Objectives. Acute Hepatitis: Symptoms. Acute Hepatitis: Signs HIHIM 409. Acute Viral Hepatitis by Type, United States,

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1 Objectives Viral Hepatitis: ABCD&E HIHIM 409 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 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 Malaise 76-94% Anorexia 71-96% Dark urine 65-94% Nausea 61-81% Abdominal pain 26-68% Scleral icterus 48% Vomiting 20-37% Uncommon Respiratory symptoms Headache Fever Muscle pain Rash Joint pain Itching Asymptomatic hepatitis is also common Acute Hepatitis: Signs Acute Viral Hepatitis by Type, United States, Jaundice 70-90% Hepatomegaly 14-69% Tender liver 20-86% Rash 40% Splenomegaly 3-21% Fever 1-8% High LFTs 100% 47% 34% 3% 16% Hepatitis A Hepatitis B Hepatitis C Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis

2 Estimates of Acute and Chronic Disease Burden for Viral Hepatitis, United States HAV HBV HCV HDV Acute infections (x 1000)/year* Fulminant deaths/year ? 35 Chronic infections million 3.5 million 70,000 Chronic liver disease deaths/year 0 5, ,000 1,000 * Range based on estimated annual incidence, Common in U.S.* Cytomegalovirus Epstein-Barr Herpes simplex Varicella zoster Measles Rubella Coxsackie Other Viruses Associated with Acute Hepatitis Exotic** Yellow fever Argentinean hemorrhagic fever Bolivian hemorrhagic fever Lassa fever Rift Valley fever Marburg Ebola * Each causes less than 1% of acute hepatitis. ** Not seen in the U.S. Hepatitis Laboratory 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 Infection IgG : Appears slightly after IgM, may persist for life Total 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% 50% of acute hepatitis in the U.S. and other developed countries High prevalence in west Pacific, Southeast Asia, Africa and other developing countries Hepatitis A Virus Geographic Distribution of HAV Infection Anti-HAV Prevalence High Intermediate Low Very Low

3 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 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: Transmission 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 Infectious Doses per ml Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160: Hepatitis A: Diagnosis Acute symptoms Elevated LFTs Confirmation: IgM anti-hav, appears early and remains detectable e 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

4 Sources of Hepatitis A Virus Infection by Mutually Exclusive Groups, United States, Drug use Personal contact t Day care center Foreign travel Outbreak Year Source: CDC, Viral Hepatitis Surveillance Program Age-specific Mortality Due to Hepatitis A Age group (years) Case-Fatality (per 1000) < > Total 4.1 Source: Viral Hepatitis Surveillance Program, 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 Hepatitis A Vaccine 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 HAVRIX R OR VAQTA R, interchangeable TWINRIX R (Hepatitis A&B combination vaccine) Three dose series Interchangeability: dose 1 with Twinrix R - give 2nd dose of HAVRIX R OR VAQTA R A and 2 & 3rd dose of HEP B vaccine Dose 1 and 2 with Twinrix R Another dose of HAVRIX R OR VAQTA R not necessary, give dose 3rd dose of HEP B vaccine Hepatitis A and Food Workers Hepatitis E Virus 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

5 Hepatitis 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 year olds Children usually have sub-clinical infection Outbreak potential 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 E Epidemiologic 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 Geographic Distribution of Hepatitis E Hepatitis E: Diagnosis Serologic test available History: Evaluate risk factors, exposure history Rule out hepatitis A IgG WILL NOT PROTECT Outbreaks or Confirmed Infection in >25% of Sporadic Non-ABC Hepatitis Mostly located in India, Central & SE Asia, Middle East, Africa, Mexico Hepatitis E Prevention and Control Measures Hepatitis B Virus 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 p by traveler: Boil it, cook it, peel it or forget it IG prepared from donors in Western countries does not prevent infection Unknown efficacy of IG prepared from donors in endemic areas No vaccine

6 Hepatitis B Virus Structure 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% Geographic Distribution of Chronic HBV Infection HBsAg Prevalence 8% - High 2-7% - Intermediate <2% - Low Hepatitis B: Clinical Aspects Incubation period: days, average 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 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

7 Hepatitis B: Diagnosis 1. Symptoms 2. Elevated LFTs 3. 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 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 h infectivity it 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 30% of 5 year olds 6% of adults } Risk of chronic infection is lower }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 i 5% will develop hepatocellular cancer HBV causes 85% of primary liver cancer worldwide

8 Chronic Carrier State 2 positive HBsAg tests 6 months apart or Positive i 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 Reported Hepatitis B by Age Group 25 United States, Hepatitis B Prevention Education Needles, sex, universal precautions Vaccine Pre-exposure exposure, active immunity HBIG Post-exposure Passive immunity Age Group (Years) Source: CDC Viral Hepatitis Surveillance Program

9 Hepatitis B Vaccine Recombivax-HE R or Engerix-B R Interchangeable - 3 dose series Day zero, day 30, 6 months 1/2 dose (0.5 ml) OK for under age 30 If a dose missed, continue where with next scheduled dose: DO NOT RESTART SERIES Hepatitis B Vaccine Required All recruits Health care workers Hospital Corps & dental techs New Medical Department t officers Patients with STDs Public safety workers Correctional facility workers Compliance with OSHA regulations Recombivax-HE R, Engerix-B R or Twinrix R : all are three-dose series Hepatitis B Vaccine Pre-vaccination screening Not recommended Post-vaccination ti testing ti Identify non-responders in high risk jobs Non-responders receive one additional 3- dose series of hepatitis B vaccine, but not a third HBIG (Hepatitis B immune globulin) Post-exposure prophylaxis Passive immunity High concentration of anti-hbs Indications Perinatal exposure to HBsAg+ mother Percutaneous or permucosal exposure to HBsAg+ blood Sexual exposure to HBsAg+ person Also need 3 dose vaccine series δ antigen Hepatitis D (Delta) Virus HBsAg Hepatitis D Virus-like particle Defective RNA virus Requires HBV co-infection to replicate ANYONE WHO IS HBsAg(+) IS AT RISK RNA

10 Hepatitis D: Transmission Similar to Hepatitis B No fecal-oral transmission Highest rates in Italy, Venezuela, Africa, Romania, central Asia and the Middle East Hepatitis D: Diagnosis Serologic test for hepatitis D antibody Hepatitis D: Complications 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. Symptoms 2. Elevated LFTs 3. Rule out other causes of hepatitis 4. 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 er Tite Symptoms Person is sick, but test for Hep C is negative HCV antibody ALT (liver function test) Normal Months Years Time after Exposure

11 Features of Hepatitis C Incubation period Average 6-7 weeks Range 2-26 weeks Acute illness (jaundice) Mild (<20%) Case fatality rate Low Chronic 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 cancer Hepatitis C Virus Epidemiology, U.S. New infections (cases)/yr : 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 (only documented in HIV) Sources of Infection for Persons with Hepatitis C Injecting drug use 60% Sexual 15% Other* 5% Unknown 10% Transfusion 10% (before screening) *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 s: 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

12 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 HCVpositive 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 Hepatitis - Review Type 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 transmission Chronic infection fecal-oral Prevention pre/postexposure immunization percutaneous permucosal percutaneous permucosal percutaneous permucosal no yes yes yes no pre/postexposure immunization blood donor screening; risk behavior modification pre/postexposure immunization; risk behavior modification fecal-oral ensure safe drinking water DIAGNOSIS Review TREATMENT A IgM ANTI-HAV IG WITHIN 2 WEEKS OF EXPOSURE B HBsAg INFECTIOUS HBeAg DEGREE OF INFECTIVITY IgM anti-hbc ACUTE INFECTION Anti-HBs VACCINATED OR CLEARED INFECTION VACCINATION AND ADMINISTRATION OF HBIG WITHIN 24 HOURS OF NEEDLE STICK, 14 DAYS AFTER SEXUAL CONTACT CHRONIC HEPATITIS TREATED WITH ALPHA 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 BUT NOT COMMERCIALLY AVAILABLE IN U.S. NONE

13 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 Case #3 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? 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 P iti ti HB Positive anti-hbs Negative HBsAg Negative anti-hav What is the diagnosis?

14 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 Questions?