1. Acute hepatitis of uncertain cause, rule out EBV related
Chapter 2
Viral Hepatitis 1
Acute hepatitis of uncertain cause, rule out EBV related
Case 2.14

2. Clinical Presentation2
Viral Hepatitis 2
Clinical Presentation
An 18-year-old woman presented with nausea, vomiting, and increased abdominal girth.
There was no past medical history of hepatitis, use of acetaminophen, illicit drug use, or alcohol intake.
Ultrasound showed a normal liver, gallbladder, and biliary system.

3. Laboratory Values Course in Hospital AST: 420 ALT: 540 Alk Phos: 224
Viral Hepatitis 3
Laboratory Values
AST: 420
ALT: 540
Alk Phos: 224
Total Bilirubin: 1.2
Total Protein: 7.0
Albumin: 3.5
Serologies:
Anti-HAV, HBsAg, anti-HCV, ANA, SMA: Negative
Course in Hospital
The etiology of the hepatitis was uncertain
and a liver biopsy was performed.

4. 2
Viral Hepatitis 4
Pathology
The portal tracts were expanded by a prominent lymphocytic infiltrate, some of these cells having irregular nuclear contours (a, b).
Figure 2.14(a)
Figure 2.14(b)

5. 2
Viral Hepatitis 5
Pathology
The parenchyma exhibited mild necroinflammatory change and sinusoidal lymphocytosis (c).
Some of the terminal hepatic venules showed lymphocytes attaching to and infiltrating beneath the endothelium (“endothelialitis”) (d).
Figure 2.14(c)
Figure 2.14(d)

6. Diagnosis Acute hepatitis of uncertain cause2
Viral Hepatitis 6
Diagnosis
Acute hepatitis of uncertain cause
Note: In conjunction with the negative viral and autoimmune hepatitis serologies, the histologic features are suggestive of possible acute Epstein-Barr virus (EBV)-related hepatitis

7. 2
Viral Hepatitis 7
Comment
In young otherwise healthy individuals who present with a hepatitis reaction, who have no risk factors for acquiring typical viral hepatitis, are on no medications, and are negative for viral and autoimmune serologies, acute hepatitis secondary to EBV or CMV are leading possibilities.
Both show portal lymphocytic infiltrates and sinusoidal lymphocytosis, the lymphocytes often having irregular nuclear contours with occasional prominent nucleoli and scanty to moderate cytoplasm (“atypical“ lymphocytes).
Also endothelial inflammation of portal and/or terminal hepatic venules by lymphocytes (“endothelialitis”) is also a feature sometimes seen in EBV-associated acute hepatitis, as present in this biopsy specimen.
Both EBV and CMV can also show small lobular granulomas.

8. 2
Viral Hepatitis 8
Comment
Serologies are very useful in making the appropriate diagnosis, although in this case example the results for EBV workup were not available in followup.
Staining for EBV in lymphocytes via the EBER-1 (Epstein-Barr-encoded RNA) probe can also aid in the diagnosis of acute EBV hepatitis; additionally identifying CMV inclusions by immunoperoxidase stain is also useful for CMV-induced hepatitis, although usually the stain is negative in known infection in the immunocompetent patients.
EBV- and CMV-induced hepatitis are limiting disorders with resolution, with fulminant EBV hepatitis known but quite rare; however, persistent infection often occurs in immunocompromised (e.g., post-transplant) patients.