Beyond the Tip of the Iceberg: Strategies to Ensure Optimal HBV Screenin g, Diagnosis, and Initial Therapy

Transcription

1 : Strategies to Ensure Optimal HBV Screenin g, Diagnosis, and Initial Therapy Sunday, November 1, 2009 Back Bay Ballroom Sheraton Boston Hotel Boston, Massachusetts This program is supported by an educational grant from

2 Program Faculty Chair Norah Terrault, MD, MPH Associate Professor of Medicine Director, Viral Hepatitis Center Department of Medicine, Division of Gastroenterology University of California, San Francisco San Francisco, California Faculty Jules L. Dienstag, MD Carl W. Walter Professor of Medicine Dean for Medical Education Harvard Medical School Physician, Gastrointestinal Unit Massachusetts General Hospital Boston, Massachusetts Faculty W. Ray Kim, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Mayo Clinic Rochester, Minnesota Albert D. Min, MD Director of Hepatitis Research Professor of Clinical Medicine Division of Digestive Diseases Beth Israel Medical Center New York, New York

3 About These Slides Our thanks to the presenters who gave permission to include their original data Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribu tion 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 Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options Disclaimer The materials published on the Clinical Care Options Web site reflect the views of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 ap proved by the United States Food and Drug Administration. A qualified healthcare professional should be consul ted before using any therapeutic product discussed. Readers should verify all information and data before treatin g patients or using any therapies described in these materials.

4 Burden of Chronic HBV Disease ~ 400 million people worldwide living with chronic HBV infection [1] Yearly, ~ 500,000 people die of HBV-related cirrhosis and HCC > 1 million US residents have chronic HBV infection Up to two thirds are unaware of their infection [2] Less than one half of patients with known HBV infection referred to specialist for evaluation [3] To reduce disease complications, need to Identify infected individuals Assess disease status and need for treatment and other monitoring Optimize treatment outcomes: issues of who, when, and how to treat 1. Sorrell MF, et al. Ann Intern Med. 2009;150: Lin SY, et al. Hepatology. 2007;46: CDC. MMWR. 2007;56:

5 HBV Screening and Diagnosis: Are Current Practices Effective at Identifying Patients at Risk and Evaluating Patients for HBV Treatment? W. Ray Kim, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Mayo Clinic Rochester, Minnesota

6 2008 CDC Guidelines for HBV Screening: New Recommendations Persons born in countries with 2% HBsAg prevalence US-born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity ( 8% HBsAg prevalen ce) Persons with behavioral exposures to HBV Injection drug users, MSM Persons needing immunosuppressive therapy Chemotherapy, organ transplantation, immunosuppression for rheumatologic or gastroenterologic disorders Persons with elevated ALT/AST of unknown etiology Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8);

7 Global Distribution of HBV Prevalence of HBsAg High 8% Intermediate 2% to 7% Low < 2% Centers for Disease Control and Prevention. CDC Health Information for International Travel 2010.

8 New HBV Cases Diagnosed in Olmsted County, Minnesota: Foreign Born (%) n = 25 n = 55 n = 102 n = 9 White African Asian Other/ Unknown Kim WR, et al. Hepatology. 2004;39:

9 Noninvasive Assessment of Fibrosis No large-scale validation specific to hepatitis B patients Elastography data (n = 173) Liver stiffness measure able to detect significant cirrhosis and fibrosis Correlation with METAVIR and Ishak scoring systems demonstrated (P <.001) Optimal cutoff for cirrhosis: 11.0 kpa Sensitivity: 93% Specificity: 87% Marcellin P, et al. Liver Int. 2009;29:

10 Liver Stiffness in Acute Hepatitis Acute hepatitis without obvious evidence of chronic liver disease 18 total patients; 8 with HBV infection ALT (U/L) Liver Stiffness (kpa) Cutoff for prediction of cirrhosis 0 Onset Recovery 0 Onset Recovery Arena U, et al. Hepatology. 2008;47:

11 Serum Markers of Fibrosis in Hepatitis B FibroTest FibroTest [1] APRI vs LSM [2] Donors Fibrosis Stage AUROC: FibroTest = 0.78 LSM = 0.84 APRI = 0.78 Sensitivity 1. Reprinted from J Hepatol, 39, Myers RP et al, Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B, , Copyright 2003, with permission from Elsevier. 2. Kim SU, et al. J Clin Gastroenterol. Liver Stiffness Measurement in Combination With Noninvasive Markers for the Improved Diagnosis of B-viral Liver Cirrhosis.2009;4 3(3): Reproduced with permission LSM APRI 0.4 LSM 0.2 AAR API APRI Specificity

12 HCC Surveillance: AASLD Practice Guideline Recommendations Hepatitis B Cirrhosis regardless of age Asian males 40 yrs of age or older Asian females 50 yrs of age or older HCC in first-degree relative (start before 40 yrs of age) African older than 20 yrs of age Cirrhosis from other causes Bruix J, et al. Hepatology. 2005;42:

13 Risk of HCC According to Baseline Factors REVEAL: long-term follow-up (mean, 11.4 yrs) of untreated HBsAg positive individuals in Taiwan (N = 3653) HCC (% per Yr) HBV DNA (copies/ml) < ,000-99, , ,999 1 million No cirrhosis Cirrhosis Chen CJ, et al. JAMA. 2006;295:65-73.

14 Surveillance Interval Optimal interval not known Randomized trial: decreased mortality based on 6-mo surveillance intervals (vs no screening) [1] Retrospective data: equivalence between 6- and 12-mo intervals [2] Absolute risk of HCC Rate of tumor growth Whether to perform surveillance Surveillance interval 1. Zhang GH, et al. J Cancer Res Clin Oncol. 2004;130: Trevisani F, et al. Am J Gastroenterol. 2002;97:

15 Take Home Points HBV screening in the target population highly justified Data indicate correlation between HBV DNA and long-term outcome Antiviral therapy able to alter natural history Target population Patients from areas with projected prevalence 2% or higher including unvaccinated US born children of immigrants from endemic areas Other groups Immunosuppressive therapy Abnormal aminotransferases

16 Take Home Points (cont d) Emerging data on noninvasive markers of fibrosis in HBV LSM probably more accurate than existing serum panel Acute flare may lead to false elevations of LSM Cirrhosis is by far the largest risk factor for HCC Correlation between HBV DNA and HCC risk well known Uncertain how that info is incorporated into surveillance strategy

17 After Diagnosis: Given the Benefits of HBV Treatment, Why Do So Few Patients Initiate Therapy When Indicated? Albert D. Min, MD Director of Hepatitis Research Professor of Clinical Medicine Division of Digestive Diseases Beth Israel Medical Center New York, New York

18 Treatment Criteria for Chronic Hepatitis B Recommended HBV DNA and ALT levels outlined in the following table Liver Society Guidelines* HBeAg Positive HBeAg Negative HBV DNA, IU/mL ALT HBV 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 (+) biopsy 20,000** 2 x ULN or (+) biopsy *Although ALT and HBV DNA are primary tests used to determine treatment candidacy, the levels of elevation that warrant consideration of treatment are not universally agreed upon. Laboratory normal. 30 U/L for men and 19 U/L for women. **In patients older than 40 yrs of age, 2000 IU/mL should be considered as a cutoff for treatment. 1. EASL. J Hepatol. 2009;50: Liaw YF, et al. Hepatol Int. 2008;3: Lok ASF, McMahon BJ. Hepatology. 2009;50:

19 What Is a Normal ALT Level? 9221 first-time potential blood donors 74% suitable donors after exclusion of anemia, seizure, sexual, and other risk 57% determined to be at low risk for liver disease Negative viral serology BMI < 25 Normal serum cholesterol, triglycerides, and glucose levels Absence of concurrent medication use Updated healthy ALT ranges determined from the group of low-risk individuals Males: 30 IU/L Females: 19 IU/L Prati D, et al. Ann Intern Med. 2002;137:1-10.

20 Patients With Normal ALT May Have Significant Fibrosis 1387 asymptomatic HBsAg-positive patients with 1-yr follow-up 189 with persistently normal ALT (PNALT)* included in analysis (HBeAg negative: 116 / 189, 61%) 21% of HBeAg-negative patients with PNALT and HBV DNA < 5 log copies/ml had HAI 3 and/or fibrosis stage 2 Patients (%) HBeAg positive HBeAg negative 0 HBV DNA 5 log copies/ml Histologic Fibrosis Stage 2 * 3 ALT values in the previous 1 yr prior to baseline liver biopsy that were all 40 IU/L and remained so until the start of treatment or the last follow-up. Kumar M, et al. Gastroenterology. 2008;134:

21 Favorable Short-term Outcomes in Patients With High HBV DNA, Normal ALT 240 HBeAg-positive individuals (male 130, female 110); mean age: 27.6 yrs Mean follow-up: 10.5 yrs (range: 3-20) Spontaneous HBeAg seroconversion in 85% between the ages of 20 and 39 yrs Reactivation of hepatitis after HBeAg seroconversion in 2.2% per yr Progression to cirrhosis in 5.4% after 10 yrs HCC: none Chu CM, et al. Am J Med. 2004;116:

22 Cumulative Risk of Liver-Related Complications in Chronic Hepatitis B Long-term follow-up of 3233 patients with chronic hepatitis B in Hong Kong Risk of developing ascites, SBP, esophageal varices, encephalopathy, or HCC determined Reference group: ALT < 0.5 x ULN Persons with ALT x ULN and x ULN had an increased risk of developing liver disease complications (P <.0001 vs reference group) Yuen M-F et al. Gut. 2005;54:

23 HBeAg-Negative Chronic HBV vs Inactive Carrier State HBeAg-Negative Disease Inactive Carrier HBsAg positive ü ü Anti-HBe positive ü ü Anti-HBc positive ü ü HBV DNA > 2000 IU/mL* < 2000 IU/mL ALT Elevated Normal *Fluctuations to < 2000 IU/mL can occur. May be elevated either persistently or intermittently. Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:

24 HBeAg-Negative Patients Require Frequent Monitoring ALT (U/L) HBV DNA HBV DNA (copies/ml) 50 x x ALT 30 x x x Mos Hadziyannis SJ, et al. Semin Liver Dis. 2006;26:

25 Disease Progression Minimal During Immune-Tolerant Phase 57 patients with high HBV DNA levels in immune-tolerant phase 48 remained in immune tolerant phase at 5-year follow-up Fibrosis Stage on Initial and Follow-up Liver Biopsy, % Initial Liver Biopsy Hui CK, et al. Hepatology. 2007;46: P = Follow-up Liver Biopsy Fibrosis Stage F2 F1 F0

26 Persistently Elevated HBV DNA Associated With Increased HCC Risk 16 Adjusted Hazard Ratio* for HCC DNA at entry: DNA at follow-up: High 10 5 High 10 5 High 10 5 Low < 10 4 Mid High 10 5 HBV DNA (copies/ml) 10.1 n = *Cox proportional hazards models. Risk is relative to < 10 4 copies/ml at entry/not tested at follow-up. Data adjusted for sex, age, cigarette smoking, and alcohol consumption. Chen CJ, et al. JAMA. 2006;295:65-73.

27 Take Home Points ALT is an imperfect measure of liver histology Normal levels should be lower than the current reference range HBeAg-negative CHB patients require frequent monitoring Severity of liver disease may not be evident from occasional testing Short-term outcome is favorable in CHB patients in immune-tolerant phase Active viral replication in CHB patients is associated with long-term risk of cirrhosis and HCC

28 Current Options for First-line HBV Treatment Norah Terrault, MD, MPH Associate Professor of Medicine Director, Viral Hepatitis Center Department of Medicine, Division of Gastroenterology University of California, San Francisco San Francisco, California

29 Goals of Hepatitis B Treatment Prevention of long-term negative clinical outcomes (eg, cirrhosis, HCC, death) by durable suppression of HBV DNA Primary treatment endpoint Sustained decrease in serum HBV DNA level to low or undetectable Secondary treatment endpoints Decrease or normalize serum ALT Improve liver histology Induce HBeAg loss or seroconversion Induce HBsAg loss or seroconversion

30 HBV Treatment Landscape in 2009 Peginterferon alfa-2a Lamivudine Entecavir Tenofovir Interferon alfa-2b Adefovir Telbivudine

31 Factors Driving Selection of Initial Therapy Nucleos(t)ide Analogues Peginterferon Safety & tolerability Barrier to resistance (d urability) Efficacy (potency) Safety & tolerability Efficacy (potency)

32 Undetectable* HBV DNA in HBV Patients After 1 Year of Treatment Undetectable* HBV DNA (%)100 Not head-to-head trials; different patient populations and trial designs HBeAg Positive LAM ADV TBV ETV 76 TDF 25 Peg- IFN HBeAg Negative LAM ADV TBV ETV 93 TDF 63 Peg- IFN *By PCR-based assay (LLD ~ 50 IU/mL) except for some LAM studies. Lok AS, et al. Hepatology. 2007;45: Lok AS, et al. Hepatology. 2009;50:

33 HBeAg Loss and Seroconversion in HBeAg+ Patients After 1 Year of Treatment Not head-to-head trials; different patient populations and trial designs HBeAg Loss HBeAg Seroconversion Outcome (%) NA 30 LAM ADV TBV ETV TDF Peg- IFN Lok AS, et al. Hepatology. 2007;45: Lau GK, et al. N Engl J Med. 2005;352: Marcellin P, et al. N Engl J Med. 2003;348: Chang TT, et al. N Engl J Med. 2006;354: Lai CL, et al. N Engl J Med. 2007;357: Marcellin P, et al. N Engl J Med. 2008;359: Janssen HL, et al, Lancet. 2005;365; Heathcote J, et al. AASLD Abstract LAM ADV TBV ETV TDF Peg- IFN

34 Cumulative Rates of Resistance With Oral Agents in Nucleos(t)ide-Naive Patients Drug Generation Not head-to-head trials; different patient populations and trial designs Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 Yr 6 1st LAM 24% 38% 49% 67% 70% 2nd 3rd ADV TBV ETV TDF 0% 3% 11% 18% 4% 17% 0.2% 0.5% 1.2% 1.2% 1.2% 1.2% 0% 0% 0% 29% EASL HBV Guidelines. J Hepatol. 2009;50: Tenny DJ, et al. EASL Abstract 20. Marcellin P, et al. AASLD Abstract 481. Heathcote E, et al. Abstract 483.

35 Tolerability and Safety: Nucleos(t)ide Analogues vs Peginterferon Nucleos(t)ide Analogues Safe at all stages of disease, including decompensated cirrhosis Safe in immunocompromised populations Selected drugs probably safe in pregnancy Reported toxicities are rare Peginterferon Contraindications Decompensated cirrhosis Pregnancy Significant cardiopulmonary disease Uncontrolled seizures, psychiatric disease Autoimmune diseases Not recommended Cirrhosis Adverse effects common Lok AS, et al. Hepatology. 2007;45: Lok AS, et al. Hepatology. 2009;50:

36 Current Guideline Recommendations for First-line Therapy Peginterferon alfa-2a Exceptions: pregnancy, chemotherapy prophylaxis, decompensated cirrhosis Entecavir Tenofovir EASL. J Hepatol. 2009;50: Liaw YF, et al. Hepatol Int. 2008;2: Lok AS, et al. Hepatology. 2009;50:

37 HBeAg Seroconversion Rates Over Time in HBeAg-Positive Patients HBeAg Seroconversion (%) Not head-to-head trials; different patient populations and trial designs Extended Treatment With Nucleos(t)ide Analogues* vs Limited Duration (1 Yr) Peginterferon Treatment Yr Yrs Yrs Entecavir Tenofovir Peginterferon *With sustained undetectable HBV DNA. Chang TT, et al. J Viral Hepat. 2009;16: Chang TT, et al. AASLD Abstract 109. Lau GK, et al. N Engl J Med. 2005;352: Marcellin P, et al. N Engl J Med. 2008;359: Buster EH, et al. Gastroenterology. 2008;135; Heathcote J, et al. AASLD Abstract 158. Heathcote J, et al. AASLD Abstract 483. Janssen HL, et al. Lanc et. 2005;365;

38 HBsAg Loss Over Time in HBeAg-Positive Patients Not head-to-head trials; different patient populations and trial designs 100 Extended Treatment With Nucleos(t)ide Analogues* vs Limited Duration (1 Yr) Peginterferon Treatment HBsAg Loss (%) *With sustained undetectable HBV DNA. NA 1.0 Yr Yrs Yrs 8 8 Entecavir Tenofovir Peginterferon Chang TT, et al. N Engl J Med. 2006;354: Marcellin P, et al. N Engl J Med. 2008;359: Buster EH, et al. Gastroenterology. 2008;135; Gish R, et al. Gastroenterology. 2007;133: Heathcote J. AASLD Abstrac t 158. Heathcote J, et al. AASLD Abstract 483. Janssen HL, et al. Lancet. 2005;365:

39 Predictors of HBsAg Loss in HBeAg- Positive Patients Race: whites > nonwhites [1] Genotype [1-3] Nucleos(t)ide analogues: A and D Peginterferon: A Decline in HBsAg level during first 24 wks with nucleos(t) ide analogues [1] HBeAg negative at or within 26 wks of completing peginterferon treatment [3] 1. Heathcote EJ, et al. EASL Abstract Gish RG, et al. J Viral Hepat. 2009;[Epub ahead of print]. 3. Buster EH, et al. Gastroenterology. 2008;135;

40 Undetectable HBV DNA Over Time in HBeAg-Negative Patients Undetectable HBV DNA (%) Not head-to-head trials; different patient populations and trial designs Extended Treatment With Nucleos(t)ide Analogues vs Limited Duration (1 Yr) Peginterferon Treatment *single center study NA * Yr 2 Yrs 3 Yrs Entecavir Tenofovir Peginterferon Lok AS, McMahon BJ. Hepatology. 2009;50: Marcellin P, et al. AASLD Abstract 146. Marcellin P, et al. AASLD Abstract 481. Marcellin P, et al. Gastroenterology. 2009;136: Baqai S, et al. AASLD Abstract 476.

41 HBsAg Loss Over Time in HBeAg-Negative Patients Not head-to-head trials; different patient populations and trial designs 100 On Extended Treatment With Nucleos(t)ide Analogues* vs Limited Duration (1 yr) Peginterferon Treatment Patients (%) Entecavir Tenofovir Peginterferon 20 0 < 1 0 *With sustained undetectable HBV DNA. 4 < 1 0 Lai CL, et al. N Engl J Med. 2006;354: Marcellin P, et al. N Engl J Med. 2008;359: Marcellin P, et al. AASLD Abstract 146. Marcellin P, et al. APASL Abstract PE086. Shouval D, et al. J Hepatol. 2009;50: Marcellin P, et al. AASLD Abstract 481. NA 1.0 Yr Yrs Yrs

42 Wk 12 HBsAg Levels Predict Outcomes in HBeAg-negative Patients 48 patients consecutively treated with pegifn alfa-2a for 48 weeks SVR defined as undetectable serum HBV DNA (< 70 copies/ml) 24 weeks after treatment cessation Change in HBsAg level from baseline to Week 12 evaluated as predictor of SVR Cutoff of 0.5 log 10 IU/mL used PPV = 89% NPV = 90% Outcome, % (n) Change in HBsAg from Baseline to Week log 10 IU/mL (n = 9) < 0.5 log 10 IU/mL (n = 39) SVR 89 (8) 10 (4) No SVR 11 (1) 90 (35) Moucari R, et al. Hepatology. 2009;49:

43 Summary of Therapy for CHB in Treatment- Naive Patients Tenofovir, entecavir, and peginterferon are preferred first-line drugs First decision is between NAs vs peginterferon 3rd generation NAs have high efficacy, very low rates of resistance, and excellent safety record Peginterferon offers finite therapy, some evidence of off-treatment benefits HBeAg seroconversion Increases over time with NAs Approximately same after 3 yrs continuous treatment with NAs vs 1 yr of peginterferon HBsAg loss Infrequent and increases slowly (< 10% at 3-4 yrs) Rare in HBeAg-negative CHB with NAs After 3-4 yrs follow-up, somewhat higher with peginterferon than NAs

44 Tip of the Iceberg: Is Determining How to Treat a Barrier to Initiating HBV Therapy? Jules L. Dienstag, MD Carl W. Walter Professor of Medicine Dean for Medical Education Harvard Medical School Physician, Gastrointestinal Unit Massachusetts General Hospital Boston, Massachusetts

45 The First Branch Point in Choosing Treatment for Hepatitis B Decision to treat PegIFN Nucleos(t)ide analogues

46 Nucleos(t)ide Analogues vs PegIFN Use of pegifn in younger patients Very small proportion will benefit Most will require longer treatment with nucleos(t)ide analogues PegIFN better in genotype A > B > C > D Favorable genotypes growing vanishingly rare This relationship between genotype and response seen for pegifn alfa-2b but not with pegifn alfa-2a HBeAg seroconversion with pegifn alfa-2a according to genotype A: 52%; B: 30%; C: 31%; D: 22% (not significant) Predictors of HBeAg response same for pegifn and nucleos(t)ide analogues (eg, high ALT, low HBV DNA) Flink HJ, et al. Am J Gastro. 2006;101: Lau GK, et al. N Engl J Med. 2005;352:

47 Long-term Outcomes With pegifn alfa-2a in HBeAg-Negative Chronic Hepatitis B 5 yrs posttreatment follow-up in patients treated with pegifn ± LAM vs LAM alone for 48 wks Patients (%) 100 Outcomes With PegIFN ± LAM (n = 230 [65%] of original 356) HBV DNA < 400 copies/ml *vs 3.5% for LAM alone at Yr 5 (P =.022). Marcellin P, et al. ILC Abstract ALT Normalization 4.8 HBsAg Loss Yr 1 Yr 3 Yr *

48 HBV DNA During Follow-up After Stopping Adefovir Patients receiving 4-5 years continuous adefovir followed long-term off treatment 33 patients who had sustained undetectable HBV DNA on treatment followed HBV DNA levels followed in 18 off-treatment sustained biochemical responders All patients initially rebounded to detectable HBV DNA Proportion of patients with HBV DNA < 1000 copies/ml 1 month after adefovir discontinuation: 5.6% 12 months after adefovir discontinuation: 55.6% 48 months after adefovir discontinuation: 66.7% Hadziyannis SJ, et al. EASL Abstract 18.

49 HBsAg Loss Off Treatment After 4-5 Years of Continuous Adefovir HBsAg Loss (n) EOT Yr 1 Yr 2 Yr 3 Yr 4 HBsAg Loss (%) Sustained Biochemical Responders, % (n = 18) Total, % (n = 33) EOT Yr 1 Yr 2 Yr 3 Yr 4 Time Off Treatment Time Off Treatment Hadziyannis SJ, et al. EASL Abstract 18. Used with permission.

50 Undesirable Virologic Responses to Oral Therapy 1.0 Antiviral Drug Change in HBV DNA (log 10 IU/mL) Primary nonresponse Suboptimal response Nadir Virologic breakthrough 1 log Mo Lok AS, et al. Hepatology. 2007;45:

51 Does the Roadmap Concept Apply to ETV or TDF During First Yr? 1.2% resistance to ETV at 6 yrs in nucleos(t)ide-naive patients [1] No resistance to TDF seen to date through 3 yrs in HBeAgnegative patients and 2 yrs in HBeAg-positive patients [2,3] Patients with positive HBV DNA at 24 and 48 wks often negative subsequently Tentative conclusion: for patients with positive HBV DNA at 48 wks on ETV or TDF, it may still be appropriate to continue monotherapy especially if HBV DNA is still declining More data needed 1. Tenny D, et al. EASL Abstract Heathcote E, et al. AASLD Abstract Marcellin P, et al. AASLD Abstract 481.

52 Take Home Points For pegifn: finite treatment for 48 wks Some consider in young, noncirrhotic patients with low HBV DNA, high ALT, favorable genotypes For nucleos(t)ide analogues Select entecavir or tenofovir in most cases HBeAg-positive chronic hepatitis B: treat until HBeAg seroconversion, stop after consolidation period HBeAg-negative chronic hepatitis B: treat indefinitely

53 Take Home Points (cont d) In the case of incomplete response to entecavir or tenofovir Distinguish between noncompliance, breakthrough resistance, and suboptimal response Roadmap approach does not apply well Suboptimal response: approach remains to be defined

54 Go Online for More From this Program! Downloadable Slides for use in your own noncommercial presentations Downloadable Worksheet: quick reference guide for HBV screening and evaluation available in English or simplified Chinese clinicaloptions.com/hbviceberg