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The Global Burden of Hepatitis Infection

The Global Burden of Hepatitis Infection. Prof. Henry LY Chan MBChB (CUHK), MD (CUHK), FRCP ( Edin , Lond ) Head, Division of Gastroenterology and Hepatology Director, Institute of Digestive Disease Director, Center for Liver Health Assistant Dean (Development), Faculty of Medicine

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The Global Burden of Hepatitis Infection

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  1. The Global Burden of Hepatitis Infection Prof. Henry LY Chan MBChB (CUHK), MD (CUHK), FRCP (Edin, Lond) Head, Division of Gastroenterology and Hepatology Director, Institute of Digestive Disease Director, Center for Liver Health Assistant Dean (Development), Faculty of Medicine The Chinese University of Hong Kong

  2. Lavanchy D. ClinMicrobiol Infect 2011; 17:107–115;CDC: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-c.htm. HCV distribution across the world • 130–170 million people world wide are infected with HCV * Estimated number of chronically infected individuals (2010) China 30 M N. Korea 0.2 M Europe18 M* S. Korea 0.8 M Americas 14 M* MiddleEast16 M* Africa28 M* Japan 3M India 18 M Prevalence of HCV >10% 5–10% Indonesia 9 M 2–5% 1–2% <1% No data Australia 0.2 M

  3. Lavanchy D. ClinMicrobiol Infect 2011; 17:107–115; Lee MH, et al. Gut 2011; 60:688–694; Prevalence of HCV in Asia-Pacific countries • Prevalence = % anti-HCV (2010); • HCC = hepatocellular carcinoma. Prevalence of HCV (%)

  4. 1. Grebely J & Dore G. Semin Liver Dis. 2011; 31:331–339; 2. Perz JF, et al. J Hepatol 2006; 45:529–538; 3. WHO Prevention and control of viral hepatitis infection:http://who.int/csr/disease/hepatitis/GHP_Framework_En.pdf?ua=1. The burden of HCV Risk of HCV-related cirrhosis increasesexponentially by duration of infection1 • Major burden comes from sequelae from chronic infection • HCV-related mortality and morbidity mainly due to cirrhosis and HCC • Estimated to be the cause of 27% of cirrhosis and 25% of HCC worldwide2 • South-East Asia ~ 75% unaware they are infected until they have symptoms of cirrhosis/HCC3 Cirrhosis (%) Years

  5. Sherman K. 2006. http://www.fda.gov; Di Bisceglie AM, et al. Hepatology2000; 31:1014–1018. The disease burden will continue to grow as the chronically infected population ages HCV exposure Chronic 85% Cirrhosis 20% HCC 4%/yr ESLD 6%/yr Resolved 15% Transplant/death 3–4%/yr Time(years) 10 20 30 Alcohol use, obesity, co-infection with HIV or HBV accelerate HCV progression • % = percent of original group.

  6. Hajarizadeh B, et al. Nat Rev GastroenterolHepatol 2013; 10:553–562. Patterns of age-specific HCV prevalence and HCV burden Age-specific prevalence of HCV infection and incidence of HCV-related advanced liver disease in four representative countries USA Australia Japan Egypt Incidence of HCV-related advancedliver diseases Prevalence (%) Age (years) Year

  7. Proportion of patients with HCV and HCC in Asia-Pacific countries • Yuen MF, et al. J GastroenterolHepatol 2009; 24:346–353;1. VenookAP, et al. The Oncologist 2010; 15:5–13.

  8. McGowan CE, et al. Hepatology 2013; 57:1325–1332. Barriers to HCV treatment by global region: physician perspective • 1. Medication expense * Each barrier rated on a 10-point Likert scale, from 0 “not a barrier” to 10 “large barrier” • 2. Fear of side effects • 3. Treatment duration Mean likert score*

  9. Need to consider effectiveness for the entire HCV population USA Japan China Ipsos HCV Monitor Q2 2013, Gilead press release 2014. Zhuang H, Asian Pacific Perspective in Hepatitis 2011, Vietnam HCV prevalence: ~ 4.1 million HCV prevalence: ~ 1.1 million HCV prevalence: ~ 10 million ~ 38% ~ 68% ~ 1.6% Diagnosed:~ 1.6 million Diagnosed:~ 745,000 Diagnosed:~ 158,000 Treated:~ 5.5% Treated:~ 5% Treated:~ 1.6%

  10. >7% 2%-7% <2% Adopted and modified from CDC website: http://www.cdc.gov/Features/dsHepatitisAwareness/

  11. Worldwide burden of HBV • >350 million are chronic HBV carriers • In the 2010 Global Burden of Disease study, HBV infection was the 10th leading cause of death (786 000 deaths per year). • About half the total liver cancer mortality in 2010 was attributed to HBV infection • From 1990 to 2010, the worldwide mortality associated with liver cancer increased by 62%, and that associated with cirrhosis increased by 29%. Trepo, Chan and Lok. Lancet 2014 (in press)

  12. HBV infection in Asia • 74% of HBV carriers are in Asia Pacific countries • Among 260 million HBV infected people in Asia, 160 million resides in Western Pacific region • In Western Pacific region • 50% of all HBV patients in the world • 60% of HCC in the world • 360,000 people died of HBV-related liver disease annually • WHO. Prevention & Control of Viral Hepatitis Infection: Framework for Global Action. 2012. Available: http://www.who.int/csr/disease/hepatitis/Framework/en/index.html

  13. HBV Infection is the Commonest Cause of HCC in Asia Proportion of HCC caused by HBV APWP-HCC, Hong Kong, June 2008

  14. Universal vaccination to newborn • First launched 1984 in Taiwan • Now 180 (3%) countries in the world has this program • Prevalence of HBsAg positivity in Taiwan 2009 after 25 years of vaccination program = 0.9% Ni YH, et al. J Hepatol 2012;57:730-5

  15. HBsAg carriage Chronic hepatitis Cirrhosis and HCC 1980 1990 2000 2010 2020 2030 2040 HBV vaccination programme launched in 1984 Prevention of HBV infection: impact of vaccination in Taiwan Adapted from 1. Lin HH, et al. J Med Virol 2003;69:471–474. 2. Chang MH, et al. N Engl J Med 1997;336:1855–9. 3. Chen DS. Hepatol Res 2007;37(Suppl. 2):S101–5

  16. By end of 2011, 180 countries has universal vaccination programme 47 European countries have universal vaccination; 6 (Denmark, Finland, Iceland, Norway, Sweden and UK) have targeted vaccination Trepo, Chan and Lok. Lancet 2014 (in press)

  17. Reimbursement policies differ across Asia-Pacific countries Low reimbursement Partial reimbursement High reimbursement Lamivudine is most commonly used Drug use according to reimbursement policy Entecavir & Tenofovir are most commonly used Drug resistance High cost Thailand, Indonesia, Philippines, Vietnam Hong Kong, Taiwan, Korea, China Japan, Singapore, Australia, New Zealand

  18. The increasing problem of HBV drug resistance in Asia • 794 patients receiving sequential/combination NUCs • Diverse drug mutations found in 306 (38.5%) • ETV-R ±LAM-R ±ADV-R in 45 (5.7%) 100% 100% Entecavir resistant mutations (%) 40% 29% 25% 24% 10% 3% LAMADV (n=136) LAMETV (n=35) LAMADV LAM+ADV (n=5) LAMADV ETV (n=38) LAM LAM+ADV (n=32) ADVLdT (n=8) LAMADV LdT+ADV (n=2) LAM LAM+ADV ETV+ADV (n=1) Adapted from Liu Y, et al. J Viral Hepat 2011;18:e29-39.

  19. Summary Large global burden of HBV and HCV infection in the world. Key cause of hepatocellular carcinoma and mortality HCV • Great advances in antiviral therapy • Challenges in accessibility and affordability of medicine HBV • Vaccination has significantly reduced burden in the younger generation • Challenges in accessibility of vaccine and antiviral therapy for existing patients

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