Disseminated Adenovirus Infection in an Adult Orthotopic Liver Transplant Recipient

Abstract

Adenovirus infections in liver transplant patients are important cause or morbidity and mortality. Our understanding of the adenovirus pathogenesis and management approach are limited. We present a rare case of self resolving disseminated adenovirus infection in a liver transplant recipient. A 60-year-old male with a history of orthotopic liver transplant 2010 for alcoholic cirrhosis and RNY hepaticojejunostomy 2011 for anastomotic stricture on cyclosporine 175 mg daily presented with fatigue, severe headache, bilateral eye pain with redness and light sensitivity for 3 weeks and fevers up to 104 F for one week. On examination left eye was swollen shut and painful to touch with minor dried blood on outside. Laboratory findings on admission were notable for ALP of 514, AST/ALT 206/237, total bilirubin 1.2, lipase 1674, amylase 201, APAP level < 2.0. Routine blood and urine cultures, serum CMV PCR, and serum cryptococcal antigen were negative. Nasopharyngeal respiratory virus panel was positive for adenovirus PCR but CXR did not show pneumonitis. Serum adenovirus PCR was strongly positive at 347014 copies/ml. Ophthalmology recommended supportive care for his acute hemorrhagic conjunctivitis likely from adenovirus. MRCP was performed and ruled out choledocholithiasis, biliary dilation, biloma or abscess of transplant liver. Since the patient did not have abdominal symptoms and his conjunctivitis improved, it was decided to manage the patient conservatively without using potentially toxic cidofovir. He was discharged 3 days later. Follow up serum adenovirus PCR showed decreasing viral load. Disseminated adenovirus infection is defined as documented disease in >= end organs and viremia is present in most but not all patients. Manifestations include hepatitis, pneumonia, pancreatitis, enterocolitis, hemorrhagic cystitis and nephritis. A high degree of clinical suspicion should be maintained for prompt diagnosis as standard diagnostic tests like blood and urine cultures do not yield adenovirus. Positive PCR (in serum or other body fluids or tissue) may suggest invasive disease in the appropriate context. Serial quantitative serum viral load is used for preemptive treatment in high risk allogeneic hematopoetic cell transplant recipients and also acts as a surrogate for clinical response to therapy. We believe that our patient probably had tissue invasive hepatitis, pancreatitis and conjunctivitis with an upper respiratory infection (without pneumonitis) along with significant adenoviremia. Interestingly, despite disseminated tissue invasive disease, the patient recovered without specific adenoviral therapy. There is no well-defined treatment for adenovirus infection. Management from limited clinical information for disseminated infections supports use of cidofovir. Unfortunately it is fraught with nephrotoxicity. A novel lipid formulation of cidofovir (brincidofovir) offers some hope as it seems to be kidney friendly. There are no good data on ribavirin and immunoglobulins, but adenovirus specific T cell therapy has occasionally been used successfully in recalcitrant disease. Our case illustrates that although disseminated adenovirus infection can be life threatening and has limited effective treatment options, it can occasionally resolve spontaneously.