Overview
Definition:
Epstein-Barr Virus (EBV) hepatitis refers to liver inflammation caused by the Epstein-Barr virus, a common human herpesvirus
While EBV is most recognized for causing infectious mononucleosis, it can also manifest with hepatic involvement, particularly in adolescents and young adults, often presenting as a mild, self-limiting hepatitis.
Epidemiology:
EBV is ubiquitous, with seroprevalence exceeding 90% in adult populations worldwide
In adolescents, primary EBV infection can lead to symptomatic infectious mononucleosis, with hepatic involvement occurring in approximately 2-10% of symptomatic cases
Peak incidence of symptomatic EBV infection is observed in adolescence and young adulthood.
Clinical Significance:
Understanding EBV hepatitis is crucial for pediatricians and residents preparing for DNB and NEET SS examinations as it forms a significant differential diagnosis for acute hepatitis in adolescents
Misdiagnosis can lead to unnecessary investigations or delayed recognition of other causes of hepatitis
Prompt and accurate diagnosis ensures appropriate supportive care and management.
Clinical Presentation
Symptoms:
Fever, which may be prolonged
Sore throat, often severe and exudative
Generalized malaise and fatigue
Loss of appetite
Nausea or vomiting
Abdominal pain, particularly in the right upper quadrant
Jaundice, manifesting as yellowing of the skin and sclera
Headache
Rash, particularly in those treated with ampicillin or amoxicillin.
Signs:
Hepatomegaly, often tender
Splenomegaly, present in up to 50% of cases
Posterior cervical lymphadenopathy, a hallmark of infectious mononucleosis
Pharyngeal erythema and exudates
Scleral icterus
Palpable liver edge extending below the costal margin
Possible signs of hepatic decompensation in severe, rare cases (e.g., ascites, encephalopathy).
Diagnostic Criteria:
While specific criteria for EBV hepatitis are not formally established, a diagnosis is typically made based on a constellation of clinical findings suggestive of infectious mononucleosis with evidence of hepatic dysfunction, supported by serological confirmation of recent EBV infection
The presence of atypical lymphocytes on peripheral blood smear further supports the diagnosis.
Diagnostic Approach
History Taking:
Detailed history of fever, pharyngitis, and lymphadenopathy
Onset and duration of symptoms
Recent exposure to individuals with infectious mononucleosis
Travel history
Use of medications, particularly antibiotics like ampicillin or amoxicillin
History of jaundice or recent viral illnesses
Assessment of hydration status and nutritional intake.
Physical Examination:
Thorough examination of the oropharynx for exudates and erythema
Palpation of cervical, axillary, and inguinal lymph nodes
Assessment for splenomegaly by percussion and palpation
Palpation of the abdomen for hepatomegaly and tenderness
Examination for jaundice, rash, and any signs of dehydration or distress.
Investigations:
Complete blood count (CBC) with differential: typically shows lymphocytosis with a significant proportion of atypical lymphocytes ( Downey cells)
Liver function tests (LFTs): Elevated transaminases (ALT and AST), usually two to three times the upper limit of normal, with fluctuating bilirubin levels and mild elevation of alkaline phosphatase
Serological tests for EBV: Heterophile antibody test (Monospot test) is useful for rapid diagnosis in adolescents but may be negative in younger children or early in the illness
EBV-specific antibodies (IgM and IgG to viral capsid antigen (VCA), and EBNA antibodies) are more definitive for confirming primary infection and timing
Viral DNA by PCR can be used in specific situations
Other tests to rule out other causes of hepatitis: Hepatitis A, B, and C serology
autoantibodies for autoimmune hepatitis
and toxicology screen if indicated.
Differential Diagnosis:
Acute viral hepatitis (Hepatitis A, B, E)
Other viral infections causing hepatitis (e.g., CMV, adenovirus)
Drug-induced liver injury
Autoimmune hepatitis
Wilson's disease
Biliary atresia (in younger infants, less likely in adolescents)
Malaria (if endemic)
Typhoid fever.
Management
Initial Management:
Primarily supportive care
Adequate rest is essential
Hydration is crucial, especially if there is anorexia, nausea, or vomiting
Nutritional support should be provided, focusing on easily digestible foods.
Medical Management:
There is no specific antiviral therapy for EBV hepatitis in immunocompetent adolescents
Management is symptomatic and supportive
Antipyretics (e.g., paracetamol, ibuprofen) for fever and pain
Avoidance of strenuous activity, especially in the presence of splenomegaly, to prevent splenic rupture
Corticosteroids are generally not recommended for uncomplicated EBV hepatitis but may be considered in rare, severe cases of hepatic or hematologic complications, under specialist guidance.
Surgical Management:
Surgery is not indicated for EBV hepatitis
Splenectomy is rarely performed only in cases of life-threatening splenic rupture, which is an extreme complication.
Supportive Care:
Monitoring of liver function tests and clinical status
Close observation for any signs of hepatic decompensation
Ensuring adequate fluid intake and nutrition
Education for the patient and family regarding the self-limiting nature of the illness and the importance of rest and avoiding high-risk activities.
Complications
Early Complications:
Splenic rupture, although rare, is the most feared acute complication and can be life-threatening, often occurring during the second or third week of illness
Fulminant hepatic failure is exceedingly rare
Neurological complications such as encephalitis or meningitis can occur
Hematological complications like autoimmune hemolytic anemia or thrombocytopenia.
Late Complications:
Chronic EBV infection is generally not associated with chronic liver disease in immunocompetent individuals
However, in immunocompromised patients, EBV can be associated with lymphoproliferative disorders
Post-viral fatigue syndrome can occasionally persist.
Prevention Strategies:
Prevention of EBV infection is challenging due to its widespread prevalence and transmission routes
Good hygiene practices (e.g., avoiding sharing utensils, cups, and toothbrushes) can reduce transmission
No vaccine is currently available.
Prognosis
Factors Affecting Prognosis:
The prognosis for EBV hepatitis in immunocompetent adolescents is generally excellent
Most cases resolve completely within weeks to a few months
Factors that may influence recovery include the severity of initial symptoms and the presence of complications
Immunocompromised status significantly worsens prognosis.
Outcomes:
The majority of adolescents with EBV hepatitis recover fully with no long-term sequelae
Complete resolution of hepatic inflammation is expected
Transient elevations in liver enzymes may persist for several weeks post-symptomatically
In very rare instances, severe hepatitis or hepatic failure can occur, leading to poorer outcomes.
Follow Up:
Follow-up is typically not required for uncomplicated EBV hepatitis
However, in cases with significant hepatic dysfunction or complications, periodic monitoring of LFTs may be advised until normalization
Patients should be advised to report any recurrence of symptoms or new symptoms to their physician.
Key Points
Exam Focus:
Recognize EBV hepatitis as a common cause of acute hepatitis in adolescents, often associated with infectious mononucleosis
Differentiate from other causes of hepatitis
Understand the typical LFT pattern: elevated transaminases, fluctuating bilirubin
Recall the diagnostic significance of atypical lymphocytes on peripheral smear and EBV serology
Know that management is primarily supportive.
Clinical Pearls:
Always consider EBV in the differential diagnosis of acute hepatitis in adolescents, especially when accompanied by fever, sore throat, and lymphadenopathy
Educate patients about the importance of avoiding contact sports and strenuous activity due to the risk of splenic rupture, especially during the acute phase of infectious mononucleosis.
Common Mistakes:
Overlooking EBV as a cause of hepatitis and focusing solely on Hepatitis A, B, or E
Initiating unnecessary antiviral therapies
Prescribing antibiotics like amoxicillin or ampicillin to patients with suspected mononucleosis, which can lead to a characteristic rash
Failing to advise on activity restrictions, increasing the risk of splenic rupture.