Hepatitis C: What s New?

Transcription

1 Hepatitis C: What s New? Naveed Zafar Janjua, MBBS, MSc, DrPH Senior Scientist, Clinical Prevention Services, BCCCDC Clinical Assistant Professor, School of Population and Public Health, UBC

2 Outline Overview Global burden of HCV Epidemiology of HCV in Canada Epidemiology of HCV in BC HIV/HCV co-infection/occurrence HCV mortality HCV Treatment update

3 Hepatitis C virus (HCV) Discovered in 1989 is an RNA virus, transmitted mainly through blood with a large reservoir of chronic carriers worldwide Major cause of post-transfusion hepatitis prior to 1992 Major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide Long latency period, most people not aware about their status until late stage disease 2-3% of world population infected with HCV ~1% (250, ,000) of Canadian population infected lower than many other countries in the world : estimated 4-fold increase in the number of patients diagnosed with HCV in Canada

4 Kamal 2008; Thein 2008; Maheshwari et al HCV Infections ~ 25% Symptomatic Prevent infections? Harm reduction? TasP? 25% Clear 75% Chronic Early treatment of new infections prevent chronic infection Pegylated INF/Rib and/or DAA cures 75% DAA s > 90% Do nothing 15% to 25% cirrhosis, ESLD, HCC, transplant Prevent complications? Most occur in PWID Poorly tolerated Support? Combo Pill Alcohol Obesity Diabetes HIV Older age Males Decades

5 Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence 185 M (2.8% (95% CI: 2.6%-3.1%)) Hanafiah et al. Hepatology 2013;57:

6 Global epidemiology of hepatitis C virus infection: Genotype distribution

7 HCV Epidemiology in Canada: Reported cases by year 60 Male Female Total 50 Rate per 100,000 population

8 HCV Epidemiology in Canada: Reported cases by sex and province, Female Male Total 100 Rate per 100,000 population NL PE NS NB QC ON MB SK AB BC YT NT NU Canada Source:

9 HCV rate by age in Canada, Female Male Total 70 Rate per 100,000 population Age (years)

10 Cumulative rate of reported acute HCV infection by age group and gender, EHSSS, Canada, Differences from overall rate: younger age & more female in younger age group. Risk factors: Mainly IDU Source: Epidemiology of Acute Hepatitis C Infection in Canada Results from the Enhanced Hepatitis Strain Surveillance System (EHSSS).

11 11 HCV in BC 73,000 individuals reported with HCV 25% clear x% deceased ~ 20,000 unknown ~60,000 living with chronic HCV >80% recent infections associated with IDU

12 HCV in BC and Canada by year Rate per 100,000 population BC Hepatitis C Reports BC Hepatitis C Rate Canadian Hepatitis C Rate

13 Age distribution of HCV cases in BC, Rate per 100,000 population < Hepatitis C Rate - Female Hepatitis C Rate - Male Hepatitis C Rate Hepatitis C Reports - Female Hepatitis C Reports - Male Hepatitis C Reports

14 HCV cases in BC by HSDA, 2012 HSDA Health Service Delivery Area Cases Rate Southwestern BC Inset # # Rates per 100,000 population by HSDA N East Kootenay Kootenay Boundary Okanagan Thompson Cariboo Shuswap Fraser East Fraser North Fraser South Richmond Vancouver North Shore/Coast Garibaldi South Vancouver Island Central Vancouver Island North Vancouver Island Northwest Northern Interior Northeast Note: Map classification by Jenks natural breaks method.

15 HCV Sero-conversions: Opportunities for Prevention of Transmission

16 HCV Rate/100,000 in BC & Canada, Seroconversion Rate/100,000 in BC (M24 Window) Rate per 100,000 population ,270,188 individuals 73,663 anti-hcv+ (8,425 seroconverters) (4,308 M24) Canada BC (lab) Acute M

17 HCV Rate/100,000 in BC and Canada Sero-conversion rate BC Rate per 100,000 population ,219,593 individuals 72,684 anti-hcv+ 8,181 seroconverters Acute rate per 100,000 population Canada rate BC rate Acute 24 M Acute 12 M

18 HCV incidence rate/100 PY among repeat anti-hcv testers, BC, Overall BC Males Females HCV seroconversions per 100 person-years Year

19 HCV incidence rate/100 PY among repeat anti-hcv testers by age group, BC years years years years 55+ years 1.4 HCV seroconversions per 100 person-years Year

20 HCV Related Mortality: Hazard ratios between HCV serological groups MNR vs. SNR REAC vs. SNR SERO vs. SNR SERO vs. MNR SERO vs. REAC Cause of Death HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI) HR (95% CI) All Age < ( ) 7.25 ( ) 7.52 ( ) 3.62 ( ) 1.03 ( ) Age ( ) 2.39 ( ) 3.36 ( ) 2.36 ( ) 1.41 ( ) Liver related 2.72 ( ) 9.62 ( ) 5.10 ( ) 1.88 ( ) 0.53 ( ) Drug related 2.62 ( ) ( ) ( ) 8.00 ( ) 1.54 ( ) HIV related Female 3.03 ( ) ( ) ( ) ( ) 0.64 ( ) Male 1.77 ( ) ( ) ( ) 6.17 ( ) 0.90 ( ) Drug related mortality higher in sero-converters (acute HCV) Liver related mortality higher in first time reactors (chronic HCV)

21 HCV Related Mortality: Standardized Mortality Ratios Author Country SMR (95% CI) All-cause Liver-related Drug-related Amin (2006) Duberg (2008) McDonald (2008) Yu (2013) Australia Sweden Scotland Canada HCV mono-infected HCV/HBV co-infected HCV mono-infected HCV/HBV co-infected HCV mono-infected HCV/HIV co-infected All HCV reactive REAC- chronic HCV SERO- Acute 3.1 ( ) 5.6 ( ) 5.8 ( ) 8.5 ( ) 4.9 ( ) 32.9 ( ) 4.8 ( ) 4.7 ( ) 10.2 ( ) 16.8 ( ) 32.9 ( ) 35.5 ( ) 46.2 ( ) 20.0 ( ) 34.8 ( ) 24.0 ( ) 24.3 ( ) 13.1 ( ) 19.3 ( ) 24.7 ( ) 20.7 ( ) 27.6 ( ) 23.5 ( ) 36.6 ( ) 20.4 ( ) 19.5 ( ) 38.1 ( ) Source: Yu A et al. BMC Public Health 2013; 13:291

22 EHSSS BC 179/220, 81% reflect PWID (ever) 83/220, 38% report previous incarceration Nationally ( ) Incidence/100,000 was 14.0 in Aboriginal people vs 2.2 in non-aboriginal people

23 HCV co-infection in the HIV positive population in BC HIV +ve (First +ve HIV cases from ) 7304 Linkable i.e. personal identifiers 5934 (81%) Not linked to combined HCV dataset 1496 (25%) Linked to combined HCV dataset 4438 (75%) HIV+/HCV (47%) HIV+/HCV (53%) HCV+ 1 st HIV+ 1070/2082 (51%) Median 3.6 yrs HIV+ & HCV+ 525/2082 (25%) +/- 2 wks HIV+ 1st HCV+ 487/2082 (23%) Median 1.7 yrs Buxton et al. BMC Public Health 2010;10:225, *data as of

24 HCV co-infection in the HIV positive population in BC HIV mono-infected individuals at baseline subsequent diagnosis of HCV associated with: PWID (both male and female) Aboriginal ethnicity (females) Younger age at HIV identification NOT MSM in males HCV infection subsequent HIV infection Older age PWID Buxton et al. BMC Public Health 2010;10:225

25 Viral Cure = No Transmission Multiplier Effect Shiino et al. Front Microbiol 2012 Core Transmitters

26 Martin et al. Hepatology 2013

27 Martin et al. Hepatology 2013

28 Chronic Infection and Baby boomers: Opportunities for Prevention of Complications

29 Age Distribution of anti-hcv reactive testers at time of diagnosis, BC, % 20% 15% Aging cohort needing screening, triage and treatment 10% 5% N = 69,692 0% <

30 Distribution of Anti-HCV Reactive Testers in BC, by Gender, & by Age at First Positive Test & Current Age, ,500 2,000 Number of Persons 1,500 1, Females N = 24,306 Males N = 45, Age at Diagnosis - F Current Age - F Age at Diagnosis - M Current Age - M Source: hcv_tests_sas7bdat Data Request: 2013_52_Mel_Present

31 BC s Baby Boomers Baby Boomer Cohort General Population BC Population (2011) 1,360,000 (31%) 4,400,000 Population screened for HCV (as of Sep 2012) 357,426 (26%) 1,020,049 (23%) HCV Positive 40,345 (3.0%) 62,758 (1.4%) % of all HCV Positive in BC 64% Population still unscreened 1,002,574 (74%) Estimated HCV Positive among those still unscreened 15,000 to 30,000 (1.5%-3.0%) Total HCV Positive 55,000 to 70,000 Total chronic HCV (i.e., RNA +) 44,000 to 56,000

32 Baby Boomer Screening: Summary Of people in BC tested to date, HCV prevalence in baby boomers is 2x that of the overall tested population (3% vs 1.4%) Among the BC 1945 to 1965 birth cohort 74% of the cohort remains unscreened an estimated 27% to 43% of HCV infections in baby boomers remain undiagnosed Treatment Counseling/behavior change (e.g., reduction of alcohol intake); linkage to care and assessment would be expected to improve health outcomes

33 Relationship between fibrosis severity (grades 1 4) and years of HCV infection 20yrs 40yrs >40 g of ETOH/day, or 3.3 drinks, for women >60 g of ETOH/day, or about 5 drinks, for men Wiley et al. 1998

34 Kaplan-Meier survival plots illustrating cumulative survival in patients with cleared HCV-infection and in an age- and gender-matched comparison cohort without comorbidity, alcohol abuse or IDU Age: yrs Age: yrs Omland LH, Christensen PB, Krarup H, Jepsen P, et al. (2011) Mortality among Patients with Cleared Hepatitis C Virus Infection Compared to the General Population: A Danish Nationwide Cohort Study. PLoS ONE 6(7): e doi: /journal.pone

35 HCV Cases among Immigrants BC & Canada N HCV Canada N HCV BC Country of Birth Pop Canada BC HCV % Eastern Asia China [19] Hong Kong Japan Korea, South [21] Taiwan Southeast Asia Philippines Viet Nam [23] Southern Asia Bangladesh India ,040 Nepal Pakistan Sri Lanka Total cases 79,906 18,883 Prevalence % 3% Population source: Statistics Canada 2013; HCV rates: published most recent estimates

36 HCV Treatment A New Landscape

37 Changing HCV Treatment Landscape Source: Dore GJ Med J Aust, (10):

38 Sustained Virological Response (SVR) HCV Treatments 100% 80% 60% 40% 20% 0% Standard Interferon % % Interferon Ribavirin 34% 1998 Pegylated Interferon Ribavirin % 39% % IFN IFN IFN/R IFN/R PegIFN PegIFN/R 6 mo 12 mo 6 mo 12 mo 12 mo 12 mo DAA 1st gen & Pegylated Interferon Ribavirin % PegIFN/R/DAA 6-12 mo

39 Sofosbuvir and Ledipasvir -oral only Combinations Phase III Results Source: Gilead

40 Sofosbuvir and Daclatasvir: Virologic Response during and after Treatment Sulkowski MS et al. N Engl J Med 2014;370:

41 HCV Treatments from AbbVie Study Patients Treatment Regimen SVR 12 PEARL-II (12 weeks) PEARL-III (12 weeks) PEARL-IV (12 weeks) TURQUOISE-II (12 & 24 weeks) SAPPHIRE-I (12 weeks) SAPPHIRE-II (12 weeks) GT1b treatment-experienced (N=179) GT1b treatment-naive (N=419) GT1a treatment-naive (N=305) GT1 treatment-naive and treatment-experienced with compensated cirrhosis (N=380) GT1 treatment-naive (N=631) GT1 treatment-experienced (N=394) AbbVie regimen + RBV (n=88) AbbVie regimen only (n=91) AbbVie regimen + RBV (n=210) AbbVie regimen only (n=209) AbbVie regimen + RBV (n=100) AbbVie regimen only (n=205) AbbVie regimen + RBV, 12 weeks (n=208) AbbVie regimen + RBV, 24 weeks (n=172) AbbVie regimen + RBV (n=473) AbbVie regimen + RBV (n=297) 97% (85/88) 100% (91/91) 99% (209/210) 99% (207/209) 97% (97/100) 90% (185/205) 92% (191/208) 96% (165/172) 96% (455/473) 96% (286/297) Source: Free-Therapy-for-the-Treatment-of-Hepatitis-C-Genotype-1

42 HCV direct-acting antiviral agents: the best interferon-free combinations Genotype 1-naïve subjects Liver International pages 69-78, 23 DEC 2013 DOI: /liv

43 HCV direct-acting antiviral agents: the best interferon-free combinations: Genotype 1 experienced subjects Liver International pages 69-78, 23 DEC 2013 DOI: /liv

44 Genotype 2 & 3 Sofosbuvir + Ribavirin for 12 or 24 Weeks for Patients With HCV Genotype 2 or 3: the VALENCE Trial

45 Treatment of hepatitis C virus genotype 3-infection Liver International pages 18-23, 23 DEC 2013 DOI: /liv

46 Treatment Summary Genotype 1 SVR12 of >95% with combination therapy Genotype 2 SVR12 of >95% with combination therapy Genotype 3 SVR12 of ~80% with combination therapy

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48 Problem: How to Best Prevent HCV Acquisition and Disease Progression? Prevent infection among younger population -Harm reduction -Active targeting of social networks -Treatment as prevention? $ $ Screen and treat older population -Prevent serious liver disease / liver cancer / need for transplant Age

49 Acknowledgements Mel Karjden Margot Kuo Jane Buxton Amanda Yu Wrency Tang Sunny Mak