Viral Hepatitis

Navy Environmental and Preventive Medicine Unit No. Five Revised April 2003

Terminal Objectives

Recognize: 5 types of Viral Hepatitis Understand: Signs and Symptoms Serological Diagnosis Epidemiology Prevention and Control Measures Treatment Reporting Requirements Case Discussions

References

NAVMEDCOMINST 6230.1a, 1 Oct 87

BUMED Note 6230, Imm. Req. & Rec, 12 Jan 93 NAVMEDCOMINST 6220.2x, DARs
BUMEDINST 6220.12A Medical Event Reports NAVMED P-5038, CCDM, 15th ed., 1990

Terms & Definitions

Hepatitis

Inflammation of the liver

Viral

Hepatitis Hepatitis caused by one of the known hepatitis viruses (A, B, C, D, E, F, G)

Enterovirus

A virus which infects the gastrointestinal system

Terms & Definitions

Antigen Any substance that stimulates production of an antibody. Viral antigen Any part of a virus that stimulates an antibody response. Antibody A protein in the blood generated in response to foreign proteins or polysaccharides. Sometimes provides protection from infection. Immune serum globulin (ISG) A sterile solution of proteins (globulins) that contains many of the antibodies that were in the original adult human blood serum from which it was extracted.

Acute Hepatitis: Signs/Symptoms

Common

Uncommon

Malaise 76-94% Anorexia 71-96% Dark urine 65-94% Nausea 61-81% Abdominal pain 26-68% Hepatomegaly 14-69% Rash 40% Scleral icterus 48% Vomiting 20-37% and sometimes . . .

Respiratory symptoms Headache Fever Myalgia Rash Arthralgia Itching

Asymptomatic

Viruses Associated with Acute Hepatitis

*Common in U.S. Cytomegalovirus Epstein-Barr virus Herpes simplex Varicella zoster Measles Rubella Coxsackie viruses **Exotic Yellow fever Argentinian hemorrhagic fever Bolivian hemorrhagic fever Lassa fever Rift Valley Fever Ebola/Marburg

* Each causes less than 1% of acute hepatitis.

** Not seen in the U.S.

Hepatitis A
infectious hepatitis, epidemic hepatitis

Causes about 25-50% of acute hepatitis in the U.S. and other developed countries High prevalence in Africa, Middle East, Asia, eastern Europe, Central and South America west Pacific, and other developing countries

Caused by a small SS RNA enterovirus of the picornavirus family.

Hepatitis A: Symptoms
Onset usually abrupt Duration Mild lasting 1-2 weeks Severe lasting months Rarely fatal (0.1- 0.3% mortality rate) 80% of children asymptomatic Adults are symptomatic & jaundiced. Nausea, vomiting, & fever are common.

Hepatitis A Transmission & Epidemiology

Person to person, Fecal Oral, Intimate contact MSM, daycare 20-50% secondary attack rate in households Poor personal hygiene, Poor sanitation Contaminated food or water Vegetables, fruit, shellfish

Not transmitted by sharing utensils, cigarettes, kissing

Hepatitis A Transmission & Epidemiology

Incubation 15-50 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

Food Water Person to person

Hepatitis A: Diagnosis
Acutely symptomatic Elevated LFTs IgM anti-HAV (antibody to hepatitis A virus) confirms diagnosis of acute hepatitis A. It appears early and remains only 4-6 months. Total anti-HAV (combination of IgM & IgG) detectable early & persists lifelong does NOT confirm acute hepatitis A

Hepatitis A: Prevention
Education Safe food, water, and ice Good personal hygiene Immune serum globulin (ISG) 80-90% effective when given early (within 2 weeks of exposure) Pre-exposure and/ or Post-exposure

Hepatitis A: Prevention

Hepatitis A Vaccines HAVRIX, VAQTA, TWINRIX-combined A &B All active duty personnel, reservists, beneficiaries in endemic areas, occupations with sewage exposure 1 ml, given at least 2 wks before travel followed by a Single 1 ml booster, 6-12 months later 95% protection after one shot Requires 2-4 weeks for antibody production Post-Exposure Prophylaxis Hepatitis A Vaccine is an option if given within one week of exposure

Hepatitis A & Food Workers

High potential for outbreaks Verify diagnosis Evaluate food related duties Type of food preparation methods: cooked or raw Some food related work is low risk Wearing gloves reduces risk Consider ISG prophylaxis Fellow food handlers are more at risk than diners

Hepatitis A: Review

Acute onset after 30 days incubation Spread by fecal contamination Good hygiene prevents spread Cook it, peel it, boil it or dont eat it ISG provides protection, but only if given within 2 weeks of exposure Vaccine can be used post exposure if given within one week of exposure Vaccine preventable, required for all active duty personnel

Hepatitis E
enterically transmitted non-A, non-B hepatitis

Similar to Hepatitis A Usually effects children and young adults Usually self-limited No chronic carriers 20-39% fatality rate in pregnant women contracted during third trimester Caused by a non-enveloped RNA calicivirus Incubation period: 15-45 days, average +40

Hepatitis E: Transmission & Epidemiology

Transmission similar to Hepatitis A Outbreaks associated with poor sanitation Waterborne epidemics & sporadic cases Person to person 5-20% secondary attack rate in households Occurs in India, central and southeast Asia, Middle East, Africa, and Mexico No cases acquired in U.S.

Hepatitis E: Diagnosis
1. Hepatitis symptoms 2. Elevated LFTs 3. No serologic test commercially available Evaluate risk factors, exposure history Rule out Hepatitis A (B, C, and D)

Hepatitis E: Prevention

Immune serum globulin does NOT protect Strict food & water precautions will prevent

Avoid contaminated water Avoid uncooked food

Hepatitis B
serum hepatitis, post-inoculation jaundice, posttransfusion hepatitis

Double shelled DNA hepadnavirus Onset insidious,Symptoms more severe Arthralgias, rash, nausea and vomiting One in 7 are hospitalized One in 400 die Prevalence: 1 million Americans 350 million people worldwide Incidence: 200,000-300,000 annually in the USA 1 million deaths annually attributed to Hep B

Hepatitis B
Major cause of acute & chronic hepatitis, cirrhosis, and hepatocellular cancer

World wide Hepatitis B is the second most preventable cause of cancer

Hepatitis B Transmission & Epidemiology

Transmitted across skin or mucous membranes Virus present in blood, semen, saliva Percutaneous Contaminated needles (tattoos, piercing, drugs, etc} Blood transfusion Perinatal Permucosal Sexual contact, Hepatitis B is an STD Continuous close contact Household contacts Institutions for the mentally retarded patients & staff

Hepatitis B Transmission & Epidemiology

Incubation period: 28-160 days, average + 80

Infectious period varies 30 days after exposure 6 months after onset Chronic carriers remain infectious > 6 months
Frequency 25-50% of new acute hepatitis cases in U.S. 0.3 % U.S. first time blood donors are HBsAg+ 10-20 % of institutionalized mentally retarded persons 13% of immigrants born in endemic countries

Hepatitis B Virus
Shell with surface antigen Inside the shell Core with core antigen Inside the core DNA DNA polymerase E antigen

Hepatitis B: Diagnosis

Symptoms Elevated LFTs Confirmed by IgM anti-HBc (core antibody) gold standard HBSAg (surface antigen) Anti-HBs/HBsAb (antibody to surface antigen ) Anti-HBc/HBcAb (antibody to core antigen) HBeAg (E antigen) 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 Anti-HBs/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 HBVirus 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

Hepatitis B: Complications

Chronic Carrier State 2 positive HBsAg tests 6 months apart or Positive HBsAg with Negative anti-HBc IgM

Hepatitis B: Complications
90% of infants 30% of 5 year olds 6% of adults

Develop chronic carrier state after Hepatitis B infection

Prolonged infection can occur without signs or symptoms of acute or chronic illness

Hepatitis B: Complications

Chronic Carriers 10% per yr lose HBeAg - become noninfectious 1-2% per yr lose HBsAg - become non-carriers 25 % will develop chronic active disease 20% will develop cirrhosis 5% will develop hepatocellular cancer
HBV causes 80% of primary liver cancer worldwide

Hepatitis B: Prevention
NAVMEDCOMINST 6230.1a, 1 Oct 87

Active duty Navy or Marine Corps personnel who become HBV carriers, but who do not have evidence of chronic persistent or recurrent active hepatitis must not be restricted from full duty. HBV carriers with persistent symptoms or elevated LFTs, who are retained on active duty, need periodic medical evaluation. Medical Department personnel who are chronic carriers are not work restricted.

Hepatitis B: Prevention

Education on transmission Unprotected sex, needles, tattoos, Universal precautions Prophylaxis Pre-exposure - Active immunity Hepatitis B vaccine 3 dose series Recombivax-HBV or Energix-B Interchangeable Twinrix Hep B and A combination 3 doses total Post-exposure - Passive immunity Hepatitis B immune globulin (HBIG)

Hepatitis B: Prevention
BUMEDNOTE 6230, 12 Jan 93

Hepatitis B vaccine required All recruits Health care workers - military and civilian Hospital Corps & dental techs - A school New Medical Department officers - OIS Public safety workers - military Marine Corps guards in endemic areas Patients with STDs - military Compliance with OSHA regulations Newborn infants - universal immunization

Hepatitis B: Review
Serious

health threat Transmitted via blood and sex Lots of antigens and antibodies HBsAg: person has infection HBsAb: person has immunity Hepatitis B vaccine prevents the disease

Hepatitis C
transfusion related non-A, non-B hepatitis Transmission similar to Hepatitis B Parenteral > sexual > perinatal Caused by RNA flavivirus Incubation period 14-160 days, average + 50 Insidious onset 90% are asymptomatic Clinically similar to Hepatitis B Symptoms mild Nausea and vomiting common

Hepatitis C Transmission and Epidemiology

Accounts for 25% acute hepatitis in U.S. Most cases are community acquired 90% of post-transfusion hepatitis in U.S. 7-12% post-transfusion risk in 1970s 1-4% risk in 1980s (ALT screening 1986) < 1% risk in 1990s (screening started 1990)

Occurs worldwide

Hepatitis C: Complications

Chronic carriers 50-80% develop chronic disease 50% progress to cirrhosis or liver cancer Chronic disease often improves after 2-3 years 1-2% fatality rate

Hepatitis C

Diagnosis Rule out other causes of acute hepatitis Serologic test detects only HCV antibody Positive in chronic cases & resolved cases May not be positive in acute phase

Prevention & Education Same risk factors as hepatitis B Blood > sex > perinatal No vaccine, ISG is not protective

Hepatitis C: Review

Clinically similar to Hepatitis B Transmission similar to Hepatitis B Blood > sex > perinatal Today, transfusion low-risk Serologic test detects antibody only May not be positive acutely Prevention Education only, no vaccine

Hepatitis D
delta hepatitis Requires HBV co-infection to replicate Transmission similar to hepatitis B Parenteral & sexual (no perinatal transmission) Caused by an incomplete RNA virus Incubation period 42-180 days Onset abrupt or insidious Symptoms severe Jaundice, fever, nausea and vomiting common

Hepatitis D

Diagnosis Serologic test for hepatitis D antibody Complications 70% eventually develop cirrhosis 10-15% develop cirrhosis within two years 2-20% fatality rate 20-50% of fulminant liver failure in Hep B is actually due to hepatitis D co-infection

Hepatitis D
Frequency Affects 3-12% of U.S. donors who are HBsAg+ Highest rates in Italy, Venezuela, Africa, Romania, central Asia, and the Middle East Prevention Hepatitis B vaccine Anyone who is HBsAg positive is at risk for Hepatitis D

Medical Event Report (MER)

Required on all acute cases of Hepatitis Include:

1. Signs and symptoms 2. Pertinent lab results

3. Possible exposures

Viral Hepatitis: Review

Caused by 5 (or more) different viruses Similar symptoms Different antigenic properties A & E are spread by fecal-oral contamination B, C, & D are spread parenterally (Blood, sex, perinatal) MER required on all cases of acute hepatitis

Viral Hepatitis: Review Prevention

Hepatitis A & E Safe food and water Hepatitis A only ISG Hep A Vaccine

Hepatitis B, C & D Avoid risk related behaviors Hepatitis B & D Hep B Vaccine Hepatitis B only HBIG

Cases for Reflection/Discussion

True life adventures in Navy epidemiology and preventive medicine

Typical Case # 1
22 yo mess specialist, born in an endemic country Positive for hepatitis B surface antigen Negative for hepatitis B surface antibody Negative for hepatitis A antibody Normal LFTs No symptoms

Can he work in the galley?

Typical Case # 1a
22 yo HM3, born in an endemic country Positive for hepatitis B surface antigen Negative for hepatitis B surface antibody Negative for hepatitis A antibody Normal LFTs No symptoms

Can he work in the blood bank?

Typical Case # 2
32 yo CHT worker
Exposed to human sewage while repairing pipes

Does he need hepatitis B vaccine? Does he need ISG? Does he need hepatitis A vaccine? Should his wife get shots?

Typical Case # 3
24 yo mess specialist
Chronic fatigue for past 4 weeks Abdominal pain about 3 or 4 weeks ago - now resolved LFTs normal Positive for hepatitis A antibody

Does everyone in the crew need ISG? Can he work in the galley?

Typical Case # 4
30 yo Sailor
Abdominal pain for 2 weeks Now has yellow eyes LFTs elevated - 5 times normal Positive for hepatitis B surface antibody Negative for hepatitis B surface antigen Negative for hepatitis A antibody

What has he got?

Typical Case # 4
More information
Negative for hepatitis C antibody No history of unsafe sex 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 without problems

What has he got?

INH Associated Hepatitis

LFTs usually rise with INH therapy
Normal 4-fold rise in LFTs returns to baseline

LFTs

Time on INH
LFTs Time on INH Greater than 4-fold rise in LFTs indicates toxicity

Acute Hepatitis: Treatment

Supportive care Avoidance of liver damaging circumstances No meds Isolation - prior to diagnosis Medical follow up Check LFTs twice per week if increasing Check LFTs once per week after plateau Check LFTs every 1-2 weeks while declining