Harrison's Practice: Hepatitis A, Acute

Harrison's Practice

Hepatitis A, Acute

Definition

An acute systemic infection caused by the hepatitis A virus (HAV) that primarily affects the liver
Transmitted by the fecal-oral route
It almost always manifests a self-limited clinical course, although fulminant destructive hepatitis can occur rarely.

Epidemiology

Incidence
- In the U.S. (2006)
  - Number of cases reported: 3579 (rate: 1.2 cases per 100,000 population)
  - Estimated actual number of new infections adjusted for asymptomatic infection and underreporting: 32,000
  - Rate in 2006 was lowest rate ever recorded.
  - Introduction of hepatitis A vaccination programs among children from high-incidence states has resulted in a >70% reduction in the annual incidence of new infections.
    - Has shifted the burden of new infections from children to young adults
- In developing countries
  - Where hygiene is poor, infection is almost universal during childhood.
  - As hygiene improves, rate of childhood infection decreases.
Prevalence
- In the U.S.
  - One-third of Americans have evidence of past infection.
  - Prevalence has been decreasing since the 1970s.
- In developing countries
  - Exposure, infection, and subsequent immunity are a function of evolving standards of hygiene.
Age
- Prevalence of anti-HAV, a marker for previous HAV infection, increases with age.
Socioeconomic status
- Prevalence of anti-HAV increases with decreasing socioeconomic status.
- Adults of higher socioeconomic status are, therefore, at greater risk of infection upon exposure later in life.
Seasonality
- Generally occurs in late fall and early winter
Epidemics
- In temperate zones, epidemic waves have been recorded every 5–20 years, as new segments of nonimmune populations appear.
  - These cyclic patterns are no longer being observed in developed countries.

Risk Factors

Ingestion of contaminated food substances
- Large outbreaks as well as sporadic cases have been traced to contaminated:
  - Food, notably:
    - Green onions
    - Raw or undercooked shellfish
    - Frozen raspberries and strawberries
  - Water
  - Milk
Family member who is affected
Institutional resident who is affected
- Child care centers
- Neonatal intensive care units
Homosexual men with multiple sexual partners
Use of injectable drugs
Poor personal hygiene
Overcrowding
Travel to endemic areas
Persons working with nonhuman primates that are susceptible to HAV infection (including Old- and New-World species) [1]

Etiology

Caused by HAV
- Nonenveloped; 27-nm; heat-, acid-, and ether-resistant RNA virus
- Genus: Hepatovirus
- Family: Picornavirus
Transmission
- Almost exclusively by the fecal-oral route
- Bloodborne (rare)
  - Several outbreaks have been seen in recipients of clotting factor concentrates.
Infectivity
- Replication is limited to the liver, but the virus is present in the liver, bile, stool, and blood during the late incubation period and acute preicteric phases of the illness.
- Despite persistence of the virus in the liver, viral shedding in feces, viremia, and infectivity diminish rapidly once jaundice becomes apparent.

Symptoms & Signs

Incubation period
- 15–45 days
- Mean: ~4 weeks
Prodromal symptoms of acute viral hepatitis are systemic and variable.
Constitutional symptoms may precede the onset of jaundice by 1–2 weeks.
- Anorexia
- Nausea
- Vomiting
- Fatigue
- Malaise
- Arthralgias
- Myalgias
- Headache
- Photophobia
- Pharyngitis
- Cough
- Coryza
- Low-grade fever
Symptoms and signs related to liver dysfunction
- Jaundice
- Dark urine
- Tender hepatomegaly
- Right upper-quadrant pain
Less common symptoms and signs
- Splenomegaly (10–20% of patients)
- Cervical adenopathy (10–20%)
- Spider angiomas

Differential Diagnosis

Other hepatitis viruses
Other viral illnesses frequently affect the liver, although they rarely cause jaundice.
Toxoplasmosis
Rare causes of liver injury confused with viral hepatitis
- Leptospira
- Candida
- Brucella
- Mycobacteria
- Pneumocystis
Many drugs and certain anesthetic agents
Alcoholic hepatitis
Acute cholecystitis
Common bile duct stone
Ascending cholangitis
Carcinoma of the pancreas
Other clinical constellations that may mimic acute hepatitis
- Right ventricular failure with passive hepatic congestion
- Hypoperfusion syndromes
  - Shock
  - Severe hypotension
  - Severe left ventricular failure
- Any disorder that interferes with venous return to the heart
  - Right atrial myxoma
  - Constrictive pericarditis
  - Hepatic vein occlusion (Budd–Chiari syndrome)
  - Veno-occlusive disease
Disorders in pregnancy that may be confused with viral hepatitis
- Acute fatty liver of pregnancy
- Cholestasis of pregnancy
- Eclampsia
- HELLP syndrome (hemolysis, elevated liver enzyme level, and low platelet count)
Genetic or metabolic liver disorders
- Wilson disease
- α₁-Antitrypsin deficiency
Nonalcoholic fatty liver disease
Cancers metastatic to the liver (rarely present similarly to acute viral hepatitis)

Diagnostic Approach

History and physical examination, with particular attention to risk factors
Diagnosis of hepatitis A is based on detection of IgM anti-HAV during acute illness.

Laboratory Tests

Diagnostic tests for acute HAV
- IgM anti-HAV is the diagnostic test of choice.
  - Appears very soon after infection
  - Disappears 3–6 months later
  - Incidental presence of rheumatoid factor can yield false-positive results.
  - IgG anti-HAV appears later in the acute phase but persists for decades.
    - Therefore not useful for distinguishing acute hepatitis A from other causes of acute hepatitis
Diagnostic tests to rule out acute hepatitis due to other viruses
- IgM anti–hepatitis B (HBV) core antigen
  - Indicative of acute HBV infection
- HBV surface antigen (HBsAg)
  - Indicative of acute or chronic HBV infection
  - Infrequently, HBsAg levels are too low to be detected during acute HBV infection.
- Anti–hepatitis C virus (HCV)
  - Indicative of acute HCV infection
Laboratory abnormalities in acute viral hepatitis
- Serum alanine aminotransferase and aspartate aminotransferase
  - Variable increases during the prodromal phase of acute viral hepatitis
    - Precede the increase in bilirubin level
  - Acute level of these enzymes does not correlate well with the degree of liver-cell damage.
  - Peak levels vary from 400–4000 IU.
- Serum bilirubin
  - Jaundice is usually visible in the sclera or skin when the serum bilirubin value is > 43 μmol/L (2.5 mg/dL).
  - In most instances, the total bilirubin is equally divided between conjugated and unconjugated fractions.
  - Bilirubin levels > 340 μmol/L (20 mg/dL) extending and persisting late into the course of viral hepatitis are more likely to be associated with severe disease.
    - In patients with underlying hemolytic anemia, such as glucose-6-phosphate dehydrogenase deficiency and sickle-cell anemia, a high serum bilirubin level is common (results from superimposed hemolysis).
    - Bilirubin levels > 513 μmol/L (30 mg/dL) have been observed and are not necessarily associated with a poor prognosis.
- Prothrombin time
  - Prolonged value may:
    - Reflect a severe hepatic synthetic defect
    - Signify extensive hepatocellular necrosis
    - Indicate a worse prognosis
- Serum alkaline phosphatase level
  - May be normal or only mildly elevated
- Albumin level
  - Decrease: uncommon in uncomplicated cases

Imaging

Not indicated

Diagnostic Procedures

Liver biopsy is rarely necessary or indicated in acute viral hepatitis.
- Exceptions
  - Uncertainty about the diagnosis
  - Clinical evidence suggesting chronic hepatitis

Treatment Approach

Mainstay of therapy is supportive care.
Specific treatment is not necessary.
Burdensome enteric precautions are no longer recommended.
- Most patients hospitalized with hepatitis A excrete little if any HAV.
- Likelihood of HAV transmission from these patients during their hospitalization is low.
  - Nonetheless, universal precautions are recommended.

Specific Treatments

Supportive care

Activity as tolerated
High-calorie diet (often tolerated best in the morning)
Intravenous hydration and feeding
- In patients with severe vomiting
- In patients who cannot maintain oral intake
Avoidance of alcohol and drugs metabolized by the liver
Avoidance of drugs capable of producing adverse reactions, such as cholestasis
Bile-salt sequestrant resins, if severe pruritus is present
- Cholestyramine, up to 4 g PO 4 times daily
No role for glucocorticoids

Monitoring

Certain patients require inpatient monitoring.
- Advanced age
- Serious underlying medical disorders
- Presenting features
  - Ascites
  - Peripheral edema
  - Hepatic encephalopathy
  - Prolonged prothrombin time
  - Low serum albumin level
  - Hypoglycemia
  - Very high serum bilirubin level
Monitor for clinical and biochemical recovery.
Monitor for complications.

Complications

Relapsing hepatitis
- Experienced by a small proportion of patients with hepatitis A weeks to months after recovery
- Relapses are characterized by:
  - Recurrence of symptoms
  - Elevated liver enzyme levels
  - Jaundice (occasionally)
  - Fecal excretion of HAV
- Even when these complications occur, hepatitis A remains self-limited and does not progress to chronic liver disease.
Cholestatic hepatitis
- Characterized by protracted cholestatic jaundice and pruritus
Fulminant hepatitis (massive hepatic necrosis)
- Rare
- Primarily in older adults and in persons with underlying chronic liver disease
Rare complications
- Pancreatitis
- Myocarditis
- Atypical pneumonia
- Aplastic anemia
- Transverse myelitis
- Peripheral neuropathy

Prognosis

Virtually all previously healthy patients with hepatitis A recover completely from their illness, with no clinical sequelae.
- Complete clinical and biochemical recovery is to be expected in 1–2 months.
- No chronic carrier state
Indications of poorer prognosis
- Advanced age
- Serious underlying medical disorders
- Underlying liver disease, particularly HCV
- Initial presenting features such as ascites, peripheral edema, and symptoms of hepatic encephalopathy
- Prolonged prothrombin time
- Low serum albumin level
- Hypoglycemia
- Very high serum bilirubin level
Case-fatality rate: approximately 0.1%
- Increased by:
  - Advanced age
  - Underlying debilitating disorders

Prevention

Preexposure immunoprophylaxis
- Vaccine
  - HAVRIX
    - Age: ≥1 years
    - Number of doses: 2
    - Adults: 1440 ELU (1.0 mL)
    - Children 1–18 years of age: 720 ELU (0.5 mL)
    - Schedule: 0, 6–12 months
  - VAQTA
    - Age: ≥1 years
    - Number of doses: 2
    - Adult: 50 U (1.0 mL)
    - Children 1–18 years of age: 25 U (1.0 mL)
    - Schedule: 0, 6–18 months
- Indications
  - Advisory Committee on Immunization Practices recommends:
    - All children should receive hepatitis A vaccine at 12–23 months of age.
    - Vaccination should be integrated into the routine childhood vaccination schedule.
    - Children who are not vaccinated by 2 years of age can be vaccinated at subsequent visits.
  - Travel to endemic areas
    - Recommended 2–4 weeks prior to travel
    - Still protective if given < 2 weeks and therefore recommended for all travel time frames[2]
  - Military personnel
  - Populations with cyclic outbreaks of hepatitis A
    - Alaskan natives
  - Employees of day care centers
  - Primate handlers
  - Laboratory workers exposed to hepatitis A or fecal specimens
  - Children in communities with a high frequency of hepatitis A
  - Patients with chronic liver disease
  - Men who have sex with men
  - Injection drug users
  - Persons with clotting disorders who require frequent administration of clotting-factor concentrates
Postexposure immunoprophylaxis
- Immune globulin, 0.02 mL/kg IM within 2 weeks recommended for all household and institutional contacts or
- Vaccine: single dose of vaccine (if not previously immunized)
- Immune globulin vs vaccine
  - Immune globulin use
    - Healthy persons < 12 months of age
    - Immunocompromised persons
    - Persons diagnosed with chronic liver disease
    - Persons for whom vaccine is contraindicated
    - Persons > 40 years of age (immune globulin preferred, vaccine is acceptable)
  - Vaccine use is preferred for:
    - Healthy persons aged 12 months through 40 years
      - Long-term protection
      - Ease of administration
  - Efficacy of immune globulin or vaccine when administered > 2 weeks after exposure has not been established.
Inactivation of HAV [1]
- Heat foods at temperatures >185^°F (>85^°C) for 1 minute
- Disinfect surfaces with a 1:100 dilution of sodium hypochlorite (i.e., household bleach) in tap water

ICD-9-CM

070.0 Viral hepatitis A with hepatic coma
070.1 Viral hepatitis A without mention of hepatic coma