(160) Predictors of responses to adefovir therapy in patients with lamivudine-resistant hepatitis B...
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Introduction: A sustained viral response (SVR) to bitherapy for chronic hepatitis C may be obtained in 55% with the association of pegylated interferon (PEGIFN) and ribavirin (RIB). However, only 30–40% of patients attend SVR with standard interferon (sIFN) and ribavirin. The aim of our study is to evaluate the efficacy of PEGIFN and ribavirin combination therapy in Tunisian patients with chronic hep- atitis C and to identify predictors to response to treatment. Material and methods: A prospective study which included active chronic hepatitis C patients recruited from gastroenterology depart- ment of Rabta hospital between January 1997 and December 2007 and who received bitherapy PEGIFN-ribavirin at a dose of 180mg/ week for PEG IFN alpha2a or 1, 5 lg/kg/week for PEG IFN alpha 2b. Ribavirin was given at a dose between 800 and 1200 mg/day accord- ing to the weight and/or the viral genotype. The duration of treat- ment was 48weeks for genotype 1, 4 and 24 weeks for genotypes 2, 3. The early virological response was evaluated only for HCV geno- type 1. The clinical end points of our study were the end-of-therapy virological response (EOT) and the sustained virological response (SVR), 24 weeks after the end of the treatment. We excluded patients who did not achieve the complete duration of treatment. The effect of sex, age, pre-treatment viral load, genotype, pre-treatment trans- aminase value, pre-treatment histological degree of fibrosis and ste- atosis on virological response were studied in unvaried analysis. Results: A total of 41 patients were included in this study: 17 male and 24 female with a mean age of 47.8years (extremes: 27– 63 years). Thirty-seven patients were infected by HCV genotype 1 (90.2%), 2 patients by genotype 2 (4.8%), one patients by genotype 3 (2.4%) and one patient by genotype 4 (2.4%), ALT value was in- creased in 34 patients (83%) cases. Fifteen patients were cirrhotic (36.6%). For other patients, the degree of fibrosis was F3 (N = 11), F2 (N = 14) and F1 (N = 1). Biochemical response was obtained in 35 cases (85.3%). At the end of treatment, 36 patients (87.8%) had virological response. SVR was achieved in 30 patients (73.2%). Among cirrhotic patients, 12 patients achieved SVR (80%) whereas 18 non cirrhotic patients had SVR (69.2%). According to genotype, SVR was obtained in 27 patients infected by HCV genotype 1 (73%) and 3 patients infected by HCV genotype non 1 (75%). Among the 36 patients with EOT, 6 patients relapsed during the 6 months after the end of therapy (16.6%). No factors were found to be significantly associated with EOT or SVR. Conclusion: The HCV genotype 1 is predominant in our serie; SVR was achieved with a high rate among cirrhotic and non cirrhotic pa- tients. No factors were found to be significantly associated with EOT or SVR. doi:10.1016/j.ajg.2009.07.084 (160) Predictors of responses to adefovir therapy in patients with lamivudine-resistant hepatitis B virus YMDD mutant before and after liver transplantation Ahmed Helmy b , Ayman. Abdo a , Hatim Mudawi a , Khalid Al-Kahtani b , Hamad Al-Ashgar b , Mohammed Al-Quiz b , Mohamed Al-Sofayan a , Mohamed Al-Saghier a , Hatem Khalaf a , Mohamed Al-Sebayel a a Department of Liver Transplantation, Hepatobiliary and Pancreatic Surgery Gastroenterology Unit, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia b Department of Internal Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Background and aims: Emergence of resistant YMDD-mutant strains is a common complication of lamivudine (LMV) treatment in hepatitis B virus (HBV) patients. This study prospectively assessed safety, biochemical, and virological responses to adefovir (ADV;10 mg daily) therapy in these patients. Patients and methods: Forty-five consecutive patients were in- cluded due to emergence of LMV-resistant YMDD mutant strain (n = 41), poor response (n = 3), and development of severe acute pan- creatitis (n = 1). Thirty-seven (86.7%) were males, 11 (24.4%) were diabetic, 12 (26.7%) were post-liver transplant, and 21 (46.7%) were HBeAg positive. The mean ± SD age and body weight were 44.0 ± 16.2 years and 70.0 ± 19.5 km, respectively. Results: The mean ± SD duration of LMV therapy and the follow up period on ADV therapy were 31.0 ± 15.4 months and 19.8 ± 10.1 months, respectively. Full biochemical response (transaminases nor- malization), partial virological (one Log 10 reduction), full virological (complete viral clearance) responses, and non response were ob- served in 32 (71.1%), 11 (24.4%), 18 (40.0%) and 16 (35.6%) patients, respectively. The mean ± SEM serum levels of ALT, AST and HBV DNA load at baseline (pre-ADV therapy) were 175 ± 40 IU/L, 89 ± 14 IU/L, and 61.40 ± 1.0 million copy/mL respectively. These were improved to 69 ± 6 IU/L, 53 ± 11 IU/L, and 35.0 ± 3.2 million copy/mL at the end of follow up (p = 0.01, p = 0.04, and p = 0.03, respectively, versus baseline levels). The mean ± SEM serum creatinine at baseline and at the end of follow up were 131 ± 22 and 144 ± 32 respectively; p > 0.05. Virological and biochemical responses to ADV therapy were similar in males and females, and in diabetic versus nondiabetics. Response was significantly better in post-transplant patients than pre-transplant cases (11 out of 12; 91.7% and 21 out of 33; 63.6% respectively; p = 0.021). HBeAg negative patients showed better response rate (17 out of 23; 73.9%) than HBeAg positive ones (11 out of 21; 52.4%) although it did not reach statistical significance (p = 0.064). Multivariate regression analysis showed that being post transplant and HBeAb positive are independent predictors of virological response (p = 0.022 and p = 0.031, respectively). Conclusion: ADV is a safe and effective therapy in pre- and post- liver transplantation patients infected with lamivudine-resistant HBV YMDD-mutant strains. The response to ADV is more in HBeAb positive and post-liver transplant cases. doi:10.1016/j.ajg.2009.07.085 (161) Sustained viral response in hepatitis C: Responders’ profile W. Khannoussi, R. Goubraim, N. Kabbaj, L. Amrani, M. El Kouhen, M. Acharki, M. Nya, N. Amrani EFD-Hepatogastroenterology Unit, Ibn Sina Universitary Hospital, Rabat, Morocco Background: In viral hepatitis C, sustained viral response (SVR) is defined as the absence of detection of viral RNA 6 months after the end of treatment. Prediction of SVR during treatment would allow clinicians to identify patients most likely to benefit from therapy. The aim of this study is to determine the characteristics of SVR patients with regard to response predictors in order to define the responders’ profile. Material and methods: A retrospective review of viral hepatitis C (VHC) patients treated in our unit from 2005 to 2008 was performed. Seventy-four patients fulfilled the selection criteria including ARN dosage 6 months after end of treatment, 44 were genotype 1 (59%) and 30 genotype 2 (41%). Out of the 74, 53 achieved SVR. We ana- lysed their profile: age, sex, comorbidities, genotype, baseline viral load, aminotransferases level, fibrosis degree, previous treatment, treatment regimen and duration, dose reduction and early viral re- sponse (EVR). We excluded the HVC-HIV or HCV-HVB co infected pa- tients. The treatment duration was adapted to the presence of SVR predictors. Though, genotype 1 naïve, relapsers and nonresponders AB66 Viral hepatitis / Arab Journal of Gastroenterology 10 (2009) AB61–AB71
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Transcript of (160) Predictors of responses to adefovir therapy in patients with lamivudine-resistant hepatitis B...
Introduction: A sustained viral response (SVR) to bitherapy forchronic hepatitis C may be obtained in 55% with the association ofpegylated interferon (PEGIFN) and ribavirin (RIB). However, only30–40% of patients attend SVR with standard interferon (sIFN) andribavirin.
The aim of our study is to evaluate the efficacy of PEGIFN andribavirin combination therapy in Tunisian patients with chronic hep-atitis C and to identify predictors to response to treatment.
Material and methods: A prospective study which included activechronic hepatitis C patients recruited from gastroenterology depart-ment of Rabta hospital between January 1997 and December 2007and who received bitherapy PEGIFN-ribavirin at a dose of 180mg/week for PEG IFN alpha2a or 1, 5 lg/kg/week for PEG IFN alpha 2b.Ribavirin was given at a dose between 800 and 1200 mg/day accord-ing to the weight and/or the viral genotype. The duration of treat-ment was 48weeks for genotype 1, 4 and 24 weeks for genotypes2, 3. The early virological response was evaluated only for HCV geno-type 1. The clinical end points of our study were the end-of-therapyvirological response (EOT) and the sustained virological response(SVR), 24 weeks after the end of the treatment. We excluded patientswho did not achieve the complete duration of treatment. The effectof sex, age, pre-treatment viral load, genotype, pre-treatment trans-aminase value, pre-treatment histological degree of fibrosis and ste-atosis on virological response were studied in unvaried analysis.
Results: A total of 41 patients were included in this study: 17male and 24 female with a mean age of 47.8years (extremes: 27–63 years). Thirty-seven patients were infected by HCV genotype 1(90.2%), 2 patients by genotype 2 (4.8%), one patients by genotype3 (2.4%) and one patient by genotype 4 (2.4%), ALT value was in-creased in 34 patients (83%) cases. Fifteen patients were cirrhotic(36.6%). For other patients, the degree of fibrosis was F3 (N = 11),F2 (N = 14) and F1 (N = 1). Biochemical response was obtained in35 cases (85.3%). At the end of treatment, 36 patients (87.8%) hadvirological response. SVR was achieved in 30 patients (73.2%).Among cirrhotic patients, 12 patients achieved SVR (80%) whereas18 non cirrhotic patients had SVR (69.2%). According to genotype,SVR was obtained in 27 patients infected by HCV genotype 1 (73%)and 3 patients infected by HCV genotype non 1 (75%). Among the36 patients with EOT, 6 patients relapsed during the 6 months afterthe end of therapy (16.6%). No factors were found to be significantlyassociated with EOT or SVR.
Conclusion: The HCV genotype 1 is predominant in our serie; SVRwas achieved with a high rate among cirrhotic and non cirrhotic pa-tients. No factors were found to be significantly associated with EOTor SVR.
doi:10.1016/j.ajg.2009.07.084
(160)Predictors of responses to adefovir therapy in patients withlamivudine-resistant hepatitis B virus YMDD mutant before andafter liver transplantation
Ahmed Helmy b, Ayman. Abdo a, Hatim Mudawi a, Khalid Al-Kahtani b,Hamad Al-Ashgar b, Mohammed Al-Quiz b, Mohamed Al-Sofayan a,Mohamed Al-Saghier a, Hatem Khalaf a, Mohamed Al-Sebayel a
a Department of Liver Transplantation, Hepatobiliary and Pancreatic SurgeryGastroenterology Unit, King Faisal Specialist Hospital and Research Centre,Riyadh, Saudi Arabiab Department of Internal Medicine, King Faisal Specialist Hospital and ResearchCentre, Riyadh, Saudi Arabia
Background and aims: Emergence of resistant YMDD-mutantstrains is a common complication of lamivudine (LMV) treatmentin hepatitis B virus (HBV) patients. This study prospectively assessed
safety, biochemical, and virological responses to adefovir (ADV;10mg daily) therapy in these patients.
Patients and methods: Forty-five consecutive patients were in-cluded due to emergence of LMV-resistant YMDD mutant strain(n = 41), poor response (n = 3), and development of severe acute pan-creatitis (n = 1). Thirty-seven (86.7%) were males, 11 (24.4%) werediabetic, 12 (26.7%) were post-liver transplant, and 21 (46.7%) wereHBeAg positive. The mean ± SD age and body weight were 44.0 ±16.2 years and 70.0 ± 19.5 km, respectively.
Results: The mean ± SD duration of LMV therapy and the followup period on ADV therapy were 31.0 ± 15.4 months and 19.8 ± 10.1months, respectively. Full biochemical response (transaminases nor-malization), partial virological (one Log10 reduction), full virological(complete viral clearance) responses, and non response were ob-served in 32 (71.1%), 11 (24.4%), 18 (40.0%) and 16 (35.6%) patients,respectively. The mean ± SEM serum levels of ALT, AST and HBV DNAload at baseline (pre-ADV therapy) were 175 ± 40 IU/L, 89 ± 14 IU/L,and 61.40 ± 1.0 million copy/mL respectively. These were improvedto 69 ± 6 IU/L, 53 ± 11 IU/L, and 35.0 ± 3.2 million copy/mL at theend of follow up (p = 0.01, p = 0.04, and p = 0.03, respectively, versusbaseline levels). The mean ± SEM serum creatinine at baseline and atthe end of follow up were 131 ± 22 and 144 ± 32 respectively;p > 0.05. Virological and biochemical responses to ADV therapy weresimilar in males and females, and in diabetic versus nondiabetics.Response was significantly better in post-transplant patients thanpre-transplant cases (11 out of 12; 91.7% and 21 out of 33; 63.6%respectively; p = 0.021). HBeAg negative patients showed betterresponse rate (17 out of 23; 73.9%) than HBeAg positive ones (11out of 21; 52.4%) although it did not reach statistical significance(p = 0.064). Multivariate regression analysis showed that being posttransplant and HBeAb positive are independent predictors ofvirological response (p = 0.022 and p = 0.031, respectively).
Conclusion: ADV is a safe and effective therapy in pre- and post-liver transplantation patients infected with lamivudine-resistantHBV YMDD-mutant strains. The response to ADV is more in HBeAbpositive and post-liver transplant cases.
doi:10.1016/j.ajg.2009.07.085
(161)Sustained viral response in hepatitis C: Responders’ profile
W. Khannoussi, R. Goubraim, N. Kabbaj, L. Amrani, M. El Kouhen, M. Acharki,M. Nya, N. AmraniEFD-Hepatogastroenterology Unit, Ibn Sina Universitary Hospital, Rabat, Morocco
Background: In viral hepatitis C, sustained viral response (SVR) isdefined as the absence of detection of viral RNA 6 months after theend of treatment. Prediction of SVR during treatment would allowclinicians to identify patients most likely to benefit from therapy.
The aim of this study is to determine the characteristics of SVRpatients with regard to response predictors in order to define theresponders’ profile.
Material and methods: A retrospective review of viral hepatitis C(VHC) patients treated in our unit from 2005 to 2008 was performed.Seventy-four patients fulfilled the selection criteria including ARNdosage 6 months after end of treatment, 44 were genotype 1 (59%)and 30 genotype 2 (41%). Out of the 74, 53 achieved SVR. We ana-lysed their profile: age, sex, comorbidities, genotype, baseline viralload, aminotransferases level, fibrosis degree, previous treatment,treatment regimen and duration, dose reduction and early viral re-sponse (EVR). We excluded the HVC-HIV or HCV-HVB co infected pa-tients. The treatment duration was adapted to the presence of SVRpredictors. Though, genotype 1 naïve, relapsers and nonresponders
AB66 Viral hepatitis / Arab Journal of Gastroenterology 10 (2009) AB61–AB71
