Long-term outcomes of persistently positive hepatitis B surface antigen after liver transplantation for chronic hepatitis B

Abstract

Background and Aims: Antiviral therapy alone without hepatitis B immune globulin (HBIG) has been shown to be effective after liver transplantation for chronic hepatitis B (CHB). However, a small proportion will have persistently positive hepatitis B surface antigen (HBsAg), of which the long-term outcome is unclear. We aim to determine the long-term outcome of recipients with persistently positive HBsAg. Method: Consecutive patients with CHB and liver transplantation from January 2003 to December 2017 were considered. All patients received HBIG-free regimen as prophylaxis with oral antiviral therapy alone. Graft survival and outcome were determined. Results: A total of 630 CHB patients were transplanted, of which 582 (92%) had over one year of follow-up and were included. Of these, 486 (84%) were male, and 250 (43%), 212 (36%), and 120 (21%) were transplanted for decompensated cirrhosis, hepatocellular carcinoma (HCC), and severe flares respectively. The median follow-up was 104 months (range, 13–199). Forty-one (7%) had persistently positive HBsAg without evidence of seroclearance, with higher rates observed in severe flares compared to cirrhosis and HCC patients (13.3% vs. 6.8% vs. 3.8% respectively, p = 0.005). The graft survival for persistently positive HBsAg was 81.9%, 76.1% and 76.1% at 5, 10, and 15 years post-transplant respectively, compared to 93.1%, 85.3% and 77.3% respectively for those patients that were not persistently positive for HBsAg (p = 0.205), as shown in the figure. There were 9 graft losses during the follow up period for persistently positive HBsAg patients, of which 4 were due to HCC recurrence, 2 from lymphoma, 2 from extra-hepatic malignancies, and 1 from sepsis. There were no cases of graft loss due to de novo HCC or reactivation of hepatitis B virus infection. At the time of last follow-up, all active patients had undetectable HBV DNA. Conclusion: Despite a persistently positive HBsAg after liver transplantation for CHB in patients receiving HBIG-free prophylaxis, there was excellent long-term graft survival, which was comparable to patients who had evidence of HBsAg loss. Importantly, there was no graft loss from de novo HCC or hepatitis B reactivation in persistently positive HBsAg patients.