1. Expert Perspectives on Hepatitis B Virus and the Infected Patient

2. HBV Virology

3. Hepatitis B Virus Key Points DNA virus DNA virus Reverse transcriptase Reverse transcriptase Multiple genotypes Multiple genotypes Human genome integration Human genome integration Cellular dormant form with replicative potential Cellular dormant form with replicative potential Generally not curable after development of chronic infection Generally not curable after development of chronic infection –Clearance of HBsAg is rare even with treatment cccDNA cccDNA –Stable intermediate –Template for viral protein production

4. Organization of the HBV Genome Reprinted from Hunt CM, et al, Hepatology, 2000;31:1037, reprinted with permission of Wiley-Liss, Inc, a subsidiary of John Wiley & Sons, Inc.

5. Uncoating Nuclear import Repair Transcription cccDNA 5’ 3’ 3.5 kb RNA Viral Entry 2.4/2.1 kb RNA Nassal M, et al. J Viral Hepat. 1996;3:217. Ganem D, et al. Fields Virology. 4th ed. Philadelphia: Lippincott-Raven Publishers; 2000:2923. Courtesy of Nezam H. Afdhal, MD. HBV Replication cccDNA Formation and mRNA Transcription

6. Uncoating Nuclear import Repair Transcription Translation Positive strand synthesis Removal of pregenome Negative strand synthesis Encapsulation cccDNA 5’ 3’ 3.5 kb RNA Viral Entry 2.4/2.1 kb RNA Nassal M, et al. J Viral Hepat. 1996;3:217. Ganem D, et al. Fields Virology. 4th ed. Philadelphia: Lippincott-Raven Publishers; 2000:2923. Courtesy of Nezam H. Afdhal, MD. HBV Replication Translation and Capsid Assembly

7. Uncoating Nuclear import Repair Transcription Translation HBsAg Positive strand synthesis Assembly & budding ER Removal of pre- genome Negative strand synthesis Encapsulation cccDNA 5’ 3’ 3.5 kb RNA Viral Entry 2.4/2.1 kb RNA Export Nassal M, et al. J Viral Hepat. 1996;3:217. Ganem D, et al. Fields Virology. 4th ed. Philadelphia: Lippincott-Raven Publishers; 2000:2923. Courtesy of Nezam H. Afdhal, MD. HBV Replication – Replenishment or Release

8. Clinical Significance of Viral Replication Worsening histology, including cirrhosis HCC Viral replication Elevated ALT

9. Goals of Suppression of Viral Replication Prevention of death, cirrhosis, and HCC Histologic improvement Virologic response Reduction in – HBV DNA – cccDNA Serologic response – HBeAg loss – HBeAg seroconversion – HBsAg loss and seroconversion Biochemicalimprovement

10. Diagnostic Testing

11. CDC. Epidemiology & Prevention of Vaccine-Preventable Diseases. “The Pink Book.” 8th ed, 2005. Lok ASF, et al. Hepatology. 2001;34:1225. Who Should Be Screened? Patients engaged in high-risk sexual behaviors (men who have sex with men, sexual contacts of HBV-infected persons) Patients engaged in high-risk sexual behaviors (men who have sex with men, sexual contacts of HBV-infected persons) Injection drug users Injection drug users Immigrants, refugees, or adoptees/orphans from areas of high endemicity Immigrants, refugees, or adoptees/orphans from areas of high endemicity Immunocompromised patients Immunocompromised patients Dialysis patients Dialysis patients Household members of known HBV carriers Household members of known HBV carriers Persons exposed occupationally Persons exposed occupationally Inmates in long-term correctional facilities or residents in institutions for the developmentally disabled Inmates in long-term correctional facilities or residents in institutions for the developmentally disabled Pregnant women Pregnant women Individuals infected with HCV or HIV Individuals infected with HCV or HIV

12. HBV Serologic and Molecular Tests in Serum CategoryTestSignificance Viral antigensHBsAg*Acute or chronic infection; infectivity HBeAgAcute or chronic infection; infectivity Viral antibodiesAnti-HBc* Anti-HBe Anti-HBs* Marker of infection Low infectivity Marker of immunity Molecular testsHBV DNAAcute or chronic infection; infectivity *Test recommended for initial screening

13. 2nd-Phase Testing in HBsAg+ Patients HBeAg HBeAg –Positive, indicates active HBV replication –Negative If HBV DNA negative, suggests HBV replication is suppressed If HBV DNA negative, suggests HBV replication is suppressed If HBV DNA positive, most likely has precore mutation If HBV DNA positive, most likely has precore mutation Anti-HBe Anti-HBe HBV DNA quantification HBV DNA quantification –Quantitative level correlates with level of HBV replication Anti-HDV Anti-HDV –Detects coinfection with delta agent

14. Each lab must validate the assay in-house and determine their own performance characteristics, which may vary from lab to lab 10 3 3 x 10 4 3 x 10 4 10 5 HBV DNA Concentration in Log 10 Copies/mL 0 2468 Digene II (Hybrid Capture) UltrasensitiveStandard Roche (PCR) AMPLICOR Monitor v2.0 COBAS Monitor v2.0 Bayer (bDNA) VERSANT HBV 1.0 VERSANT HBV 3.0 TaqMan HBV ASR (PCR) ? 1000–40,000,000 200–200,000 700,000–5,000,000,000 2000–100,000,000 4700–57,000,000 142,000–1,700,000,000 170–640,000,000 Courtesy of Robert G. Gish, MD. Ranges of HBV DNA Assays

15. *Conversion factors given by the manufacturers. AssayConversion Factor Versant HBV DNA 3.0 (bDNA)5.2 copies/mL = 1 IU/mL Cobas Amplicor HBV Monitor5.6 copies/mL = 1 IU/mL Cobas TaqMan 48 HBV5.8 copies/mL = 1 IU/mL 1 pg = 283,000 copies Zeuzem S. Methods Mol Med. 2004;95:3. Viral Load Testing Copies/mL to IUs*

16. Bruix J, et al. Hepatology. 2005;42:1208. Diagnostic Tests Screening for HCC–New AASLD Practice Guidelines Diagnostic Tests Screening for HCC–New AASLD Practice Guidelines At-risk hepatitis B carriers At-risk hepatitis B carriers –Asian males ≥40 years –Asian females ≥50 years –All cirrhotic HBV carriers –Family history of HCC –Africans older than age 20 years –Those with high HBV DNA concentrations and ongoing hepatic inflammation remain at risk for HCC Ultrasound scanning of liver every 6–12 months Ultrasound scanning of liver every 6–12 months

17. *Keeffe EB, et al. Clin Gastroenterol Hepatol. 2004;4:936. Diagnostic Tests Liver Biopsy—Pros Excludes other diseases Excludes other diseases Guides decisions on initiation of treatment Guides decisions on initiation of treatment –See US Algorithm guidelines* Predicts prognosis Predicts prognosis –Grade and stage Utilizes change from baseline as marker for treatment response Utilizes change from baseline as marker for treatment response –Nucleoside/nucleotide analogs FDA-approved for histologic improvement

18. 1. Lok ASF, et al. Hepatology. 2001;34:1225. 2. Lok ASF, et al. Hepatology. 2004;39:857. Diagnostic Tests Liver Biopsy—Cons Risks and patient reluctance Risks and patient reluctance Not required by AASLD guidelines as a factor in deciding to treat 1,2 Not required by AASLD guidelines as a factor in deciding to treat 1,2 HBV DNA/serology/ALT could dictate treatment HBV DNA/serology/ALT could dictate treatment Cancer risk may be independent of cirrhosis Cancer risk may be independent of cirrhosis

19. Natural History

20. Inactive carrier <5% HBeAg+ chronic hepatitis B Adulthood Chen DS, et al. J Gastroenterol Hepatol. 1993:8:470. Seeff L, et al. N Engl J Med. 1987;316:965. Courtesy of W. Ray Kim, MD. Immune tolerance Cirrhosis Early childhood >95% HBeAg- chronic hepatitis B Natural History of HBV Infection

21. *Precore mutant † Expert opinions vary as to this value Lai CL, et al. Lancet. 2003:362:2089. Lok AS, et al. Gastroenterology. 2001;120:1828. ImmuneHBeAgInactive HBeAg TolerantPositiveHBsAg Negative PhaseCHBCarrierCHB* HBsAg++++ HBeAg++–– Anti-HBe––++ ALTNormal  Normal  HBV DNA>10 5 >10 5 10 4† copies/mL copies/mL copies/mL copies/mL HistologyNormal/mildActive Inactive Active Phases of Chronic HBV Infection

22. HBeAg Negative Patients HBeAg positive patients may develop antibodies (anti-HBe) HBeAg positive patients may develop antibodies (anti-HBe) When HBeAg is lost, 2 possible scenarios When HBeAg is lost, 2 possible scenarios –Inactive carrier (normal ALT, low or negative HBV DNA level) –Precore mutant chronic HBV (moderate to high HBV DNA, elevated ALT)

23. Sherman M. Semin Liver Dis. 2005;25:143. Inactive Carriers HBeAg negative, normal ALT, low/negative HBV DNA HBeAg negative, normal ALT, low/negative HBV DNA “Healthy carriers” = oxymoron “Healthy carriers” = oxymoron All patients who are HBsAg positive need ongoing monitoring as part of management All patients who are HBsAg positive need ongoing monitoring as part of management –Monitor for increased ALT or HBV DNA every 6 months –Monitor for HCC in at-risk groups

24. 146810 0 20 40 60 80 100 Years Patients (%) 23579 HBeAg clearance (up to 80%) HBsAg clearance (5%) Lok ASF, et al. Hepatology. 2001;34:1225. Spontaneous Viral Clearance at 10 Years

25. 1. Torresi J, et al. Gastroenterology. 2000;118:S83. 2. Fattovich G, et al. Hepatology. 1995;21:77. Chronic infection Cirrhosis Death 5%–10% 1 Liver failure 30% 1 23% in 5 years 2 Liver cancer (HCC) Liver transplantation Acute flare 6% in 5 years 2 HBV Disease Progression

26. 1. Weissberg JI, et al. Ann Intern Med. 1984;101:613. 2. De Jongh FE, et al. Gastroenterology. 1992;103:1630. 132450 20 40 60 100 80 Cirrhosis 1 (n = 130) Decompensated cirrhosis 2 (n = 21) 14% 55% Patients Surviving (%) Years 0 Actuarial Survival in HBV-Related Liver Disease Historical Studies

27. Reprinted from Gastroenterology, 103, De Jongh FE, et al, 1630, copyright 1992, with permission from the American Gastroenterological Association. Survival with Compensated Cirrhosis HBeAg Positive vs Negative Patients Surviving (%) 12345 HBeAg positive (n = 43) HBeAg negative (n = 34) 97% 72% 0 20 40 60 80 100 Years 0

28. Yang H-I, et al. N Engl J Med. 2002;347:168. Copyright 2002, Massachusetts Medical Society. All rights reserved. 121086420 Cumulative Incidence (%) 012345678910 Year HBsAg+, HBeAg+ (RR = 60.2) HBsAg+, HBeAg– (RR = 9.6) HBsAg–, HBeAg– RR = relative risk HBe Antigen Status and Risk of HCC

29. Age- and Race-Specific HBV Mortality White Other Black/African American 0 1 2 3 4 5 6 <2525–3435–4445–5455–6465–7475+ Age (Years) Death Rate (/100,000) CDC. Underlying Cause of Death. 1994–1998. Compressed Mortality File (CMF) compiled from CMF 1968-1988, Series 10, No. 2A 2000, CMF 1989– 1998, Series 20, No. 2E 2003, and CMF 1999–2001, Series 20, No. 2G 2004 pm. CDC WONDER On-line Database.

30. HBV Vaccination Effect on HCC Incidence and Mortality* Chang M-H, et al. N Engl J Med. 1997;336:1855. *Nationwide vaccination in Taiwan, implemented 7/84 Incidence 0 0.2 0.4 0.6 0.8 1 1981–861986–901990–94 Per 100,000 Children (6–14 Years) Per 100,000 Children (6–14 Years) 0.70 0.57 0.36 Mortality 0 0.2 0.4 0.6 0.8 1 1981–861986–901990–94 0.80 0.58 0.34

31. Abstracts from 40th EASL; April 13-17, 2005: 1. Iloeje UH, et al. Abstract 497. 2. Chen G, et al. Abstract 476. 3. Chen G, et al. Abstract 477. 4. Iloeje UH, et al. Abstract 496. 5. Iloeje UH, et al. Abstract 495. HBV DNA Level Predicts Morbidity and Mortality Elevated HBV DNA level Elevated HBV DNA level –Strong predictor of cirrhosis regardless of ALT level 1 or HBeAg status 2 –Associated with increased mortality from chronic liver disease and HCC 3 Incidence of cirrhosis increases with HBV DNA level in dose-dependent manner 4 Incidence of cirrhosis increases with HBV DNA level in dose-dependent manner 4 Incidence of HCC risk in people with normal ALT levels increases with HBV DNA level in dose-dependent manner 5 Incidence of HCC risk in people with normal ALT levels increases with HBV DNA level in dose-dependent manner 5

32. 1. Chen CJ, et al. JAMA. 2006;295:65. 2. Iloeje UH, et al. Gastroenterology. 2006;130:678. Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL) HBV Study, Taiwan Prospective, multicenter, observational cohort study Prospective, multicenter, observational cohort study 3851 HBsAg positive patients with adequate sample for baseline 1 HBV DNA 3851 HBsAg positive patients with adequate sample for baseline 1 HBV DNA –3653 patients seronegative for anti-HCV were included in study and followed for HCC 1 and cirrhosis 2 –HCC detected by health exam or through Taiwan national cancer registry for January 1, 1991 through June 30, 2004 1 –Patients were evaluated for cirrhosis via ultrasound every 6-12 months for a mean of 11 years through June 30, 2004 2

33. Persistent HBV Viral Load Elevation Is Associated with Greatest Risk of HCC REVEAL Study 289 study participants, last follow-up serum samples not available Cohort Entry Examination <10 4 10 4 –10 5  10 5 Serum level of HBV DNA (copies/mL) Multivariate-Adjusted HR* (95% CI) 1.0 (referent) 1.6 (0.7–3.9) 0.5 (0.1–3.6) 3.5 (1.4–9.2) 3.8 (1.7–8.4) 7.3 (3.5–15.3) 10.1 (6.3–16.2) Follow-Up Examination Not tested <10 4 10 4 –10 5  10 5 <10 4 10 4 –10 5  10 5 *Adjustment for gender, age, cigarette smoking, and alcohol consumption. Chen CJ, et al. JAMA. 2006;295:65. Reprinted with permission.

34. Baseline HBV DNA Level and Cumulative Incidence of HCC Entire Cohort 0 2 4 6 8 10 12 14 16 <300 300–<10 4 10 4 –<10 5 10 5 –<10 6 ≥10 6 N = 3653, 13-year follow-up Cumulative Incidence of HCC (%) Chen C-J, et al. JAMA. 2006;295:65. HBV DNA (Copies/mL) 1.3 1.37 3.57 12.17 14.89 1IU = ~5 copies/mL

35. Baseline HBV DNA Level and Cumulative Incidence of HCC Subgroup of Noncirrhotic HBeAg– Patients with Normal ALT 0 2 4 6 8 10 12 14 16 <300 300–<10 4 10 4 –<10 5 10 5 –<10 6 ≥10 6 N = 2925 Cumulative Incidence of HCC (%) Chen C-J, et al. JAMA. 2006;295:65. HBV DNA (Copies/mL) 0.74 0.89 3.15 7.96 13.50

36. Baseline HBV DNA Level and Relative Risk of Cirrhosis Iloeje UH, et al, Gastroenterology. 2006;130:678. 0 10 <300 300–9.9x10 3 1.0–9.9x10 4 1.0–9.9x10 5 ≥10 6 N = 3582, 11-year follow-up Relative Risk 1 1.4 2.5 5.9 9.8 Adjusted for gender, age, smoking, alcohol consumption HBV DNA (Copies/mL) 7 6 5 4 3 2 1 9 8

37. HBV Genotypes

38. Global Distribution of the 8 HBV Genotypes A, D, E A A, B, C, D, G D D H, F F B, C Arauz-Ruiz P, et al. J Gen Virol. 2002;83:2059. Bell SJ, et al. J Clin Virol. 2005;32:122. Kidd-Ljunggren K, et al. J Gen Virol. 2002;83:1267. G A, B, C, D

39. Chu C-J, et al. Gastroenterology. 2003;125:444. 35 22% 31 10 0.4 0.61 0 20 40 60 80100ABCDEFG HBV Genotype Prevalence (%) N = 694 US Prevalence of HBV Genotypes

40. HBV Genotypes Role in Pathogenesis May affect rate of chronicity (A > D) May affect rate of chronicity (A > D) Relationship to precore mutation (G  A 1896 ) (B, C, D > A) Relationship to precore mutation (G  A 1896 ) (B, C, D > A) –T 1896 —A stabilizes the stem-loop structure in genotype B, ~ C, D –Genotype A has C 1896 favoring wild-type G base pairing Association with HBeAg seroconversion Association with HBeAg seroconversion –Earlier seroconversion (B > C) –More likely to be sustained Relationship to antiviral response 1,2 Relationship to antiviral response 1,2 –IFN response: genotype A > D, B > C –HBeAg negative: A > D/E –Transplant outcome: A better than D (n = 22) 1. Enomoto M, et al. Clin Lab. 2006;52:43. 2. Devarbhavi HC, et al. Liver Transpl. 2002;8:550.

41. A 1. Sanchez-Tapias JM, et al. Gastroenterology. 2002;123:1848. 2. Sumi H, et al. Hepatology. 2003;37:19. D 5 F 21 BC 13 33 P =.002 P =.034 Western Patients 1 Asian Patients 2 1 Patients (%) 30 20 40 Patients (%) 0 10 Frequency of Liver-Related Death Incidence of Advanced Fibrosis (F3/F4) P =.02 Association Between HBV Genotype and Disease Severity N = 585 N = 258 30 20 40 0 10

42. Whom to Treat

43. Liver disease (abnormal ALT) HBV replication (HBV DNA+) Candidacy for Anti-HBV Treatment Principle In general, a patient with chronic HBV is a treatment candidate if there is evidence of

44. Factors to Consider in Initiating Anti-HBV Therapy? HBV DNA levels HBV DNA levels ALT levels ALT levels HBeAg status HBeAg status Cirrhosis vs no cirrhosis Cirrhosis vs no cirrhosis Compensated vs decompensated disease Compensated vs decompensated disease

45. HBV DNA HBeAg(Copies/mL)ALTManagement +>10 5 ≤2 x ULNFollow +>10 5 >2 x ULNTreat –>10 5 >2 x ULNTreat ––≤2 x ULNFollow +/–>10 5 CirrhosisIf compensated, treat; if decompensated*, refer for liver transplant +/––CirrhosisIf compensated, observe; if decompensated*, refer for liver transplant Which Patients Should Be Treated? AASLD Guidelines Lok ASF, et al. Hepatology. 2004;39:857. Reprinted with permission of Wiley-Liss, Inc, a subsidiary of John Wiley & Sons, Inc. *Do not use IFN or PEG IFN if patient has decompensated cirrhosis. Specific treatment recommendations will be discussed in an upcoming audioconference in this series.

46. US Treatment Algorithm Update HBeAg Positive Without Cirrhosis No treatment Monitor every 6–12 months Monitor every 3–12 months (immune tolerant) Consider biopsy, if age >35–40 years; treat if significant disease Treat HBeAg positive ALT elevatedALT normal HBV DNA ≥10 5 copies/mL HBV DNA <10 5 copies/mL Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936. Courtesy of Emmet Keeffe, MD.

47. US Treatment Algorithm Update HBeAg Negative Without Cirrhosis No treatment Monitor every 6–12 months Monitor ALT, or Consider biopsy, since ALT often fluctuates; treat if significant disease Long-term treatment required Treat Long-term treatment required HBeAg negative ALT elevatedALT normal HBV DNA ≥10 4 copies/mL HBV DNA <10 4 copies/mL Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936. Courtesy of Emmet Keeffe, MD.

48. May choose to treat or observe Treat HBV DNA (PCR) HBV DNA <10 4 copies/mL HBV DNA ≥10 4 copies/mL US Treatment Algorithm Update Compensated Cirrhosis Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936. Courtesy of Emmet Keeffe, MD.

49. Observe Wait list for transplant Treat Wait list for transplant HBV DNA Detectable by PCR? NoYes US Treatment Algorithm Update Decompensated Cirrhosis Keeffe EB, et al. Clin Gastroenterol Hepatol. 2006;4:936. Courtesy of Emmet Keeffe, MD.

50. Monitoring for Patients Not Considered for Treatment Check ALT every 3–6 months Check ALT every 3–6 months –If ALT is persistently elevated, re-evaluate for treatment HCC surveillance in relevant population HCC surveillance in relevant population Lok ASF, et al. Hepatology. 2001;34:1225. Lok ASF, et al. Hepatology. 2004;39:857.

51. Challenges in Special Patient Populations

52. Considerations for Special Populations with HBV Infection Pregnancy Pregnancy –Mother needs treatment –Prevention of vertical transmission (neonatal infection) Patients receiving chemotherapy Patients receiving chemotherapy –Prevent reactivation of hepatitis B, which may be fatal

53. van Zonneveld M, et al. J Viral Hepat. 2003;10:294. Lamivudine Treatment During Pregnancy to Prevent Perinatal Transmission of HBV 8 highly viremic (HBV DNA ≥1.2 × 109 geq/mL) mothers treated with lamivudine 150 mg/d in last month of pregnancy 8 highly viremic (HBV DNA ≥1.2 × 109 geq/mL) mothers treated with lamivudine 150 mg/d in last month of pregnancy Historical controls: 24 children born to untreated, highly viremic, HBsAg positive mothers Historical controls: 24 children born to untreated, highly viremic, HBsAg positive mothers All children had passive-active immunization at birth, then were followed for 12 months All children had passive-active immunization at birth, then were followed for 12 months 1 of 8 children (12.5%) in the lamivudine group still HBsAg and HBV DNA positive at 12 months 1 of 8 children (12.5%) in the lamivudine group still HBsAg and HBV DNA positive at 12 months –All others seroconverted to anti-HBs and maintained seroprotection –HBV DNA temporarily detected by PCR in 3 children Control group: 7 of 25 children (28%) were infected perinatally Control group: 7 of 25 children (28%) were infected perinatally

54. Preventing Perinatal Transmission Screen all expectant mothers for HBV Screen all expectant mothers for HBV Particularly if highly viremic, HBV-infected pregnant women may transmit HBV to their infants Particularly if highly viremic, HBV-infected pregnant women may transmit HBV to their infants Lamivudine treatment in last month of pregnancy reduces risk of transmission Lamivudine treatment in last month of pregnancy reduces risk of transmission American College of Obstetricians and Gynecologists, “Hepatitis B Virus in Pregnancy.” Available at: www.acog.org/publications/patient_education/bp093.cfm

55. Fatal Reactivation of HBV Infection in Chemotherapy Patients 4 Chinese patients with lymphoma who were carriers of HBV developed fulminant hepatitis within 1 month after chemotherapy 4 Chinese patients with lymphoma who were carriers of HBV developed fulminant hepatitis within 1 month after chemotherapy –1 initially HBeAg positive; 3 anti-HBe positive –All initially had normal ALT levels Reactivation: jaundice; HBV DNA in serum; and seroreversion from anti-HBe to HBeAg positivity Reactivation: jaundice; HBV DNA in serum; and seroreversion from anti-HBe to HBeAg positivity All died within 3 weeks All died within 3 weeks Lau JYN, et al. Q J Med. 1989;73:911.

56. Lamivudine Prophylaxis Before Chemotherapy for HBV Reactivation Review of 9 prospective studies and 1 randomized trial Kohrt HE, et al. Aliment Pharmacol Ther. 2006;24:1003. Lamivudine Prophylaxis Placebo Controls Rate of hepatitis*0%–20%33%–67% Rate of HBV reactivation † 0%–24%29%–56% *ALT increased ≥3-fold over baseline and exceeded ULN, or absolute increase of ≥100 IU/mL over baseline † HBV DNA increased ≥10-fold over baseline, or absolute increase ≥1000 x 10 6 geq/mL

57. Preventing HBV Reactivation in Chemotherapy Patients Chemotherapy can reactivate HBV and allow hepatocyte infection Chemotherapy can reactivate HBV and allow hepatocyte infection Withdrawal of chemotherapy causes immunologic rebound with resultant destruction of hepatocytes Withdrawal of chemotherapy causes immunologic rebound with resultant destruction of hepatocytes –Massive liver necrosis; potentially fatal Test patients for HBsAg before chemotherapy Test patients for HBsAg before chemotherapy If HBsAg positive, start antiviral therapy before chemotherapy to prevent clinically significant reactivation If HBsAg positive, start antiviral therapy before chemotherapy to prevent clinically significant reactivation

58. Summary and Conclusions

59. Practical Implications for Patient Management It is critical to identify patients with chronic hepatitis B by screening at-risk individuals It is critical to identify patients with chronic hepatitis B by screening at-risk individuals Once identified, they can Once identified, they can –Have family members screened and vaccinated –Receive education about lifestyle modification –Enroll in suitable follow-up programs –Be considered for antiviral therapy

60. Newly Diagnosed Hepatitis B New chronic hepatitis B Determine activity and severity of hepatitis ALT, HBeAg, HBV DNA Liver biopsy? Screen and vaccinate sexual contacts and household members Counsel about alcohol use Initiate antiviral therapyInitiate regular scheduled follow-up and monitoring Refer to practice guidelines AASLD US Tx algorithm

61. Summary and Conclusions HBV infection is a worldwide epidemiologic and clinical challenge HBV infection is a worldwide epidemiologic and clinical challenge Screening at-risk individuals identifies those with HBV infection Screening at-risk individuals identifies those with HBV infection –HBsAg, anti-HBe, anti-HBc Pretreatment evaluation includes history, physical examination, and additional diagnostic testing Pretreatment evaluation includes history, physical examination, and additional diagnostic testing –HBeAg, ALT, HBV DNA, liver biopsy? Candidates for anti-HBV treatment include patients with active liver disease and high levels of HBV replication Candidates for anti-HBV treatment include patients with active liver disease and high levels of HBV replication