remains unresolved. Danazol, an attenuated androgen has been succesfully used in patients with autoimmune thrombocytopenia. The aim of the present study was to investigate the effects of Danazol treatment for thrombocytopenia associated to peginterferon alfa-2a and ribavirin therapy in naive HCV patients.
Methods: A prospective study carried out in patients with chronic hepatitis C or liver cirrhosis patients who were under antiviral therapy. The protocol was approved by the Review Board/Ethics committee of the Hospital. The inclusion criteria including both gender, age (20 to 70 yr), without co-infection with hepatitis B virus or human immunodeficiency virus (HIV-1/2), thrombocytopenia during peginterferon alfa-2a and ribavirin therapy was defined when the count was ≦ 90,000 platelets/mL in the last month. Danazol 300-600 mg/day was administered until the end of therapy. We considere as a control patients those on antiviral therapy who did not receive adjuvant danazol due to only mild thrombocytopenia on antiviral therapy, matched for baseline platelet count, presence of cirrhosis, age, sex and HCV genotype. Efficacy was evaluated as the capacity to increase in platelet counts until the end of the treatment period.
Results: A total of 41 patients with HCV-associated thrombocytopenia with PEG IFN/ribavirin treatment were studied: 26 patients (20 females, 6 males), mean age of 54.57± 8.40 yr who received danazol and 15 controls (9 females, 6 males), mean age of 55.8 ± 13 yr. Ninety percent of 41 patients had cirrhosis and the HCV genotypes were similar between groups. The platelet count increases in the Danazol group from baseline (75300 ± 11502) after treatment (123,900 ± 30411 p=0.0063). Whereas in the control group the mean count range from (238953.3 ± 141962.9 to 174200± 91643, p=0.9246) respectively. No association between genotypes and thrombocytopenia was observed (P>0.05). Danazol safety was assessed by the absence of collateral negative effects, except colestasis reversible in two patients.
Conclusions: Adjuvant use of Danazol is associated with increased platelets counts in patients on antiviral therapy with interferon and rivabirin for HCV infection and cirrhosis. This is new therapeutic option to treat thrombocytopenia and maximize the sustained virologic response
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