- Email: [email protected]
Impressive Gains in Patient-Reported Outcomes are Observed in Chronic Hepatitis C Patients with or without Cirrhosis who are Treated with Sofosbuvir and Velpatasvir: Results from Astral-1, -2, -3 and-4
POSTER PRESENTATIONS Kaplan-Meier estimates of portal hypertensive complications by baseline MELD strata after adjustment for SVR are shown (Figure).
Conclusions: While achieving HCV cure remains important, MELD score increase during HCV treatment among patients with compensated and decompensated cirrhosis significantly increases risk of future portal hypertensive complications. As a result, ontreatment MELD score changes may be helpful in discriminating between patients with cirrhosis that will go on to further decompensate and need liver transplant rescue. FRI-199 CHARACTERIZATION OF THE LONGITUDINAL FIBROSIS CHANGES IN HEPATITIS C PATIENTS AFTER VIROLOGIC CURE: A META-ANALYSIS OF THE HISTOLOGIC DATA Y. Wang1, Z. Liu1, X. Wei1, T. Chen1, C. Huang1. 1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Southern Medical University Nanfang Hospital, Guangzhou, China E-mail: [email protected] Background and Aims: Virologic cure becomes available for most patients with chronic hepatitis C (CHC), but the residual fibrosis burden remains an independent risk factor for liver-related complications. Characterization of the fibrosis changes in the virologically-cured patients could provide meaningful information for guiding follow-up. Methods: Databases from inception to November 4, 2015 were searched for the cohort studies that had pre- and post- treatment evaluation of histologic fibrosis in CHC patients with sustained virologic response (SVR). The association of SVR with the incidence, extent and rate of fibrosis changes and the possible involving factors were identified. Results: A total of 3,023 eligible participants were included in the meta-analyses. 65% were male. Mean age was 45 yrs old. Antiviral regimens were based on interferon or the combination of interferon and ribavirin. Mean incidence of SVR was 41.3%. Biopsy interval ranged from 1.5 to 4.6 yrs. Mean baseline fibrosis score was 2.3 points (METAVIR). The incidence of fibrosis regression was higher in SVR (34.8%) vs Non-SVR (16.9%) patients (RR: 2.15; 95%CI: 1.61–2.87; p < 0.001), regardless of the definition of fibrosis change, baseline fibrosis, or the baseline BMI. Rate of fibrosis regression ranged from −0.12 to −0.67 points/yr in SVR patients, while from 0.12 to −0.21 points/yr in Non-SVR patients. More decrease of fibrosis occurred in SVR (−0.54 ± 0.34 points) vs Non-SVR (0.01 ± 0.23 points) patients ( p = 0.004). Severe baseline fibrosis (F > 2) might have a more rapid change in regression than the significant baseline fibrosis (F ≤ 2) in the SVR patients (−0.73 points/yr vs −0.12 points/yr, p = 0.000). The incidences of fibrosis progression and no change of fibrosis were significantly greater in Non-SVR vs SVR patients by 22.6% vs 4.4% (RR: 5.33; 95%CI: 3.11–9.13, p < 0.001) and 55.7% vs 43.5% (RR: 1.37; 95%CI: 1.18–1.59, p < 0.001), respectively.
S628
Conclusions: There could be a beneficial characteristic of fibrosis change in CHC SVR patients in terms of the incidence, extent and rate of fibrosis regression. However, the issue of residual fibrosis could still be critical even after SVR due to the unignorable incidence of no change in fibrosis in these patients within 5 yrs after treatment. FRI-200 IMPRESSIVE GAINS IN PATIENT-REPORTED OUTCOMES ARE OBSERVED IN CHRONIC HEPATITIS C PATIENTS WITH OR WITHOUT CIRRHOSIS WHO ARE TREATED WITH SOFOSBUVIR AND VELPATASVIR: RESULTS FROM ASTRAL-1, -2, -3 AND-4 Z.M. Younossi1, M. Stepanova2, J. Feld3, S. Zeuzem4, M. Sulkowski5, G.R. Foster6, A. Mangia7, M. Charlton8, J.G. O’Leary9, M.P. Curry10, S. Hunt2. 1Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church; 2Center for Outcomes Research, Washington, D.C., United States; 3Toronto Center for Livef Disease, Toronto, Canada; 4Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 5Johns Hopkins University, Baltimore, United States; 6Queen Mary University London, London, United Kingdom; 7Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; 8Intermountain Medical Center, Salt Lake Cioty; 9Baylor University Medical Center, Dallas; 10Beth Israel Deaconess Medical Center, Boston, United States E-mail: [email protected] Background and Aims: Patients with HCV and cirrhosis report significant impairment of patient-reported outcomes (PROs) such as health-related quality of life and fatigue. Our aim was to compare the effect of sofosbuvir and velpatasvir (SOF/VEL) on PROs in HCV patients with and without cirrhosis. Methods: Efficacy, safety and patient-reported outcomes (SF-36, CLDQ-HCV, FACIT-F, WPAI:HCV) were assessed in four prospectively designed phase 3 clinical trials of SOF/VEL (ASTRAL-1 through ASTRAL-4). The baseline PROs and treatment-emergent changes in PRO scores were compared between patients with and without cirrhosis who were treated with SOF/VEL. Results: A total of 1,213 patients received SOF/VEL for 12 or 24 weeks: 813 without cirrhosis and 400 with cirrhosis. Patients with cirrhosis were older, more frequently male, had lower employment rate, as well as more pre-treatment anxiety, fatigue and type 2 diabetes (all p < 0.05). At baseline, patients with cirrhosis also had significantly lower PRO scores (up to −18.9 points on a universal 0–100 scale, p < 0.05 for 21 out of 25 studied PROs). In multivariate analysis, adjusted for demographics and clinical factors at baseline, having cirrhosis was independently associated with substantial impairment of PROs (−5.2 to −11.4 points to the summary PROs, all p < 0.05). The SVR-12 rates were 98.5% in non-cirrhotic and 91.0% in cirrhotic patients who were treated with SOF/LDV ( p < 0.0001). By the end of treatment, significant improvements in PRO scores were observed in patients with cirrhosis (the average improvement across 25 PRO domains was +5.6 points, maximum +14.6, p < 0.05 for 21/25 PROs), as well as in patients without cirrhosis (average +2.6 points, maximum +9.8 points, p < 0.05 for 19/25 PROs). After 12 weeks of follow-up, these improvements remained significant in both cirrhotics (up to +14.3 points, p < 0.05 for 21/25 PROs) and noncirrhotics (up to +10.9 points, p < 0.05 for 23/25 PROs). After 24 weeks of follow-up, more improvements were noted in some PRO scores (up to +14.6 points, p < 0.0001) regardless of the presence or absence of cirrhosis. In multivariate analysis, improvements in physical health-related PROs during treatment were more substantial in cirrhotic patients than in non-cirrhotic patients (by +1.6 to +6.2 points, p < 0.05). Conclusions: Patients with and without cirrhosis experience significant improvement of their PROs during treatment with an all-oral SOF/VEL regimen and after achieving SVR.
Journal of Hepatology 2016 vol. 64 | S425–S630
Conclusions: While achieving HCV cure remains important, MELD score increase during HCV treatment among patients with compensated and decompensated cirrhosis significantly increases risk of future portal hypertensive complications. As a result, ontreatment MELD score changes may be helpful in discriminating between patients with cirrhosis that will go on to further decompensate and need liver transplant rescue. FRI-199 CHARACTERIZATION OF THE LONGITUDINAL FIBROSIS CHANGES IN HEPATITIS C PATIENTS AFTER VIROLOGIC CURE: A META-ANALYSIS OF THE HISTOLOGIC DATA Y. Wang1, Z. Liu1, X. Wei1, T. Chen1, C. Huang1. 1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Southern Medical University Nanfang Hospital, Guangzhou, China E-mail: [email protected] Background and Aims: Virologic cure becomes available for most patients with chronic hepatitis C (CHC), but the residual fibrosis burden remains an independent risk factor for liver-related complications. Characterization of the fibrosis changes in the virologically-cured patients could provide meaningful information for guiding follow-up. Methods: Databases from inception to November 4, 2015 were searched for the cohort studies that had pre- and post- treatment evaluation of histologic fibrosis in CHC patients with sustained virologic response (SVR). The association of SVR with the incidence, extent and rate of fibrosis changes and the possible involving factors were identified. Results: A total of 3,023 eligible participants were included in the meta-analyses. 65% were male. Mean age was 45 yrs old. Antiviral regimens were based on interferon or the combination of interferon and ribavirin. Mean incidence of SVR was 41.3%. Biopsy interval ranged from 1.5 to 4.6 yrs. Mean baseline fibrosis score was 2.3 points (METAVIR). The incidence of fibrosis regression was higher in SVR (34.8%) vs Non-SVR (16.9%) patients (RR: 2.15; 95%CI: 1.61–2.87; p < 0.001), regardless of the definition of fibrosis change, baseline fibrosis, or the baseline BMI. Rate of fibrosis regression ranged from −0.12 to −0.67 points/yr in SVR patients, while from 0.12 to −0.21 points/yr in Non-SVR patients. More decrease of fibrosis occurred in SVR (−0.54 ± 0.34 points) vs Non-SVR (0.01 ± 0.23 points) patients ( p = 0.004). Severe baseline fibrosis (F > 2) might have a more rapid change in regression than the significant baseline fibrosis (F ≤ 2) in the SVR patients (−0.73 points/yr vs −0.12 points/yr, p = 0.000). The incidences of fibrosis progression and no change of fibrosis were significantly greater in Non-SVR vs SVR patients by 22.6% vs 4.4% (RR: 5.33; 95%CI: 3.11–9.13, p < 0.001) and 55.7% vs 43.5% (RR: 1.37; 95%CI: 1.18–1.59, p < 0.001), respectively.
S628
Conclusions: There could be a beneficial characteristic of fibrosis change in CHC SVR patients in terms of the incidence, extent and rate of fibrosis regression. However, the issue of residual fibrosis could still be critical even after SVR due to the unignorable incidence of no change in fibrosis in these patients within 5 yrs after treatment. FRI-200 IMPRESSIVE GAINS IN PATIENT-REPORTED OUTCOMES ARE OBSERVED IN CHRONIC HEPATITIS C PATIENTS WITH OR WITHOUT CIRRHOSIS WHO ARE TREATED WITH SOFOSBUVIR AND VELPATASVIR: RESULTS FROM ASTRAL-1, -2, -3 AND-4 Z.M. Younossi1, M. Stepanova2, J. Feld3, S. Zeuzem4, M. Sulkowski5, G.R. Foster6, A. Mangia7, M. Charlton8, J.G. O’Leary9, M.P. Curry10, S. Hunt2. 1Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church; 2Center for Outcomes Research, Washington, D.C., United States; 3Toronto Center for Livef Disease, Toronto, Canada; 4Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 5Johns Hopkins University, Baltimore, United States; 6Queen Mary University London, London, United Kingdom; 7Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; 8Intermountain Medical Center, Salt Lake Cioty; 9Baylor University Medical Center, Dallas; 10Beth Israel Deaconess Medical Center, Boston, United States E-mail: [email protected] Background and Aims: Patients with HCV and cirrhosis report significant impairment of patient-reported outcomes (PROs) such as health-related quality of life and fatigue. Our aim was to compare the effect of sofosbuvir and velpatasvir (SOF/VEL) on PROs in HCV patients with and without cirrhosis. Methods: Efficacy, safety and patient-reported outcomes (SF-36, CLDQ-HCV, FACIT-F, WPAI:HCV) were assessed in four prospectively designed phase 3 clinical trials of SOF/VEL (ASTRAL-1 through ASTRAL-4). The baseline PROs and treatment-emergent changes in PRO scores were compared between patients with and without cirrhosis who were treated with SOF/VEL. Results: A total of 1,213 patients received SOF/VEL for 12 or 24 weeks: 813 without cirrhosis and 400 with cirrhosis. Patients with cirrhosis were older, more frequently male, had lower employment rate, as well as more pre-treatment anxiety, fatigue and type 2 diabetes (all p < 0.05). At baseline, patients with cirrhosis also had significantly lower PRO scores (up to −18.9 points on a universal 0–100 scale, p < 0.05 for 21 out of 25 studied PROs). In multivariate analysis, adjusted for demographics and clinical factors at baseline, having cirrhosis was independently associated with substantial impairment of PROs (−5.2 to −11.4 points to the summary PROs, all p < 0.05). The SVR-12 rates were 98.5% in non-cirrhotic and 91.0% in cirrhotic patients who were treated with SOF/LDV ( p < 0.0001). By the end of treatment, significant improvements in PRO scores were observed in patients with cirrhosis (the average improvement across 25 PRO domains was +5.6 points, maximum +14.6, p < 0.05 for 21/25 PROs), as well as in patients without cirrhosis (average +2.6 points, maximum +9.8 points, p < 0.05 for 19/25 PROs). After 12 weeks of follow-up, these improvements remained significant in both cirrhotics (up to +14.3 points, p < 0.05 for 21/25 PROs) and noncirrhotics (up to +10.9 points, p < 0.05 for 23/25 PROs). After 24 weeks of follow-up, more improvements were noted in some PRO scores (up to +14.6 points, p < 0.0001) regardless of the presence or absence of cirrhosis. In multivariate analysis, improvements in physical health-related PROs during treatment were more substantial in cirrhotic patients than in non-cirrhotic patients (by +1.6 to +6.2 points, p < 0.05). Conclusions: Patients with and without cirrhosis experience significant improvement of their PROs during treatment with an all-oral SOF/VEL regimen and after achieving SVR.
Journal of Hepatology 2016 vol. 64 | S425–S630