Hepatitis C: Whats New? Naveed Zafar Janjua, MBBS, MSc, DrPH Senior - - PowerPoint PPT Presentation

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

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

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% (250,000-450,000) of Canadian population infected

– lower than many other countries in the world

• 1990-2015: estimated 4-fold increase in the number of patients diagnosed

with HCV in Canada

HCV Infections

~ 25%

Symptomatic 75% Chronic 25% Clear Alcohol Obesity Diabetes HIV Older age Males Poorly tolerated Support ? Combo Pill

Early treatment

• f 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 Most

• ccur in

PWID

Kamal 2008; Thein 2008; Maheshwari et al. 2010

Decades

Prevent infections? Harm reduction? TasP? Prevent complications?

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;57:1333–1342 http://onlinelibrary.wiley.com/doi/10.1002/hep.26141/full#fig3

Global epidemiology of hepatitis C virus infection: Genotype distribution

HCV Epidemiology in Canada: Reported cases by year

10 20 30 40 50 60

2005 2006 2007 2008 2009

Rate per 100,000 population

Male Female Total

HCV Epidemiology in Canada:

Reported cases by sex and province, 2009

Source: http://www.phac-aspc.gc.ca/sti-its-surv-epi/hepc/hepc_pt-eng.php

20 40 60 80 100 120 NL PE NS NB QC ON MB SK AB BC YT NT NU Canada

Rate per 100,000 population

Female Male Total

HCV rate by age in Canada, 2009

10 20 30 40 50 60 70 80 90 0-4 5-9 10-14 15-19 20-24 25-29 30-39 40-59 60+

Rate per 100,000 population Age (years)

Female Male Total

Cumulative rate of reported acute HCV infection by age group and gender, EHSSS, Canada, 2004-2008

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). http://www.phac-aspc.gc.ca/sti-its-surv-epi/hcv-epi-eng.php

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

11

HCV in BC and Canada by year

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 BC Hepatitis C Reports 3523 3043 2834 2907 2882 2508 2479 2218 1968 1885 BC Hepatitis C Rate 85.5 73.2 67.5 68.5 66.9 57.2 55.6 49.0 43.0 40.8 Canadian Hepatitis C Rate 46.8 45.2 40.4 36.9 36.6 35.8 33.2 31.1 28.8 0.0 50.0 100.0 150.0

Rate per 100,000 population

Age distribution of HCV cases in BC, 2012

<1 1-4 5-9 10-14 15-19 20-24 25-29 30-39 40-59 60+ Hepatitis C Rate - Female 18.9 2.3 0.9 0.0 8.2 28.1 43.3 38.3 43.6 20.8 Hepatitis C Rate - Male 4.4 1.1 0.0 0.8 4.2 21.5 37.6 63.1 100.0 50.4 Hepatitis C Rate 11.5 1.6 0.4 0.4 6.1 24.7 40.4 50.5 71.6 34.8 Hepatitis C Reports - Female 4 2 1 11 45 70 117 303 113 Hepatitis C Reports - Male 1 1 1 6 37 63 187 677 243 Hepatitis C Reports 5 3 1 1 17 82 133 304 982 357 0.0 25.0 50.0 75.0 100.0 125.0

Rate per 100,000 population

HCV cases in BC by HSDA, 2012

47.1 48.5

18.5

S

• uthwestern BC In

set

Note: Map classification by Jenks natural breaks method.

N

63.4 49.5 21.7 36.4 34.8 33.4 50.6

C ases R ate Northeast Northern Interior Northwest North Vancouver Island Central Vancouver Island South Vancouver Island North Shore/Coast Garibaldi Vancouver Richmond F raser South F raser North F raser East T hompson Cariboo Shuswap Okanagan Kootenay Boundary East Kootenay H ealth Service Delivery Area H SDA 11 12 13 14 21 22 23 31 32 33 41 42 43 51 52 53

39.7 48.5 43.4 21.7 47.1 28.7 41.9 45.4 65.1 21.7 63.4 50.6

R ates per 100,000 p

• pulatio

n by H SDA 38 35 65.1 50.6 21.7 18.5 39.7 23 28.7 161 45.4 94 41.9 188 65.1 208 33.4 257 34.8 37 18.5 339 49.5 63 21.7 137 36.4 135 50.6 77 63.4 30 39.7 63 43.4

HCV Sero-conversions: Opportunities for Prevention of Transmission

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Canada 5 6 10 48 42 65 76 64 58 54 51 47 45 40 37 37 36 33 31 29 BC (lab) 40 59 90 125 141 186 150 119 97 91 88 78 68 63 68 64 61 57 50 45 44 Acute M24 0.1 0.7 2.3 2.8 3.4 5.6 6.3 6.6 7.0 6.9 7.7 6.7 5.9 5.5 6.9 5.6 5.5 4.5 3.7 3.1 3.3

0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 20 40 60 80 100 120 140 160 180 200

Rate per 100,000 population

1,270,188 individuals 73,663 anti-HCV+ (8,425 seroconverters) (4,308 M24)

HCV Rate/100,000 in BC & Canada, 1992-2012 Seroconversion Rate/100,000 in BC (M24 Window)

HCV Rate/100,000 in BC and Canada Sero-conversion rate BC

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Canada rate 51 47 45 40 37 37 36 34 32 29 BC rate 88 78 68 63 68 64 62 56 50 45 44 Acute 24 M 7.7 6.7 5.9 5.5 6.9 5.6 5.5 4.5 3.7 3.1 3.1 Acute 12 M 4.2 3.7 3.0 2.5 3.4 2.5 3.1 2.3 1.8 1.6 1.2 1 2 3 4 5 6 7 8 9 10 20 30 40 50 60 70 80 90 100

Acute rate per 100,000 population Rate per 100,000 population

1,219,593 individuals 72,684 anti-HCV+ 8,181 seroconverters

2013-03-19

HCV incidence rate/100 PY among repeat anti-HCV testers, BC, 2000-2011

0.5 1

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 HCV seroconversions per 100 person-years Year Overall BC Males Females

HCV incidence rate/100 PY among repeat anti-HCV testers by age group, BC

0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 HCV seroconversions per 100 person-years Year 15-24 years 25-34 years 35-44 years 45-54 years 55+ years

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 <40 2.07 (1.82-2.36) 7.25 (6.54-8.06) 7.52 (5.85-9.52) 3.62 (2.79-4.65) 1.03 (0.80-1.31) Age ≥40 1.42 (1.36-1.49) 2.39 (2.27-2.51) 3.36 (2.49-4.41) 2.36 (1.75-3.11) 1.41 (1.04-1.85) Liver related 2.72 (2.34-3.14) 9.62 (8.55-10.87) 5.10 (2.30-9.62) 1.88 (0.85-3.55) 0.53 (0.24-0.99) Drug related 2.62 (2.11-3.25) 13.70 (11.76-16.13) 20.83 (15.15-28.57) 8.00 (5.71-11.11) 1.54 (1.12-2.05) HIV related Female 3.03 (0.90-9.52) 83.33 (40.00- 200.00) 52.63 (11.49- 200.00) 17.54 (3.62- 71.43) 0.64 (0.16-1.75) Male 1.77 (1.11-2.74) 12.05 (9.09-16.13) 10.87 (5.24-20.41) 6.17 (2.84-12.35) 0.90 (0.44-1.63)

Drug related mortality higher in sero-converters (acute HCV) Liver related mortality higher in first time reactors (chronic HCV)

HCV Related Mortality: Standardized Mortality Ratios

Author

Country

SMR (95% CI) All-cause Liver-related Drug-related Amin (2006)

Australia

HCV mono-infected 3.1 (3.0-3.2) 16.8 (15.4-18.3) 19.3 (18.1-20.5) HCV/HBV co-infected 5.6 (4.8-6.6) 32.9 (23.1-46.7) 24.7 (18.2-33.5) Duberg (2008)

Sweden

HCV mono-infected 5.8 (5.6-6.0) 35.5 (32.9-38.3) 20.7 (18.9-22.7) HCV/HBV co-infected 8.5 (7.3-9.8) 46.2 (31.5-62.3) 27.6 (19.6-39.6) McDonald (2008)

Scotland

HCV mono-infected 4.9 (4.6-5.1) 20.0 (17.9-22.2) 23.5 (21.3-25.7) HCV/HIV co-infected 32.9 (29.2-37.0) 34.8 (23.3-50.0) 36.6 (25.2-51.4) Yu (2013)

Canada

All HCV reactive 4.8 (4.6-5.0) 24.0 (22.2-25.9) 20.4 (18.8-22.0) REAC- chronic HCV 4.7 (4.5-4.8) 24.3 (22.4-26.2) 19.5 (17.9-21.1) SERO- Acute 10.2 (8.5-12.0) 13.1 (5.6-25.7) 38.1 (29.0-49.1)

Source: Yu A et al. BMC Public Health 2013; 13:291

2000-2011 EHSSS BC

• 179/220, 81% reflect PWID (ever)
• 83/220, 38% report previous incarceration
• Nationally (2004-2009) Incidence/100,000 was 14.0 in

Aboriginal people vs 2.2 in non-Aboriginal people

HCV co-infection in the HIV positive population in BC

HIV +ve

(First +ve HIV cases from 1995-2011)

7304 Linkable i.e. personal identifiers 5934 (81%) Linked to combined HCV dataset 4438 (75%) HIV+/HCV+ 2082 (47%) Not linked to combined HCV dataset 1496 (25%) HCV+ 1st → 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 2012-01-09

HIV+/HCV- 2356 (53%)

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

Viral Cure = No Transmission Multiplier Effect

Core Transmitters

Shiino et al. Front Microbiol 2012

Martin et al. Hepatology 2013

Martin et al. Hepatology 2013

Chronic Infection and Baby boomers: Opportunities for Prevention of Complications

0% 5% 10% 15% 20% 25%

<15 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80+

1993-1997 1998-2002 2003-2007 2008-2012

N = 69,692

Age Distribution of anti-HCV reactive testers at time of diagnosis, BC, 1993-2012

Aging cohort needing screening, triage and treatment

500 1,000 1,500 2,000 2,500 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

Number of Persons Distribution of Anti-HCV Reactive Testers in BC, by Gender, & by Age at First Positive Test & Current Age, 1992-2012

Age at Diagnosis - F Current Age - F Age at Diagnosis - M Current Age - M

Females N = 24,306 Males N = 45,651

Source: hcv_tests_sas7bdat Data Request: 2013_52_Mel_Present

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

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

• >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

Relationship between fibrosis severity (grades 1–4) and years of HCV infection

20yrs 40yrs

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

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): e22476. doi:10.1371/journal.pone.0022476 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022476

Age: 20-39 yrs Age: 40-69 yrs

HCV Cases among Immigrants BC & Canada

Country of Birth Pop Canada BC HCV % N HCV Canada N HCV BC Eastern Asia 1038605 363300 China [19] 585555 178435 3.2 18738 5710 Hong Kong 209775 76300 0.5 1049 382 Japan 33330 15715 1 333 157 Korea, South [21] 132940 46625 1.7 2260 793 Taiwan 69550 43515 4.4 3060 1915 Southeast Asia 787600 160435 Philippines 502295 104460 3.6 18083 3761 Viet Nam [23] 168420 26355 6.1 10274 1608 Southern Asia 927775 163065 Bangladesh 47180 1685 2.4 1132 40 India 572435 146910 2.75 15742 4,040 Nepal 9050 960 0.6 54 6 Pakistan 161380 8835 4.8 7746 424 Sri Lanka 135400 4610 1.06 1435 49 Total cases 79,906 18,883 Prevalence 2627310 654405 3% 3%

Population source: Statistics Canada 2013; HCV rates: published most recent estimates

HCV Treatment – A New Landscape

Changing HCV Treatment Landscape

Source: Dore GJ Med J Aust, 2012. 196(10):629-632

0% 20% 40% 60% 80% 100%

IFN IFN IFN/R IFN/R PegIFN PegIFN/R

Sustained Virological Response (SVR) 16% 55% 6%

HCV Treatments

34% 42% 39%

6 mo 12 mo 6 mo 12 mo 12 mo

1991 1995 1998 2002 2001

Interferon Ribavirin Standard Interferon

6-12 mo

65% 2011

PegIFN/R/DAA 12 mo

Pegylated Interferon Ribavirin DAA 1st gen & Pegylated Interferon Ribavirin

Sofosbuvir and Ledipasvir -oral only Combinations Phase III Results

Source: Gilead http://gilead.com/news/press-releases/2013/12/gilead-announces-svr12-rates-from-three-phase-3-studies-evaluating-a-

• ncedaily-fixeddose-combination-of-sofosbuvir-and-ledipasvir-for-genotype-1-hepatitis-c-patients

Sofosbuvir and Daclatasvir: Virologic Response during and after Treatment

Sulkowski MS et al. N Engl J Med 2014;370:211-221.

HCV Treatments from AbbVie

Study Patients Treatment Regimen SVR12

PEARL-II (12 weeks) GT1b treatment-experienced (N=179) AbbVie regimen + RBV (n=88) 97% (85/88) AbbVie regimen only (n=91) 100% (91/91) PEARL-III (12 weeks) GT1b treatment-naive (N=419) AbbVie regimen + RBV (n=210) 99% (209/210) AbbVie regimen only (n=209) 99% (207/209) PEARL-IV (12 weeks) GT1a treatment-naive (N=305) AbbVie regimen + RBV (n=100) 97% (97/100) AbbVie regimen only (n=205) 90% (185/205) TURQUOISE-II (12 & 24 weeks) GT1 treatment-naive and treatment-experienced with compensated cirrhosis (N=380) AbbVie regimen + RBV, 12 weeks (n=208) 92% (191/208) AbbVie regimen + RBV, 24 weeks (n=172) 96% (165/172) SAPPHIRE-I (12 weeks) GT1 treatment-naive (N=631) AbbVie regimen + RBV (n=473) 96% (455/473) SAPPHIRE-II (12 weeks) GT1 treatment-experienced (N=394) AbbVie regimen + RBV (n=297) 96% (286/297)

Source: http://abbvie.mediaroom.com/2014-01-31-AbbVie-Completes-Largest-Phase-III-Program-of-an-All-Oral-Interferon-

Free-Therapy-for-the-Treatment-of-Hepatitis-C-Genotype-1

HCV direct‐acting antiviral agents: the best interferon‐free combinations Genotype 1‐naïve subjects

Liver International pages 69-78, 23 DEC 2013 DOI: 10.1111/liv.12423 http://onlinelibrary.wiley.com/doi/10.1111/liv.12423/full#liv12423-fig-0002

HCV direct‐acting antiviral agents: the best interferon‐free combinations: Genotype 1 experienced subjects

Liver International pages 69-78, 23 DEC 2013 DOI: 10.1111/liv.12423 http://onlinelibrary.wiley.com/doi/10.1111/liv.12423/full#liv12423-fig-0003

Genotype 2 & 3

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

Treatment of hepatitis C virus genotype 3‐infection

Liver International pages 18-23, 23 DEC 2013 DOI: 10.1111/liv.12405 http://onlinelibrary.wiley.com/doi/10.1111/liv.12405/full#liv12405-fig-0002

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

Problem: How to Best Prevent HCV Acquisition and Disease Progression?

35 15 55 25 65 45 Age Screen and treat older population

• Prevent serious liver disease /

liver cancer / need for transplant Prevent infection among younger population

• Harm reduction
• Active targeting of social

networks

• Treatment as prevention?

$ $

Acknowledgements

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