Hepatitis Due to Human Herpesvirus 6 after Hematopoietic Stem Cell Transplantation

Human herpesvirus 6 type B (HHV-6B) is an important opportunistic pathogen in immunocompromised patients. Approximately 95% of adults have evidence of past infection, and HHV-6B reactivation occurs in approximately 30-80% of allogeneic hematopoietic stem cell transplantation (HCT) recipients 2-6 weeks after transplantation. HHV-6B has been associated with a variety of diseases that result in significant morbidity and mortality. We report a case of acute hepatitis likely caused by HHV-6B in a HCT recipient who was successfully treated with ganciclovir.

There are multiple reports of HHV-6B-associated hepatitis following primary HHV-6 infection and liver transplantation, but it has been well documented in only one patient after HCT. We cared for a 23-year-old man with sickle cell disease who underwent a matched related myeloablative HCT. His early post-transplant course was notable for CMV reactivation and gastrointestinal graft-versus-host disease for which he completed treatment with ganciclovir and steroids, respectively. He was admitted on D+98 for evaluation of epigastric abdominal pain.

Initial work up was largely unremarkable, but he underwent uncomplicated cholecystectomy on D+103 for persistent symptoms and ultrasonographic evidence of cholelithiasis. While recovering, new right upper quadrant tenderness, fever and transaminitis developed (Fig. 1). Extensive workup was negative except for plasma PCR for HHV-6B DNA (170,000 copies/mL) on D+108, and he was started on ganciclovir 5 mg/kg intravenously every 12 hours. Donor and patient testing for chromosomally integrated HHV-6 was negative. Liver biopsy on D+113 revealed non-specific lobular hepatitis. PCR of biopsy samples were negative for CMV, EBV, adenovirus and HHV-7 but positive for HHV-6 (180,000 copies/reaction). Transaminases peaked at AST 719 IU/mL, ALT 814 IU/mL and AP 378 IU/mL on D+112 and returned to baseline on D+122. HHV-6B viral load decreased to <5,000 copies/mL by D+115. He defervesced but had mild persistent abdominal pain at discharge. Retrospective immunohistochemical stains for multiple anti-HHV-6 antibodies localized to hepatocytes and Kupffer cells, consistent with active infection (Fig. 2).

      Determining the cause of organ dysfunction after HCT is challenging. This is the second reported case of likely HHV-6B-associated hepatitis following HCT, which may be an underappreciated cause of liver disease in this population. Prompt testing and initiation of treatment for HHV-6 after appropriate evaluation resulted in a good outcome for the patient. It is reasonable to consider treating HHV-6 in the setting of reactivation and hepatitis while diagnostic workup is underway.