ERADICATION, ELIMINATION, OR DISEASE CONTROL OF HEPATITIS C. Alfredo Alberti

Transcription

1 ERADICATION, ELIMINATION, OR DISEASE CONTROL OF HEPATITIS C 2017 Alfredo Alberti Department of Molecular Medicine University of Padova ITALY

2 MY DISCLOSURES Research Grants : Roche, Gilead, Janssen, MSD, BMS Advisor : Gilead, MSD, Janssen, BMS, Abbvie, Roche Speaker Fees : Roche, Abbvie, Janssen, Gilead, BMS, MSD

3 1975 Non A non B Hepatitis is Described in Blood Recipients and transmitted to Chimps Feinstone SM et al, N Engl J Med 1975;292: HCV is identified and a diagnostic assay is developed 3

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5 SVR12 REGISTRATA NEI DATA-BASE DI 4 REGIONI ITALIANE AL 12/ % CASI

6 PERFECTOVIR with 100% SVR TREAT AND CURE 100% OF INFECTED No animal reservoir Large carrier pool as reservoir Therapy as cure and prevention PREVENT ALL NEW CHRONIC INFECTIONS Eradication achieved AFFORDABILITY IS THE ISSUE!!

7 ACCESS TO DAAs THERAPY MAIN BARRIER : DRUG COST AND SUSTAINABILITY NEGOTIATION COMPETITION GENERICS by VOLUNTARY LICENSE GENERICS by COMPULSORY LICENSE (TRIPS 2006)

8 FROM INDIVIDUAL LEVEL TO POPULATION LEVEL TARGET : DISEASE CONTROL HCV ELIMINATION HCV ERADICATION

9 SOME DEFINITIONS PROPEDEUTIC TO THIS TALK Dowdle WR, WHO Bull 2006 DISEASE CONTROL : reduction in morbidity and mortality ELIMINATION : no transmission/zero incidence and reduced prevalence to an «acceptable» level in a given region Continued interventions needed Example : POLIOMYELITIS ERADICATION : Global and Total absence of human cases, no reservoir in nature Interventions can be stopped Example : SMALLPOX 9

10 STRATEGY TARGET TARGET POPULATION DISEASE CONTROL Tx for significant/progressive disease HCV ELIMINATION Tx for high prevalence cohorts HCV ERADICATION Tx for all HCV infected

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13 COMPLICANZE REGISTRATE IN PAZIENTI CON CIRROSI CHILD A TRATTATI CON DAAs NEL DATABASE NAVIGATORE ESITI TRATTATI* NON TRATTATI** SANGUINAMENTO GI 0.51%/anno 1.5%/anno ASCITE 1.6%/anno 3%/anno SCOMPENSO EPATICO 2.1%/anno 4.2%/anno EPATOCARCINOMA 1.6%/anno 3%/anno DECESSO PER CAUSA EPATICA 0.39%/anno 1-3%/anno * NAVIGATORE ** STORIA NATURALE DELLA CIRROSI da D AMICO et al,2014

14 RESIDUAL DISEASE PROGRESSION STILL POSSIBLE AFTER SVR IN F3 PATIENTS Van der Meer, J Hepatol 2016

15 FIBROSIS PROGRESSION IN HEPATITIS C IS NOT LINEAR AND ACCELERATES FROM F2 TO F4 STAGE BY METAVIR SYSTEMATIC REVIEW AND SYSTEMATIC REVIEW AND META-ANALYSIS OF 111 OF STUDIES WITH INDIVIDUALS 111 STUDIES WITH INDIVIDUALS F4 Thein et al HEPATOLOGY 2008 YEARS AFTER INFECTION

16 Median Time to Cirrhosis and Cofactors in Hepatitis C HIV coinfection 9 years Alcohol > 50 g / day 13.5 years HBV coinfection 15 years Stetosis/Type 2 Diabetes/MS 19 years NO cofactors 27 years YEARS FROM ESTIMATED DATE OF INFECTION Alberti, 2002

17 O.R: 1.58 O.R.: 2.39 Pooled Prevalence and Odd Ratios Rheumatoid arthritis O.R. : 2.30 O.R. : O.R. : 1.23 O.R.: 1.60 O.R: 11.5 O.R: 8.53 Negro et al Gastroenterology 2015, Younossi et al Gastroenterology 2016

18 BARRIERS FOR SUCCESSFUL DISEASE CONTROL BY CASE FINDING Undiagnosed, asymptomatic progressors Late Diagnosis Uncertainly on prognostic markers of hepatic disease extrahepatic disease WHOM TO SCREEN AND WHEN TO TREAT

19 DISEASE CONTROL BY HCV ELIMINATION* reduction of HCV prevalence by 90% and/or to «rare disease» in a given area by a given time frame

20 The Goal of Hepatitis C Elimination Elimination of HCV infection in the country through treating 80% eligible hepatitis C patients strengthened by effective prevention interventions Diagnosis Treatment Prevention HCV incidence to 0% and HCV prevalence reduced by > 90% 65% reduction in HCV deaths

21 CDA MODELLING OF DISEASE CONTROL AND HCV ELIMINATION IN ITALY

22 WHOM TO TREAT BY PRIORITY INCREASED RISK OF HCV RELATED DEATH RISK OF ACCELERATED FIBROSIS HIV, HBV, METABOLIC, ALCOHOL EXTRA-HEPATIC DAMAGE VASCULITIS, LYMPHOMA, DEBILITATING FATIGUE SIGNIFICANT PHYCOSOCIAL MORBIDITY MAXIMISING REDUCTION IN INCIDENCE PWID MSM SEX WORKERS HEALTH CARE WORKERS, WOMEN IN CHILDBEARING AGE

23 WHAT NEEDS TO BE DEFINED AT FRONT TO PLAN SUCCESSFUL HCV ELIMINATION CURRENT EPIDEMIOLOGY, including stratification by Age, Stage and Diagnosis MAJOR RISK GROUPS and SPREADERS Target TIME FRAME

24 HCV treatment: linkage to care National HCV strategy Regional Networks and Decentralised models of HCV care Enhanced HCV screening and diagnosis Increased and broadened HCV prescribers Specific strategies for marginalised patients and risk groups

25 THE NAVIGATORE PLATFORM Rete Regionale HCV del Veneto 27 HUB e 15 SPOKE Registrazione dei flussi dei casi osservati, stratificati per età, stadio, Comorbilità, genotipo virale Registrazione dei trattamenti Registrazione degli esiti REFERRAL Altri Specialisti MMG SERT Centri dialisi etc..

26 Projected Cascade of HCV Care in VENETO % 100% 80% 60% 50% 40% 20% 0% # persons: 50% 25% 12.5% 50% 50% HCV Infected Diagnosed Referred Treated Tx CANDIDATES

27 WHERE IN EUROPE THERE IS AN ACTIVE NATIONAL HCV ELIMINATION PLAN?

28 LA FILIERA DEL CHI FA COSA E COME DIAGNOSIS REFERRAL TREATMENT FOLLOW-UP

29 HCV in Egypt EXTENSIVE TREATMENT PER SE NOT ENOUGH FOR HCV ELIMINATION Inhabitants HCV infected (7%) : (90% HCV-4) HCV Drugs Brands 1% USA price Generics by Voluntary License Treated : Target NEW INFECTIONS / YEAR :

30 HCV VICIOUS CIRCLE IN PWID Martin et al. J Hepatology 2011; J Theoretical Biology 2011 Allow for re-infection Antiviral treatment Non-SVR infected PWID Uninfected PWID Spontaneous clearance Chronically infected PWID Acutely infected PWID RESERVOIR FOR TRANSMISSION

31 Where the epidemic is driven by High Risk Groups high quality harm reduction needed NSP OST

32 The end of the Story : Hepatitis C Vaccine Epidemic varies between countries for some a vaccine will be vital In some countries unlikely to have high quality harm reduction Even in countries with high treatment coverage models show HCV vaccine would be effective in stopping reinfection. Most useful for HCV elimination Imperative for Global HCV eradication

33 IT IT TOOK US 40 YEARS TO BRING HIM TO HIS KNEES.. NOW LET S FINISH HIM OFF..!!!