Uses and Misuses of Viral Hepatitis Testing Richard S Lang, MD, MPH, FACP Chairman, Preventive Medicine Vice-Chair, Wellness Institute Raul J Seballos, MD, FACP Vice-Chair, Preventive Medicine Wellness Institute February 22, 2011 April 5, 2011 1 DOS CME Course 2011 Origins of Liver Science The earliest representation of a LIVER Clay Model (Assyro-Babylonia civilization 3000-2000 B.C.) British Museum at London. 2 DOS CME Course 2011 1
Liver models from Mari, Syria (2000 B.C.) The point of portal vein swelling CuniformC Alphabet 3 DOS CME Course 2011 Viral Hepatitis - Historical Perspectives Infectious A E Enteric Viral hepatitis NANB Serum B D C Parenteral F, G, TTV? other 4 DOS CME Course 2011 2
Type of Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces virus blood-derivedderived blood-derivedderived blood-derivedderived body fluids body fluids body fluids Route of transmission fecal-oral percutaneous permucosal percutaneous permucosal percutaneous permucosal fecal-oral Chronic infection no yes yes yes no Prevention blood donor screening; risk behavior modification pre/post- exposure immunization pre/post- exposure immunization pre/post- exposure immunization; risk behavior modification ensure safe drinking water 5 DOS CME Course 2011 Hepatitis A Virus 6 DOS CME Course 2011 3
Hepatitis A - Clinical Features Incubation period: Average 30 days Range 15-50 50 days Jaundice by <6 yrs, <10% age group: 6-14 yrs, 40%-50% >14 yrs, 70%-80% Complications: Chronic sequelae: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis None 7 DOS CME Course 2011 Hepatitis A Infection Typical Serological Course Symptoms Total anti-hav Titre ALT Fecal HAV IgM anti-hav 0 1 2 3 4 5 6 12 24 Months after exposure 8 DOS CME Course 2011 4
Hepatitis A Virus Transmission Close personal contact (e.g., household contact, sex contact, child day care centers) Contaminated food, water (e.g., infected food handlers, raw shellfish) Blood exposure (rare) (e.g., injecting drug use, transfusion) 9 DOS CME Course 2011 10 DOS CME Course 2011 5
Laboratory Diagnosis Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA. Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA. Caution: routine lab test measures total anti HAV so does not distinguish acute v resolved 11 DOS CME Course 2011 Hepatitis E Virus 12 DOS CME Course 2011 6
Hepatitis E - Clinical Features Incubation period: Average 40 days Range 15-60 days Case-fatality rate: Overall, 1%-3% Pregnant women, 15%-25% Illness severity: Chronic sequelae: Increased with age None identified* *Except recently in immunocompromised transplant recipients 13 DOS CME Course 2011 Hepatitis E Virus Infection Typical Serologic Course Symptoms ALT IgG anti-hev Titer IgM anti-hev Virus in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Weeks after Exposure 14 DOS CME Course 2011 7
Hepatitis E - Epidemiologic Features Most outbreaks associated with faecally contaminated drinking water. Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico. In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-hev (<2%) has been found in healthy populations. The source of infection for these persons is unknown. Minimal person-to-person transmission. 15 DOS CME Course 2011 16 DOS CME Course 2011 8
Prevention and Control Measures for Travelers to HEV-Endemic Regions Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler. IG prepared from donors in Western countries does not prevent infection. Unknown efficacy of IG prepared from donors in endemic areas. Vaccine? 17 DOS CME Course 2011 Chronic Viral Hepatitis Most often due to HBV, HCV May be mistaken for other causes of chronic hepatitis Chronic viral hepatitis is disease lasting > 6 months Symptoms and histology don t match 18 DOS CME Course 2011 9
Hepatitis B Virus 19 DOS CME Course 2011 Spectrum of Chronic Hepatitis B Disease 1. Acute 2. Chronic 3. Cirrhosis 4. Hepatocellular Carcinoma 20 DOS CME Course 2011 10
Acute Hepatitis B Virus Infection with Recovery Symptoms HBeAg anti-hbe Titer Total anti-hbc HBsAg IgM anti-hbc anti-hbs 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 21 DOS CME Course 2011 Progression to Chronic Hepatitis B Virus Acute (6 months) HBeAg Chronic (Years) anti-hbe HBsAg Titer Total anti-hbc IgM anti-hbc 0 4 8 12 16 20 24 28 32 36 52 Years Weeks after Exposure 22 DOS CME Course 2011 11
Hepatitis B affects millions around the world and is a major cause of morbidity and death. Why is it so prevalent? What steps could be taken to reduce disease burden? 2 billion have been infected 400 million chronically infected 50 million new cases per year 15%-25% will die from complications 23 DOS CME Course 2011 24 DOS CME Course 2011 12
Concentration of Hepatitis B Virus in Various Body Fluids High Moderate Low / Not Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breast milk 25 DOS CME Course 2011 Hepatitis B Virus Modes of Transmission Sexual -sex workers and homosexuals are particular at risk. Parenteral -IVDA, Health Workers are at increased risk. Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. 26 DOS CME Course 2011 13
HBV Prevention Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries. Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions. 27 DOS CME Course 2011 Hepatitis D (Delta) Virus antigen HBsAg RNA 28 DOS CME Course 2011 14
29 DOS CME Course 2011 Hepatitis D Virus Modes of Transmission Percutaneous exposures injecting drug use Permucosal exposures sex contact 30 DOS CME Course 2011 15
HBV HDV Coinfection Symptoms ALT Elevated Titer IgM anti-hdv anti-hbs HDV RNA HBsAg Total anti-hdv Time after Exposure 31 DOS CME Course 2011 HBV - HDV Superinfection Jaundice Symptoms Titer ALT Total anti-hdv HBsAg HDV RNA IgM anti-hdv Time after Exposure 32 DOS CME Course 2011 16
Hepatitis D - Clinical Features Coinfection severe acute disease low risk of chronic infection Superinfection usually develop chronic HDV infection high risk of severe chronic liver disease may present as an acute hepatitis 33 DOS CME Course 2011 Hepatitis D - Prevention HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection 34 DOS CME Course 2011 17
Hepatitis C Virus capsid envelope protein protease/helicase RNA- RNA polymerase dependent c22 33c c-100 5 3 core E1 E2 NS2 NS3 NS4 NS5 hypervariable region 35 DOS CME Course 2011 Hepatitis C Virus Infection Typical Serologic Course Symptoms anti- HCV Titre HCV RNA ALT Normal 0 1 2 3 4 5 6 1 2 3 4 Months Years Time after Exposure 36 DOS CME Course 2011 18
Risk Factors for HCV Transmission Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment) Accidental injuries with needles/sharps Sexual/household exposure to anti-hcv HCV- positive contact Multiple sex partners Birth to HCV-infected mother 37 DOS CME Course 2011 38 DOS CME Course 2011 19
Laboratory Diagnosis HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy. 39 DOS CME Course 2011 Patient Profiles During HCV Therapy HCV RNA Relapser Null Responder Partial Responder HCV RNA negative Sustained Responder 4 (RVR) 12 (EVR) 24 48 (EOT) Time (weeks) 72 (SVR) Davis GL, et al. Hepatology. 2003;38:645-652. Fried MW, et al. N Engl J Med. 2002;347:975-982. Sanchez-Tapias JM. Gastroenterology 2006;131:451-460 40 DOS CME Course 2011 20
Prevention of Hepatitis C Screening of blood, organ, tissue donors High-risk behavior modification Blood and body fluid precautions 41 DOS CME Course 2011 Acknowledgements William Carey, M.D. Ana Bennett, M.D. Nizar Zein, M.D. Department of Gastroenterology and Hepatology 42 DOS CME Course 2011 21
43 DOS CME Course 2011 22