- Email: [email protected]
Sa1061 Similar GI Side Effects With Once-Daily Versus Twice-Daily Dosing Ribavirin in HCV-Positive Patients on Triple Therapy
the antigen specificity as B cell receptor on the cell surface was used to isolate single HCVspecific IgG+ memory B cells by Fluorescence Assisted Cell Sorting (FACS). We used a RTPCR based approach to clone and in vitro monoclonally express antibodies from single memory B cells obtained from patients with spontaneous viral clearance and from chronically infected individuals. By characterizing the individual heavy and light chain sequences of each cell we could show higher numbers of somatic hypermutation as sign of affinity maturation as well as a biased repertoire of V-gene usage in heavy chains of patients with spontaneous viral clearance. The characterisation of the antibody reactivity profile of IgG+ memory B cells of spontaneous resolvers and patients with chronic hepatitis C will give insights to the selection of human anti-HCV antibodies and will offer the opportunity to identify and amplify protective antibodies against HCV. Human anti-HCV antibodies will help understanding humoral responses to viral antigens and may as well serve as a potential therapeutic option in infection prophylaxis by passive immunisation. Sa1063 Hematological Indices Improve With Eradication of HCV in Cirrhosis and Predict Clinical Decompensation in Non Responders Raffi Karagozian, Norman D. Grace, Amir A. Qamar Background: The prevalence of anemia, thrombocytopenia, and leukopenia (alone or in combination) is relatively high in patients with cirrhosis from HCV. Abnormal hematological indices (HI) occur in HCV cirrhosis due to a number of causes including portal hypertension, low thrombopoietin levels and bone marrow suppression. Aims: To assess if HI improve with HCV eradication and whether post treatment HI can predict clinical decompensation in patients who do not respond to treatment. Methods: A total of 153 patients with HCV cirrhosis treated with Peg-interferon and Ribavirin were identified. Inclusion criteria: .18 years, therapy with Peginterferon and Ribavirin, compensated liver disease and Metavir score of 4 on biopsy. Exclusion criteria: early stage fibrosis, post-liver transplant, HIV co-infection, untreated patients. Abnormal HI was defined as Thrombocytopenia (TH) , 150,000, Leukopenia (LE) , 4,000 and Anemia , 13.5 g/dl (male) 11.5 g/dl (female). Patients who decompensated on therapy or with missing data points on follow-up were excluded. Clinical and laboratory data were collected throughout follow-up. Repeated 2-way ANOVA was performed to compare means. Clinical decompensation (CD) was defined by new ascites, jaundice, encephalopathy or variceal hemorrhage during follow-up. Univariate and multivariate analysis was used to assess clinical decompensation. Results: A total of 131 patients met criteria. The SVR rate was 26%. During a median follow-up of 56.5 months, PLT and WBC counts improved in patients with HCV eradication compared to those where treatment was unsuccessful (p,0.05) (FIGURE). On univariate analysis, the presence of TH (OR 15.6, pvalue , 0.001) 6 months after completing therapy was significantly associated with CD while LE (OR 2.6, p-value 0.06) and anemia (OR 2.28, p-value 0.09) were not. Multivariate analysis of variables at 6 months after completion of therapy continued to show TH (15.1, p-value , 0.001) predicted CD when controlled for albumin (OR 0.5, p-value 0.27), MELD (OR 1.1, p-value 0.63) and age (OR 0.98, p-value 0.54. Conclusion: PLT and WBC counts improve significantly in patients with cirrhosis who respond to antiviral therapy against HCV. The presence of thrombocytopenia 6 months after completion of antiviral therapy predicts a higher risk of clinical decompensation. After anti viral therapy, thrombocytopenia may be considered as a predictor of poor prognosis in compensated cirrhosis after unsuccessful therapy.
AASLD Abstracts
Hemoglobin Response to Pegylated Interferon, Ribavirin, and Boceprevir or Telaprevir Sa1061 Similar GI Side Effects With Once-Daily Versus Twice-Daily Dosing Ribavirin in HCV-Positive Patients on Triple Therapy Kian Bichoupan, Valerie Martel-Laferriere, Michel Ng, Andrea D. Branch, Douglas T. Dieterich BACKGROUND: Ribavirin (RBV) is part of triple therapy for HCV infection. RBV is approved for twice-daily (divided) dosing, but its long half-life should allow once-daily dosing unless this increases toxicity and/or side effects. AIM: To assess side effects of twice-daily (2x/d) vs. once-daily (1x/d) RBV dosing during triple therapy. METHODS: A structured interview was used to collect information from 74 subjects whose medical records were also reviewed, with IRB approval. Patients provided data about RBV dosing, changes in dosing over time, dosing preferences, and Gl side effects (nausea, diarrhea, and vomiting). RESULTS: Fiftyeight patients were on telaprevir-based and 16 patients were on boceprevir-based triple therapy; 71 took 180 μg peg-IFN, 3 took 135 μg peg-IFN, all took weight-based RBV ( ,61 kg, 800 mg/d; ,75 kg, 1000 mg/d; ≥75 kg,1200 mg/d). Mean age was 57 yr (SD=9.3); 32 had advanced fibrosis/cirrhosis. Median duration of treatment was 25 wk (range 8 to 48). AEs were frequent and often severe: 10 patients had an ER visit, 11 were hospitalized, 7 were transfused, and 34 took EPO. Among the 74 patients, 35 (47%) had nausea, 13 (18%) had vomiting, and 25 (34%) had diarrhea. Importantly, among 9 patients on full-dose RBV who switched from 2x/d to 1x/d RBV, 7 had nausea on 2x/d (5 improved on 1x/d), 5 had vomiting on 2x/d (3 improved on 1x/d), 3 had diarrhea on 2x/d (one improved on 1x/d). None reported worse GI symptoms on 1x/d than on 2x/d dosing, despite taking the same amount of RBV per day; most (8/9) preferred 1x/d dosing. For comparison, among 33 patients on full-dose RBV 2x/d throughout treatment, 13 had nausea, 3 had vomiting, 10 had diarrhea; 13/33 expressed a preference for 1x/d, 12 expressed a preference for 2x/d (primarily because this matched the drug label), and 8 had no preference. In a second comparison group, 6 patients took full-dose RBV 1x/d throughout, 2 had nausea, 2 had vomiting, and 3 had diarrhea; all preferred 1x/d dosing. Nineteen people in a third comparison group started on full-dose RBV 2x/d and switched to 1x/d coincident with a 25-50% dose reduction; 11 had nausea on 2x/d (4 improved on 1x/d, with dose reduction); 3 had vomiting on 2x/d (1 improved on 1x/d, with dose reduction); 5 had diarrhea on 2x/d (2 improved on 1x/d-dose, with reduction); 13/19 preferred 1x/d, one had no preference. Finally, among a mixed group of 7 patients who had a dose reduction without a change in dosing schedule (one on 1x/d, 6 on 2x/d), 2 had nausea, none had vomiting, and 4 had diarrhea. CONCLUSION: Once-daily use of RBV did not increase GI side effects compared to divided dosing, and most patients expressed a preference for 1x/d dosing. Our sample was small, however, with 35 people who took RBV 1x/d (in some cases at a reduced amount). Clinical management was complex. A randomized trial is needed to confirm our promising findings. Sa1062 Characterization of anti-HCV Antibody Repertoire of IgG+ Memory B Cells in Patients With Chronic Hepatitis C and Spontaneous Resolvers in a Single Source Outbreak Anne Olbrich, Thomas Berg, Hedda Wardemann, Julia Benckert While in most cases acute hepatitis C virus (HCV) infection leads to the development of chronic hepatitis C, spontaneous viral clearance occurs in a smaller percentage of individuals. For the successful control of the viral replication in the early phase of infection the adaptive immune system is crucial. Several studies have shown that protective anti-HCV antibodies are able to prevent an infection with HCV. However, it is unknown whether differences in antibody repertoire mediate the ability to spontaneously eradicate the infection. The persistence of antibodies years and even decades after spontaneous (or treatment-induced) eradication of HCV infection indicates that humoral memory is maintained even in the absence of viral antigen over long periods. We isolated HCV specific IgG+ memory B cells from peripheral blood of 3 patients with chronic hepatitis C and 3 patients with spontaneous viral clearance that were infected in a single-source outbreak by an identical HCV-strain in the context of a contaminated Rhesus prophylaxis in the years 1978/79 in East Germany. Presentation of
AASLD Abstracts
Figure 1: Long term follow-up of platelets, leukocytes and hemoglobin post therapy. SVR patients show significant improvement in platelets and leukocytes compared to non-SVR patients in follow-up (p,0.05) while no difference in hemoglobin between SVR and NonSVR groups was observed (p=0.96).
S-986
AASLD Abstracts
Hemoglobin Response to Pegylated Interferon, Ribavirin, and Boceprevir or Telaprevir Sa1061 Similar GI Side Effects With Once-Daily Versus Twice-Daily Dosing Ribavirin in HCV-Positive Patients on Triple Therapy Kian Bichoupan, Valerie Martel-Laferriere, Michel Ng, Andrea D. Branch, Douglas T. Dieterich BACKGROUND: Ribavirin (RBV) is part of triple therapy for HCV infection. RBV is approved for twice-daily (divided) dosing, but its long half-life should allow once-daily dosing unless this increases toxicity and/or side effects. AIM: To assess side effects of twice-daily (2x/d) vs. once-daily (1x/d) RBV dosing during triple therapy. METHODS: A structured interview was used to collect information from 74 subjects whose medical records were also reviewed, with IRB approval. Patients provided data about RBV dosing, changes in dosing over time, dosing preferences, and Gl side effects (nausea, diarrhea, and vomiting). RESULTS: Fiftyeight patients were on telaprevir-based and 16 patients were on boceprevir-based triple therapy; 71 took 180 μg peg-IFN, 3 took 135 μg peg-IFN, all took weight-based RBV ( ,61 kg, 800 mg/d; ,75 kg, 1000 mg/d; ≥75 kg,1200 mg/d). Mean age was 57 yr (SD=9.3); 32 had advanced fibrosis/cirrhosis. Median duration of treatment was 25 wk (range 8 to 48). AEs were frequent and often severe: 10 patients had an ER visit, 11 were hospitalized, 7 were transfused, and 34 took EPO. Among the 74 patients, 35 (47%) had nausea, 13 (18%) had vomiting, and 25 (34%) had diarrhea. Importantly, among 9 patients on full-dose RBV who switched from 2x/d to 1x/d RBV, 7 had nausea on 2x/d (5 improved on 1x/d), 5 had vomiting on 2x/d (3 improved on 1x/d), 3 had diarrhea on 2x/d (one improved on 1x/d). None reported worse GI symptoms on 1x/d than on 2x/d dosing, despite taking the same amount of RBV per day; most (8/9) preferred 1x/d dosing. For comparison, among 33 patients on full-dose RBV 2x/d throughout treatment, 13 had nausea, 3 had vomiting, 10 had diarrhea; 13/33 expressed a preference for 1x/d, 12 expressed a preference for 2x/d (primarily because this matched the drug label), and 8 had no preference. In a second comparison group, 6 patients took full-dose RBV 1x/d throughout, 2 had nausea, 2 had vomiting, and 3 had diarrhea; all preferred 1x/d dosing. Nineteen people in a third comparison group started on full-dose RBV 2x/d and switched to 1x/d coincident with a 25-50% dose reduction; 11 had nausea on 2x/d (4 improved on 1x/d, with dose reduction); 3 had vomiting on 2x/d (1 improved on 1x/d, with dose reduction); 5 had diarrhea on 2x/d (2 improved on 1x/d-dose, with reduction); 13/19 preferred 1x/d, one had no preference. Finally, among a mixed group of 7 patients who had a dose reduction without a change in dosing schedule (one on 1x/d, 6 on 2x/d), 2 had nausea, none had vomiting, and 4 had diarrhea. CONCLUSION: Once-daily use of RBV did not increase GI side effects compared to divided dosing, and most patients expressed a preference for 1x/d dosing. Our sample was small, however, with 35 people who took RBV 1x/d (in some cases at a reduced amount). Clinical management was complex. A randomized trial is needed to confirm our promising findings. Sa1062 Characterization of anti-HCV Antibody Repertoire of IgG+ Memory B Cells in Patients With Chronic Hepatitis C and Spontaneous Resolvers in a Single Source Outbreak Anne Olbrich, Thomas Berg, Hedda Wardemann, Julia Benckert While in most cases acute hepatitis C virus (HCV) infection leads to the development of chronic hepatitis C, spontaneous viral clearance occurs in a smaller percentage of individuals. For the successful control of the viral replication in the early phase of infection the adaptive immune system is crucial. Several studies have shown that protective anti-HCV antibodies are able to prevent an infection with HCV. However, it is unknown whether differences in antibody repertoire mediate the ability to spontaneously eradicate the infection. The persistence of antibodies years and even decades after spontaneous (or treatment-induced) eradication of HCV infection indicates that humoral memory is maintained even in the absence of viral antigen over long periods. We isolated HCV specific IgG+ memory B cells from peripheral blood of 3 patients with chronic hepatitis C and 3 patients with spontaneous viral clearance that were infected in a single-source outbreak by an identical HCV-strain in the context of a contaminated Rhesus prophylaxis in the years 1978/79 in East Germany. Presentation of
AASLD Abstracts
Figure 1: Long term follow-up of platelets, leukocytes and hemoglobin post therapy. SVR patients show significant improvement in platelets and leukocytes compared to non-SVR patients in follow-up (p,0.05) while no difference in hemoglobin between SVR and NonSVR groups was observed (p=0.96).
S-986