Hepatitis B: A Preventable Cause of Liver Cancer Saira Khaderi MD, MPH Assistant Professor of Surgery Associate Director, Project ECHO June 17, 2016
Overview Epidemiology HBV and cancer Screening, Diagnosis and Treatment Prevention 2
Hepatitis B Double-stranded DNA virus that attacks the liver Can cause both acute and chronic disease More than 780,000 deaths from HBV related cirrhosis and liver cancer Most patients are asymptomatic 50 to 100 times more infectious than HIV HBsAg HBV DNA HBcAg
Prevalence of HBV: Global Estimates HBsAg Prevalence High (>8%) Intermediate (2%-7%) Low (<2%) Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. Liang X, et al. Vaccine. 2009;27:6550-6557.
HBV Infection in the United States Current estimates 1.2 to 2.2 million are living with chronic HBV infection Underlying cause of an estimated 2000 to 4000 deaths each year The number of foreign-born persons living in the United States has increased from 20 million in 1990 to 41 million in 2009 This represents 4.7% to 13.6% of the total US population An estimated 2 million HBsAg positive* Average chronic HBV prevalence rate among foreign-born persons living in the United States is 2.0% to 5.4% Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. Kowdley KV, et al. Hepatology. 2012;56:422-433. *Gish RG, et al. Hepatology. 2015;62:1339-1341. 5
Foreign-Born Persons in the US: Overall and By Place of Birth (2009) Number of Foreign Born Persons in the United States 45 40 41.3 Number (millions) 35 30 25 20 15 10 5 16.1 11.0 5.1 3.6 2.9 1.7 0.9 0 Total Central America Asia Europe Caribbean South America Africa North America Kowdley KV, et al. Hepatology. 2012;56:422-433.
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Hepatitis B in Houston The fourth largest Asian population of any US metropolitan area Third largest Vietnamese population in the US 1 in 10 Asian-Americans has hepatitis B 8
HBV and Cancer Dominant cause of hepatocellular carcinoma (HCC) worldwide Second cause of cancer death worldwide Most common carcinogen after tobacco Lifetime risk of developing HCC is 10 to 25-fold greater for chronic HBV patients 1 in 4 adults with chronic HBV will die from liver cancer or liver cirrhosis 2 nd most common cause of cancer death in Asian men 9
Asian-American Age-Adjusted Liver Cancer Rates (California, 2000-2002) Incidence Mortality 60 50 54.3 Male Female 60 50 Male Female Rate (per 100,000) 40 30 20 10 0 15.8 33.7 15.9 23.3 7.6 16.8 5.4 9.3 8.1 6.8 2.5 Korean Chinese Filipino Japanese White Rate (per 100,000) 40 30 20 10 0 35.5 10.4 Vietnamese Vietnamese 26.6 11.5 19.9 7.8 12.0 4.2 8.3 7.8 6.0 2.7 Korean Chinese Filipino Japanese White Approximately 3.7 million Asians in California. Cancer data from California Cancer Registry. McCracken M, et al. CA Cancer J Clin. 2007;57:190-205.
How is HBV transmitted? Sex with an infected partner Injection drug use Birth to an infected mother Contact with blood or open sores of an infected person Needle sticks or sharp instrument exposures Sharing items such as razors or toothbrushes with an infected person HBV is NOT spread through food or water, breastfeeding, hugging, hand holding, kissing sneezing, coughing 11
Candidates for Screening for HBV Persons born in high and intermediate endemic areas (>2% prevalence) US born children of immigrants from high-risk areas Household and sexual contacts of HBsAg-positive persons Persons who have ever injected drugs Persons with multiple sexual partner, 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 All pregnant women Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20. LeFevre ML on behalf of the U.S. Preventive Services Task Force. Ann Intern Med. 2014;161:58-66. 12
HBV Infection, Diagnosis, and Care in the United States 2.5 2 1.4-2.0 Million 2.5% to 5% of the Total HBV-Infected Population Number (millions) 1.5 1 0.5 400,000-600,000 350,000-500,000 200,000-300,000 0 Chronic HBV Infection Persons Aware of Their Infection Potentially Eligible for Treatment Entering Care 50,000 Annual HBV Prescriptions Cohen C, et al. J Viral Hepat. 2011;18:377-383.
HBV Diagnosis HBsAg Serologic Marker Results Total Anti-HBc IgM Anti-HBc Anti-HBs Interpretation - - - - Never infected and no evidence of immunization, needs vaccination + + + - Acute infection + + - - Chronic infection - + - - Exposure with occult HBV, false positive (rare) or chronic infection - + - + Exposure and clearance of HBV infection from the blood, with occult HBV Modified from Weinbaum CM, et al. MMWR Recomm Rep. 2008;57(RR-8):1-20.
Candidates for HBV Treatment HBV DNA threshold (IU/mL) HBeAg positive HBeAg negative ALT: Normal range When to treat: key factors Biopsy APASL (2012) HBV DNA, ALT, severity of liver disease EASL (2012) HBV DNA, ALT, severity of liver disease Treatment Algorithm (2015) Not all patients with hepatitis B need treatment 20,000 2000 Decision to 2000 treat is based 2000on 2000 Viral load- - Use revised, lower range (M: 30 U/L; F: 19 U/L) Liver enzymes Fibrosis in the liver Consider in certain groups Consider in certain groups HBV DNA, ALT, severity of liver disease Consider in certain groups AASLD (2016) 20,000 2000 Use revised, lower range (M: 30 U/L; F: 19 U/L) HBV DNA, ALT, severity of liver disease Consider in certain groups Terrault NA, et al. Hepatology. 2016;63:261-283. Martin P, et al. Clin Gastroenterol Hepatol. 2015;13:2071-2087. EASL. J Hepatol. 2012:57:167-185. Liaw Y-F, et al. Hepatol Int. 2012;6:531-561.
HBV Treatment Antiviral options include entecavir and tenofovir Achieve sustained suppression of HBV replication and remission of hepatic disease Prevent the development of cirrhosis, hepatic failure, and hepatocellular carcinoma HBV probably is never cured*, but rather controlled by limiting viral replication *HBV ccc DNA persists, making HBV incurable with current treatments. Terrault NA, et al. Hepatology. 2016;63:261-283. Martin P, et al. Clin Gastroenterol Hepatol. 2015;13:2071-2087. 16
HBV Vaccination WHO named the hepatitis B vaccine the first anti-cancer vaccine Series of three intramuscular injections 0, 3, and 6 months Single-antigen: ENGERIX-B, RECOMBIVAX HB Combination: PEDIARIX, TWINRIX, COMVAX Protection remains intact for at least twenty years Infants receive first dose within 24 hours of birth Locarnini S, et al. J Hepatol. 2015;62(suppl):S76-S86. 17
Eliminating Transmission of HBV in the United States and Globally Universal vaccination of infants beginning at birth (dose <24 hours from birth) Prevention of perinatal HBV infection through Routine screening of all pregnant women for HBsAg Immunoprophylaxis with combined vaccine and HBIG of infants born to HBsAg-positive women or women with unknown HBsAg status Routine vaccination of previously unvaccinated children Vaccination of previously unvaccinated adults at risk for HBV infection Updated from Mast EE, et al. MMWR Recomm Rep. 2006;55(16):1-33. 18
New HBV Infections by Year: United States (1980-2013) Reported Number of Cases 30000 25000 20000 15000 10000 5000 Vaccine Licensed HBsAg Screening of Pregnant Women Recommended Infant Immunization Recommended OSHA Rule Enacted Adolescent Immunization Recommended 0 80 82 84 86 88 90 92 94 96 98 00 02 04 06 08 10 12 13 Year CDC. http://www.cdc.gov/hepatitis/hbv/hbvfaq.htm#overview.
Current HBV Patient Barriers Culture Chronic HBV persons are discriminated against in most Asian countries Education message gap Patients understand link of chronic HBV and liver complications, but many fail to recognize link to cancer www.sfhepbfree.org 20
Current HBV Provider Barriers Many providers are not aware that HBV disproportionately affects the Asian/Pacific Islander community Educate providers Appropriately identify chronic HBV Understand HBV blood test results Understanding who should be treated Understand treatment options 21
Project ECHO Extension for Community Healthcare Outcomes 22
Project ECHO Extension for Community Healthcare Outcomes People need access to specialty care for their complex health conditions. There aren't enough specialists to treat everyone who needs care, especially in rural and underserved communities. ECHO trains primary care clinicians to provide specialty care services. This means more people can get the care they need. Patients get the right care, in the right place, at the right time. This improves outcomes and reduces costs.
ECHO Clinics Current Clinics Hepatitis C Hepatitis B Advanced Liver Disease Infectious Diseases Cardiology Oncology Upcoming Clinics LVAD/Heart MRB Rheumatology Behavioral Health Pulmonary Nephrology
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Summary HBV is a highly infectious virus that leads to more than 780,000 deaths from HBV related cirrhosis and liver cancer Up to 2.2 million people are living with chronic HBV infection in the US Dominant cause of hepatocellular carcinoma (HCC) worldwide Hepatitis B surface antigen is the screening test for HBV Antivirals are an effective way to suppression HBV replication Hepatitis B vaccination is a series of three intramuscular injections Vaccination is an effective form of protection which remains intact for at least twenty years 26