Beating viral hepatitis worldwide vaccine antiviral village health

Beating viral hepatitis worldwide: vaccine$, antiviral$, village health care worker$, and informed public health official. S Kathleen B. Schwarz, M. D. Pediatric Liver Centers UCSD; Johns Hopkins

Disclosure slide • I have the following financial relationships to disclose: • Gilead* – research grants and consulting • BMS* – research grant • Roche/Genentech* – research grant • NIDDK • Up to Date • * Products or services produced by this company are relevant to my presentation.

Outline • Dimensions of the problem • WHO Global Viral Hepatitis Strategy • Epidemology • Vaccines: triumphs and tribulation • Treatment • Conventional solutions • Innovative solutions

Dimensions of the problem • Global Burden of Disease Study in 2013, between 1990 - 2013 • deaths from viral hepatitis in the world increased from 0· 89 million to 1· 45 M In 2013, • viral hepatitis was the seventh leading cause of death globally compared with tenth in 1990 • chronic HBV and/or HCV – leading cause of cirrhosis and liver cancer • HAV 212 M • HBV 248 M • HDV 15 -20 M • HCV 170 M (including 11 M children) • HEV >200 M

World Health Organization (WHO) targets for reducing new cases of and deaths from chronic viral hepatitis B and C infection. (From WHO, global health sector strategy on viral hepatitis 2016– 2021, June 2016)

epidemiology

Distribution of HAV Number of cases of acute HAV occurring worldwide increased from 177 million in 1990 to 212 million in 2005

Prevalence of chronic hepatitis B infection (a) in children 5– 9 years old and (b) in adults 19– 49 years old in 2005. (From WHO, guidelines for the prevention, care, and treatment of persons Despite having made major progress in developing a safe and effective vaccine for HBV and having administered >1 billion doses worldwide, the number of people infected with the virus is actually increasing, from 223 million in 1990 to 240 million in 2005!

. Percentage of expected cases of hepatitis C virus infection in children in the United States actually reported to health authorities Delgado-Borrego et al estimated that from 2000 ~2009 only 12% of the children in the state of Florida who were estimated to have HCV infection were identified as having positive anti-HCV tests. Furthermore, only 1. 6% of those with positive tests were actually followed by a pediatric gastroenterologist. For the United States as a whole she estimated that only 4. 9% of the expected cases were identified.

Hepatitis D

Vaccines: triumphs and tribulations

Incidence* of reported acute hepatitis A cases-National Notifiable Diseases Surveillance System, United States, 1966 -2013. Despite safe and effective HAV vaccines the number of cases world wide has increased

Comparing with the cohorts born before the hepatitis B immunization program (rate ratio as 1. 00), the ratios of the incidence rate of acute hepatitis B, the prevalence rate of chronic hepatitis B virus (HBV) infection, and the incidence rate of hepatocellular carcinoma (HCC) were reduced to 0. 34, 0. 09, and 0. 30 in children and adolescents born after the vaccination program in Taiwan

Status of Vaccines for A - E • HAV – funding, anti-vaxxers • HBV – birth dose only recently funded, doesn’t reach outborn infants, vaccine only 70% effective if maternal high viral load • HCV – under development – given that HCV is increasing in young adolescent drug users there is a need • HEV – effective vaccine available only in China

Statu$ of treatment$

Gaps between the number of individuals in the United States estimated to have hepatitis B virus infection and those aware of their infection and actually receiving treatment (28)

Treatments • HAV – none • HBV – evolving – no cure yet • HCV – highly successful, very costly DAA’s • HDV – evolving • HEV – ribavirin for chronic infections

Need for inexpensive anti-virals! • The annual cost of entecavir for the US for an adult with HBV in 2015 when the patent expired was $15, 111 for the brand drug and $6, 127 for the generic version. • The global lowest price was $427. • Production of the active pharmaceutical ingredient was only $4/year based on quotations of generic suppliers • Adding $20 per year formulation and packaging and a 50% profit margin, entecavir was estimated to cost a minimum of $36 per year, much lower than current originator and generic prices.

Conventional solutions for global eradication • Educate health care workers (217 Asian American primary care providers (PCPs) who treat Asian adults who are living in the US and were asked about HBV screening practices and the barriers to performing them. . The vast majority of these PCP’s reported ever having screened a patient for HBV but almost half of these caregivers stated that they screened < ¼ of their Asian American patients. ) • Improve food safety (HAV, HEV) • Base global responses to control of viral hepatitis by learning from the HIV epidemic • Develop safe and effective treatments for HBV/HDV, HEV • Improve delivery of treatment for all

Lessons from success in controlling HIV • Lobby for affordable drugs • Simplify international guidelines • Decentralize care strategies and involve patients and local health care workers • Develop deliverable goals and then to hold players responsible • Develop effective financing

Innovative Solutions – RNA viruses • to eradicate HAV • Give only 1 dose in resource poor countries? • Decrease HAV and HEV contamination in repurposed municipal waste water by down hanging sponge • To eradicate HCV • Develop safe and effective vaccine for high risk individuals • To eradicate HEV • Make Chinese vaccine widely available and test it

Innovative solutions to eradicate HBV • Deliver birth dose to outborn infants • Smart phone technology for vaccine reminders • Fingerstick screening – dried blood spots • Bundle HBV vaccines with other infant vaccines • Government support for prenatal screening and treatment of HBV+ mothers during third trimester

It takes a village! • Health care workers • Governments • Pharma • NGO’s • Professional organizations such as FISPGHAN – please see JPGN 2019 • J Pediatr Gastroenterol Nutr. 2019 Sep 9. Survey of Impediments to Prevention of Mother-to-Infant Transmission of Hepatitis B Virus by International Societies. Chang MH, Fischler B, Blauvelt B, Ciocca M, Dhawan A, Ekong U, Ni YH, Porta G, Sibal A, DAgostino D, Wirth S, Morhan N, Schwarz KB; and the FISPGHAN Hepatitis B Study Group.