1. Prevention of Viral Hepatitis B in Republic of Korea Ok Park, M.D., Ph.D., MPH Vaccine-Preventable Disease Control & National Immunization Program Korea Center for Disease Control and Prevention 11 July, 2014 The 5 th Asia Pacific Primary Liver Cancer Expert Meeting Taipei, Taiwan

2. Presentation outline Ⅱ Ⅱ Ⅲ Ⅲ IV Ⅰ Ⅰ

3. Ⅰ. Epidemiology of Viral Hepatitis B in Korea

4. Disease Burden of HCC and viral hepatitis B & C 1.Liver cancer is the 4 th most common cancer in Korea Incidence : 21.6 / 100,000 in 1999, 17.6/100,000 in 2010 Gastric ca(14.9%), colon ca(12.8%), lung ca(10.3%), liver ca(7.9%) M/C in males in their 50s 2.Major cause of liver cancer is hepatitis B in Korea Over 70% of HCC is related with Hepatitis B infection Hepatitis C (11.6%), alcoholic liver disease(10.4%) 3.The HBsAg positive rate is still high though the HBsAg positive rate is decreasing 8.6% in 1982, 3.0% in 2011 4. Hepatitis C infection rate is less than 1% in general population.

5.  In Korea, m/c genotype chronic viral hepatitis B : genotype C (difficult to treat, tendency of rapid progression to LC and HCC)  Mode of HBV transmission in Korea : perinatal transmission (m/c)  Geographic distribution of HBsAg positivity Characteristics of HBV infection in Korea HBsAg positivityAnti-HBs Ab positivity (N=290,210) Korea CDC (2009)

6. HBsAg-positive population aged ≥10 years in Korea is 4% (2012).  Positivity of HBsAg decreases continuously [4.0~5.1%(’98) → 3.0~4.8%(’12)]  Positivity of HBsAg increases with age  More prevalent among male [male(4.8%) > female(3.0%)(’11)]  Positivity of HBsAg decreases continuously [4.0~5.1%(’98) → 3.0~4.8%(’12)]  Positivity of HBsAg increases with age  More prevalent among male [male(4.8%) > female(3.0%)(’11)] HBsAg positivity of Korea (1998-2012) : aged ≥ 10 years, age-standardized by population in 2005 Source : Korea CDC Male Female Male Female HBsAg positivity by gender and age (2012)

7. Absence of disposable syringes (~’70) Wide use of disposable syringes (’90~ ) Introduction of HepB vaccine in NIP(’95) Introduction of HepB Vaccine (’85)  Near-elimination status was achieved by enhancing blood safety and quality regulation, wide use of disposable syringes, and integrating HBV vaccine to childhood vaccination HBsAg-positive population aged <20 years in Korea is less than 1%. HBsAg positivity by gender and age Korea Health and nutrition examination survey, 2012

8.  Positivity of HCV Ab increases with age. Positivity HCV Ab by age group, 2012-2014 Age (years)TotalMaleFemale ≥10 6,308 (0.8) 2,761 (0.8) 3,547 (0.7) 10-18 720 (0.0) 385 (0.0) 335 (0.0) 19-29 624 (0.1) 252 (0.1) 372 (0.0) 30-39 970 (0.3) 402 (0.1) 568 (0.5) 40-49 980 (0.9) 426 (1.3) 554 (0.4) 50-59 1,087 (1.1) 457 (0.9) 630 (1.4) 60-69 996 (1.5) 444 (1.9) 552 (1.1) ≥70 931 (2.4) 395 (2.3) 536 (2.4) * Interim data HCV Ab positive-population aged ≥ 10 years in Korea is less than 1%. Source : Korea CDC, Korea Health and nutrition examination survey, 2012

9.  Risk of developing LC increases significantly after their 50s among HCV infected.  Risk of developing HCC increases after their 50s.  Risk of developing LC increases significantly after their 50s among HCV infected.  Risk of developing HCC increases after their 50s. Cumulative incidence of LC by age group among HCV infected population Disease burden of LC and HCC has been increased among population aged above 50 years in Korea. Contribution of HBV, HCV, and Alcoholic liver disease to HCC by age group in Korea Duration of illness (years) >50 years old41-50 years old 31-40 years old 21-30 years old <20 years old Age (years) HBV HCV Alcoholic liver dz, etc.

10. Ⅱ. Major Policies Related with Viral Hepatitis B & C

11. HepBHepC Vaccine development√- National Immunization Program (R EIMBURSEMENT ) √- National Perinatal Hepatitis B Prevention Program√- National check-up for health*√- Diagnosis/Treatment Guideline for diagnosis and treat(ment of hepatitis) √√ Guidelines for safe clinical use of blood** (pre-donation, pre-transfusion) √√ Registry system-- Policy to control HCC (National Registry) √√ * National check-up for health : people aged ≥ 40 years. ** Blood from HepA is discarded by donor’s self-report or Liver function test. Major preventive measures to control hepatitis in Korea is…

12. Major public health measures to control hepatitis B in Korea is… Immunization (1,2,3 rd dose) Diagnosis & Treatment by NHI Ch.Hep B Registry (Under review) Ch.Hep B Registry (Under review) Regular follow-up (Under review) Regular follow-up (Under review) Support medical cost by NHI Acute Chronic Cancer Monitor Case-based surveillance (National Infectious Disease Surveillance System) Seroepidemiologic study (Korea National Health and Nutrition Examination Survey) Data from National Check-up for Health (National Health Insurance) Cancer registry (National Cancer Center) HepB Death Birth Guidelines for safe clinical use of blood (screening at pre-donation, pre-transfusion) National Perinatal Hepatitis B Prevention Program National Check-up for Health (aged ≥40years)

13. Diagnosis & Treatment by NHI Ch.Hep C Registry (Under review) Ch.Hep C Registry (Under review) Support medical cost Major public health measures to control hepatitis C in Korea is… Acute Chronic Cancer HepC Death Birth Monitor Case-based surveillance (National Infectious Disease Surveillance System) Seroepidemiologic study (Korea National Health and Nutrition Examination Survey) Data from National Check-up for Health (National Health Insurance) Cancer registry (National Cancer Center) Guidelines for safe clinical use of blood (screening at pre-donation, pre-transfusion)

14. HepB vaccine coverage rate in Korea is high. Source : Korea CDC Hepatitis B vaccine coverage rate by year

15. Protocols for safe clinical use of blood in Korea. Tests for donated blood Blood type & subtype HBV HCV HTLV Syphilis ALT/TP Neucleic Acid Amplification Test Blood Information Management System (BIMS): ’03~ Comprehensive, web-based system From health history of donor to blood distribution 1.Inform donors 2.Health history 3.Seach for adequacy 4.Monitor Environment 5.Screening test 6.Quality control 7.Transfusion 8.Monitor AE Backward tracing 8.Monitor AE Backward tracing Source : Korea CDC, 2012

16. 2006-2010201120122013 Reported cases HBV12246 HCV1058117 Confirmed for transfusion-related infection HBV1*000 HCV3**000  Investigation of adverse events following transfusion(recipient triggered lookback) - When adverse events from HBV, HCV or HIV are suspected, causality investigation is conducted.  Investigation of adverse events following transfusion(recipient triggered lookback) - When adverse events from HBV, HCV or HIV are suspected, causality investigation is conducted. 2006-2010201120122013 Reported cases HBV3215197 HCV1,95096179139 Confirmed for transfusion- related infection HBV0000 HCV1000  Backward tracing of transfusion associated adverse events(donor triggered lookback) - Backward tracing of transfusion recipients conducted when contamination with HBV or HCV suspected.  Backward tracing of transfusion associated adverse events(donor triggered lookback) - Backward tracing of transfusion recipients conducted when contamination with HBV or HCV suspected. Transfusion related viral hepatitis has occurred, and continued monitoring is necessary. Source : Korea CDC

17. Ⅲ. Perinatal viral hepatitis B prevention program in Korea

18.  Launched in July 2002  Provide Birth dose HepB + HBIG at birth Two doses of HepB vaccine (1 and 6 months) HBsAg & Ab test for infants (9~15 months) Supplementary 3 doses of HepB and tests  Participate 254 public health centers 3,500 private clinics  Budget Annual 2million USD KCDC(50%) + Provincial Government(50%) National Perinatal Hepatitis B Prevention Program: Overview

19. National Perinatal Hepatitis B Prevention Program: Scheme Public Health Centers Public Health Centers Private Clinics KCDC Perinatal HepB Registry DB in National Immunization Registry system KCDC Perinatal HepB Registry DB in National Immunization Registry system Infants HBsAg(+) Mother HepB vaccine+HBIG HBsAg & Ab tests Payment Input Claim (Immunization registry system) Confirm Input National Health insurance National Health insurance HBsAg,Ab Test All pregnant women HBsAg(+)

20. National Perinatal Hepatitis B Prevention Program: Supplements

21. Test results (’02.7~’13.12)Babies (No.)% Prevented (96.95%) HBsAg(-), anti-HBs(+)79,33196.9 HBsAg(-), anti-HBs(-)400.05 Failed (3.05%) HBsAg(+), anti-HBs(-)2,4943.05 HBsAg(+), anti-HBs(+)30 Total81,868100 2002 (Jul-Dec) 200320042005200620072008200920102011 Perinatal hepatitis B exposed neonates 7,85716,67816,07414,79115,23715,78314,90914,23515,04515,084 New-enrollment (%) 5,394 (68.7) 14,586 (87.5) 15,410 (95.9) 14,411 (97.4) 15,002 (98.5) 16,483 (104.4) 15,266 (102.4) 14,547 (102.2) 14,760 (98.1) 14,612 (96.9) * Perinatal hepatitis B exposed neonates = Neonates in the year X HBsAg positivity in pregnant women * National Perinatal Hepatitis B Prevention Program was initiated from 2002 Outcome from the National Perinatal Hepatitis B Prevention Program Still perinatal HBV transmission occurs, though significantly decreased… Source : Korea CDC

22.  Title Prevention of perinatal hepatitis B infection in its risk pregnant women through antenatal anti-viral agent (Telbivudine)  Objective To evaluate the efficacy and safety of using anti-viral agent in pregnant women with high risk of hepatitis B vertical transmission in view of the application in hepatitis B perinatal infection program  Study Preriod 2012.4.1~2014.12(31months) Additional prevention research for high risk group are on-going…

23. IV. Perspectives

24. Strategy to eliminate hepatitis B and HBs Ag positive rate (%) Licensed recombinant vaccine (’87) Introduction HepB vaccine in NIP (’95) Launched Perinatal HepB Prevention Program (’02) HBsAg-positive Year Licenced plasma derived vaccine (’85)

25. Prevalence of HBV <1% is expected within 10-15 years Elimination of hepatitis B is feasible with successful HepB control policy. (%) HBsAg-positive Year

26. Republic of Korea is the first country in WHO/WPRO to be certified for achievement of hepatitis B control goal. HepB vaccine coverage rate: 94.5% HBsAg positivity 0.2% in 10~14 years old 0.2% in 4~6 years old Republic of Korea is the first country in WHO/WPRO to be certified for achievement of hepatitis B control goal. HepB vaccine coverage rate: 94.5% HBsAg positivity 0.2% in 10~14 years old 0.2% in 4~6 years old Korea has achieved goal for control of Hepatitis B (2008) WHO criteria for certification : Population aged > 5 years - HBsAg positivity <1% - HepB vaccine coverage rate > 85%

27. National Perspectives in Korea 1. Strategy to reduce the failure of perinatal HBV transmission are being developed. 2. Prevention of LC and HCC among 1.25 million HBV-infected patients will be supported by proactive management. 3. Implementation of viral hepatitis registry is under consideration. 4. We are expecting the HBsAg positivity would reach elimination status soon in Korea.

28. Thank you for listening!