HBIg-Induced Transient Hepatitis B Core Antibody in Liver Transplant Recipient: Misleading Serology Testing?

Abstract

Introduction: The rate of HBV transmission in liver transplantation from donors with positive Hepatitis B core Antibodies is reported to be higher in liver transplants when compared to other solid organ transplants due to the fact that HBV resides in donor hepatocytes. The administration of hepatitis B immune globulins (HBIg) and effective antiviral therapy has been successful in reducing the rate of is transmission. In this case, we describe a patient who received a deceased donor liver transplant from an HBcAb positive donor and developed a transient seropositive HBcAb from HBIg administration. Case Presentation: A 61-year-old woman with a history of end-stage liver disease secondary to hepatitis C genotype 1a liver cirrhosis who underwent a deceased donor orthotopicliver transplant on August 7th,2015. HCV viral PCR on August 13th, 2015 was 54,787 IU/mL. She was treated with simeprevir plus sofosbuvir for 12 weeks with sustained viral response. RepeatHCV viral PCRs in October and November 2015 as well as February2016 were all undetectable. Patient's donor serology was noted to have negative Hepatitis B Surface Antigen (HBsAg) and a positive HBcAb total but and a negative HBcAbIgM while HBV PCR, and HCV PCR were both negative. The transplant procedure was uneventful. The recipient received a single dose of 10,000 units of HBIg intravenously during the hospitalization per protocol and was continued on entecavir 0.5 mg daily.Of note, she was immunized with hepatitis B vaccine series (total 3 doses) and acquired immunity to Hepatitis B in March 2013 but lost her immunity to hepatitis B in February 2015 prior liver transplant. Upon follow up in transplant infectious disease clinic 1 month following her liver transplant, she was doing well. Interestingly enough, hepatitis B serology during that time showed positive HBsAb and HBcAb testsand negative HBsAg and HBV DNA. We continued to monitor recipient hepatitis B serology (table1) and found that her HBcAb which was positive became negative 9 months after the transplant and her HBsAb which was positive became negative after 9 months following the transplant despite after receiving a hepatitis B booster dose in December 2015. In our patient, she was initially non-immune to hepatitis B and received HBIg plue entecavir after the transplant. A recent study of 80 consecutive patients with chronic HBV undergoing liver transplantation on an HBIg-free regimen of entecavir monotherapy found a 91% loss of HBsAg and 98.8% achievement of serum HBV DNA clearance over a median follow-up time of 26 months post orthotopic liver transplant makes the role of HBIg diminish. HBIg is a polyclonal purified preparation of human anti-HBs (hepatitis B surface antibody) derived from pooled plasma and has maximum benefit during the first 6-12 months after the transplant when recipients were receiving intense immunosuppressant. In our patient, she initially was non-immune toHBV and then her HBcAb became positive, however HBV DNA was negative and HBsAb was positive for the first 6-7 months after the transplant. HBsAb seropositive may be explained by passive immunity from HBIg which can last long for 6-12 months.Figure 1