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Induction therapy with interferon-alpha 2b associated to ribavirin and ketoprofen in patients with chronic hepatitis C non-responders to interferon. A pilot study
Category 6: Viral hepatitis: clinical aspects -] INDUCTION THERAPY WITH INTERFERON-alpha 2b ASSOCIATED TO RIBAVIRIN AND KETOPROFEN IN PATIENTS WITH CHRONIC HEPATITIS C NON-RESPONDERS TO INTERFERON. A PILOT STUDY Alberto E. Munoz 1, Diana Levi 1, Carlos Miguez 1, Mafia Silvia Munne 2, Daniel Cisterna 1, Sandra Vladimirsky 2, Jorge Gonzalez 2, Ruben Terg 1.
1Liver Unit, Hospital Udaondo, Buenos Aires; 2Viral Hepatitis Section, Instituto Malbran, Buenos Aires, Argentina Aim" To assess the efficacy and safety of an induction regimen of IFN associated to Ribavarin (RBV) and Ketoprofen (KPF), followed by IFN tiw and RBV qd, in patients with chronic hepatitis C non-responders to IFN. Methods: We included 22 patients with HCVRNA positive at the end of previous treatment with IFN. RT nested PCR qualitative: in house. Genotype: InnoLipa. Induction schedule: IFN 10 MU at day 1 followed by 3 MU daily, RBV 1.0-1.2 g qd, KPF 400 mg qd and Pantoprazole 20 mg qd, during 4 weeks or 8 weeks if PCR was positive at week 4. Post-induction therapy: IFN 3 MU tiw and RBV 1.0--1.2 g qd, until week 48. Treatment would be stopped if PCR was positive at week 24. Results: Mean age was 53 4- 10 years; 12 were male, 13 had fibrosis in liver biopsy (4-6, Ishak, 1995). Genotype: 5 were la, 14 were lb and 1 was 2a. Virological responses: 27% at week 4, 45% at week 8, 45% at week 24, 36% at week 48 and 23% at week 72. These responses were independent of chronic hepatitis or fibrosis in liver biopsy and genotype. No patient was withdrawn from the study due to adverse events; IFN dose was reduced in 18% of patients due to neutropenia and/or thrombocytopenia and RBV was reduced in 41% due to anemia. Flu-like syndrome was observed in 50% of patients. Conclusions: This schedule of treatment produced a sustained virological response higher than previously reported and was well tolerated.
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LONG TERM FOLLOW UP CHRONIC HEPATITIS B PATIENTS TREATED WITH INTERFERON
Hulya Cetinkaya 1, Ozden Uzunalimoglu 2, Mustafa Safioglu ], Hakan Bozkaya 1, Mithat Bozdayi 2, Selim Karayalcin 1, Cihan Yurdaydin I . 1Ankara University School of Medicine, Dept. of
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241
HEPATITIS C VIRUS GENOTYPES IN MEXICO CITY
Nahum Mendez-Sanchez I , Daniel Leon 2, Laura Trejo-Avila 2, Francisco Sanchez-Giron 1, Hector Baptista 1, Raul Pichardo-Bahenal, Misael Uribe 1.1Department of Biomedical Research, Medica Sur Clinic
& Foundation, Mexico City; 2Faculty of Biological Sciences, University Autonomous of Nuevo Leon, Mexico Background: Clinical and epidemiological observations suggest that genetic differences in hepatitis virus C (HCV) genotypes, difference it's biological behavior. It's suggested that genotype differences influence disease outcome. Aim: Investigate HCV genotypes in Mexico City. Methods: We studied 123 HCV positive patients. HCV genotypes were determined with a commercial assay based on reverse hybridization. Source of HCV and duration of infection were obtained from documentation; liver cirrhosis (LC) was diagnosed by clinical, biochemical, and sonographic data. Results: Genotypes 1, 2, 3, 4, 5, 6 were found in 76.7%, 18.6%, 0%, 7.0%, 0%, 2.3% of patients. Patients with genotypes 1 (mean age 52.8 years), 2 (51.0 years) were older than patients with genotypes 3 (37.2 years), 4 (37.2 years). Patients with subtype lb (58.1 years) were older than patients with subtype la (40.8 years), 3a (37.5 years). Sources of infection were blood transfusions (70.0%), blood products (3.0%), intravenous drug use (2.5%; genotype 1 in 53% and genotype 3 in 40%). Source was unknown in 24.8% of patients. No patients with genotypes 2, 3 had more than 20 years of CHC recorded. Prevalence of genotype 4 was higher in, short duration, patients (less than 10 years) of CHC. LC was diagnosed in 13.6% of patients (97.1% genotype 1). Patients with LC were older than asymptomatic patients (63.8 vs. 51.3 years). Conclusion: The main subtype our population was lb, it's the major contributor to LC. Patients with subtype 1a have similar risk of developing LC. Genotype 4 is an increasing problem for development of liver disease.
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EARLY CLEARANCE KINETICS OF HEPATITIS C VIRUS (HCV) IN PATIENTS WITH CHRONIC HEPATITIS C UNDER THERAPY WITH PEGYLATED-INTERFERON (PEG-IFN) alpha-2b OR CONSENSUS-INTERFERON (CIFN) PLUS RIBAVIRIN
Gastroenterology; 2Ankara University Institute of Hepatology, Ankara, Turkey
L.C. Da Silva, S.K. Ono-Nita., F.J. Carrilho, J.E.M. Medeiros-Filho, J.R.R. Pinho. Hepatology Branch, Department of Gastroenterology,
In this study, the long term follow-up of chronic hepatitis B(HBV) pts with sustained response to an interferon (IFN) regimen, is presented. A total of 53 biopsy-proven chronic active HBV pts, 32 HbeAg+ (mean age: 29.8 yrs, 23 male, 9 female, 21 H b e A g - / A n t i - H b e + (mean age: 38.2 yrs, 20 male, 1 female) had received 5-10 mU/IFN tiw for 6 months. A sustained response was defined as undetectable HBV DNA by a hybridisation assay, normal ALT, and HBeAg negativity for HBeAg(+) cases 6 months after treatment completion. Baseline ALT levels were similar in HBeAg(+) and HBeAg(-) cases (168 4- 139 [x 4- SD] vs. 164 4- 142 IU/1, respectively) but HBV DNA was lower in H B e A g ( - ) pts than in HBeAg(+) pts (1434 4- 654 pg/ml Ix 4- SD] vs. 1501 + 923, respectively). A sustained response was obtained in 21 (65.6%) of HBeAg(+) and in 13 (61.9%) of H B e A g ( - ) cases. These 34 cases were followed for a mean of 7 years (4-13 years). Relapse (detectable HBV DNA, high ALT) was observed in 9 of 21 (42.9%) HBeAg(+) cases and in 6 of 13 (46.2%) H B e A g ( - ) cases. Of these 15 relapses, 6 occurred within the first observation year, 3 after 1-3 yrs, 3 after 4 and 3 after 6 yrs. At the end of the long term follow-up, 12 pts (12/32, 37.5%) in the HBeAg(+) pts and 7 pts (7/21, 33.3%) in the H B e A g ( - ) group were long term sustained responders. In conclusion, in our series, HBeAg(-)/anti HBe(+) chronic hepatitis B behaved similar to HBeAg(+) cases in terms of short term and long term treatment response to IFN treatment. Our data also suggest that late relapse is not uncommon in IFN-treated chronic hepatitis B pts.
Introduction: Several reports emphasized the role of 4th week HCV RNA to predict sustained response (SR). Accordingly, it would be interesting to determine the early HCV clearance kinetics under PEG-IFN or CIFN. Methods: Group 1: Eight patients consecutively received 15 meg of CIFN plus ribavirin daily during four weeks and 9 to 15 meg every other day and ribavirin daily for the last 44 weeks. Group 2: Sixteen patients received I. 1 to 1.5 mcg/kg of PEG-IFN-alpha-2b weekly plus daily ribavirin for 48 weeks. HCV RNA (Amplicor Monitor) levels were checked during the first twelve weeks of treatment and the negativation rate was analysed. Results: The median HCV viral load (logl0) at pre-treatment (TO), week 2 (T2), week 4 (T4) are TO = 5.6 + 0.6; T2 = 1.1 + 2.1 and T4 = 0.9 + 1.8 for group 1 and TO = 5.9 + 0.7; T2 = 3.8 + 2.0 and T4 = 2.5 + 1.8 for group 2. Week 4 HCV RNA negativation was 6/8 (75%) and 5/16 (31%) of pts receiving CIFN and PEG-IFN respectively (Fisher test = 0.055). Week 12 negativation was 8/8 (100%) and 10/12 (83%) of patients receiving CIFN and PEG-IFN respectively. Conclusions: CIFN showed tendency to greater efficacy than PEG-IFN at week four, but not at week 12. We speculate that some aspects of early viral kinetics to predict SR could not be applied to PEG-IFN or if it is really important, the use of CIFN in the first few days just before starting PEG-IFN could increase SR rate.
University of Sao Paulo, School of Medicine, Sao Paulo, Brazil
1Liver Unit, Hospital Udaondo, Buenos Aires; 2Viral Hepatitis Section, Instituto Malbran, Buenos Aires, Argentina Aim" To assess the efficacy and safety of an induction regimen of IFN associated to Ribavarin (RBV) and Ketoprofen (KPF), followed by IFN tiw and RBV qd, in patients with chronic hepatitis C non-responders to IFN. Methods: We included 22 patients with HCVRNA positive at the end of previous treatment with IFN. RT nested PCR qualitative: in house. Genotype: InnoLipa. Induction schedule: IFN 10 MU at day 1 followed by 3 MU daily, RBV 1.0-1.2 g qd, KPF 400 mg qd and Pantoprazole 20 mg qd, during 4 weeks or 8 weeks if PCR was positive at week 4. Post-induction therapy: IFN 3 MU tiw and RBV 1.0--1.2 g qd, until week 48. Treatment would be stopped if PCR was positive at week 24. Results: Mean age was 53 4- 10 years; 12 were male, 13 had fibrosis in liver biopsy (4-6, Ishak, 1995). Genotype: 5 were la, 14 were lb and 1 was 2a. Virological responses: 27% at week 4, 45% at week 8, 45% at week 24, 36% at week 48 and 23% at week 72. These responses were independent of chronic hepatitis or fibrosis in liver biopsy and genotype. No patient was withdrawn from the study due to adverse events; IFN dose was reduced in 18% of patients due to neutropenia and/or thrombocytopenia and RBV was reduced in 41% due to anemia. Flu-like syndrome was observed in 50% of patients. Conclusions: This schedule of treatment produced a sustained virological response higher than previously reported and was well tolerated.
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LONG TERM FOLLOW UP CHRONIC HEPATITIS B PATIENTS TREATED WITH INTERFERON
Hulya Cetinkaya 1, Ozden Uzunalimoglu 2, Mustafa Safioglu ], Hakan Bozkaya 1, Mithat Bozdayi 2, Selim Karayalcin 1, Cihan Yurdaydin I . 1Ankara University School of Medicine, Dept. of
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241
HEPATITIS C VIRUS GENOTYPES IN MEXICO CITY
Nahum Mendez-Sanchez I , Daniel Leon 2, Laura Trejo-Avila 2, Francisco Sanchez-Giron 1, Hector Baptista 1, Raul Pichardo-Bahenal, Misael Uribe 1.1Department of Biomedical Research, Medica Sur Clinic
& Foundation, Mexico City; 2Faculty of Biological Sciences, University Autonomous of Nuevo Leon, Mexico Background: Clinical and epidemiological observations suggest that genetic differences in hepatitis virus C (HCV) genotypes, difference it's biological behavior. It's suggested that genotype differences influence disease outcome. Aim: Investigate HCV genotypes in Mexico City. Methods: We studied 123 HCV positive patients. HCV genotypes were determined with a commercial assay based on reverse hybridization. Source of HCV and duration of infection were obtained from documentation; liver cirrhosis (LC) was diagnosed by clinical, biochemical, and sonographic data. Results: Genotypes 1, 2, 3, 4, 5, 6 were found in 76.7%, 18.6%, 0%, 7.0%, 0%, 2.3% of patients. Patients with genotypes 1 (mean age 52.8 years), 2 (51.0 years) were older than patients with genotypes 3 (37.2 years), 4 (37.2 years). Patients with subtype lb (58.1 years) were older than patients with subtype la (40.8 years), 3a (37.5 years). Sources of infection were blood transfusions (70.0%), blood products (3.0%), intravenous drug use (2.5%; genotype 1 in 53% and genotype 3 in 40%). Source was unknown in 24.8% of patients. No patients with genotypes 2, 3 had more than 20 years of CHC recorded. Prevalence of genotype 4 was higher in, short duration, patients (less than 10 years) of CHC. LC was diagnosed in 13.6% of patients (97.1% genotype 1). Patients with LC were older than asymptomatic patients (63.8 vs. 51.3 years). Conclusion: The main subtype our population was lb, it's the major contributor to LC. Patients with subtype 1a have similar risk of developing LC. Genotype 4 is an increasing problem for development of liver disease.
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EARLY CLEARANCE KINETICS OF HEPATITIS C VIRUS (HCV) IN PATIENTS WITH CHRONIC HEPATITIS C UNDER THERAPY WITH PEGYLATED-INTERFERON (PEG-IFN) alpha-2b OR CONSENSUS-INTERFERON (CIFN) PLUS RIBAVIRIN
Gastroenterology; 2Ankara University Institute of Hepatology, Ankara, Turkey
L.C. Da Silva, S.K. Ono-Nita., F.J. Carrilho, J.E.M. Medeiros-Filho, J.R.R. Pinho. Hepatology Branch, Department of Gastroenterology,
In this study, the long term follow-up of chronic hepatitis B(HBV) pts with sustained response to an interferon (IFN) regimen, is presented. A total of 53 biopsy-proven chronic active HBV pts, 32 HbeAg+ (mean age: 29.8 yrs, 23 male, 9 female, 21 H b e A g - / A n t i - H b e + (mean age: 38.2 yrs, 20 male, 1 female) had received 5-10 mU/IFN tiw for 6 months. A sustained response was defined as undetectable HBV DNA by a hybridisation assay, normal ALT, and HBeAg negativity for HBeAg(+) cases 6 months after treatment completion. Baseline ALT levels were similar in HBeAg(+) and HBeAg(-) cases (168 4- 139 [x 4- SD] vs. 164 4- 142 IU/1, respectively) but HBV DNA was lower in H B e A g ( - ) pts than in HBeAg(+) pts (1434 4- 654 pg/ml Ix 4- SD] vs. 1501 + 923, respectively). A sustained response was obtained in 21 (65.6%) of HBeAg(+) and in 13 (61.9%) of H B e A g ( - ) cases. These 34 cases were followed for a mean of 7 years (4-13 years). Relapse (detectable HBV DNA, high ALT) was observed in 9 of 21 (42.9%) HBeAg(+) cases and in 6 of 13 (46.2%) H B e A g ( - ) cases. Of these 15 relapses, 6 occurred within the first observation year, 3 after 1-3 yrs, 3 after 4 and 3 after 6 yrs. At the end of the long term follow-up, 12 pts (12/32, 37.5%) in the HBeAg(+) pts and 7 pts (7/21, 33.3%) in the H B e A g ( - ) group were long term sustained responders. In conclusion, in our series, HBeAg(-)/anti HBe(+) chronic hepatitis B behaved similar to HBeAg(+) cases in terms of short term and long term treatment response to IFN treatment. Our data also suggest that late relapse is not uncommon in IFN-treated chronic hepatitis B pts.
Introduction: Several reports emphasized the role of 4th week HCV RNA to predict sustained response (SR). Accordingly, it would be interesting to determine the early HCV clearance kinetics under PEG-IFN or CIFN. Methods: Group 1: Eight patients consecutively received 15 meg of CIFN plus ribavirin daily during four weeks and 9 to 15 meg every other day and ribavirin daily for the last 44 weeks. Group 2: Sixteen patients received I. 1 to 1.5 mcg/kg of PEG-IFN-alpha-2b weekly plus daily ribavirin for 48 weeks. HCV RNA (Amplicor Monitor) levels were checked during the first twelve weeks of treatment and the negativation rate was analysed. Results: The median HCV viral load (logl0) at pre-treatment (TO), week 2 (T2), week 4 (T4) are TO = 5.6 + 0.6; T2 = 1.1 + 2.1 and T4 = 0.9 + 1.8 for group 1 and TO = 5.9 + 0.7; T2 = 3.8 + 2.0 and T4 = 2.5 + 1.8 for group 2. Week 4 HCV RNA negativation was 6/8 (75%) and 5/16 (31%) of pts receiving CIFN and PEG-IFN respectively (Fisher test = 0.055). Week 12 negativation was 8/8 (100%) and 10/12 (83%) of patients receiving CIFN and PEG-IFN respectively. Conclusions: CIFN showed tendency to greater efficacy than PEG-IFN at week four, but not at week 12. We speculate that some aspects of early viral kinetics to predict SR could not be applied to PEG-IFN or if it is really important, the use of CIFN in the first few days just before starting PEG-IFN could increase SR rate.
University of Sao Paulo, School of Medicine, Sao Paulo, Brazil