HSV Hepatitis in an immunocompetent female: do the non-fulminant cases go undiagnosed?

Elevated transaminases are commonly encountered in clinical practice, and have a broad differential that includes viral illnesses. While HSV-2 is a ubiquitous virus that is known to cause fulminant hepatic presentations in the immunocompromised, it is not commonly reported as a cause of mild symptomatic transaminitis in the immunocompetent host. A 32-year-old female without significant medical history presented to the emergency department with one day of nausea, vomiting and moderately severe right upper quadrant abdominal pain which worsened with fatty food intake. On examination she did not have any mucocutaneous lesions and a benign abdomen except for a tender liver edge. Laboratory tests revealed AST of 54 IU/L ALT of 110 IU/L with a normal alkaline phosphatase, bilirubin, albumin, PT/INR and leukocyte count. An abdominal ultrasound and computerized tomography of the abdomen/pelvis were unremarkable. An esophagogastroduodenoscopy was performed which was unrevealing. Hepatobiliary iminodiacetic acid scan showed delayed visualization of tracer in the small bowel, prompting laparoscopic cholecystectomy for suspected biliary dyskinesia. During laparoscopy, extensive miliary lesions of the right and left lobes of the liver were visualized on gross inspection of the liver, varying in size from a few millimeters to about a centimeter (figure 1). The biopsy showed patchy areas of hepatocyte necrosis, microabscesses, with a mixed inflammatory infiltrate. Several hepatocytes within areas of necrosis revealed characteristic intranuclear ground glass inclusions (figure 2) that stained strongly positive with confirmatory HSV immunostains (figure 3). The patient\u27s serology was positive for IgG against HSV 2, but negative against HSV. She and her husband denied any prior history of symptomatic oral or genital herpes. A Pap smear was negative for any evidence of genital herpes infection. HIV screening was negative. She was treated with valacyclovir for 2 months after which she underwent a laparoscopic tubal ligation which incidentally noted significantly improved liver surface. On her follow-up visit after 4 months, she reported improvement of the abdominal pain with normalization of her hepatic panel. While HSV Hepatitis is often reported as a fulminant hepatic failure in the immunocompromised host with high mortality, this case demonstrates that there may be milder cases that go undiagnosed in immunocompetent individuals. In light of the very high prevalence of exposure of this virus, physicians should consider HSV as a potential cause of acute, symptomatic transaminitis, even in those without classic immunosuppressive risks (steroid use, pregnancy, transplant recipients)