6. Mai 2018 Michael Gschwantler. S F U M E D Hepatitis C: Was ist aktuell im Jahr 2018?

Transcription

1 6. Mai 2018 Michael Gschwantler S F U M E D Hepatitis C: Was ist aktuell im Jahr 2018?

2 Wie können wir die chronische Hepatitis C am effektivsten behandeln und was bringt das für unsere Patienten?

3 HCV Lebenszyklus und mögliche Angriffspunkte neuer Virostatika Rezeptorbindung und Endozytose Fusion und Uncoating Transport und Freisetzung NS3/4 Protease- Inhibitoren - Boceprevir - Translation Telaprevir and - Simeprevir Polyprotein- - Paritaprevir Prozessierung - Grazoprevir - Glecaprevir - Voxilaprevir (+) RNA ER Lumen NS5A* Inhibitors - Daclatasvir - Ledipasvir -Ombitasvir - Velpatasvir - Elbasvir - Pibrentasvir LD LD ER Lumen LD Virion Assembly NS5B Polymerase-Inhibitoren Nukleosidische/nukleotidische RNA Replikation Nicht-Nukleosidische - Sofosbuvir - Dasabuvir

4 Derzeit in Österreich zugelassene DAA-Regime

5 SVR12 (%) ASTRAL Phase 3 Program (ASTRAL-1, ASTRAL-2, ASTRAL-3, ASTRAL-4) Efficacy Summary (ITT Analysis) SOF/VEL SOF+RBV SOF/VEL + RBV 618/ / / / / 35 41/ / / / / / 90 82/ 87 77/ 90 Overall GT 1 GT 2 GT 4 GT 5 GT 6 12 Weeks ASTRAL-1 (GT 1, 2, 4 6) 12 Weeks 12 Weeks ASTRAL-2 (GT 2) 24 Weeks ASTRAL-3 (GT 3) In ASTRAL 1-3, 98% (1015/1035) overall SVR rate among patients who received SOF/VEL for 12 weeks 2% (20/1035) did not achieve SVR 1.3% (13) relapsed <1% (7) were either lost to follow up or withdrew consent 12 Weeks 24 Weeks ASTRAL-4 (GT 1 6 CTP-B Cirrhosis) Feld, AASLD, 2015, LB-2. Feld JJ, et al. N Engl J Med DOI: /NEJMoa ; Sulkowski, AASLD, 2015, 205. Foster GR, et al. New Engl J Med DOI: /NEJMoa ; Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med DOI: /NEJMoa ; Charlton, AASLD, 2015, LB-13. Curry MP, et al. New Engl J Med DOI: /NEJMoa

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7 SVR12 IN THE IMMEDIATE TREATMENT GROUP: FULL ANALYSIS SET (FAS) Dore GJ et al. Ann Intern Med 2016; 165:

8 Survival Probability ANRS CO22 HEPATHER Cohort Decreased Mortality After DAAs 1,00 All-Cause Deaths Weighted survival curves (IPTW) According to the Cause of Deaths HR Crude (DAA+ vs DAA-) HR IPWfixed (DAA+ vs DAA-) 0,98 DAA- DAA+ 0,96 0,94 HR= 0.65 p value = Liver-Related deaths (n=58) , DAA- (wghts) DAA+ (wghts) 0, Months First prospective evidence that DAA treatment is associated with a decreased risk of death, and particularly liver-related deaths *29 deaths were not yet adjudicated Carrat, ANRS-AFEF HEPATHER Study Group, AASLD 2017, Poster LB-28

9 Probability free from HCC diagnosis Veterans Affairs Evaluation of HCV Treatment and de novo HCC Risk Retrospective study in 167 medical centers including 35,871 IFN-only regimens, 4,535 DAA+IFN and 21,948 DAA-only (80% SOF-based regimens); mean f/u of 6.1 years (range: 2-18); incident HCCs=3, DAA-Treated No Cirrhosis, SVR No Cirrhosis, No SVR Cirrhosis, SVR 0.85 Cirrhosis, No SVR Years after start of HCV treatment Ioannou, G, AASLD 2017, Oral 142 DAA-induced SVR is associated with 71% reduction in HCC risk

10 What are the Clinical Manifestations of HCV Beyond the Liver? Skin manifestations Neuropsychiatric manifestations Ocular manifestations Hematologic disorders/ malignancies Mixed cryoglobulinemia Peripheral neuropathy Hypothyroidism Papillary thyroid cancer Pulmonary fibrosis Cardiovascular/ metabolic diseases Renal impairment Musculoskeletal and connective tissue disorders 10

11 Laufen wir beim Rennen im Kampf gegen die Hepatitis C wirklich schon durch das Ziel...oder hat das Rennen eigentlich gerade erst so richtig begonnen??

12 Wie können wir die chronische Hepatitis C am effektivsten behandeln und was bringt das für unsere Patienten? Wie können wir die chronische Hepatitis C eliminieren?

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14 Percentage WHO goals Ambitious global targets have been set by the WHO in order to control viral hepatitis by % reduction in new cases of chronic hepatitis C 80% of treatmenteligible people with chronic hepatitis C treated 65% reduction in hepatitis C deaths New cases of chronic hepatitis C Treatment-eligible people with chronic hepatitis C Hepatitis C deaths WHO Global Health Sector Strategy on Viral Hepatitis, Available at: (accessed January 2018) WHO: World Health Organization

15 Epidemiology It is estimated that 71.1 million people worldwide are chronically infected with HCV Viraemic infected 0 200, , , ,001 1,000,000 1,000,001 4,500,000 >4,500,000 Every year, an estimated 700,000 people with chronic HCV infection die untreated Blach S, et al. Lancet Gastroenterol Hepatol 2017;2:161 76; WHO. Global report on access to hepatitis C treatment. Focus on overcoming barriers. Available at: (accessed January 2018)

16 The Road to Elimination of HCV: Analysis of Cures Versus New Infections in 91 Countries In 2016, WHO called for a 90% reduction in new HCV infection by 2030 Epidemiological data available for 91/210 countries (>80% of world HCV cases) An annual net cure of 7% is the target goal needed to reach the WHO goal Annual Net Cure Worldwide reduction in HCV prevalence was 0.4%; Far higher rates of treatment are required for elimination of HCV Hill AM et al J Virus Erad Jul; 3(3): Net Cure = Cures + HCV Related Deaths - New Infections

17 The Road to Elimination of HCV: Analysis of Cures Versus New Infections in 91 Countries 10/91 countries where there were >5 times more people reaching SVR than there were new infections in 2016 The guideline represents the mark of five people reaching SVR for every single new HCV infection Hill AM et al J Virus Erad Jul; 3(3):

18 WHO goals Many countries have developed ambitious national hepatitis plans National action plans and strategies. Available at: Strategy2014-v3.pdf; _hepatitisplan_een_strategie_voor_actie (all accessed January 2018) WHO: World Health Organization

19 Reported Prevalence Age and Gender Distribution Based on the Austrian age and sex distribution, where US data from 2000 were used as an analogue. Prevalence after 2000 was matched to total diagnosis data, provided by Prof. Zoller, adjusted for deaths and cures 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% HCV Prevalence by Age and Sex Tyrol, Total Viremic Cases by Age Group and Gender Male Female Cumulative dx viremic cases Model cases A 2000 US analog was used for the age and sex distribution. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through Ann.Intern.Med May 16;144(10): Manuscript submitted by Dr Benedikt Schäfer 19

20 Base Treatment decreases by 50% in 5 years Diagnosis remains constant through 2019, when there will be fewer patients available to diagnose SVR increases to 98% in 2018 Open treatment to all fibrotic stages Treated Newly Diagnosed Fibrosis Stage F2 F0 F0 F0 F0 F0 Treated Age SVR 95% 95% 98% 98% 98% 98% Manuscript submitted by Dr Benedikt Schäfer 20

21 Greater impact in reducing total infected, liver related deaths, HCC, and decompensated cirrhosis Total Infected Cases (Viremic) Tyrol Liver Related Deaths Tyrol 2, , , , Base WHO 2030 Targets Base WHO 2030 Targets Total Infected - HCC Tyrol 25 Total Infected - Decompensated Cirrhosis Tyrol Base WHO 2030 Targets Base WHO 2030 Targets Incident HCC cases decline 60% in 2030 as compared to base Manuscript submitted by Dr Benedikt Schäfer 21

22 Risiko für HCV? Die 6 Fragen Bestehen erhöhte Leberwerte? Drogenkonsum derzeit oder in der Vergangenheit? Piercing oder Tatoos? Blutkonserven vor 1991? Hat jemand, der im selben Haushalt lebt, Hepatitis C? Gibt es einen Migrationshintergrund? Wird eine der 6 Fragen mit ja beantwortet, so ist das Risiko für das Vorliegen einer HCV-Infektion hoch Modifiziert nach Petra Munda

23 Epidemiology People who inject drugs, men who have sex with men and prisoners have the highest risk of infection In high-income countries 80% of new HCV infections are in PWID 1 PWID People in prison MSM Globally, 26% of prison inmates are HCV+ 2. High prevalence coupled with unsafe IDU, tattooing and unsafe sex put prisoners at high risk of HCV 2 Increasing incidence of HCV in HIV+ MSM: from 7.3% in 2004 to 9.9% in Grebely J, Dore GJ. Antiviral Res 2014;104:62 72; 2. Larney S, et al. Hepatology 2013;58: ; 3. Martin N, et al. Clin Infect Dis 2016;62: IDU: injecting drug use; MSM: men with have sex with men; PWID: people who inject drugs

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