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Preliminary treatment results of pegylated interferon alpha 2B and ribavirin in liver transplant recipients with recurrent hepatitis C virus nonresponsive to interferon alpha2B and ribavirin
160 disease activity during treatment. treatment response.
I550
AN OPEN-LABEL,
PIIINP was the only marker predicting
MULTICENTER
SAFETY
OF PEGINTERFERON
HlV/liCV
COINFECTION
STUDY OF EFFICACY
ALFA-SAIRIBAVIRIN
AND
IN
E. Ortega’, C. Barros2, F. Pulido3, R. Rubio3, .I. A. Garcia4, K. Aguirrebengoa’, V. Asensi6e’ ‘.. ’Hospital General Universitah, Valencia; 2Hospital De Mostoles, Madrid; ‘Hospital 12 De Octubre, Madrid; 4Hospital Del Resell, Cartagena, (Murcia); ‘Hospital De Cruces, Bilbao; 6Hospital Central De Astwias, Oviedo, Spain Background: Highly active antiretroviral therapy (HAART) has significantly improved the life expectancy of HIV infected patients. As a consequence, liver disease has emerged as a major cause of morbidity and mortality in this population, mainly as a result of coinfection with HCV or hepatotoxicity induced by antiretroviral drugs. Objective: To evaluate the efficacy and safety of peginterferon alfa-2a (40KD) treatment alone or with ribavirin in HIV/HCV coinfected patients. Methods: Patients initially received peginterferon alfa-2a (40KD) 180 mcglweek alone. HCV-RNA levels were monitored to assess virological response (VR). At week 4, patients with VR (1.50 IU/mL HCV RNA) remained on peginterferon alfa-2a (40KD) alone while those with continual viremia (>50 IU/mL HCV RNA) had ribavirin 800 mglday added to the peginterferon alfa-2a (40KD) regimen. This study is ongoing. Results: 238 patients were recruited (168 males/70 females, mean age 39 years, 50% HCV genotype 1, mean ALT 11.5 U/l, 94% had bridging fibrosis or cirrhosis, mean CD4 cells were 638/mm3, 85% were on HAART). 230 patients completed 4 weeks of therapy, of which 21% had an early VR. 50% (88/177) and 64% (90040) of patients had a VR at weeks 12 and 24, respectively. Both treatment regimens were generally well tolerated. Discontinuation due to adverse events was observed in only 15 patients of these 10 experienced serious adverse events: neuropsychiatric disorders (n=2), gastrointestinal disorders (n=6) and anemia (n=2). Conclusion: Peginterferon alfa-2a (40KD) alone or in combination with ribavirin seems to be an effective and safe treatment in patients coinfected with HIV/HCV.
I
551
IMPACT OF THE HEPATITIS C VIRUS ON THE ACUTE REJECTION
RATE IN KIDNEY TRANSPLANT
Conclusions: There is a higher rate of acute rejection of transplanted kidney in those patients who are HCV carriers. In HCV+ patients the response to treatment with steroids is more positive than in non-infected patients.
PATIENTS
M.L. Ortiz, M. Miras, L. Jimeno, S. Llorente, .I. Mercader. Transplantation Unit. Hospital U. V Arrixaca., Murcia., Spain Objetives: To compare the frecuency of acute rejection (AR) in patients who have undergone a kidney transplant and who are infected with the hepatitis C virus (HCV) with other patients not infected. Material and Methods: One hundred kidney transplant patients between January 1992 and November 2001, were studied retrospectively: - Group A: 43 patients HCV positive before the transplant (30% women and 70% men), average age 44.15. - Group B 48 patients HCV negative before the transplant (26% women and 74% men), average age 37.8. Group C: 9 patients infected after the transplant (75% women and 25% men) with an average age of 34.25 years. All patients received immunesuppressant therapy with ciclosporin, azatioprin and steroids. Episodes of AR were treated, with boluses of steroids, and in the case of partial or non-existent response the treatment was changed to Mofetil Micofenolato (MMF). Results: In Group A, 61.2% (27/43) of the HVC+ patients presented al least one episode of AR (32 episodes in 27 individuals). None of them needed changing to MMF. In Group B, 33.3% (16/48) of the patients presented episodes of AR (21 episodes in 16 individuals). 50% of the rejections required conversion to MMF. In the Group C, the AR rate was 44,5% (4/9) (3 episodes in 2 individuals), none of them rejection requiring conversion to MMF.
I552
PRELIMINARY INTERFERON TRANSPLANT
TREATMENT
RESULTS
OF PEGYLATED
ALPHA 2B AND RIBAVIRIN RECIPIENTS
VIRUS NONRESPONSIVE
IN LIVER
WITH RECURRENT TO INTERFERON
HEPATITIS C
ALPHASB
AND
RIBAVIRIN
G.W. Neff2, M. Montalbano’, N. 0zden2, H. Muslu2, Y.M. Lee2, K. Safdar’, R. Morrero2, J. Nery’, D. Weppler’, J. Madariaga’, D. Levi’, S. Nashida’, T. Kate’, E. Schiff2, A. Tzakis’. ‘University OfMiami Liver/GI/Transplantation, Miami, FL, USA; 2 University of Miami Hepatology, Miami, FL, USA Introduction: Recurrent HCV in the liver recipients is a major concern. We present data from a prospective trial of pegylated interferon and ribavirin combination treatment in recurrent HCV nonresponder (HCV-NR). Methods: Treatment: pegylated interferon-2b (1.5 mcglkglwk) and ribavirin (400-600 mg/d) therapy. Side effects recorded: anemia, neutropenia, thrombocytopenia and depression. T HCV-R was defined: increase in liver chemistries, histopathologic findings consistent with inflammation along with viral recurrence and HCV viremia. HCV RNA serology was done using COBAS AMPLICORTM Hepatitis C virus Test, version 2.0 (HCV RNA Qualitative PCR) and COBAS AMPLICORTM HCV MONITOR TESTversion 2.0 (HCV RNA quantitative PCR) assays. Results: Thirty-two OLT patients were given combination treatment. 8 Hispanics (25%), 24 Caucasians (75%). Mean time from transplant (24.2 mos) and Mean age was 53.lyrs. Biochemical improvements was seen in 16/32 (50%) and 6/32 (18%) became HCV nondetectable. Side effects included; clinical depression 16/32 (50%), neutropenia 14/32 (43%), reduced pegylated interferon dosing 19/32 (60%), reduced ribavirin 9/32 (28%) and blood transfusions related to ribavirin 2/32 (6%). Combination therapy had to be discontinued secondary to drug intolerance in 9 out of 32 patients (28%). Conclusion: Although treatment of HCV-NR with combination pegylated alpha-2b interferon and ribavirin was beneficial in 18% of patients, several transplant recipients suffered from depression, neutropenia, thrombocytopenia or anemia. Safety data that we obtained from this study has prompted us to start HCV liver transplant recipients with lower doses of pegylated interferon-2b and ribavirin and increase in escalating dosages if tolerated by the recipient.
I553
TREATMENT
OF NAVE
IN LIVER TRANSPLANT INTERFERON
G.W. Neff2, G. Slapak’, A. Tzakis’. Miami, FL, FL, USA
ALPHA-2B
HEPATITIS C RECURRENCE RECIPIENTS
(HCV-R)
WITH PEGYLATED
AND RIBAVIRIN
M. Montalbano’, N. 0zden2, H. Muslu2, Y.M. Lee2, K. Safdar’, R. Morrero2, J. Nery’, D. Weppler’, E. Schiff2, ‘University of Miami, Division of Liver/GI Transplantation, USA; 2 University of Miami, Division of Hepatology, Miami,
Introduction: Recurrent HCV in the liver recipients is a major concern. We present our preliminary data using pegylated alpha-2b interferon and ribavirin in na ve HCV-R patients. Methods: Treatment: pegylated alpha-2b interferon (1.5mcg/kg) and ribavirin (400.600mg/d) therapy for at least 24 weeks. Side effects recorded: neutropenia (1750 cells), anemia (hemoglobin < 8grams), thrombocytopenia and depression. Definition of HCV-R: increase in liver chemistries, histopathologic findings with inflammation along with COBAS AMPLICORTM Hepatitis C virus Test, version 2.0 (HCV RNA Qualitative PCR) and COBAS AMPLICORTM HCV MONITOR TESTversion 2.0 (HCV RNA quantitative PCR) assays. Immunosuppression: tacrolimus with steroid tapering by week 12-20.
I550
AN OPEN-LABEL,
PIIINP was the only marker predicting
MULTICENTER
SAFETY
OF PEGINTERFERON
HlV/liCV
COINFECTION
STUDY OF EFFICACY
ALFA-SAIRIBAVIRIN
AND
IN
E. Ortega’, C. Barros2, F. Pulido3, R. Rubio3, .I. A. Garcia4, K. Aguirrebengoa’, V. Asensi6e’ ‘.. ’Hospital General Universitah, Valencia; 2Hospital De Mostoles, Madrid; ‘Hospital 12 De Octubre, Madrid; 4Hospital Del Resell, Cartagena, (Murcia); ‘Hospital De Cruces, Bilbao; 6Hospital Central De Astwias, Oviedo, Spain Background: Highly active antiretroviral therapy (HAART) has significantly improved the life expectancy of HIV infected patients. As a consequence, liver disease has emerged as a major cause of morbidity and mortality in this population, mainly as a result of coinfection with HCV or hepatotoxicity induced by antiretroviral drugs. Objective: To evaluate the efficacy and safety of peginterferon alfa-2a (40KD) treatment alone or with ribavirin in HIV/HCV coinfected patients. Methods: Patients initially received peginterferon alfa-2a (40KD) 180 mcglweek alone. HCV-RNA levels were monitored to assess virological response (VR). At week 4, patients with VR (1.50 IU/mL HCV RNA) remained on peginterferon alfa-2a (40KD) alone while those with continual viremia (>50 IU/mL HCV RNA) had ribavirin 800 mglday added to the peginterferon alfa-2a (40KD) regimen. This study is ongoing. Results: 238 patients were recruited (168 males/70 females, mean age 39 years, 50% HCV genotype 1, mean ALT 11.5 U/l, 94% had bridging fibrosis or cirrhosis, mean CD4 cells were 638/mm3, 85% were on HAART). 230 patients completed 4 weeks of therapy, of which 21% had an early VR. 50% (88/177) and 64% (90040) of patients had a VR at weeks 12 and 24, respectively. Both treatment regimens were generally well tolerated. Discontinuation due to adverse events was observed in only 15 patients of these 10 experienced serious adverse events: neuropsychiatric disorders (n=2), gastrointestinal disorders (n=6) and anemia (n=2). Conclusion: Peginterferon alfa-2a (40KD) alone or in combination with ribavirin seems to be an effective and safe treatment in patients coinfected with HIV/HCV.
I
551
IMPACT OF THE HEPATITIS C VIRUS ON THE ACUTE REJECTION
RATE IN KIDNEY TRANSPLANT
Conclusions: There is a higher rate of acute rejection of transplanted kidney in those patients who are HCV carriers. In HCV+ patients the response to treatment with steroids is more positive than in non-infected patients.
PATIENTS
M.L. Ortiz, M. Miras, L. Jimeno, S. Llorente, .I. Mercader. Transplantation Unit. Hospital U. V Arrixaca., Murcia., Spain Objetives: To compare the frecuency of acute rejection (AR) in patients who have undergone a kidney transplant and who are infected with the hepatitis C virus (HCV) with other patients not infected. Material and Methods: One hundred kidney transplant patients between January 1992 and November 2001, were studied retrospectively: - Group A: 43 patients HCV positive before the transplant (30% women and 70% men), average age 44.15. - Group B 48 patients HCV negative before the transplant (26% women and 74% men), average age 37.8. Group C: 9 patients infected after the transplant (75% women and 25% men) with an average age of 34.25 years. All patients received immunesuppressant therapy with ciclosporin, azatioprin and steroids. Episodes of AR were treated, with boluses of steroids, and in the case of partial or non-existent response the treatment was changed to Mofetil Micofenolato (MMF). Results: In Group A, 61.2% (27/43) of the HVC+ patients presented al least one episode of AR (32 episodes in 27 individuals). None of them needed changing to MMF. In Group B, 33.3% (16/48) of the patients presented episodes of AR (21 episodes in 16 individuals). 50% of the rejections required conversion to MMF. In the Group C, the AR rate was 44,5% (4/9) (3 episodes in 2 individuals), none of them rejection requiring conversion to MMF.
I552
PRELIMINARY INTERFERON TRANSPLANT
TREATMENT
RESULTS
OF PEGYLATED
ALPHA 2B AND RIBAVIRIN RECIPIENTS
VIRUS NONRESPONSIVE
IN LIVER
WITH RECURRENT TO INTERFERON
HEPATITIS C
ALPHASB
AND
RIBAVIRIN
G.W. Neff2, M. Montalbano’, N. 0zden2, H. Muslu2, Y.M. Lee2, K. Safdar’, R. Morrero2, J. Nery’, D. Weppler’, J. Madariaga’, D. Levi’, S. Nashida’, T. Kate’, E. Schiff2, A. Tzakis’. ‘University OfMiami Liver/GI/Transplantation, Miami, FL, USA; 2 University of Miami Hepatology, Miami, FL, USA Introduction: Recurrent HCV in the liver recipients is a major concern. We present data from a prospective trial of pegylated interferon and ribavirin combination treatment in recurrent HCV nonresponder (HCV-NR). Methods: Treatment: pegylated interferon-2b (1.5 mcglkglwk) and ribavirin (400-600 mg/d) therapy. Side effects recorded: anemia, neutropenia, thrombocytopenia and depression. T HCV-R was defined: increase in liver chemistries, histopathologic findings consistent with inflammation along with viral recurrence and HCV viremia. HCV RNA serology was done using COBAS AMPLICORTM Hepatitis C virus Test, version 2.0 (HCV RNA Qualitative PCR) and COBAS AMPLICORTM HCV MONITOR TESTversion 2.0 (HCV RNA quantitative PCR) assays. Results: Thirty-two OLT patients were given combination treatment. 8 Hispanics (25%), 24 Caucasians (75%). Mean time from transplant (24.2 mos) and Mean age was 53.lyrs. Biochemical improvements was seen in 16/32 (50%) and 6/32 (18%) became HCV nondetectable. Side effects included; clinical depression 16/32 (50%), neutropenia 14/32 (43%), reduced pegylated interferon dosing 19/32 (60%), reduced ribavirin 9/32 (28%) and blood transfusions related to ribavirin 2/32 (6%). Combination therapy had to be discontinued secondary to drug intolerance in 9 out of 32 patients (28%). Conclusion: Although treatment of HCV-NR with combination pegylated alpha-2b interferon and ribavirin was beneficial in 18% of patients, several transplant recipients suffered from depression, neutropenia, thrombocytopenia or anemia. Safety data that we obtained from this study has prompted us to start HCV liver transplant recipients with lower doses of pegylated interferon-2b and ribavirin and increase in escalating dosages if tolerated by the recipient.
I553
TREATMENT
OF NAVE
IN LIVER TRANSPLANT INTERFERON
G.W. Neff2, G. Slapak’, A. Tzakis’. Miami, FL, FL, USA
ALPHA-2B
HEPATITIS C RECURRENCE RECIPIENTS
(HCV-R)
WITH PEGYLATED
AND RIBAVIRIN
M. Montalbano’, N. 0zden2, H. Muslu2, Y.M. Lee2, K. Safdar’, R. Morrero2, J. Nery’, D. Weppler’, E. Schiff2, ‘University of Miami, Division of Liver/GI Transplantation, USA; 2 University of Miami, Division of Hepatology, Miami,
Introduction: Recurrent HCV in the liver recipients is a major concern. We present our preliminary data using pegylated alpha-2b interferon and ribavirin in na ve HCV-R patients. Methods: Treatment: pegylated alpha-2b interferon (1.5mcg/kg) and ribavirin (400.600mg/d) therapy for at least 24 weeks. Side effects recorded: neutropenia (1750 cells), anemia (hemoglobin < 8grams), thrombocytopenia and depression. Definition of HCV-R: increase in liver chemistries, histopathologic findings with inflammation along with COBAS AMPLICORTM Hepatitis C virus Test, version 2.0 (HCV RNA Qualitative PCR) and COBAS AMPLICORTM HCV MONITOR TESTversion 2.0 (HCV RNA quantitative PCR) assays. Immunosuppression: tacrolimus with steroid tapering by week 12-20.