- Email: [email protected]
Model for Endstage Liver Disease (MELD) Score Changes during Hepatitis C Virus Treatment of Patients with Cirrhosis Predicts Long-Term Portal Hypertensive Complications
POSTER PRESENTATIONS for a potentially faster improvement of liver function after HCVcuring. FRI-197 DXN VERIS SYSTEM FOR HCV VIRAL LOAD MONITORING IN THE ERA OF SECOND WAVE DIRECT-ACTING ANTIVIRAL AGENTS V. Micheli1, A. Lombardi1, A. Mancon1, D. Mileto1, N. Zanchetta1, C.F. Magni2, L. Milazzo3, E. Angeli2, G. Gubertini2, M. Galli3, M.R. Gismondo1. 1Clinical Microbiology, Virology and Bioemergencies; 2 Division of Infectious Disease; 3Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Milan, Italy E-mail: [email protected] Background and Aims: The treatment of chronic HCV infection has been deeply modified by the introduction of the second wave of direct-acting antiviral agents (DAAs) combination regimens (±Ribavirin) that strongly correlate with a high rate of therapy success and tolerability, minimizing relapse rate. Viral load (VL) quantification through high sensitive, accurate and rapid methods plays a central role in therapy follow-up. The aim of this study was to evaluate DxN Veris System (Beckman Coulter) performance in this clinical setting.
this value the result is labelled as < 12D (if detectable/not quantifiable) or TND (if target not detected). DxN Veris System is a highly automated random access technology, while m2000rt system works in batch. Results: The good correlation between the methods is shown in Fig. 1, regardless the VL levels and viral genotype. The comparison analysis on 429 valuable samples provided concordant results in 327 samples: 243 quantified (58 and 14 with a difference >0.5 and >1.0 Log IU/mL, respectively), 3 < 12D and 81 TND; the highest discrepancy concerns 75 samples TND by Veris vs quantified (n = 27) and < 12D (n = 48) by m2000rt. For 19 patients with known virological outcome, 7 showed comparable trend with both systems, while 8/11 reached TND at earlier time points according to Veris vs m2000rt system; the reliability of these results is confirmed by a documented eradication of HCV infection by both methods at week 12 after discontinuation. Conclusions: DxN Veris System proved suitable for use in new HCV treatment monitoring; its positive predictive value of treatment success at earlier time points, as TND results in patients really eradicating the infection, deserves further investigation on a wider panel of patients. Moreover, thanks to its random access and the fast results, this platform could revolutionize the clinical approach in the management of HCV therapy, advantaging the cost-benefits balance. FRI-198 MODEL FOR ENDSTAGE LIVER DISEASE (MELD) SCORE CHANGES DURING HEPATITIS C VIRUS TREATMENT OF PATIENTS WITH CIRRHOSIS PREDICTS LONG-TERM PORTAL HYPERTENSIVE COMPLICATIONS V. Saxena1, L. Nyberg2, A. Dasgupta1, S. Straley1, L. Catalli1, A. Nyberg2, N. Terrault1. 1University of California San Francisco, San Francisco; 2 Kaiser Permanente Southern California, San Deigo, United States E-mail: [email protected]
Methods: A total of 86 HCV+ patients was evaluated for VL quantification during the administration of a DAAs combination regimen. According to therapy history and viral genotype, plasma samples were collected at baseline, day 2, week 1, 2, 4 or 8, and for a subgroup of patients (n = 19) at additional time points, including week 4 and week 12 after the treatment discontinuation. Independent aliquots of frozen plasma samples were tested by DxN Veris System and compared with the results previously obtained by our routine system (m2000rt by Abbott). Both methods provide the same limit of quantification (12 IU/mL): below
Background and Aims: All-oral antiviral therapy for hepatitis C virus (HCV = results in high rates of sustained virologic response (SVR) and on-treatment MELD score improvements among patients with cirrhosis. The impact of MELD score changes on longer-term hepatic outcomes in patients with cirrhosis, especially those who are Child-Pugh (CP) B/C, is currently unknown. We aimed to compare the liver-related events in a cohort of HCV-infected patients with compensated and decompensated cirrhosis treated with all oral antiviral therapy vs. untreated matched controls. Methods: Adults with HCV genotype 1 cirrhosis treated with simeprevir (SMV) + sofosbuvir (SOF) ± ribavirin (RBV) were followed for a median of 0.95 yrs (IQR: 0.88-0.99) after treatment discontinuation. Randomly selected, untreated controls (1–3/pt) matched on site, age ± 5 yrs, CP (A vs. B/C) and MELD score ± 2 were followed for a similar duration. Safety outcome included presence of portal hypertensive complications (new/worsening ascites, varices, encephalopathy and/or spontaneous bacterial peritonitis). Time to portal hypertensive complications was compared in treated patients and matched controls over equivalent timeframes. On-treatment MELD score change was calculated by subtracting MELD score after treatment discontinuation from baseline MELD score. Results: Of 371 patients, 93 were treated with SMV+SOF ± RBV and 278 were matched, untreated controls. Cohort median age was 62yrs (IQR: 58–68), 32% female, 25% Hispanic, 5% Black, 24% diabetes, median (range) platelet count 133 K/mm3 (20–341), albumin 3.5 g/dL (2.3–4.7), MELD 8 (6–18), 35% CP-B/C, 22% ascites, 22% encephalopathy, 8% varices. Of the SMV+SOF ± RBV treated patients, 78 (84%) achieved SVR and median on-treatment MELD change was 0 (range: −5 to 29). In multivariate Cox survival analysis controlling for baseline MELD score, non-SVR/untreated vs. SVR (HR 6.4, 95% CI 3.0-21) and on-treatment MELD change (HR 1.2 per point, 95% CI 1.1–1.3) predicted portal hypertensive complications.
Journal of Hepatology 2016 vol. 64 | S425–S630
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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.
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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
this value the result is labelled as < 12D (if detectable/not quantifiable) or TND (if target not detected). DxN Veris System is a highly automated random access technology, while m2000rt system works in batch. Results: The good correlation between the methods is shown in Fig. 1, regardless the VL levels and viral genotype. The comparison analysis on 429 valuable samples provided concordant results in 327 samples: 243 quantified (58 and 14 with a difference >0.5 and >1.0 Log IU/mL, respectively), 3 < 12D and 81 TND; the highest discrepancy concerns 75 samples TND by Veris vs quantified (n = 27) and < 12D (n = 48) by m2000rt. For 19 patients with known virological outcome, 7 showed comparable trend with both systems, while 8/11 reached TND at earlier time points according to Veris vs m2000rt system; the reliability of these results is confirmed by a documented eradication of HCV infection by both methods at week 12 after discontinuation. Conclusions: DxN Veris System proved suitable for use in new HCV treatment monitoring; its positive predictive value of treatment success at earlier time points, as TND results in patients really eradicating the infection, deserves further investigation on a wider panel of patients. Moreover, thanks to its random access and the fast results, this platform could revolutionize the clinical approach in the management of HCV therapy, advantaging the cost-benefits balance. FRI-198 MODEL FOR ENDSTAGE LIVER DISEASE (MELD) SCORE CHANGES DURING HEPATITIS C VIRUS TREATMENT OF PATIENTS WITH CIRRHOSIS PREDICTS LONG-TERM PORTAL HYPERTENSIVE COMPLICATIONS V. Saxena1, L. Nyberg2, A. Dasgupta1, S. Straley1, L. Catalli1, A. Nyberg2, N. Terrault1. 1University of California San Francisco, San Francisco; 2 Kaiser Permanente Southern California, San Deigo, United States E-mail: [email protected]
Methods: A total of 86 HCV+ patients was evaluated for VL quantification during the administration of a DAAs combination regimen. According to therapy history and viral genotype, plasma samples were collected at baseline, day 2, week 1, 2, 4 or 8, and for a subgroup of patients (n = 19) at additional time points, including week 4 and week 12 after the treatment discontinuation. Independent aliquots of frozen plasma samples were tested by DxN Veris System and compared with the results previously obtained by our routine system (m2000rt by Abbott). Both methods provide the same limit of quantification (12 IU/mL): below
Background and Aims: All-oral antiviral therapy for hepatitis C virus (HCV = results in high rates of sustained virologic response (SVR) and on-treatment MELD score improvements among patients with cirrhosis. The impact of MELD score changes on longer-term hepatic outcomes in patients with cirrhosis, especially those who are Child-Pugh (CP) B/C, is currently unknown. We aimed to compare the liver-related events in a cohort of HCV-infected patients with compensated and decompensated cirrhosis treated with all oral antiviral therapy vs. untreated matched controls. Methods: Adults with HCV genotype 1 cirrhosis treated with simeprevir (SMV) + sofosbuvir (SOF) ± ribavirin (RBV) were followed for a median of 0.95 yrs (IQR: 0.88-0.99) after treatment discontinuation. Randomly selected, untreated controls (1–3/pt) matched on site, age ± 5 yrs, CP (A vs. B/C) and MELD score ± 2 were followed for a similar duration. Safety outcome included presence of portal hypertensive complications (new/worsening ascites, varices, encephalopathy and/or spontaneous bacterial peritonitis). Time to portal hypertensive complications was compared in treated patients and matched controls over equivalent timeframes. On-treatment MELD score change was calculated by subtracting MELD score after treatment discontinuation from baseline MELD score. Results: Of 371 patients, 93 were treated with SMV+SOF ± RBV and 278 were matched, untreated controls. Cohort median age was 62yrs (IQR: 58–68), 32% female, 25% Hispanic, 5% Black, 24% diabetes, median (range) platelet count 133 K/mm3 (20–341), albumin 3.5 g/dL (2.3–4.7), MELD 8 (6–18), 35% CP-B/C, 22% ascites, 22% encephalopathy, 8% varices. Of the SMV+SOF ± RBV treated patients, 78 (84%) achieved SVR and median on-treatment MELD change was 0 (range: −5 to 29). In multivariate Cox survival analysis controlling for baseline MELD score, non-SVR/untreated vs. SVR (HR 6.4, 95% CI 3.0-21) and on-treatment MELD change (HR 1.2 per point, 95% CI 1.1–1.3) predicted portal hypertensive complications.
Journal of Hepatology 2016 vol. 64 | S425–S630
S627
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.
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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