Hepatitis B Epidemiology and Prevention in the Elimination Era John W. Ward, MD Director, Program for Viral Hepatitis Elimination, Task Force for Global Health Senior Scientist, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention 1
Key Attributes of Successful Disease/Elimination Programs Political will/ community support (advocacy) Agreement on time limited goals and action plan Adequate public health/ clinical infrastructure Implementation of feasible, cost effective interventions Data for monitoring progress and program improvement Hinman A NY State J of Med 1984; Dowdle W, Bull WHO 1998; 2
HBV Burden of Disease Globally, 257 million HBV infected persons Regional variation in prevalence and genotype distribution 816, 000 deaths, 43% related liver cancer; 45% cirrhosis 3 Sources WHO (LSHTM); Lancet 2016; 388: 1459 544; Lancet 2017
HDV Infection Estimates 15-20 million persons with HDV Can increase disease progression and risk of HCC Regional differences in HDV prevalence West Scotland - <3% most were PWID Brazil 3% W. Africa 15% (persons with HIV) Northern Vietnam- 13% Taiwan- 4% general pop. 45-75% of PWID US 36% of PWID Often no HDV testing; only12% HBsAg+ patients tested in US for HDV Distribution of HDV globally. No FDA approved assays 4 C Jackson J Vir Hep 2018;P Mahale J Infect Dis 2018; Mi Binh Sci rep 2018; BV Lage J Med Virol 2018; HH Lin Hepatology 2015; M Rezzetto, Cold Spring Harb Perspect Med. 2015 Jul
Contribution of Hepatitis B and Hepatitis C to Liver Cancer Deaths Globally and by Region, 2015 Date of download: 11/15/2017 JAMA Oncol. Published online October 05, 2017. doi:10.1001/jamaoncol.2017.3055
Largest Causes of Infectious Disease Deaths, 2006, 2016 2000000 1800000 1600000 1400000 1200000 1000000 800000 600000 400000 200000 0 HIV/AIDS TB Malaria HBV HCV 2006 2016 In 2016, a total of 816, 000 deaths, 43% related to liver cancer; 45% to cirrhosis Global Burden of Disease, The Lancet 2017
Deaths from Viral Hepatitis, HIV, TB and Malaria, 2005-2040 2500000 2000000 1500000 1000000 500000 0 2005 2015 2017 2040 TB HIV Malaria Viral Hepatitis Lancet 2018; 392: 1736 88; Lancet 2018; 392: 2052 90 7
CASCADE: 9% OF 257 MILLION DIAGNOSED, 1.7 MILLION ON TREATMENT IN 2015 HBV 8 Sources WHO (Center for Disease Analysis )
HBV Therapy Can Suppress HBV Replication and Lower Risk of HCC Reliable tests available for diagnosis Six studies of 2,394 patients; - Two RCTs 1,372 received lamivudine or adefovir Variable disease stages, sample size, gender, treatment duration Observation period -2.7-8.2 yrs. Therapy reduced HCC risk (0.26; 95% CI, 0.12 0.48) Observational cohort study of 2671 HBsAg+ patients, 1992-2011 Observed for 5.2 years Therapy reduced HCC risk (0.39; 95% CI, 0.27-0.56) Meta-analysis of randomized trials and observational studies differences in outcomes by study design 9 Cabibbo, G Semin Oncol. 2012.; Brown Clin Gastroenterol Hepatol. 2013; Thiele, BMJ Open2013
Research Can Improve Effectiveness of HBV Therapies Current Therapies 40-50% decrease in cirrhosis, liver cancer, all cause mortality Safe and relatively inexpensive ($10-!5K/yr US; $450/yr. generic global) Therapy is life long and not curative HCV success has increased research interest Research for New Therapies Target other steps of viral replication Interrupt replenishment of cccdna Stimulate immune response 10 Liang TJ, Hepatology 2015; Lok A, Hepatology 2015; http://apps.who.int/hiv/amds/price/hdd/default0.aspx
Recommendations for Identification and Management of Persons with Chronic HBV Infection HBV testing for populations with > 2% prevalence o Foreign born- (e.g. Asia, Africa) o MSM, IDU o HIV o Candidates for immunosuppression therapy Management guidance o Contact management o Referral for care and treatment Screening and treatment cost effective ($29,230/QALY 2) USPSTF Grade B- 2014 1 MMWR 2008; 57 (No. RR-8):1-20; 2 Eckman, MH, CID 2011:52 11
Feasible Strategies Improve HBV Testing and Linkage to Care- United States Educational curricula Training protocols Implementation Strategies Patient navigation services Community outreach Screening events Testing voucher coupons Electronic medical record alert tool N=419 for each bar *Attended > medical visit HBeAg, HBV DNA, ALT all done Antiviral treatment given Harris A, et al. AASLD 2016 Community-Based Strategies, Three Sites, 2014-2016 5,940 tested 419 (7.1%) HBsAg-positive 12
13 Pilot HBV Testing and Linkage to Care Program The Gambia 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 Offered HBsAg testing Random household surveys of persons > 30 yrs. of age, 2011-2014 69% of those offered testing 8.8 % of tested 81% of HBsAg+ Accepted HBsAg+ Linked to care Acceptance of testing similar to HIV programs Burden of treatment not as large as expected Reveals importance of testing; feasibility of treatment Program is cost effective - $540 per DALY; country GDP ($487) 4% of those in care Eligible for treatment Accepted treatment Lemoine M, The Lancet Global Health 2016; S Nayagam, The Lancet Global health 2016; Chamie G, PLoS One, 2014; 13
Relative Cost of HBV and HCV Elimination Strategies HCV HBV HBV/HCV HIV/TB/ HIV TB Malaria Total Cost 2018-2030 ( $ billions) 0 50 100 150 200 250 300 350 400 Total 2015-2030 Pedrana A, et al. Eliminating Viral Hepatitis: The Investment Case. Doha, Qatar: World Innovation Summit for Health, 2018; Nayagam S, et al. Requirements for global elimination of hepatitis B: a modelling study, Lancet Infection Dis 2016
Summary Hepatitis B is a large global health problem with largest burden in Asia and Africa and among persons from these regions HBV transmission and mortality are now targets for elimination WPRO countries have developed exemplary HepB prevention programs with virtual HBV elimination among vaccinated children Increases in childhood vaccination led to large declines in HBV prevalence; elimination of perinatal HBV is the remaining challenge Globally, urgent improvements in HBV testing, care, and treatment are needed to achieve elimination goals for mortality
Thank you For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: cdcinfo@cdc.gov Web: www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention Division of Viral Hepatitis