clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B Diagnose chronic HBV infection When in slideshow mode, click the symbols for additional information Lok AS, et al. Hepatology. 2009;50: Tests to perform at initial visit: HBeAg, anti-HBe, HBV DNA, ALT, AFP, anti-HAV, anti-HCV, anti-HDV If ALT < ULN, HBV DNA < 2000 IU/mL: Inactive phase and no treatment Monitor HBsAg, ALT, HBV DNA, AFP q6-12m ALT ≤ 2 x ULN* *ULN for ALT: 19 for women and 30 for men. Consider testing HBV genotype, precore and basal core promoter mutations HBsAg+, monoinfection confirmed Consider treatment with entecavir, tenofovir, or pegIFN alfa-2a On-treatment management pegIFN alfa-2a, entecavir, tenofovir Management of Chronic HBV Infection ALT > 2 x ULN* or positive biopsy ALT > 2 x ULN* or positive biopsy ALT ≤ 2 X ULN* Check ALT and HBV DNA q3-6 m, consider liver biopsy for > yrs of age, treat as needed HBeAg-, HBV DNA ≥ 20,000 IU/mL HBeAg+, HBV DNA > 20,000 IU/mL

clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B Susceptible, offer vaccination HBsAg-, total anti-HBc-, anti-HBs- HBsAg-, total anti-HBc+, anti-HBs+ Immune due to natural infection HBsAg-, total anti-HBc-, anti-HBs+ Immune due to HBV vaccine HBsAg+, total anti-HBc+, IgM anti-HBc-, anti-HBs- Chronic HBV infection HBsAg+, total anti-HBc+, IgM anti-HBc+, anti-HBs- Acute HBV infection HBsAg-, total anti-HBc+, anti-HBs- Unclear* *Could be any one of the following: 1. Resolved infection (most common) 2. False-positive anti-HBc; susceptible 3. “Low-level” chronic infection 4. Resolving acute infection If HBsAg+: Test for IgM anti-HBc Lok AS, et al. Hepatology. 2009;50: Diagnosis of HBV Infection Test for HBsAg, anti-HBs, and total anti-HBc Person at risk for HBV infection presents Return to “Algorithm for Management of Chronic HBV Infection”

clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B Implications of Genotype, Core, and Precore Results  HBV genotype performed for possible consideration of pegIFN alfa-2a for genotype A patients [1]  Genotype C predictive of poor clinical outcomes and the development of HCC, particularly in patients with basal core promoter mutations [2-4]  Precore mutations most often detected in HBeAg-negative CHB patients and are associated with ALT elevations and persistent hepatic necroinflammatory activity in CHB [5-6] 1. Lok AS, et al. Hepatology. 2009;50: Chan HL, et al. Gut 2004;53: Kao JH, et al. Gastroenterology 2003;124: Tong MJ, et al. Liver Int. 2007;27: McMahon BJ. Hepatology 2009;49:S Chen CJ, Yang HI. J Gastroenterol Hepatol 2011;26: Return to “Algorithm for Management of Chronic HBV Infection”

clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B GuidelinesHBeAg PositiveHBeAg Negative HBV DNA, IU/mL ALTHBV DNA, IU/mL ALT EASL 2009 [1] > 2000> ULN> 2000> ULN APASL 2008 [2] ≥ 20,000> 2 x ULN≥ 2000> 2 x ULN AASLD 2009 [3] > 20,000> 2 x ULN or positive biopsy ≥ 20,000≥ 2 x ULN or positive biopsy NIH consensus conference 2009 [4] > 20,000> 2 x ULN or positive biopsy ≥ 20,000≥ 2 x ULN or positive biopsy US algorithm 2008 [5] ≥ 20,000> ULN or positive biopsy ≥ 2000> ULN or positive biopsy 1. EASL. J Hepatol. 2009;50: Liaw YF, et al. Hepatol Int. 2008;3: Lok AS, et al. Hepatology. 2009;50: Degerekin B, et al. Hepatology. 2009;49(5 suppl):S129-S Keefe EB, et al. Clin Gastroenterol Hepatol. 2008;6: Treatment Criteria for Chronic Hepatitis B: Comparison of Guidelines Return to “Algorithm for Management of Chronic HBV Infection”

clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B Groups at High Risk for HBV Infection Who Should Be Screened  Persons born in geographic regions with HBsAg prevalence of ≥ 2%  US-born persons, not vaccinated as infants, whose parents were born in geographic regions with HBsAg prevalence of ≥ 8%  Persons with chronically elevated aminotransferases  Persons needing immunosuppressive therapy  Men who have sex with men  Persons with multiple sexual partners or history of sexually transmitted disease  Inmates of correctional facilities  Persons who have ever used injection drugs  Dialysis patients  HIV- or HCV-infected individuals  Pregnant women  Family members, household members, and sexual contacts of HBV-infected persons Lok AS, et al. Hepatology. 2009;50: Return to “Algorithm for Diagnosis of HBV Infection”

clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B Guideline Monitoring Recommendations for Interferon Liver Chemistry, CBC HBV DNA, TSH HBeAg, Anti-HBe HBsAg During treatmentq4wq12wq24w* q6m † Posttreatment 12 and 24 wks Lok AS, et al. Hepatology. 2009;50: EASL. J Hepatol. 2009;50: *If HBeAg positive. † If HBeAg negative with serum HBV DNA persistently undetectable by PCR assay. Return to “Algorithm for Management of Chronic HBV Infection”

clinicaloptions.com/hepatitis Using Virologic and Serologic Tests in the Management of Hepatitis B Guideline Monitoring Recommendations for Nucleos(t)ides Liver Chemistry HBV DNA HBeAg, Anti-HBe Serum Creatinine HBsAg During treatmentq12wq12-24wq24w*q12w † q6-12m ‡ 1. EASL. J Hepatol. 2009;50: Lok AS, et al. Hepatology. 2009;50: *If HBeAg positive. † For patients receiving adefovir or tenofovir. ‡ If HBeAg negative with serum HBV DNA persistently undetectable by PCR assay. Consider change of therapy Assess for compliance and resistance and consider rescue therapy § Partial virologic response assessed at Wk 24 for lamivudine, telbivudine, and adefovir and Wk 48 for entecavir and tenofovir. [1] If < 1 log 10 decrease in HBV DNA after 12 wks of therapy (EASL) [1] or < 2 log 10 decrease after 24 wks of therapy (AASLD) [2] (primary nonresponse) If > 1 log 10 IU/mL decrease in HBV DNA but detectable [1] (partial response) § If > 1 log 10 increase in HBV DNA above nadir after response (breakthrough) Return to “Algorithm for Management of Chronic HBV Infection”