Kenneth E. Sherman, MD, PhD Gould Professor of Medicine Director, Division of Digestive Diseases University of Cincinnati College of Medicine Cincinnati, Ohio State-of-the-Art Prevention and Management of Hepatitis B Virus Infection Washington, DC: August 25, 2016

Slide 2 of 39 Financial Relationships With Commercial Entities Dr Sherman has received research grants or contracts awarded to his institution from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Inc, Inovio Pharmaceuticals, Intercept Pharmaceuticals, Inc, MedImmune, and Merck & Co, Inc. He has served as an advisory board member or a consultant to Merck & Co, Inc, MedImmune, and ViiV Healthcare. He has also served on data safety monitoring boards for SynteractHCR and Medpace. (Updated 08/15/16)

Slide 3 of 39 Learning Objectives After attending this presentation, participants will be able to: Describe principles of hepatitis B Virus (HBV) prevention through vaccination Be aware of current and emerging therapies for HBV infection Know about risk of hepatocellular carcinoma (HCC), screening, and surveillance for early detection and management

Slide 4 of Baseline HBV DNA ≥10 6 copies/mL 10 5 –< –< –<10 4 <300 RR Cumulative rate of HCC No of patients =3,653* Years *HBeAg negative n=3088 HCC RISK REVEAL COHORT

Slide 5 of 39 NATURAL HISTORY Kwon and Lok, NATURE REVIEWS GASTROENTEROL HEPATOL, 2011

Slide 6 of 39 HBV VACCINE EFFICACY IN HIV HIV NEGATIVE Adapted from Sun et al, WORLD J GASTRO, 2014

Slide 7 of 39 HBV VACCINATION IN HIV Altered Dose/Schedule N= Study Arms (1:1:1) –3 doses 20 ug IM(0,4,24) –4 doses 40ug IM(0, 4, 8, 24 –4 doses 4 ug intradermal (0,4,8,24) Primary Outcome –% >10 mIU/ml at Week 28 % Launay et al, JAMA, 2011

Slide 8 of 39 HBV/HIV COINFECTION TREATMENT GUIDELINES Prior to initiation of antiretroviral therapy (ART), all patients who test positive for hepatitis B surface antigen (HBsAg) should be tested for hepatitis B virus (HBV) DNA using a quantitative assay to determine the level of HBV replication (AIII). Because emtricitabine (FTC), lamivudine (3TC), and tenofovir (TDF) have activity against both HIV and HBV, if HBV or HIV treatment is needed, ART should be initiated with the combination of TDF + FTC or TDF + 3TC as the nucleoside reverse transcriptase inhibitor (NRTI) backbone of a fully suppressive antiretroviral (ARV) regimen (AI). If HBV treatment is needed and TDF cannot safely be used, the alternative recommended HBV therapy is entecavir in addition to a fully suppressive ARV regimen (BI). (BII). DHHS Guidelines for Use of Antiretroviral Agents in HIV-1 Infected Adults And Adolescents. Accessed 2/9/2016 at

Slide 9 of 39 RISK OF RESISTANCE Sarin et al., HEPATOL INT, 2016

Slide 10 of 39 HCC SURVEILLANCE Who? –Asian male over 40 –Asian Female over 50 –Any with family history of HCC –African/North American Blacks –ALL Patients with Cirrhosis –HIV??? How? –US every 6 months but some might need CT/MRI –?AFP

Kenneth E. Sherman, MD, PhD Gould Professor of Medicine Director, Division of Digestive Diseases University of Cincinnati College of Medicine Cincinnati, Ohio State-of-the-Art Prevention and Management of Hepatitis B Virus Infection Washington, DC: August 25, 2016