1. Candidacy and Guidelines for HBV Therapy This program is supported by educational grants from

2. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Faculty Program Director Danny Chu, MD Clinical Instructor Albert Einstein School of Medicine New York, New York Chul S. Hyun, MD, PhD Clinical Assistant Professor Division of Gastroenterology and Hepatology Weill Cornell Medical College Attending Physician Division of Gastroenterology and Hepatology NewYork Presbyterian Hospital New York, New York Charles G. Phan, MD, AGAF Assistant Professor of Surgery Department of Surgery Baylor College of Medicine Houston, Texas

4. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Faculty Disclosures Danny Chu, MD, has disclosed that he has received consulting fees and fees for non-CME/CE services from Bristol-Myers Squibb and Gilead Sciences. Chul S. Hyun, MD, PhD, has no significant financial relationships to disclose. Charles G. Phan, MD, AGAF, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, and Merck and fees for non-CME/CE services from Bristol-Myers Squibb, Gilead Sciences, Merck, Otsuka, and Procter & Gamble.

5. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Overview of Current Presentation  Scope of the Problem  Assessing Patients for Treatment Candidacy: To Treat or Not to Treat  Case Discussion  Selecting Optimal First-line Therapy

6. Scope of the Problem

7. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty HBV: A Global Problem  2 billion people worldwide have been infected with HBV [1]  ~ 350 million chronic carriers [2]  Leading cause of cirrhosis and HCC worldwide [2]  Causes 80% of all HCC in Asian Americans [3]  30% to 50% of HCC associated with HBV in the absence of cirrhosis [4]  Second only to tobacco in causing the most cancer deaths [5]  HBV is 50-100 times more infectious than HIV [1] 1. World Health Organization. HBV fact sheet. 2. Conjeevaram HS, et al. J Hepatology. 2003;38(suppl 1):s90-s103. 3. Stanford Asian Liver Center. For hepatitis B and liver cancer patients. 4. Bosch FX, et al. Clin Liver Dis. 2005;9:191-211. 5. World Health Organization. Global alert and response: hepatitis B- Introduction.

8. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Candidates for HBV Screening  Persons born in high and intermediate endemic areas (≥ 2% prevalence)  US-born children of immigrants from high endemic areas (≥ 8%; only if not vaccinated as infants in the US)  Household and sexual contacts of HBV carriers  Persons who have injected drugs  Persons with multiple sexual partners or history of STDs  Men who have sex with men  Inmates of correctional facilities  Individuals with chronically elevated ALT/AST  Individuals infected with HIV or HCV  Patients undergoing dialysis  Patients undergoing immunosuppressive therapy  All pregnant women  Infants born to HBV carrier mothers Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. Lok AS, et al. Hepatology. 2009;50:661-662.

9. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Assess HBsAg Positive CHB* Evaluate for treatment Negative Assess anti-HBs Negative (no antibodies) Positive (antibodies present) VaccinateImmune to HBV *Time from positive HBsAg test to diagnosis of CHB is 6 mos. HBV Screening Algorithm Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:1315-1341.

10. Assessing Patients for Treatment Candidacy: To Treat or Not to Treat?

11. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty When to Start HBV Treatment? BenefitsRisks Patient’s age and preference Costs Likelihood of  Adverse outcome without treatment  Long-lasting response Adverse effects Drug resistance Likelihood of adverse outcome without treatment Activity and stage of liver disease at presentation Risk of cirrhosis/HCC in the next 10-20 yrs Likelihood of long-term benefit with treatment

12. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Natural History of HBV Infection Childhood Adulthood Immune tolerance HBeAg+ CHB Inactive carrierHBeAg- CHB Cirrhosis < 5% > 95% Chen DS, et al. J Gastroenterol Hepatol. 1993;8:470-475. Seeff L, et al. N Engl J Med. 1987;316:965-970. Fattovich G, et al. J Hepatol. 2008;48:335-352. 5-Yr Incidence Rates Cirrhosis: 8% to 38% of chronically infected patients HCC: 10% to 17% of patients with cirrhosis

13. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty PhaseImmune Tolerant Immune Clearance Inactive Carrier State Reactivation Liver Minimal inflammation and fibrosis Chronic active inflammation Mild hepatitis and minimal fibrosis Active inflammation Optimal treatment times Anti-HBe HBV DNA ALT activity Current Understanding of HBV Infection 4 Phases of Chronic HBV Infection HBeAg Yim HJ, et al. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006;43:S173-S181. Copyright © 1999–2012 John Wiley & Sons, Inc. All Rights Reserved.

14. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Goals and Benefits of Hepatitis B Treatment  Prevention of long-term negative clinical outcomes (eg, cirrhosis, liver transplantation, HCC, death) by durable suppression of HBV DNA  Primary endpoint –Sustained decrease in serum HBV DNA level to undetectable  Secondary endpoints –Decrease or normalize serum ALT –Improve liver histology –Induce HBeAg loss or seroconversion in HBeAg-positive disease –Induce HBsAg loss or seroconversion  Treatment is often long term or lifelong, particularly in HBeAg-negative patients

15. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty What Information Is Needed to Determine HBV Treatment Candidacy?  HBeAg  ALT  HBV DNA  Liver histology  Family history?

16. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Keeffe EB, et al. Clin Gastroenterol Hepatol. 2004;2:87-106. Chu CJ, et al. Gastroenterology. 2003;125:444-451. Chronic Hepatitis B Disease Types  HBeAg positive –Also known as “wild type” –Antibody to HBeAg negative –HBV DNA > 20,000 IU/mL (> 10 5 copies/mL)  HBeAg negative –Also known as “precore mutant” –Antibody to HBeAg positive –HBV DNA > 2000 IU/mL (> 10 4 copies/mL)

17. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty What Is an Elevated ALT Level?  Reference ranges for ALT vary between 2 most widely used commercial laboratories –Men: 4-60 IU/L; women: 6-40 IU/L –Men: 0-55 IU/L; women: 0-40 IU/L  Both AASLD and US treatment algorithms recommend lower ULN levels for ALT when making treatment-initiation decisions –30 IU/L for men –19 IU/L for women Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:1315-1341. Prati D, et al. Ann Intern Med. 2002;137:1-10. Lok AS, et al. Hepatology. 2009;50:661-662.

18. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Histology  Liver biopsy –Establishes disease baseline before initiation of therapy –Helps to exclude other causes of liver disease –More sensitive and accurate than ALT –May be considered in patients who meet criteria for chronic hepatitis –Limitations –Invasive procedure –Sampling error –Interobserver variability

19. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty HBV DNA Testing  Indicates chronic hepatitis when still positive 6 mos after diagnosis of acute HBV infection –Can differentiate chronic, inactive carrier (< 2000 IU/mL) vs resolved HBV infection (undetectable)  Change in HBV DNA level used to monitor response to therapy  Increasing HBV DNA level during antiviral therapy indicates emergence of resistant variants  HBV DNA level correlates with disease progression  HBV DNA levels reported as IU/mL (standard) or copies/mL –For conversion: 1 IU/mL = ~ 5 copies/mL Adapted from Keeffe EB, et al. Clin Gastroenterol Hepatol. 2004;2:87-106.

20. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Guidelines HBeAg PositiveHBeAg Negative HBV DNA, IU/mL ALTHBV DNA, IU/mL ALT AASLD 2009 [1] > 20,000 > 2 x ULN or positive biopsy* ≥ 20,000 ≥ 2 x ULN or positive biopsy* EASL 2009 [2] > 2000> ULN> 2000> ULN APASL 2008 [3] ≥ 20,000> 2 x ULN≥ 2000> 2 x ULN NIH Consensus Conference 2009 [4] > 20,000 > 2 x ULN or positive biopsy* ≥ 20,000 ≥ 2 x ULN or positive biopsy* 1. Lok AS, et al. Hepatology. 2009;50:661-662. 2. EASL. J Hepatol. 2009;50:227-242. 3. Liaw YF, et al. Hepatol Int. 2008;3:263-283. 4. Degerekin B, et al. Hepatology. 2009;S129-S137. 5. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:1315-1341. 6. Tong MJ, et al. Dig Dis Sci. 2011;56:3143-3162. Determining Treatment Candidacy for Chronic Hepatitis B: Guidelines *Moderate/severe inflammation or significant fibrosis.  Expert guidelines also published with recommendations specific for HBV management in US [5] and more recently for Asian Americans [6] –Some key differences between these guidelines

21. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty q3-6 mos ALT q6-12 mos HBeAg q3 mos ALT q6 mos HBeAg Consider biopsy if persistent or older than 40 yrs of age Treat as needed q1-3 mos ALT, HBeAg Treat if persistent Liver biopsy optional Immediate treatment if jaundice or decompensated HBeAg positive HBsAg positive Lok AS, et al. Hepatology. 2009;50:661-662. 2009 AASLD Guidelines: Treatment Candidacy for HBeAg-Positive Patients ALT < 1 x ULN HBV DNA < 20,000 IU/mL ALT 1-2 x ULN HBV DNA > 20,000 IU/mL ALT > 2 x ULN HBV DNA > 20,000 IU/mL

22. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Treat if persistent Liver biopsy optional q3 mos ALT and HBV DNA Consider biopsy if persistent Treat as needed q3 mos ALT x 3, then q6-12 mos if ALT still < 1 x ULN HBeAg negative ALT ≥ 2 x ULN HBV DNA ≥ 20,000 IU/mL HBsAg positive ALT 1-2 x ULN HBV DNA 2000-20,000 IU/mL ALT < 1 x ULN HBV DNA < 2000 IU/mL 2009 AASLD Guidelines: Treatment Candidacy for HBeAg-Negative Patients Lok AS, et al. Hepatology. 2009;50:661-662.

23. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Who Should Be Treated?  Not a question of who to treat, but when: treat now or monitor and treat later when indicated  All HBV carriers are potential treatment candidates  A patient who is not a treatment candidate now can be a treatment candidate in the future –Changes in HBV replication status and/or activity/stage of liver disease –Availability of new or improved treatments

24. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty What Challenges Might You Face in Determining Treatment Candidacy?  Busy practice  Dealing with patients’ other health concerns (ie, the primary reason they were in your office)  Dealing with patient resistance  Knowing the right tests to order  Knowing how to interpret test results

25. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty When Should You Seek the Advice of an HBV Expert Before Initiating Therapy?  Seek advice in the following situations –Treatment-experienced patients –Patients with advanced disease stage, especially decompensated cirrhosis –Concern for antiviral resistance –Patients with HIV or HCV coinfection –Pregnant women –Any time you have concerns about how best to manage a patient

26. Case Discussion

27. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 1: Patient History  47-yr-old woman, born in Korea, came to the US at 35 yrs of age, recently found to be HBsAg positive during life insurance checkup  No previous history of jaundice or acute hepatitis  No symptoms  Only medical problem: mild hypertension  Family history –No known history of hepatitis B or liver cancer –Husband and 2 sons aged 20 and 25 yrs not yet tested for HBV

28. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 1: Current Presentation  Exam: normal, no jaundice or hepatosplenomegaly  Labs –Hb 14 g/dL, WBC 5200 cells/mm 3, platelets 142,000 cells/mm 3 –AST 11 IU/L, ALT 12 IU/L –Alb 4.4 g/dL, alk phos 105 IU/L, T bil 0.8 mg/dL –AFP 4.3 ng/mL –HBsAg positive, HBeAg negative, anti-HBe positive –HBV DNA 110 IU/mL  Ultrasound –Liver normal size and texture with no mass, borderline splenomegaly

29. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty For Discussion: What Would You Recommend for This Patient? A.Start treatment now B.Order liver biopsy; start treatment if cirrhosis confirmed C.Observe, repeat labs q3 mos, start treatment if ALT/HBV DNA increase D.Reassure and discharge patient

30. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Inactive Carrier State vs HBeAg-Negative Chronic Hepatitis B  Inactive carrier state –HBeAg negative –Persistently normal ALT –Serum HBV DNA persistently undetectable or < 2000 IU/mL  Serial follow-up necessary to differentiate inactive carriers from patients with HBeAg-negative chronic hepatitis B and intermittently normal ALT

31. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 1: Follow-up  Repeat labs Time PointPlatelet Count, cells/mm 3 AST, IU/LALT, IU/LHBV DNA, IU/mL Mo 3 154,000252945 Mo 6 148,00035411180 Mo 9 137,00042597375

32. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty For Discussion: What Would You Recommend for This Patient at This Time? A.Start treatment B.Liver biopsy C.Continue to observe

33. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 1: Management Decisions  Liver biopsy performed –Mild inflammation, bridging fibrosis  Oral antiviral therapy started

34. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 1: Recommended Monitoring for This Patient During Oral Antiviral Therapy  Serum HBV DNA: q3-6 mos  Liver panel, platelets: q3 mos  HBsAg: q12 mos (after HBV DNA undetectable)  Virologic breakthrough: check medication compliance before drug resistance

35. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 2: Patient History  40-yr-old Filipino male  ALT 28 IU/L  HBsAg positive, HBeAg positive  Serum HBV DNA 60,000,000 IU/mL  Negative viral serologies for hepatitis A and C and HIV  Abdominal ultrasound without any significant abnormalities  Previous medical history noncontributory  No family history of liver disease  No tobacco use; EtOH: 3-4 drinks/wk (wine)

36. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Case 2: Further Workup  6 mos later, ALT level increased to 34 IU/L and patient agreed to a liver biopsy –Liver biopsy showed grade 1 inflammation and stage 1 fibrosis  The patient continued to be monitored q6 mos  2 yrs later, ALT level was 92 IU/L and HBV DNA (PCR) level was 48,000,000 IU/mL  HBV serology repeated –HBeAg positive, anti-HBe antibody negative

37. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty For Discussion: How Would You Classify His Chronic Hepatitis B Infection? A.Chronic carrier B.Immune clearance C.Immune tolerance D.Reactivation

38. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty For Discussion: Should We Start Therapy in This Patient? A.Yes B.No

39. Selecting Optimal First-line Therapy

40. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Interferon alfa-2b Lamivudine Adefovir Peginterferon alfa-2a Telbivudine Tenofovir 199019982002200520062008 HBV Treatment Landscape in 2011 Entecavir

41. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Current Guideline Recommendations for First-line Therapy  Peginterferon alfa-2a –Exceptions: pregnancy, chemotherapy prophylaxis, decompensated cirrhosis, acute infection  Entecavir  Tenofovir EASL. J Hepatol. 2009;50:227-242. Liaw YF, et al. Hepatol Int. 2008;2:263-283. Lok AS, et al. Hepatology. 2009;50:661-662.

42. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty 5-Yr Rates of Resistance With Oral Agents in Nucleos(t)ide-Naive Patients 70 29 17 1.2 0 0 20 40 60 80 100 Lamivudine [1] Adefovir [1] Telbivudine* [1] Entecavir [1] Tenofovir [2] Cumulative Resistance Rate (%) 1. EASL. J Hepatol. 2009;50:227-242. 2. Marcellin P, et al. AASLD 2011. Abstract 1375. *Telbivudine rate determined at Yr 2.

43. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Selection of Entecavir vs Tenofovir: Either Is an Excellent Choice for Most Patients Lok AS. Hepatology. 2010;52:743-747. 21 2 < 1 21 3 0 0 5 10 15 20 25 HBeAg seroconversion HBsAg loss Entecavir Tenofovir HBeAg Negative HBsAg loss HBeAg Positive Response at Wk 48-52 (%) ParameterEntecavirTenofovir Log HBV DNA ↓ at Wk 48-52  HBeAg positive6.96.2  HBeAg negative5.04.6 Genotypic resistance, %  NA naive1.2 (Yr 5)0 (Yr 3)  Lamivudine experienced 51 (Yr 5)NR Pregnancy ratingClass CClass B AEsNone Renal toxicity; ↓ BMD

44. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty How to Use Entecavir or Tenofovir  Dosage and administration –Entecavir: oral administration –Patients naive to lamivudine therapy: 0.5 mg QD –Patients who are refractory/resistant to lamivudine: 1.0 mg QD –Dose adjustment needed if eGFR < 50 mL/min –Tenofovir: oral administration –300 mg QD –Dose adjustment needed if eGFR < 50 mL/min Lok AS, et al. Hepatology. 2009;50:661-662.

45. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty How to Use Entecavir or Tenofovir  Duration, based on clinical endpoints –HBeAg positive: continue treatment until HBV DNA undetectable and HBeAg seroconversion achieved; continue for ≥ 6 mos after anti-HBe appearance –Close monitoring for relapse required after treatment discontinuation –HBeAg negative: continue treatment until HBsAg clearance Lok AS, et al. Hepatology. 2009;50:661-662.

46. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Monitoring of Patients Receiving Nucleos(t)ide Analogue Therapy Time PointMonitoring q12 wks  Liver panel  Serum creatinine (if receiving TDF or ADV) q12-24 wks  HBV DNA levels q24 wks  HBeAg/anti-HBe (if initially HBeAg positive) q6-12 mos  HBsAg in HBeAg-negative patients with persistently undetectable HBV DNA Lok AS, et al. Hepatology. 2009;50:661-662.

47. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Clinical Scenarios of Concern Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661-662. Copyright © 1999–2012 John Wiley & Sons, Inc. All Rights Reserved. HBV DNA (log 10 IU/mL) ALT (U/L) Yrs Biochemical breakthrough ULN Virologic rebound Virologic breakthrough Hepatitis flare 8 6 4 2 0 0123

48. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty PegIFN vs Nucleos(t)ide Analogues PegIFNNucleos(t)ide Analogues ProConProCon  Finite course of therapy  No resistance  Higher rate of HBeAg loss in 1 yr  Higher rate of HBsAg loss with short duration therapy*  SQ administration  Frequent AEs  Contraindicated in patients with cirrhosis, in pregnancy, with acute hepatitis B, and who are immunosuppressed  PO administration  Infrequent AEs  Safe at all stages of disease, including decompensated cirrhosis †  Safe in immuno- compromised populations  Selected drugs probably safe in pregnancy  Need for long- term or indefinite therapy  Potential for drug resistance *Particularly for HBeAg-positive patients with genotype A infection. † Recent case report of lactic acidosis in severe liver failure. Lok AS, et al. Hepatology. 2007;45:507-539. Lok AS, et al. Hepatology. 2009;50:661-662. Lok AS. Hepatology. 2010;52:743-747. Buster EH, et al. Gastroenterology. 2008;135:459-467. Lange CM, et al. Hepatology. 2009;50:2001-2006.

49. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty When to Consider PegIFN  Favorable predictors of response [1,2] –Low HBV DNA* –High ALT* –Genotype A or B > C or D [3-5] –Not advanced disease 1. Lok AS, et al. Hepatology. 2009;50:661-662. 2. Lok AS. Hepatology. 2010;52:743-747. 3. Janssen HL, et al, Lancet. 2005;365;123-129. 4. Lau GK, et al. N Engl J Med. 2005;352:2682-2695. 5. Flink HJ, et al. Am J Gastroenterol. 2006;101:297-303.  Specific patient demographics [1,2] –Generally young people –Young women wanting pregnancy in near future –Absence of comorbidities  Patient preference [1,2]  Concomitant HCV infection *Also predictive of response to nucleos(t)ide analogues.

50. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty How to Use PegIFN alfa-2a  Dosage/administration –180 µg/wk by SQ injection  Duration of therapy –48 wks  Treatment endpoints: how to determine success or failure –Finite duration therapy; not based on specific endpoints –Virologic response to therapy defined as decrease in serum HBV DNA to undetectable levels by PCR at end of treatment and loss of HBeAg in patients who were initially HBeAg positive Lok AS, et al. Hepatology. 2009;50:661-662.

51. clinicaloptions.com/hepatitis A Mentorship Program Linking Primary Care Providers With Expert HBV Faculty Potential Barriers to HBV Treatments  Patient resistance or cultural beliefs about treatment  Potential adverse effects (particularly interferon)  Challenges with long-term therapy  Understanding endpoints and monitoring strategies  Lack of symptoms  Lack of ability to cure disease with current regimens in most patients  Adherence

52. Go Online for More CCO Coverage of HBV Infection Interactive Virtual Presentations review and consider challenging patient cases with guidance from expert faculty members Text-Based Modules plus downloadable PowerPoint slides clinicaloptions.com/hepatitis