AASLD Talk

Robert Gishrobertgish.comrgish@robertgish.com

San Diego, CA USAMedical Director Hepatitis B Foundation

Senior Medical Director St Josephs Medical Center, Phoenix Arizona

Current Therapy of Hepatitis BPlanning for 2014 and beyond

SOTA 2014 HBV Relevant DisclosuresAdvisory BoardBMS, Gilead, Genentech, Arrowhead, ISIS

Honorarium, speakers bureauBMS, Gilead,

Investment (stock options)Arrowhead#HEV Relevant DisclosuresAdvisory BoardNone

Honorarium, speakers bureauNone

#Hepatitis B: The FactsHepatitis B is the worlds most common serious liver infection1 and is a widespread global health issueHBV is not curable but controllable and suppressibleHBsAg clearance is a functional cureHBV is 100 times more infectious than HIV (human immunodeficiency virus)2 10 times more infectious than hepatitis C3The virus is transmitted via the blood and bodily fluids1Hepatitis B progresses slowly over time Complications generally involve vague symptoms or none at all, and are often undetected for many years1. Hepatitis Australia. Available at http://www.hepatitisaustralia.com/about_hepatitis/hep_b.html. Accessed April 2009; 2. World Health Organization. Hepatitis B Fact Sheet. Available at http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed April 2009; 3. Ulmer T, et al.(2007) European orientation towards the Better Management of Hepatitis B in Europe .

#Hepatitis B: By The Numbers

1. WHO. Available at: www.who.int/csr/disease/hepatitis/en/; 2. Ferlay, et al. Globocan 2002, Cancer incidence, mortality and prevalence worldwide, IARC Press, Lyon 2004;3. Records of the thematic press conference of the Ministry of Health of the PRC at April 21, 2008, from the website of the Ministry of Health of the People's Republic of China;4. Ulmer T, et al. (2007). European orientation towards the better management of hepatitis B in Europe;5. CDC. Hepatitis B FAQs for Health Professionals. Available at http://www.cdc.gov/hepatitis/HBV/HBVfaq.htm#overview.

More than 350 million or 1 in 20 people worldwide have chronic hepatitis B infection1 (Compared with the 33 million living with HIV2)14 million in Europe1,41.46-2.2 million people in the United States are chronically infected5112 million in Asia-Pacific(93 million people in China)1,3#An Unmet Medical NeedWorldwide, hepatitis B is significantly Under-diagnosed Under-treated1

1. BMS Market Research. Information available upon request from Bristol-Myers Squibb; 2. Mohamed R, et al. J Gastroenterol Hepatol 2004;19:958-69; 3. Decision Resources. Hepatitis B virus in China Emerging markets study #5; 4. BMS Market Research.14 million chronic infections1112.6 million chronic infections21.46 - 2 million chronic infections4EuropeAsia-pacificUSA5% are diagnosed3

Less than 1%are treated312% are diagnosed1

12% are treated119% are diagnosed4

4% are treated4#

New figures from Global Burden of Disease Survey 2010: number of people infectedViral Hepatitis TuberculosisHIV/AIDSMalaria1,012,873304,628827,567106,729Total Asia Pacific Mortality FiguresAttribution: Seng Gee Lim AASLD 2013#Viral hepatitis consists of a number of different viruses and as such there are a lot of facts and figures to digest. I have talked about some of these today, but if I were to leave you with one figure today it would be 1 million. This is the number of people that die every year as a result of viral hepatitis infection in Asia Pacific. This is a new figure that deserves attention.

A systematic and coordinated response across Asia Pacific is essential to combat these diseases. Every day clinicians witness the significant challenges that national health services face in combating viral hepatitis and we hope the Global Hepatitis Network will inject new vigor into the global and regional response. With that I would like to officially welcome Dr Hande Harmanci to launch the Global Hepatitis Network.

7HBV Infection, Diagnosis,and Care in the United StatesModified and updated from : Cohen C, et al. J Viral Hepat. 2010

ChronicHBV InfectionNumber (millions)1.4-2.2Million400,000-600,000PersonsAware ofTheir InfectionPotentiallyEligible forTreatmentEnteringCareAnnual HBVPrescriptions350,000-500,000200,000-300,00050,0002.5% to 5%of theTotal HBV-InfectedPopulation(Low to High Estimate)888Importance of RxCohen and colleagues used prescription information from the US Food and Drug Administration and found that approximately 50,000 people in the United States are currently receiving prescription treatment for HBV. This represents 2.5% to 5% of the total chronically infected population, and, overall, possibly 90% of infected children progress to chronic disease 15% Lifetime Risk> 25% Lifetime RiskAnti-HBc (+)Risk for reactivation15Natural history does not always progress in a linear fashion. Complicated. Requires lifelong, regular monitoring. Because of fluctuating nature of activity- recurrent flares interspersed with prolonged periods of normal ALT. Need INDEFINITE monitoring.23% of patients decompensate within 5 years of developing cirrhosis3

HBV Diagnostic MarkersSerologic Marker ResultsHBsAgTotalAnti-HBcIgMAnti-HBcAnti-HBsInterpretation----Never infected and no evidence of immunization+++-Acute infection++--Chronic infection-+-+Recovered from past infection and not immune, low level carrier---+Immune (immunization)Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20.HBeAg- High infectivityHBeAb- Low infectivity16Slide: Typical Interpretation of Serologic Test Results for HBV Infection

Antigens and antibodies associated with HBV infection include HBsAg, anti-HBs, HBcAg, anti-HBc, HBeAg, and anti-HBe. At least one serologic marker is present during each of the different phases of HBV infection.1

The serologic markers typically used to differentiate between acute, resolving, and chronic infection are HBsAg, anti-HBc, and anti-HBs, as noted in the slide.1

ReferenceWeinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20. Testing ParadigmAlways test: anti-HBc

If anti-HBc + > does not need vaccination>>> risk for reactivation#Hepatitis B: By The NumbersIf it is not treated, in 1/3 of patients, hepatitis B can cause liver damage leading to cirrhosis and liver cancer1

Hepatitis B is responsible for 80% of primary liver cancer globally, which is almost always fatal2Historically: Liver cancer was the 3rd highest cause of death by cancer in men3Now 2014: Liver cancer is the 2rd highest cause of caner death worldwide3Without appropriate treatment or monitoring, 1 in 4 persons with chronic hepatitis B will die of liver cancer or liver disease

1. WHO. Available at: www.who.int/csr/disease/hepatitis/en/;2. Hepatitis B Foundation. Hepatitis B and Primary Liver Cancer. Available at http://www.hepb.org/professionals/hepb_and_liver_cancer.htm. Accessed 4 February 2010;3. WHO. Cancer Fact Sheet. Available at http://www.who.int/mediacentre/factsheets/fs297/en/index.html. #ChildhoodAdulthoodImmune ToleranceHBeAg- CHBHCCAnd or cirrhosis95%Inactive carrierHBeAg+ CHB