Living related liver transplantation for hepatitis B-related liver disease without hepatitis B immune globulin prophylaxis

Abstract

Hepatitis B immune globulin (HBIG) is routinely used in liver transplantation for hepatitis B virus (HBV)-related liver disease. With potent oral antivirals, HBIG may not be required. We conducted a prospective trial to evaluate living related liver transplantation (LRLT) without HBIG. Eighty-nine patients with HBV-related liver disease underwent LRLT between January 2005 and January 2012. All donors were vaccinated with the HBV vaccine. All patients were given oral antivirals for HBV before transplantation. Patients with HBV DNA levels 2000 IU/mL were not given HBIG, and patients with HBV DNA levels > 2000 IU/mL were given HBIG. Recurrence was defined as HBV DNA positivity 6 months after transplantation. Seventy-five of the 89 patients who underwent LRLT for HBV-related liver disease were not given HBIG. Nineteen patients received a combination of lamivudine and adefovir, 42 received entecavir, 12 received tenofovir, and 2 received a combination of entecavir and tenofovir. At the last follow-up (median 5 21 months, range 5 1-83 months), all patients were HBV DNA-negative. Sixty-six patients cleared hepatitis B surface antigen (HBsAg), and 19 patients formed antibody to hepatitis B surface antigen (anti-HBs). The cumulative probabilities of clearing HBsAg were 90% and 92% at 1 and 2 years after transplantation, respectively. Nine patients were HBsAg-positive with undetectable DNA at the last follow-up. The recurrence rate in our series was 8% (6/75). Five of these 6 patients had stopped taking oral antivirals, and 1 had entecavir resistance. All recurrences were salvaged with changes in the oral antivirals. The actuarial probability of survival in this cohort was 73.7% at 83 months. There was no mortality due to HBV recurrence. In conclusion, HBV prophylaxis with oral antivirals and without HBIG is safe and effective in LRLT. A majority of the patients will clear HBsAg, and some will develop anti-HBs antibodies. Patients undergoing transplantation for hepatitis B virus (HBV) cirrhosis require prophylactic antiviral therapy. The risk of HBV reinfection after liver transplantation without prophylaxis is approximately 80%, and the rate is higher for patients with high HBV DNA levels at the time of transplantation. 1,2 The current recommendation for HBV prophylaxis is a combination of a nucleoside/tide analogue and high-dose hepatitis B immune globulin (HBIG) for life. 3 Recently, low-dose HBIG in combination with lamivudine has been shown to be equally efficacious. 4 The combination of HBIG with antivirals (lamivudine and adefovir) has reduced the risk of reinfection to 10% during the first 2 years after transplantation. 5-7 However, with the advent of newer, more effective oral antivirals with lower resistance rates, the role of HBIG in the transplant setting needs to be re-evaluated. 8 There are published data on the transfer of immunity from HBV-immunized donors to recipients of liver transplantation for HBV-related indications. 9,10 Living donor liver transplantation offers a unique opportunity for vaccinating ...

Donor vaccination: Is it necessary to prevent hepatitis B virus recurrence after living donor liver transplantation?

“…As shown in this study by Wadhawan et al, 1 5 of 19 patients had undetectable anti-HBs titers 6 months after LDLT. However, the ultimate goal of the adoptive transfer of immunity to HBV to liver transplant patients may be the long-term maintenance of serum anti-HBs titers after transplantation, preferably at levels higher than 100 IU/L.…”

“…We read with great interest the report by Wadhawan et al 1 recently published in Liver Transplantation. The authors proposed that the transfer of adoptive immunity from vaccinated donors to recipients may eliminate the need for hepatitis B immune globulin after living donor liver transplantation (LDLT).…”

“…In addition, some questions regarding this study by Wadhawan et al 1 come to mind. First, what were the anti-HBs titers after vaccination for those donors receiving a double-dose vaccine?…”

Controversies Regarding the Hepatitis B Immune Globulin Prophylaxis (HBIG) for Liver Transplantation Recipients

“…The rate of recurrence after LT was 0%. Similarly, entecavir, Telbivudine monotherapy [78,[88][89][90][91] pre-and post LT resulted in 0% to 8% HBV recurrence rate (Table 2). Only one study found a relatively high rate of recurrent HBV infection (22.5%) using ENT [91] (Table 3).…”

Reply: Donor vaccination: Is it necessary to prevent HBV recurrence after living donor liver transplantation?

“…1 The ultimate proof of the engraftment of donor lymphocytes would come from bone marrow studies, which we did not perform in this trial. However, the fact that engraftment does occur is quite evident from the fact that 19 of 75 patients developed significant antibody titers.…”