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Hepatitis A
Daniel J. Stein, MD, MPH
Stephen K. Lane, MD, FAAFP
image BASICS
DESCRIPTION
One of the world's most common diseases, hepatitis A is an infection with the hepatitis A virus (HAV) primarily involving the liver (1).
EPIDEMIOLOGY
Pediatric Considerations
  • Disease is often milder or asymptomatic in children; severity increases with age.
  • Infections are asymptomatic in 70% of children age <6 years.
  • In 2009, <50% of 13- to 17-year-olds in the United States had been vaccinated.
Pregnancy Considerations
  • Pregnant women with HAV have increased risk of complications including preterm labor (2).
  • Vertical transmission has been reported; fecal-oral transmission during birth is possible.
  • Breastfeeding is not contraindicated.
Incidence
  • HAV is cause of roughly 50% of reported cases of viral hepatitis in the United States (3).
  • 1.4 million cases globally each year
  • Since the hepatitis A vaccine has been in routine use (1995), the incidence of HAV has decreased by 95%.
  • Approximately 3,000 HAV infections in 2009, lowest ever recorded in the United States (1)
  • Incidence in the United States: 0.5/100,000 (1)
  • No difference based on sex
  • As many as 1/2 of current HAV infections in the United States are acquired from travel to endemic countries.
Prevalence
Serologic evidence of prior HAV infection: 1/3 of United States population. Anti-HAV prevalence related to age, ranging from 9% in children ages 6 to 11 years to 75% of those >70 years. Related inversely to income
ETIOLOGY AND PATHOPHYSIOLOGY
  • HAV is a single-stranded linear RNA enterovirus of the Picornaviridae family.
  • Infection is limited to liver hepatocytes and macrophages.
  • HAV is excreted into the bile and then stool, providing major route of spread.
  • Primary transmission is fecal-oral.
  • Humans are the only natural host.
  • Incubation is 2 to 6 weeks (mean 4 weeks).
  • Greatest infectivity is during 2 weeks before and one week after the onset of clinical illness.
  • Infection occurs primarily after consuming food or water contaminated with HAV, or via direct contact with HAV-infected person with poor hygiene.
  • Outbreaks can occur related to a common food or water source with multiple individuals exposed
  • Virus is stable in water and on surfaces, but is easily killed with high heat or cleaning agents.
  • Shellfish (clams and oysters) may be contaminated if harvested from waters contaminated with HAV.
  • Blood-borne transmission is rare.
  • HAV is not a chronic disease, but can last for months.
Genetics
Autoimmune hepatitis is rarely associated with human leukocyte antigen class II; DR3 and DR4 after active infection with HAV.
RISK FACTORS
  • Travel to developing countries accounts for >50% of cases in North America and Europe.
  • Employment in health care
  • Household exposure
  • Intimate exposure, especially men who have sex with men
  • Injection of illicit drugs
  • Child care centers, schools
  • Institutionalized individuals
  • Clotting factor disorders, such as hemophilia
  • Blood exposure/transfusion (rare)
  • No identifiable risk factor in 50%
GENERAL PREVENTION
  • Proper sanitation and personal hygiene (including hand washing), especially for food handlers, health care, and daycare workers
  • Active immunization: HAV vaccines: Havrix and Vaqta; Twinrix-combination HAV and HBV
  • Vaccine is recommended for (1)[C],(4)[A]:
    • All children aged 12 to 23 months, with catch-up administration until 18 years old
    • All travelers to countries with a high endemic rate of hepatitis A
    • Men who have sex with men
    • Illicit IV drug users
    • Anyone with chronic liver disease (including preand postliver transplant)
    • Individuals with a clotting factor disorder
    • Household members and close contacts of children adopted from countries with a high HAV prevalence (prior to arrival)
    • Anyone exposed during an outbreak
  • Per the CDC, routine vaccination is no longer routinely recommended for food service, child care, or health care workers (1)[C].
  • HIV-infected patients who are negative for HAV IgG should receive HAV vaccine series, preferably early in course of HIV infection
    • If CD4 count is <200 cells/mm3 or the patient has symptomatic HIV disease, defer vaccination until several months after initiation of antiretroviral (ARV) therapy to maximize the antibody response to the vaccine.
  • HAV is not killed by freezing.
  • HAV is killed by
    • Heating to 185°F for 60 seconds
    • Chlorine
    • Iodine
image DIAGNOSIS
PHYSICAL EXAM
  • Fever (variable)
  • Jaundice and icterus present in >70% of adults and older children
  • Hepatomegaly is also common; splenomegaly is less common.
  • Right upper quadrant abdominal tenderness
  • Rarely can have lymphadenopathy (cervical), arthritis, or rash
  • Asterixis can indicate acute hepatic failure.
DIFFERENTIAL DIAGNOSIS
  • Hepatitis B, C, D, E. Not clinically distinguishable from other forms of viral hepatitis; diagnosis may be suspected with typical symptoms during an outbreak.
  • Drug-induced hepatitis; toxin-induced hepatitis
  • Alcoholic hepatitis
  • Hemochromatosis (adults) or Wilson disease
  • Autoimmune hepatitis
  • Malaria
  • Infectious mononucleosis, cytomegalovirus (CMV)
  • Primary or secondary hepatic malignancy
  • Ischemic hepatitis or Budd-Chiari syndrome
  • Nonhepatobiliary disease (elevated AST/ALT): celiac disease, congestive heart failure, thyroid disease
  • Bacterial infections (Q fever, leptospirosis, syphilis, Rocky Mountain spotted fever)
  • Parasites (liver flukes or toxocariasis)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Anti-HAV IgM: positive at time of onset of symptoms sensitivity and specificity >95%. Primary test used to diagnose acute infection.
  • Anti-HAV IgG: appears soon after IgM and generally persists from years to lifetime
  • AST and ALT elevated ˜500 to 5,000: ALT usually > AST (3)
  • Alkaline phosphatase: mildly elevated
  • Bilirubin: conjugated and unconjugated fractions usually increased. Usually follows rises in ALT/AST, consistent with hepatocellular injury pattern
  • Prothrombin time and partial thromboplastin time usually remain normal or near normal.
    • Significant rises should raise concern of possible acute hepatic failure or coexistent chronic liver disease
  • CBC: mild leukocytosis; aplasia and pancytopenia are rare.
    • Thrombocytopenia may predict illness severity.
    • Autoimmune hemolytic anemia (rare)
  • Albumin, electrolytes, and glucose to evaluate for hepatic and renal function (rare renal failure)
  • Urinalysis (not clinically necessary): bilirubinuria
  • Consider ultrasound (US) to rule out biliary obstruction only if lab pattern is cholestatic.
Follow-Up Tests & Special Considerations
Illness usually resolves within 4 weeks from onset of symptoms. Repeat labs are not generally indicated unless symptoms persist or new ones develop.
Diagnostic Procedures/Other
Liver biopsy is usually not necessary. US can evaluate other causes (e.g., thrombosis or concurrent cirrhosis)
P.467

Tests Interpretation
  • Positive serum markers in hepatitis A
    • Acute disease: anti-HAV IgM only
    • Recent disease (last 6 months): anti-HAV IgM and IgG positive
    • Previous disease: anti-HAV IgM negative and IgG positive
  • If liver biopsy obtained, shows portal inflammation; immunofluorescent stains for HAV antigen positive
image TREATMENT
GENERAL MEASURES
  • Maintain appropriate nutrition/hydration.
  • Avoid alcohol.
  • Attend to personal hygiene to prevent spread.
  • Monitor coagulation defects, fluid and electrolytes, acid-base imbalance, hypoglycemia, and impairment of renal function.
  • Report to local public health department.
  • Laboratory evaluation including coagulation factors is important to rule out fulminant hepatic failure.
  • Referral to liver transplant center for fulminant failure (rare)
MEDICATION
  • Preexposure vaccination should be given according to recommended guidelines.
  • Give postexposure prophylaxis to persons within 2 weeks of exposure to HAV who have not previously received HAV vaccine (5)[A],(6)[C].
    • Administer hepatitis A vaccine to healthy persons between the ages of 1 and 40 years at age-appropriate dose (7)[A].
    • Administer immunoglobulin (0.02 mL/kg) to persons <1 or >40 years of age, or to patients with significant comorbidities (immunosuppression, liver disease) who are at risk for poor immune response (5)[A],(6)[C].
  • Use immunoglobulin for passive preexposure prophylaxis in those not eligible for the vaccine (5)[A],(6)[C].
    • 0.02 mL/kg provides 1 to 2 months of coverage; 0.06 mL/kg provides 3 to 5 months of coverage
    • Long-term prophylaxis should be with 0.06 mL/kg every 5 months for sustained risk (e.g., travelers)
    • Use immunoglobulin with the vaccine in cases where travelers need immediate protection and are older than 40 years.
    • Use immunoglobulin alone in children under 1 year old and unvaccinated pregnant women who will be traveling.
    • Do not give immunoglobulin with the MMR or varicella vaccines.
First Line
  • No antiviral medications indicated; spontaneous resolution occurs in almost all patients.
  • Limit acetaminophen use to 2 g/day or less.
  • Avoid hepatoxic agents.
Second Line
  • Antiemetics (e.g., ondansetron)
  • IV fluids
  • Pruritus: diphenhydramine 50 mg PO IM q6h, consider cholestyramine 4 g BID if cholestasis
ISSUES FOR REFERRAL
  • Dictated by severity of illness
  • Hepatic failure, refer to a high-volume liver transplant program
SURGERY/OTHER PROCEDURES
Liver transplant in fulminant hepatic failure—rare
COMPLEMENTARY & ALTERNATIVE MEDICINE
Avoid botanicals with potential hepatotoxicity, including barberry, comfrey, golden ragwort, groundsel, huang qin, kava kava, pennyroyal, sassafras, senna, valerian, wall germander, and wood sage.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Treatment is usually outpatient unless signs of liver failure; dictated by severity of illness
IV Fluids
Treat dehydration and any noted electrolyte imbalances.
Nursing
Enteric isolation. Private rooms, gowns, and masks are not necessary. Frequent hand washing. Use gloves when handling material potentially contaminated with feces.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Return to work/school 10 to 14 days after onset of symptoms with diligence to hygiene (patients remain infectious for up to 4 weeks from symptom onset).
Patient Monitoring
Monitor coagulation defects, fluid and electrolytes, acid-base imbalance, hypoglycemia, and renal function.
DIET
  • Adequate balanced nutrition
  • Avoid alcohol.
PATIENT EDUCATION
  • Segregate food handlers with HAV.
  • HAV immunity persists after infection
  • CDC Hepatitis A FAQs Link: http://www.cdc.gov/hepatitis/hav/afaq.htm
PROGNOSIS
  • Excellent; mortality is 0.3% (1)
  • Risk increased with underlying chronic liver disease and in the elderly (1.8% mortality age >50) (1)
REFERENCES
1. Centers for Disease Control and Prevention. Hepatitis A questions and answers for health professionals. http://www.cdc.gov/hepatitis/hav/havfaq.htm. Accessed August 18, 2015.
2. Almashhwari AA, Ahmed KT, Rahman RN, et al. Liver diseases in pregnancy: diseases not unique to pregnancy. World J Gastroenterol. 2013;19(43): 7630-7638.
3. Matheny SC, Kingery JE. Hepatitis A. Am Fam Physician. 2012;86(11):1027-1034.
4. Irving GJ, Holden J, Yang R, et al. Hepatitis A immunisation in persons not previously exposed to hepatitis A. Cochrane Database Syst Rev. 2012;(7):CD009051.
5. Liu JP, Nikolova D, Fei Y. Immunoglobulins for preventing hepatitis A. Cochrane Database Syst Rev. 2009;(2):CD004181.
6. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-7):1-23.
7. Victor JC, Monto AS, Surdina TY, et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med. 2007;357(17):1685-1694.
See Also
&NA;
  • Hepatitis B; Hepatitis C
  • Algorithm: Hyperbilirubinemia, Cirrhosis, and Jaundice
Codes
&NA;
ICD10
B15.9 Hepatitis A without hepatic coma
Clinical Pearls
&NA;
  • HAV disease severity directly correlates with age; children are often asymptomatic.
  • HAV vaccine is indicated for all children, travelers, those at elevated risk of disease, and anyone with liver impairment.
  • Check HAV IgG in all HIV-positive patients; provide HAV vaccine to those who are negative.
  • Treatment of acute disease is supportive
  • Give postexposure prophylaxis to eligible patients within 14 days of exposure