Donor Derived Hsv Hepatitis In A Kidney Transplant Patient

INTRODUCTION: It is estimated that worldwide 66% of the population is infected with herpes simplex virus type 1 (HSV-1). Despite its commonality, liver manifestations are particularly infrequent, and in most cases can lead to fulminant liver disease. In especially rare cases the infection has been reported as being donor-derived after a solid organ transplant leading to HSV hepatitis as shown in this case. CASE DESCRIPTION/METHODS: Forty-three-year-old male with end-stage renal disease presented 10 days after undergoing a deceased donor kidney transplant with a fever of 102.4ºF and diarrhea over 3 days. Initial labs show a WBC of 13 × 10^3 uL, INR of 1.9, total bilirubin 1.2 mg/dL, alkaline phosphatase 127 IU/L, alanine aminotransferase (ALT) > 5000 IU/L, aspartate aminotransferase (AST) 6,788 IU/L. He previously had no known liver disease. Empiric antibiotics were started with cefepime and vancomycin and with suspicion for HSV hepatitis, acyclovir 750mg every 8 hours. In the pre-transplant workup 6 months prior, the HSV 1 and 2 PCR, Hepatitis A, B and C panel were all negative. His medication list included levofloxacin, allopurinol and atorvastatin. Immunosuppression was tacrolimus 4mg twice daily, mycophenolic acid 1 gm twice daily and prednisone 20mg twice daily. The liver enzymes peaked at ALT > 5000 IU/L and AST > 10,000 IU/L and INR of 3.2 after 24 hours. He had no signs of encephalopathy and/or metabolic acidosis and repeat serology Hepatitis A, B, C were negative. Viral loads for HBV DNA, HCV RNA, EBV and CMV were all undetectable. HSV 1 PCR serum was not detected however HSV 2 PCR serum was > 1.0 × 10^8 copies/ mL. Later, a trans-jugular liver biopsy confirmed the diagnosis showing sub-massive hepatic necrosis with HSV. Necrosis involved 60-70% of hepatocytes and immunostain for HSV was strongly positive in necrotic areas. After 11 days of treatment with acyclovir 750mg every 8 hours his labs improved with an INR of 1.2, ALT 325 IU/L, AST 46 IU/L. HSV 2 PCR viral load trended down to 70,070 copies/mL. He remained asymptomatic and was eventually discharged home. DISCUSSION: Although rare, HSV hepatitis is a life threatening disease that we see in 75% of cases lead to liver transplantation or death. Early identification and treatment is particularly important since serology is unreliable and cutaneous lesions only occur in about 30% of cases. Without therapy one report shows in donor derived disease transmission mortality is 100%. In this clinical scenario with high suspicion, treatment can never be delayed.Figure 1.: This graph shows 8 days prior to presentation normal LFTs. Upon admission LFTs are elevated and is the day treatment began. Over time we see the gradual improvement while on treatment.