Viral H Hepatititis: s: A ABC BCDE NEPMU-2 Norfolk, VA (757) 444-7671
Objectives • Describe the Clinical Syndromes of Viral Hepatitis • List the modes of Transmission • Understand and be able to interpret Diagnostic (laboratory) tests • Know the Treatment and Occupational Impact of Viral Hepatitis • List Preventive Measures for each Hepatitis type • Describe Immunization protocols
Hepatitis is • Inflammation of the Liver that can be viral, chemical or drug-induced • Viral Hepatitis: Systemic infection which causes inflammation of the liver • Currently 5 recognized types of viral hepatitis: A, B, C, D, E • All 5 viruses cause similar illness, but have distinct antigenic properties
Acute Hepatitis: Symptoms Common Uncommon • Malaise 76-94% • Respiratory symptoms • Anorexia 71-96% • Headache • Dark urine 65-94% • Fever • Nausea 61-81% • Muscle pain • Abdominal pain 26-68% • Rash • Scleral icterus 48% • Joint pain • Vomiting 20-37% • Itching Asymptomatic hepatitis is also common
Acute Hepatitis: Signs Jaundice 70-90% Hepatomegaly 14-69% Tender liver 20-86% Rash 40% Splenomegaly 3-21% Fever 1-8% High LFTs 100%
Acute Viral He H patitis by Type, United S tates , 1982-1 – 993 34% 47% 16% Hepatitis AHepatitis B 3% Hepatitis C Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis
Estimates of Acute an and Chronic ic Dis Disease Burden e n for Viral He H p epatititis, Unitited ed States HAV HBV HCV HDV Acute infections (x 1000)/year* 125-200 140-320 35-180 6-13 Fulminant deaths/year 100 150 ? 35 Chronic 0 1-1.25 3.5 infections million mil ion 70,000 Chronic liver disease deaths/year 0 5,000 8-10,000 1,000 * Range based on estimated annual incidence, 1984-1994.
Other Viruses Associated with Acute Hepatitis Common in U.S.* Exotic** • Cytomegalovirus • Yellow fever • Epstein-Barr • Argentinean hemorrhagic fever • Herpes simplex • Bolivian hemorrhagic fever • Varicella zoster • Lassa fever • Measles • Rift Valley fever • Rubella • Marburg • • Coxsackie Ebola * Each causes less than 1% of acute hepatitis. ** Not seen in the U.S.
Hepatit itis Labora ratory T Tests • Liver function tests Enzymes produced by liver cells that increase when the liver is stimulated or inflamed • Antigen and Antibody tests • Immunology Terms ANTIBODY (Immunoglobulin, Ig, Anti- ) A protein in the blood generated in response to foreign proteins or polysaccharides. Sometimes antibodies provide protection from infection. IgM : Acute InfectionIgG : Appears slightly after IgM, may persist for lifeTotal Ig = IgM + IgG – Examples: Anti-HAV, Anti-HBsAg ANTIGEN (Ag) Substances that stimulate production of an antibody, Usually protein components of an infectious agent Examples: HBsAg, HAV
Hepatitis A “infectious hepatitis, epidemic hepatitis” • Caused by a small RNA enterovirus of the picornavirus family • Causes about 25-50% of acute hepatitis in the U.S. and other developed countries • High prevalence in west Pacific, Southeast Asia, Africa and other developing countries
He H patitis A Viru r s
Geographic Dis tribution of HA H V In I fection Anti-HAV Prevalence High Intermediate Low Very Low
Hepatitis A: Clinical Aspects • Onset: usually abrupt• Duration Mild lasting 1-2 weeks Severe lasting months Rarely fatal • Children usually asymptomatic 5-10% jaundiced 1-2 week duration • Adults are usually symptomatic Jaundiced Nausea, vomiting, & fever are common.
Hepatitis A: Clinical Aspects • Incubation 15-45 days, average 30 days • Greatest infectivity 2 wks before jaundice appears • Fecal viral shedding Greatest during late incubation and prodrome Diminishes rapidly after jaundice occurs
Hepatitis A: Tr Transmission on • PERSON TO PERSON (Fecal-Oral Routes)• Poor personal hygiene• Intimate contact• Contaminated food or water• Poor sanitation• NOT transmitted by sharing utensils, cigarettes, kissing
Concentration of Hepatitis A Virus in Various Body Fluids Feces Serum Saliva Urine 100 102 104 106 108 1010 Infectious s Dose ses per r ml Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890
Hepatitis is A A: D Dia iagnosis • Acute symptoms• Elevated LFTs• Confirmation: IgM anti-HAV, appears early and remains detectable for 4-6 months • Total anti-HAV (combination of IgM & IgG) is detectable early and persists lifelong. It is not diagnostic of acute Hepatitis A. • About 1/3 of the US population has anti- HAV IgG
Sources of Hepatitis A Virus Infection by Mutual y Exclusive Groups, United States, 1983-93 40 30 sesa f C o Personal ge 20 ge Drug use contact ta Day care center rcen eP 10 Foreign trave vel Outbr break 0 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 Year Source: CDC, Viral Hepatitis Surveillance Program
Age-s – pecific Mortality Due to He H pa titis A Age group Cas e-F atality (years ) (per 1000) <5 3.0 5-14 1.6 15-29 1.6 30-49 3.8 >49 17.5 Total 4.1 Source: Viral Hepatitis Surveillance Program, 1983-1989
Hepatitis A: Prevention • Immunization• Sanitation & Education Safe food, water and ice Good personal hygiene • Standard Immune globulin prophylaxis (IG) 80 – 90% effective if given within two weeks of exposure Immunization 2 weeks prior eliminates need Indications: Close personal contacts Day Care center outbreaks Fellow food handlers Restaurant patrons if deficiencies in hygiene or if handler prepared unheated food
Hepatit itis is A A V Vaccin ine • Two dose series: Initial plus booster in 6-12 months All Active duty and Select Reserves 95% protection after first dose Four week period for antibody development • HAVRIXR OR VAQTAR, interchangeable• TWINRIXR (Hepatitis A&B combination vaccine) Three dose series Interchangeability: dose 1 with TwinrixR – give 2nd dose of HAVRIXR OR VAQTAR A and 2 & 3rd dose of HEP B vaccine Dose 1 and 2 with TwinrixR – Another dose of HAVRIXR OR VAQTAR not necessary, give dose 3rd dose of HEP B vaccine
Hepatitis A and Food Wo W rkers • High potential for outbreaks• Verify Diagnosis• Evaluate food related duties, types of food & preparation methods Some food related work low-risk Wearing gloves reduces risk Fellow food handlers are more at risk than diners
He H patitis E Viru r s
Hepatit itis E E • Symptoms similar to hepatitis A: Malaise, lethargy, anorexia, nausea and vomiting, followed by dark urine, pale stools, and jaundice • Caused by Calicivirus Produces symptoms mostly in 15-40 year olds Children usually have sub-clinical infection Outbreak potential 15-60 day incubation period, usually 5-6 weeks • No chronic carriers: self-limited• Severely affects pregnant women with a the mortality rate of 10-20% • Overall mortality rate is 0.5-3%
Hepatitis is E Epidemiolo gic Features • Found mostly in less developed countries • Most outbreaks associated with drinking water contaminated with feces • Minimal person-to-person transmission • U.S. cases usually have history of travel to HEV-endemic areas
Geographi phic Distr tribution on of Hepatitis E • Outbreaks or Confirmed Infection in >25% of Sporadi dic Non o – n-ABC Hepatitis • Mostly located d in India, Central & SE Asia, Middle East, Africa, Mexico
Hepatit itis is E E: D Diagnosis is • Serologic test available• History: Evaluate risk factors, exposure history • Rule out hepatitis A• IgG WILL NOT PROTECT
Hepatititis s E E Preve vention a and Control Measu sures • Travelers to HEV-Endemic Regions: Avoid drinking water (and beverages with ice) of unknown purity, uncooked s hellfis h, and uncooked fruit/vegetables not peeled or prepared by traveler: “Boil it, cook it, peel it or forget it” IG prepared from donors in Wes tern countries does not prevent infection Unknown efficacy of IG prepared from donors in endemic areas • No vaccine
Hepatitis B Virus
Hepatitis is B B V Vir i u rus S Stru ructure
Hepatitis B “serum hepatitis, post-transfusion hepatitis” • Double shelled DNA hepadnavirus• Spread by sex, blood, and body fluids• Severe disease• Prolonged illness• Chronic problems in ~ 10%
G eographic Dis tribution of Chronic HB H V In I fection HBsAg Prevalence ≥8% – High 2-7% – Intermediate <2% – Low
Hepatitis B: Clinical Aspects • Incubation period: 45-180 days, average 60-90 days • Onset insidious (subtle and treacherous)• Symptoms more severe Malaise, arthralgias, rash, nausea & vomiting • Often hospitalized• One in 200 die from acute disease• Chronic liver disease kills ten times as many
Hepatitis B: Transmission • Virus present in blood, semen, saliva • Percutaneous Contaminated needles (tattoos, piercing, drugs, etc) Blood transfusion Perinatal • Permucosal Sexual contact Continuous close contact
Concentration o f He H patitis B Virus in Various Body F luids Low/Not High Moderate Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breast milk
Hepatitis B: Diagnosis 1. Symptoms2. Elevated LFTs3. Confirmed by serology IgM anti-HBc (IgM core antibody) HBsAg (surface antigen) HBsAb/anti-HBs (antibody to surface antigen ) HBcAb/anti-HBc (antibody to core antigen) HBeAg (E antigen) HBeAb/anti-HBe (antibody to E antigen)
Hepatitis B Serology IgM anti-HBc (core antibody) Appears early Persists for 6 months HBsAg (surface antigen) Detectable 30-60 days after exposure May indicate chronic carrier status HBsAb (antibody to surface antigen) Develops after resolved infection Indicates long term immunity
Hepatitis B Serology Anti-HBc/HBcAb (antibody to core antigen) Develops in all HBV infections HBeAg (E antigen) Indicates HBV replication Correlates with high infectivity Present in acute or chronic infection Anti-HBe (antibody to E antigen) Develops in most HBV infections Correlates with lower infectivity
Chronic Carrier State 90% of infants Risk of chronic 30% of 5 year olds infection is lower } 6% of adults after acute illness Prolonged infection can occur without signs or symptoms of acute or chronic illness
Chronic Carrier State • 10% / yr lose HBeAg – become noninfectious• 1-2% / yr lose HBsAg – become non-carriers• 25 % will develop chronic active disease• 20% will develop cirrhosis• 5% will develop hepatocellular cancer • HBV causes 85% of primary liver cancer worldwide
Chronic Carrier State 2 positive HBsAg tests 6 months apart or Positive HBsAg with Negative anti-HBc IgM
Chronic Carriers • Active duty Navy or Marine Corps HBV carriers, who do not have evidence of chronic persistent or recurrent active hepatitis not restricted from full duty • Asymptomatic HBV carriers need annual evaluation • HBV carriers with persistent symptoms or elevated LFTs, need periodic evaluation • Medical Department personnel who are chronic carriers are not restricted
Hepatitis B is an STD • Many prostitutes in the Philippines, Thailand, and developing countries are hepatitis B carriers • Sexual activity is #1 risk factor in U.S.
Rate of Rep eported Hepat atitis B by Ag Age Group 25 United St States, s, 1990 20 )00 15 0,001 re 10 p( etaR 5 0 0-14 15-19 20-29 30-39 40+ Age Group (Years) Source: CDC Viral Hepatitis Surveillance Program
Hepatitis B Prevention • Education Needles, sex, universal precautions • Vaccine Pre-exposure, active immunity • HBIG Post-exposure Passive immunity
Hepatitis B Vaccine • Recombivax-HER or Engerix-BR Interchangeable – 3 dose series Day zero, day 30, 6 months1/2 dose (0.5 ml) OK for under age 30 • If a dose missed, continue where with next scheduled dose: DO NOT RESTART SERIES • Recombivax-HER, Engerix-BR or TwinrixR: all are three-dose series
Hepatitis B Vaccine • Required All recruits Health care workers Hospital Corps & dental techs New Medical Department officers Patients with STDs Public safety workers Correctional facility workers Compliance with OSHA regulations
Hepatitis B Vaccine • Pre-vaccination screening Not recommended • Post-vaccination testing Identify non-responders in high risk jobsNon-responders receive one additional 3- dose series of hepatitis B vaccine, but not a third
HBIG (Hepatitis B immune globulin) • Post-exposure prophylaxis Passive immunityHigh concentration of anti-HBs • Indications Perinatal exposure to HBsAg+ motherPercutaneous or permucosal exposure to HBsAg+ blood • Sexual exposure to HBsAg+ person Also need 3 dose vaccine series
He H patitis D (D ( elta) )Virus δ antigen HBsAg RNA
Hepatit itis is D D • Virus-like particle• Defective RNA virus• Requires HBV co-infection to replicate • ANYONE WHO IS HBsAg(+) IS AT RISK
Hepatitis D: Tr Transmission on • Similar to Hepatitis B• No fecal-oral transmission• Highest rates in Italy, Venezuela, Africa, Romania, central Asia and the Middle East
Hepatitis is D D: D Dia iagnosis • Serologic test for hepatitis D antibody
Hepatitis D: : Compl plications • 10-15% develop cirrhosis within two years• 70% eventually develop cirrhosis• 2-20% fatality rate• 25-50% of fulminant liver failure in hepatitis B actually due to hepatitis D co-infection • Hepatitis D Prevention: Hepatitis B vaccine
Hepatitis C “transfusion related non-A, non-B hepatitis” • Caused by RNA flavivirus• Accounts for 16% acute hepatitis in U.S.• Transmission similar to hepatitis B Blood, sex, body fluids • Usually asymptomatic or mild disease• Chronic infection very common• 20% of community acquired hepatitis• 90% post-transfusion hepatitis• Blood banks started screening in 1990: <1% risk now
Hepatitis C Diagnosis 1. Symptoms2. Elevated LFTs3. Rule out other causes of hepatitis4. Confirmed by serology Serologic test detects HCV antibody Positive in chronic cases May not be positive in acute phase Rule out other causes of acute hepatitis Submit MER on acute cases only
Hepatitis C: Typical Serologic Course HCV antibody Symptoms Person is sick, but test for Hep C is negative Titer ALT (liver function test) Normal 0 1 2 3 4 5 6 1 2 3 4 Months Years Time after Exposure
Features of Hepatitis C Incubation period Average 6-7 weeks Range 2-26 weeks Acute illness (jaundice) Mild (<20%)Case fatality rate LowChronic infection 75%-85%Chronic hepatitis 70% (most asx)Cirrhosis 10%-20% Chronic Liver Disease Mortality 1%-5% Chronic disease often improves after 2-3 years Increases risk of liver can cer
Hepatitis C Virus Epidemiology, U.S. • New infections (cases)/yr 1985-89: 242,000 (42,000) 1998: 40,000 (6,500) • Deaths from acute liver failure: Rare • Persons ever infected (1.8%): 3.9 million • Persons with chronic infection: 2.7 million Percent of chronic liver disease – HCV-related 40% – 60% • Deaths from chronic disease/year 8,000-10,000
Transmission of HCV • Percutaneous Injecting drug use Clotting factors before viral inactivation Transfusion, transplant from infected donor Therapeutic (contaminated equipment, unsafe injection practices) Occupational (needle stick) • Permucosal Perinatal Sexual
Sources of Infection for Persons with Hepatitis C Injecting drug use 60% Sexual 15% Transfusion 10% (before screening) Other* 5% Unknown 10% *Nosocomial; Health-care work; Perinatal Source: Centers for Disease Control and Prevention
Post-transfusion Hepatitis C • Responsible for 90% of post-transfusion hepatitis in U.S. prior to 1990 • 1960s: 25%• 1970s: 7-12% post-transfusion risk• 1980s: 1-4% risk (ALT screening 1986)• 1990s: < 1% risk in (screening started 1990)• Most cases now community acquired• Problem among Viet Nam veterans
Routine HCV Testing Not Recommended (Unless Risk Factor Identified) • Ever injected illegal drugs• Received clotting factors made before 1987• Received blood/organs before July 1992 • Ever on chronic hemodialysis• Evidence of liver disease• Children born to HCV-positive women • Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood
Medical Evaluation and Management for Chronic HCV • Assess for biochemical evidence of chronic liver disease • Assess for severity of disease and possible treatment • Vaccinate against hepatitis A and B • Counsel to reduce further harm to liver and prevent transmission to others • Refer to support group
Hepatitis C Prevention • Screening of blood, organ, tissue donors• Blood and body fluid precautions • Education High-risk behavior modification Same risk factors as hepatitis B Blood > sex > Perinatal • No vaccine• IG does not protect
Viral Hepa titis – Review Typ ype of Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces blood-derived blood-derived blood-derived virus body fluids body fluids body fluids Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification
Review DIAGNOSIS TREATMENT A IgM ANTI-HAV IG WITHIN 2 WEEKS OF EXPOSURE B HBsAg – INFECTIOUS VACCINATION AND ADMINISTRATION OF HBIG HBeAg – DEGREE OF INFECTIVITY WITHIN 24 HOURS OF NEEDLE STICK, 14 DAYS IgM anti-HBc – ACUTE INFECTION AFTER SEXUAL CONTACT Anti-HBs – VACCINATED OR CLEARED CHRONIC HEPATITIS TREATED WITH ALPHA INFECTION INTERFERON AND LAMIVUDINE C ANTI-HCV Peginterferon alfa-2b, Peginterferon alfa-2a, Ribavirin D ANTI-HDV SAME AS HEPATITIS B E ANTI-HEV SEROLOGY DEVELOPED NONE BUT NOT COMMERCIALLY AVAILABLE IN U.S.
Review: Disposition of Carries/Chronic Infections • Hepatitis A/E Enteric precautions for first 2 weeks but no more than one week after jaundice • Hepatitis B No restrictions on chronic carriers including medical personnel HBeAg positive Medical personnel need expert review before performing invasive procedures • Hepatitis C No restrictions on chronic carriers
Case #1 • 22 y/o Food handler Positive for HBsAg Negative for Anti-HBs Negative for HAV antibody Normal LFTs No Symptoms • Is galley work permitted?
Case #2 • 22 y/o HM3 Positive for HBsAg Negative for anti-HBs Negative for anti-HAV Normal LFTs No Symptoms • Can the HM3 work in the blood bank?
Case #3 • CHT worker Exposed to human sewage while repairing pipes • Is hepatitis B vaccine needed?• Is immune globulin needed?• Does spouse need shots?
Case #4 • 24 y/o Mess specialist Chronic fatigue for past 4 wks Abdominal pain 3-4 weeks ago — resolved LFTs not elevated Positive for anti-HAV • DOES EVERYONE IN THE CREW NEED IgG?
Case #5 • 30 y/o Sailor Abdominal pain for 2 wks Now has yellow eyes LFTs significantly elevated Positive anti-HBs Negative HBsAg Negative anti-HAV • What is the diagnosis?
Case #5 • Additional info: Negative for HEP C antibody No history of unsafe sex in past 6 months No history of tattoos or other needle use No history of alcohol abuse PPD converter • Taking INH for past 2 months