scaetc.HIVECHO_SVR_Deming.pptx

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Benefits of SVR Post-DAA Therapy

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Project ECHO - UNM HIV TeleECHO Clinic Benefits of SVR Post-DAA Therapy 10 August 2021 Paulina Deming, PharmD, PhC Associate Professor of Pharmacy- College of Pharmacy Assistant Director HCV Programs- ECHO institute University of New Mexico Health Sciences Center Version_ 08 2021 1 Conflict of Interest Disclosure Statement Speaker has nothing to disclose. This presentation was reviewed by UNMHSC and SCAETC faculty to ensure it meets Continuing Education guidelines. This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS). Under grant number U1OHA33225 (South Central AIDS Education and Training Center). It was awarded to the University of New Mexico. No percentage of this project was financed with non-governmental sources. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. 2 Learning Objectives Describe the impact of sustained virologic response (SVR) on the risk of diabetes in patients treated with direct-acting antivirals (DAAs) for Hepatitis C virus (HCV) compared to untreated patients Describe the impact of SVR on development of liver complications including hepatocellular carcinoma in patients with HCV 3 Background Chronic Hepatitis C virus (HCV) infections known to confer risk of diabetes HCV direct-acting antiviral (DAA) therapy reported to have beneficial impact on diabetic control in patients treated for HCV with known diabetes 4 Objective: determine the impact of newer DAA regimens upon incidence and risk of diabetes Methods: data from the Veterans Health Administration (ERCHIVES: electronically retrieved cohort of HCV-infected veterans) All persons with confirmed chronic HCV infection Excluded patients with prevalent diabetes, co-infection with HIV or HBV, or received both interferon and DAA therapy Used a propensity matched control for each identified patient Butt AA et al. Clin Infect Dis.2020;70(6):1153-1160. Did allow patients who received IFN plus boc or telap 5 Butt AA et al. Clin Infect Dis.2020;70(6):1153-1160. Probability of DM-free Survival Butt AA et al. Clin Infect Dis.2020;70(6):1153-1160. 7 Long-Term Follow Up of F2/F3 Fibrosis After Achieving SVR in SOF-based Clinical Trials Zeuzem, EASL 2018, FRI-366 Gilead SVR Registry Achieving SVR after DAA treatment is linked to low likelihood of development of HCC, decompensation, and death in F2 and F3 patients 2348 patients with F2 or F3 fibrosis who achieved SVR with DAA treatment were enrolled for long-term follow up to 144 weeks Complication F2 N=1456 F3 N=838 HCC, n Exposure-adjusted incidence rate/100 p-y 2 0.06 5 0.25 Liver related events (Ascites/Varices/Encephalopathy/Jaundice) 7 21 Deaths 4 5 HCV relapse, n 0 1 HCV re-infection, n 4 2 Liver-Related Complications After SVR F2 n=1490 F3 n=858 Mean age, years (range) 55 (1980) 57 (1982) Male, % 856 (57) 615 (72) Median registry f/u, years (range) 2.5 (03.8) 2.3 (03.3) Demographics Patients were enrolled in the Gilead SVR Registry within 3 months of achieving SVR. 8 Long-Term Follow Up on Patients with Cirrhosis After Achieving SVR in SOF-based Clinical Trials Mangia, EASL 2018, GS-018 Gilead Cirrhosis Registry 1245 patients with decompensated and compensated cirrhosis followed after SVR with a SOF-based regimen The majority of patients with decompensated cirrhosis showed improvement in CTP class and the rate of de novo HCC was decreased with the achievement of SVR *13 reported deaths were excluded from the analysis. 6 were due to liver-related causes. Integrated Analysis: Gilead Long-Term SVR Registries, EASL 2018 F2 N= 1490 (0) 1453 (1) 1380 (1) 1176 (1) 1070 (1) 965 (2) F3 N= 858 (0) 832 (4) 782 (4) 648 (4) 572 (4) 508 (5) CPT A N= 1037 (0) 1014 (2) 868 (7) 677 (7) 592 (12) 466 (16) CPT B+C N= 205 (0) 200 (4) 185 (11) 174 (16) 151 (19) 90 (20) Cumulative events over time : at risk (events) Proportion of patients with no HCC event (%)* Kaplan-Meier Analysis of Time to HCC Since Achieving SVR12 Registry Entry *0-60% is not included Gilead Long-Term SVR Registries The rate of de novo HCC was decreased with the achievement of SVR, including patients with decompensated cirrhosis. 10 SVR as a Predictor of De Novo and Recurrent HCC in HCV Patients Lleo, EASL 2018, SAT-PS-154 Multicenter, prospective cohort of 1927 HCV-infected cirrhotic patients from Italy SVR with DAA regimens is associated with a significant reduction of incidence and recurrence of HCC p<0.0001 p<0.0001 161 patients with previously treated HCC; 38 patients developed HCC; average annual incidence of 24.8% 1766 patients no previous history of HCC; 50 patients developed HCC (50/1766 2.8%); Average annual incidence of 2.4% De Novo HCC HCC Recurrence HCC Incidence (%) HCC Recurrence (%) Long-Term Real-Life Follow-Up of Patients with Chronic HCV and Decompensated Cirrhosis After DAAs Cheung, EASL 2018, LBP-009 Outcomes in 449 patients with decompensated cirrhosis treated with LDV/SOF or SOF+DCVRBV N=449 Male, % 74 Median age, years 54 (28-79) MELD, mean 12 (7-32) Achieved SVR, n 383 Treatment failures, n 66 Median f/u, weeks 136 (24-174) Demographics SVR in decompensated patients is associated with improved transplant-free survival and reduced risk of HCC NHS England Expanded Access Program (EAP) De Novo HCC Development Transplant-Free Survival Fernandez Alvarez P, EASL 2021, Poster PO-578 321 patients 68.8% male, median age 57, median follow up 52 months (41-63) 44 patients developed liver related events: 32 with portal hypertension decompensation 12 patients developed HCC (3.7%); 22 patients died Patients who developed HCC were older, had cirrhosis, GT3, and diabetes 13 Long-Term Event-free Survival of Patients with SVR Wedemeyer, H et al. Persistent long-term risk of liver related complications in HCV patients after antiviral therapy- Data from the German Hepatitis C-Registry. EASL June 23-26 2021. Results: Overall SVR: 95% (9,951/10,448) ITT 97% (9,824/10,157) PP 181 patients died 415 patients (5.7%) had liver related clinical events (liver transplantation, HCC, hepatic decompensation, or increase in MELD by > 3 points Risk of de novo HCC 0.6%/yr In pts with cirrhosis: 1.2% in yr 1-2, then 0.8% from yr 3-7 About 1/3 (32%) of patients had liver cirrhosis at baseline 26% (2,712/10,448) had a follow up of at least 3 years 2,359 got ribavirin, 8,089 did not 14 Key Points Successful treatment of HCV associated with lower incidence of diabetes as compared to patients with untreated HCV Rates of HCC, decompensation, and death due to liver disease are decreased in patients with F2 or F3 who achieve SVR Rates of de novo HCC reduced in patients after SVR In patients with HCC who achieve SVR, HCC recurrence is reduced Long-term liver disease complications reduced after SVR, especially among patients without cirrhosis Patients with advanced fibrosis/cirrhosis need Follow-up and management for their liver disease On-going HCC surveillance every 6 months indefinitely 15 References Butt AA, Yan P, Aslam S, Shaikh OS, Abou-Samra AB. Hepatitis C Virus (HCV) Treatment With Directly Acting Agents Reduces the Risk of Incident Diabetes: Results From Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES). Clin Infect Dis. 2020 Mar 3;70(6):1153-1160. Mangia A, et al. Long-term follow-up of patients with chronic HCV infection and compensated or decompensated cirrhosis following treatment with sofosbuvir-based regimens. 53rd EASL; Paris, France; April 11-15, 2018. Abstract GS-018. Lleo A, et al. SVR is the strongest predictor of occurrence and recurrence of hepatocellular carcinoma in HCV cirrhotic patients after treatment with DAAs: a prospective multi-centric Italian study. 53rd EASL; Paris, France; April 11-15, 2018. Abstract PS-154. Cheung M, et al. LBP-009 Long-term real-life follow-up of patients with chronic hepatitis C virus and decompensated cirrhosis after direct acting antivirals what is the clinical benefit of antiviral treatment? Journal of Hepatology 68;s109-s110. Wedemeyer, H et al. Persistent long-term risk of liver related complications in HCV patients after antiviral therapy- Data from the German Hepatitis C-Registry. EASL June 23-26, 2021. PO-52. Fernandez Alvarez, P et al. Long-term follow up in patients with hepatitis C virus treated with direct-acting-antiviral agents. EASL June 23-26, 2021. PO-578. Resources National Clinician Consultation Center http://nccc.ucsf.edu/ HIV Management Perinatal HIV HIV PrEP HIV PEP line HCV Management Substance Use Management Present case on ECHO http://echo.unm.edu [email protected] AETC National HIV Curriculum https://aidsetc.org/nhc Hepatitis C Online https://www.hepatitisc.uw.edu/ AETC National Coordinating Resource Center https://targethiv.org/library/aetc-national-coordinating-resource-center-0 Additional trainings [email protected] www.scaetc.org Find additional TeleECHO sessions in your area: https://echo.unm.edu/locations-2/echo-hubs-superhubs-united-states/ https://hsc.unm.edu/echo/get-involved/join-an-echo/ IDEA Platform: Infectious Diseases Education & Assessment. https://idea.medicine.uw.edu/ AETC National HIV Curriculum: 6 core modules for self study; regularly updated; CME, CNE Hepatitis C Online Curriculum: https://www.hepatitisc.uw.edu/ Hepatitis B Online Curriculum: https://www.hepatitisb.uw.edu/ National STD Curriculum: https://www.std.uw.edu/ 17