Faculty: Hannah M. Lee, MD Geneve Allison, MD

Transcription

1 pmicme Updates April 11, 2012 Anaheim, California Faculty: Hannah M. Lee, MD Geneve Allison, MD

2 Session 3: SCALE HBV: Screening, Counseling and Linkage to Care Education Learning Objectives 1. Apply the guidelines for hepatitis B virus (HBV) screening in appropriate at-risk populations. 2. Develop tactics to overcome patient objections to HBV screening, treatment, and/or vaccination. 3. Demonstrate how to correctly interpret screening/diagnostic results. 4. Appropriately manage HBV patients with respect to treatment, monitoring, and/or referral. Faculty Hannah M. Lee, MD Assistant Professor of Medicine Division of Gastroenterology and Hepatology Director, Asian-Pacific Liver Wellness Tufts University School of Medicine Boston, Massachusetts Dr Hannah Lee is assistant professor of medicine in the Division of Gastroenterology/Hepatology and director of the Asian- Pacific Liver Wellness Program at Tufts Medical Center Tufts University School of Medicine, located in the heart of Boston s Chinatown. Dr Lee specializes in general hepatology and transplant hepatology, and has a particular interest in viral hepatitis. Her research is currently focused on best practices among primary care physicians in hepatitis B screening in the Boston area and improving screening rates within the city s Asian community. Dr Lee is actively involved in addressing Asian health disparities, particularly in the area of hepatitis B, both at the local and national levels. She is a board committee member of the Asian Health Initiative at Tufts Medical Center and serves on the advisory board of the Asian Health Foundation. Both in her clinical practice and in her involvement in community health, Dr Lee has been a strong advocate in addressing practice and knowledge gaps in HBV screening, counseling, and linkage to care. Geneve Allison, MD, FACP Assistant Professor of Medicine Division of Geographic Medicine and Infectious Diseases Tufts University School of Medicine Boston, Massachusetts Dr Geneve Allison is an assistant professor of medicine at Tufts University School of Medicine and an attending physician in the Division of Geographic Medicine and Infectious Diseases at Tufts Medical Center in Boston. Dr Allison graduated cum laude from Harvard College in Cambridge, Massachusetts, in 1993 with an AB in biology, and received her MD from University of Massachusetts Medical School in Worcester in She was an intern, resident, and chief resident at the Alameda County Medical Center in Oakland, California, from 2000 to 2004, and was Resident of the Year. Dr Allison joined Tufts Medical Center as an infectious diseases fellow in During her T32 National Institutes of Health (NIH) funded research years, she studied humoral immunity to Cryptosporidium in Bangladeshi children with diarrhea. In 2005, she was awarded the Tufts Gorbach prize for best clinical/translational research by an infectious diseases fellow. Two years later, Dr Allison became an infectious diseases attending at Tufts. From 2007 to 2011, Dr Allison served as assistant, then associate, director of the Infectious Diseases Fellowship Program at Tufts. In July 2011, she began a two-year NIH-funded career development grant through the Tufts Clinical and Translational Science Institute (CTSI) focusing on Outpatient Parenteral Antibiotic Therapy (OPAT) outcomes. Dr Allison s clinical interests include patient safety and care coordination stemming from her role as OPAT director. Session 3

3 Faculty Financial Disclosure Statements The presenting faculty report the following: Dr Lee reports that she has received honoraria from Gilead Sciences Medical Affairs. Dr Allison has no financial relationships to disclose. Education Partner Financial Disclosure Statement The following content collaborators at DKBmed, LLC, report the following: Josh Kilbridge;., Crystal Johnson; Pat Galinski, EdD; Stan Pogroszewski, JD; and Dean Beals have no financial relationships to disclose. Suggested Reading List American Association for the Study of Liver Diseases. HBV Specialty-Based Slide Sets. Accessed March 21, Chang MH. Natural history of hepatitis b virus infection in children. J Gastroenterol Hepatol. 2000;15 Suppl:E16-E19. Chen CJ, Yang HI, Su J, et al.; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1): Leung N. Chronic hepatitis B in Asian women of childbearing age. Hepatol Int. 2009;3(Suppl 1): McCracken M, Olsen M, Chen MS Jr, et al. Cancer incidence, mortality, and associated risk factors among Asian Americans of Chinese, Filipino, Vietnamese, Korean, and Japanese ethnicities. CA Cancer J Clin. 2007;57(4): Shepard CW, Simard EP, Finelli L, et al. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev. 2006;28: Stanford School of Medicine Asian Liver Center. FAQs about Hepatitis B. Accessed March 21, Weinbaum CM, William I, Mast EE, et al.; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20. World Health Organization. Department.. of Communicable Diseases Surveillance and Response. Hepatitis B. WHO/CDS/LYO/2002.2:Hepatitis B. Accessed March 21, Session 3

4 PROGRAM GOAL Geneve Allison, MD, FACP Assistant Professor of Medicine Division of Geographic Medicine Tufts University School of Medicine Boston, MA The goal of this activity is to address key practice and knowledge gaps in hepatitis type B screening, counseling, and linkage to care, and adherence to clinical guidelines when treating Asian, Asian-American, and African immigrant patients. EDUCATIONAL OBJECTIVES Apply the guidelines for hepatitis B virus (HBV) screening in appropriate at-risk populations Develop tactics to overcome patient objections to HBV screening, treatment, and/or vaccination Demonstrate how to correctly interpret screening/diagnostic results Explain the need to properly treat, monitor, or refer their HBV patients PRE SEMINAR QUESTIONS How many Asian/Asian-American patients do you see each week How many African immigrant patients do you see each week 1. < >20 1. < >20 1

5 Please rate your confidence in correctly identifying a patient s risk for chronic HBV. Please rate your confidence in treating patients for chronic HBV. 1. Not Confident 2. Somewhat Confident 3. Neutral 4. Confident 5. Very Confident 1. Not Confident 2. Somewhat Confident 3. Neutral 4. Confident 5. Very Confident PATIENTS IN WHICH OF THE FOUR PHASES OF HBV LIFECYCLE SHOULD BE TARGETED FOR TREATMENT How often do you screen Asian/Asian American patients for chronic HBV 1. Immune tolerant 2. Immune active/clearance phase 3. Inactive carrier 4. Precore mutant with normal ALT 1. Rarely 2. Sometimes 3. Often 4. Always How often do you screen African immigrant patients for chronic HBV 1. Rarely 2. Sometimes 3. Often 4. Always Please rate your confidence in your ability to interpret hepatitis B screening test results correctly. 1. Not Confident 2. Somewhat Confident 3. Neutral 4. Confident 5. Very Confident 2

6 GEOGRAPHIC DISTRIBUTION OF CHRONIC HBV INFECTION EPIDEMIOLOGY AND RISKS OF UNTREATED HBV Hannah Lee, MD Assistant Processor of Medicine Division of Gastroenterology & Hepatology Director, Asian-Pacific Liver Wellness Program Tufts Medical Center Boston, MA HBsAg Prevalence* 8% (high) 2% to 7% (intermediate) < 2% (low) Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. *HBsAg, Hepatitis B surface antigen IMMIGRATION HAS A HIGH IMPACT ON US HBV PREVALENCE Immigration Numbers by Continent: ~ 3.6 million Asians 50 MILLION HBV INFECTED IN AFRICA Worldwide, one in seven persons with Chronic Hepatitis B lives in Africa. In some African countries, prevalence of marker of past exposure or infection to HBV as high as 98% 1 HBsAg Prevalence 2 8% (high) 2% to 7% (intermediate) < 2% (low) ~ 1.3 million Europeans ~ 875,000 South Americans 1. US Department of Homeland Security. Yearbook of Immigration Statistics: Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. ~ 804,000 Africans Rates of HBSag carrier range from 9% in South Africa to 20% in Democratic Republic of Congo. 2 Estimated 12.5 million deaths will occur in this population because of HBV (230,000 deaths per year) 2 Acute viral hepatitis, chronic hepatitis, cirrhosis and HCC responsible for at least 12% of hospital admissions, and over 20% of hospital mortality in many parts of Africa. 3 1 Kiire et al Gut 1996; 38 (suppl2):s5-s and-hiv-in-africa-being-ignored/page/ Eldryd et al. AIDS. In: Principles of Medicine in Africa. 3rd ed. Cambridge 2004; PREVALENCE OF HBV AMONG ASIAN AMERICANS POTENTIAL CONSEQUENCES OF CHRONIC HBV Survey of screening programs in 5 large US cities ( ) Chinese Korean Vietnamese Median age: 43 (12-80) HBsAg positive: 558/5341 (10.4%) 0% 2% 4% 6% 8% 10% 12% 14% 16% Philadelphia San Francisco Boston Chicago NY(1) NY(2) 11% 14% 10% 11% 15% 11% Cirrhosis End-stage Liver Disease Hepatocellular Carcinoma (HCC) HBV causes 60-80% of liver cancer cases worldwide. HBV is a carcinogen that is second only to smoking tobacco in causing cancer deaths worldwide. Overall 10.4% Guan R, et al. AASLD Abstract

7 HEPATITIS B DISEASE PROGRESSION Liver Cancer (HCC) HBV DNA ASSOCIATED WITH INCREASED RISK OF HCC AND CIRRHOSIS REVEAL: Prospective Observational Study with Long-Term Follow-up: Untreated HBsAg-positive individuals in Taiwan Acute Infection Chronic Infection 1. Moyer LA, Mast EE. Am J Prev Med. 1994;10(suppl): Perrillo RP et al. Hepatology. 2001;33: % -40% 1 Cirrhosis Liver Failure (Decompensation) Liver Transplant Death 6th leading cause of liver transplantation in the United States 2 Patients (%) Cumulative Incidence of HCC at Year 13 Follow-up 1 (N = 3653) < , ,000 99, Chen CJ, et al. JAMA. 2006;295: Iloeje UH, et al. Gastroenterology. 2006;130: Baseline HBV DNA (copies/ml) Cumulative Incidence of Cirrhosis at Year 13 Follow-up 2 (N = 3582) < ,000-99, ,000-1 million 999,999 HBV IS A SILENT KILLER Chronic HBV infection usually asymptomatic, even with liver cancer and well-compensated cirrhosis Liver panel may be normal As many as 2 out of 3 chronically infected persons are unaware of HBV infection HBV RISK FACTORS FOR PERSONS OF ASIAN AND SUB- SAHARAN DESCENT MYTHS OF HBV TRANSMISSION HBV: MODES OF TRANSMISSION Hepatitis B is not transmitted through: Endemic Countries Non-endemic Countries Casual contact such as hugging or shaking hands Kissing, sneezing, or coughing Breastfeeding Sharing eating utensils or drinking glasses Air/food/water Mother to baby at time of birth (~50% of cases, most common among Asians) Horizontal within household during early childhood (Virus can survive at least 7 days outside body) Health care (Re-use of non-sterilized needles and syringes in resource-poor areas, contaminated blood products) Traditional medicine (Acupuncture, coining, cupping, scarification, etc.) Adult sexual activity (~54% of cases, most common) IV drug use (~20% of cases) Shepard CW, et al. Epidemiol Rev. 2006;28: Stanford Liver Center Hepatitis B FAQs. Accessed March 4, 2011 Shepard, CW et al. Epidemiol Rev. 2006;28: Leung N. Hepatol Int. Dec 2009;3 Suppl 1: WHO Dept. Communicable Diseases Surveillance and Response. Hepatitis B. Accessed March 4,

8 HEPATITIS B SEROLOGY 101 HBsAg: hepatitis B surface antigen Marker of active infection Chronic HBV: HBsAg positive for at least 6 months Anti-HBs (or HBsAb): antibody to HBsAg Marker of immunity to hepatitis B Anti-HB core antibody (IgG) Previous exposure HEPATITIS B SEROLOGY 101 HBeAg: hepatitis B e antigen Surrogate marker of high viral load Anti-HBe: antibody to HBeAg Precore mutation: associated with lower viral load Inactive carrier state HBV DNA: active viral replication Adapted from McMahon, BJ, Peters, M. Accessed March 12, Adapted from McMahon, BJ, Peters, M. Accessed March 12, CLINICAL PROFILES OF CHRONIC HBV INFECTION INTERPRETING SEROLOGIES: MATCHING PATIENTS AND HBV STATUS Marker Patient Populations in Chronic Hepatitis B Immune Tolerant HBeAg+ CHB Inactive HBsAg Carrier HBeAg CHB (Precore Mutant) HBsAg HBeAg + + Anti-HBe + + ALT Normal Normal HBV DNA (copies/ml) > 10 5 > 10 5 < 10 3 > 10 4 Histology Normal/Mild Active Normal Active Korean male, 52 yo HBsAg+, HBeAg-, anti-hbe+ HBV DNA- ALT normal Vietnamese male, 38 yo HBsAg+, HBeAg+, anti-hbe- HBV DNA ALT elevated Nigerian female, 25 yo HBsAg+, HBeAg+, anti-hbe- HBV DNA ALT normal Taiwanese female, 52 yo HBsAg-, anti-hbs-, anti-hbc+ ALT normal Immune active infection Most commonly, resolved infection with waning surface antibody titer Immune tolerant Inactive carrier Lai CL, et al. Lancet. 2003:362: Lok AS, et al. Gastroenterology. 2001;120: WHICH OF THE FOLLOWING IS CORRECT 1. Asian Americans in the United States have lower rates of chronic hepatitis B compared to Asians living in Asia 2. Vertical transmission accounts for at least 50% transmission of hepatitis B infections among Asians. 3. Infection with hepatitis B in infancy results in a 33% risk of developing chronic hepatitis B THE ROLE OF THE PRIMARY CARE PROVIDER (PCP) IN HBV SCREENING, COUNSELING, TREATMENT 4. 1 in 10 Asian Americans are living with chronic hepatitis B 5. Both 2 and 4 5

9 PRESENTATION GOALS THE INSTITUTE OF MEDICINE FINDINGS 2010 Identify factors contributing to the disproportionate burden of cirrhosis and HCC among Asian/Pacific Islanders and Sub-Saharan Africans in US Morbidity and Mortality Related to Hepatitis B Assess system, provider, and patient barriers to HBV screening Lack of Public Awareness Lack of Provider Awareness Develop strategies to overcome these barriers Lack of Public Resource Allocation Adapted from McMahon, BJ, Peters, M. Accessed March 12, POTENTIAL BARRIERS TO SCREENING FOR PHYSICIANS POSSIBLE SOLUTIONS TO BARRIERS FOR PHYSICIANS Primary care visit: too many things to keep track of & accomplish in too short a time Serological results are confusing HBV guidelines are conflicting and/or confusing No reminders built into clinic system (electronic health records, etc.) Use physician extenders to do screening and counseling Use social services for insurance, immigration and care access issues Add HBV risk factor assessment to standard intake forms Use flow sheet to track HBV screening, results and follow-up Programmed alerts in electronic health records POSSIBLE SOLUTIONS TO BARRIERS FOR PATIENTS SYSTEM SOLUTIONS No insurance: Local community health centers provide free screening and vaccination and can refer to appropriate specialist Counseling and education to fight stigma, myths, lack of adherence and follow-up Provide appropriate patient education materials in waiting rooms, examination rooms Work with your physician group, practice, clinic, hospital, etc to make HBV risk assessment and appropriate screening routine part of care 6

10 2008 CDC RECOMMENDATIONS FOR HBV SCREENING Persons born in geographic regions with HBsAg prevalence of 2%: Eastern Europe, Asia, Africa, Middle East, and the Pacific Islands U.S. born persons not vaccinated as infants who parents were born in regions with high HBV endemicity ( 8%) Persons receiving cytotoxic or immunosuppressive therapy Injection drug users Individuals with abnormal liver enzymes of unknown etiology Multiple sex partners Men who have sex with men Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. SCREENING THOSE WHO HAVE BEEN VACCINATED. Some may have been infected with HBV before they received hepatitis B vaccination. Therefore, HBsAg testing is recommended regardless of vaccination history for the following populations: Persons born in geographic regions with HBV prevalence of >2%. US-born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity (>8%) Persons who received hepatitis B vaccination as adolescents or adults after the initiation of risk behaviors Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. INDICATIONS FOR REFERRAL AND WHEN TO TREAT Referral to specialist based on PCP s comfort level Two categories of patients with active disease should be considered for treatment (AASLD guidelines 1 ): Anyone with persistently elevated ALT > 2x ultrasound and elevated HBV DNA 10 5 copies/ml Patients who have active disease monitor regularly with blood work every 3-6 months and liver cancer screening with US q 6 months if meet criteria CASE PRESENTATION 1 Amadu Abbasi 1 Lok AS, et al. Hepatology. 2009;50: * Moderate/severe inflammation or significant fibrosis HOW SHOULD WE EDUCATE THIS PATIENT ON HIS RISK FACTORS AND OBTAIN CONSENT FOR SCREENING WHAT DOES THE FINDING OF AN ISOLATED HB CORE ANTIBODY MEAN 1. Emphasize the role of sexual and injection-drugrelated transmission in HBV acquired outside US 2. Explain HBV is a chronic disease, patients who have it usually have no symptoms for decades 3. Tell him that the CDC recommends screening all Africans 4. 1 & 2 1. False positive 2. Previously exposed to HBV, but surface antigen and/or surface antibody not detectable 3. In the setting of acute hepatitis B infection, immune system is clearing virus, but surface antibody is not detectable yet 4. All of the above 7

11 WHAT FOLLOW-UP TESTS ARE APPROPRIATE FOR A PATIENT WHO HAS A POSITIVE TEST FOR HBV SURFACE ANTIGEN 1. HBeAg and anti-hbeag CASE PRESENTATION 2 Brian Lin 2. HBV DNA 3. Liver function tests 4. All of the above HOW SHOULD PATIENTS IN THE INACTIVE CARRIER PHASE BE MANAGED PATIENTS IN WHICH OF THE FOUR PHASES OF HBV LIFECYCLE SHOULD BE TARGETED FOR TREATMENT 1. Initiate antiviral medications 2. Monitor serology and liver function every 6 months 3. Evaluate with liver biopsy annually 4. Monitor with abdominal CT annually 1. Immune tolerant 2. Immune active/clearance phase 3. Inactive carrier 4. Precore mutant with normal ALT WHICH PHASE OF THE HBV LIFECYCLE IS REFLECTED IN MR. LIN S TEST RESULTS 1. Immune tolerant 2. Immune active/clearance phase 3. Inactive carrier 4. Precore mutant POST-SEMINAR ASSESSMENT 8

12 Please now rate your confidence in correctly identifying a patient s risk for chronic HBV 1. Not Confident 2. Somewhat Confident 3. Neutral 4. Confident 5. Very Confident Please now rate your confidence in treating patients for chronic HBV 1. Not Confident 2. Somewhat Confident 3. Neutral 4. Confident 5. Very Confident PATIENTS IN WHICH OF THE FOUR PHASES OF HBV LIFECYCLE SHOULD BE TARGETED FOR TREATMENT 1. Immune tolerant 2. Immune active/clearance phase 3. Inactive carrier 4. Precore mutant with normal ALT How often will you screen Asian/Asian American patients for chronic HBV 1. Rarely 2. Sometimes 3. Often 4. Always How often will you screen African immigrant patients for chronic HBV 1. Rarely 2. Sometimes 3. Often 4. Always Please now rate your confidence in your ability to interpret hepatitis B screening test results correctly 1. Not Confident 2. Somewhat Confident 3. Neutral 4. Confident 5. Very Confident 9