1. C LINICAL PRESENTATIONS RELATED TO HEPATITIS AND ALCOHOL, PRACTICE IMPLICATIONS OF NEW THERAPIES : AN ANALYSIS OF THE 2008-2012 F RENCH N ATIONAL H OSPITAL D ISCHARGE D ATABASE M. Schwarzinger, S.P. Thiébaut, V. Mallet, J. Rehm

2. C ONFLICTS OF INTEREST M. SCHWARZINGER, MD, PHD — CEO of THEN (Translational Health Economics Network), Paris, France S.P. THIÉBAUT, PHD — researcher at THEN (Translational Health Economics Network), Paris, France V. MALLET, MD, PHD — has been a scientific advisor or consultant for Gilead, Abbvie, Merck and co., JJ/Janssen-Cilag and Bristol Myers Squibb, and has received payment for lectures including service on speakers bureaus for Abbvie, Bristol Myers Squibb, Gilead, JJ/Janssen-Cilag, Novartis and Roche, outside and unrelated to this work J. RHEM, PHD — has received grants, personal fees and is a board member (Nalmefene) for Lundbeck, outside and unrelated to this work 2

3. L OU R EED ’ S CASE AND CAUSES OF DEATH IN REAL - LIFE HEP C PATIENTS We may remember H EP C: THE UNDERLYING CAUSE OF DEATH ( AFTER LIVER TRANSPLANT ) 3

4. L OU R EED ’ S CASE AND CAUSES OF DEATH IN REAL - LIFE HEP C PATIENTS We may rememberLou Reed’s quote H EP C: THE UNDERLYING CAUSE OF DEATH ( AFTER LIVER TRANSPLANT ) A LCOHOL U SE D ISORDERS : A MAJOR CAUSE OF LIVER TRANSPLANT AND OVERALL DEATH 4

5. STUDY RATIONALE Higher rates of severe comorbidities are expected in real-life Hep C patients in Western countries Injection Drug Use (reported by ≥ 50%) Receipt of donated blood, blood products, and organs (once a common means of transmission) 5

6. Drug addiction Alcohol use disorders Bloodborne viruses HIV HBV Iatrogenic transmission Solid organ transplant recipient Liver Kidney Other Chronic dialysis IG-IV; blood transfusion Diabetes mellitus Hemophilia

7. RESEARCH AIMS AND OBJECTIVES 1.To study the confounding role of alcohol use disorders and severe comorbidities on prognosis in Hep C patients in a real-life, large, and representative setting 2.To estimate the health benefits of alcohol abstinence in Hep C patients 7

8. M ETHODS (1): STUDY POPULATION Data source: 2008-2012 French National Hospital Discharge database  all public and private acute and post-acute care Inclusion criteria:  all 28,953,755 adult individuals residing in Metropolitan France with at least one hospital stay  51.6% of the French adult population [National Vital Statistics, 2008] 8

9. M ETHODS (2): C OMORBIDITIES * Chronic Hepatitis C Virus (HCV) infection Alcohol Use Disorders (AUD) [Rehm Lancet 2009] – Alcohol abstinence recorded at least once in 2008-2012 Other comorbidities of HCV – Drug addiction – HIV/Aids infection – Chronic Hepatitis B virus infection – Solid organ transplant receipt before 2008 – Diabetes mellitus – Chronic dialysis – Hemophilia 9 * Based on primary and associated discharge codes (ICD-10 French version)

10. M ETHODS (3): OUTCOMES Liver-related event – Decompensated cirrhosis: 490,056 (1.69%) pts* – Primary liver cancer: 77,333 (0.27%) pts* – Liver transplant: 4,521 (0.02%) pts In-hospital death: – 1,506,453 (5.20%) pts  57.4% of all deaths [National Vital Statistics, 2008- 2012] 10 * Based on primary and associated discharge codes (ICD-10 French version)

11. B URDEN OF CHRONIC HCV INFECTION IN F RANCE IN 2008-2012 : RAW DATA End-stage liver disease, primary liver cancer, liver transplant 11

12. B ASELINE C HARACTERISTICS OF HCV (1) 12

13. B ASELINE C HARACTERISTICS OF HCV (2) 13

14. L IVER -R ELATED E VENT IN HEP C (1) 14

15. L IVER -R ELATED E VENT IN HEP C (2) 15

16. L IVER -R ELATED E VENT IN HEP C (3) 16

17. I N -H OSPITAL D EATH IN HEP C (1) 17

18. I N -H OSPITAL D EATH IN HEP C (2) 18

19. 19 B ENEFITS OF ALCOHOL WITHDRAWAL / ABSTINENCE ON THE RISK OF LIVER - RELATED EVENT OR DEATH IN 112,146 HEP C PATIENTS * Stratified on gender, 5 French regions, and teaching hospital care

20. CONCLUSIONS / 1 Poor prognosis of Hep C patients is largely explained by the selection of a high-risk subpopulation – Alcohol Use Disorders => liver (+++) and nonliver death – Severe comorbidities => liver and nonliver (+++) death 20

21. CONCLUSIONS / 1 Poor prognosis of Hep C patients is largely explained by the selection of a high-risk subpopulation – Alcohol Use Disorders => liver (+++) and nonliver death – Severe comorbidities => liver and nonliver (+++) death  Expected value of IFN-free treatments in cost-effectiveness models is overestimated in patients without AUD or severe comorbidities 21

22. CONCLUSIONS / 2 Health benefits of alcohol withdrawal and abstinence should be promoted – in real-life Hep C patients: HR= 0.71 [0.67-0.75] – in the general population: HR= 0.75 [0.74-0.76] 22

23. CONCLUSIONS / 2 Health benefits of alcohol withdrawal and abstinence should be promoted – in real-life Hep C patients: HR= 0.71 [0.67-0.75] – in the general population: HR= 0.75 [0.74-0.76]  Expected value of alcohol withdrawal should be investigated in Hep C patients 23

24. A CKNOWLEDGMENT LOU REED who inspired this original research work S.P. Thiébaut: THEN (Translational Health Economics Network), Paris, France Prof V. MALLET: INSTITUT COCHIN, Université Paris Descartes; INSTITUT PASTEUR; Hepatology, Groupe Hospitalier Cochin Port-Royal, ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS, Paris, France Prof J. REHM: CENTRE FOR ADDICTION AND MENTAL HEALTH; Dalla Lana School of Public Health, Institute of Medical Science, Department of Psychiatry, UNIVERSITY OF TORONTO, Toronto, Canada; Institute of Clinical Psychology and Psychotherapy, TECHNISCHE UNIVERSITÄT DRESDEN, DRESDEN, Germany 24