Development of antibody to hepatitis B surface antigen after liver transplantation for chronic hepatitis B

Abstract

Patients with chronic hepatitis B virus (HBV) infection have a defective HBV-specific immune response, and the spontaneous development of antibody against hepatitis B surface antigen (anti-HBs) after liver transplantation has not been observed. We report the spontaneous production of anti-HBs in 21 of 50 (42%) patients receiving lamivudine monoprophylaxis after liver transplantation. Seroconversion to anti-HBs status (>10 mIU/mL) was found at a median of 8 days (range, 1 to 43 days) after transplantation. In each case, serial serum samples showed a >100% increase in antibody titer as compared with that of day 7 after transplantation in the absence of any blood product transfusion. The anti-HBs titer increased to a maximum within 3 months, and the peak titer was <100 mIU/mL in 10 patients, 100 to 1000 mIU/mL in 5 patients, and >1,000 mIU/mL in 6 patients. In 12 patients, anti-HBs disappeared from serum at a median of 201 days (range, 24 to 414 days), whereas the other 9 patients remained positive for anti-HBs at a median of 221 days (range, 94 to 1,025 days) after transplantation. Patients in whom anti-HBs in serum developed had a more rapid clearance of serum hepatitis B surface antigen (HBsAg) (log rank test, P ‫؍‬ .011). Using logistic regression analysis, the only predictor of anti-HBs production was an HBV-immune donor (odds ratio, 18.9; 95% confidence interval, 3.2 to 112.4; P ‫؍‬ .001). In conclusion, patients who undergo liver transplantation for chronic hepatitis B using lamivudine prophylaxis may develop anti-HBs spontaneously. The antibody is likely to be of donor origin, suggesting the possibility of adoptive immunity transfer through a liver graft. L iver transplantation in patients who are chronic carriers of hepatitis B surface antigen (HBsAg) is associated with a high risk of graft reinfection that rapidly progresses to graft failure. 1 Polyclonal hepatitis B immunoglobulin (HBIg) is an effective form of prophylaxis that has been widely adopted. [2][3][4] More recently, the advent of nucleoside analog reverse transcriptase inhibitor, such as lamivudine, which inhibits hepatitis B virus (HBV) replication, has provided an alternative approach. 5 As a result of a significant rate of failure with single-agent prophylaxis with either HBIg or lamivudine, 2,6,7 combination therapy using both HBIg and lamivudine is increasingly regarded as the most effective approach. [8][9][10][11] Nevertheless, both forms of prophylaxis, either alone or in combination, do not completely eradicate the virus, but keep the viral load at a level low enough to prevent clinical disease. 5,7,12 Therefore, there is potentially an indefinite risk of graft infection on discontinuation of the prophylaxis unless the host can resume an adequate immune response.The development of antibody against hepatitis B surface antigen (anti-HBs) has been shown to be important in protecting against HBV infection. In patients with acute HBV infection, seroconversion to anti-HBs status is associated with complete recovery and lifelong immunity. 13...

Living donor liver transplantation for hepatitis B cirrhosis

“…Lamivudine therapy was discontinued 1 year after DLT, maintaining HBIG prophylaxis. However, their protocol seems exceptional, and indefinite lamivudine use 3,4,[22][23][24] after DLT is now in trend. In a recent study, 3 47 patients underwent DLT and were administered lamivudine indefinitely.…”

Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients

“…Several clinical studies have demonstrated that in chronic HBV-infected patients receiving liver transplantation, the adoptive HBV humoral immunity from donors potentially clears the residual virus and protects the liver graft from HBV reinfection. [6][7][8][9] In lymphoma patients with HBV infection, treatment with rituximab (a chimeric mouse human monoclonal antibody (mAb) against CD20 that induces profound and durable B-cell depletion) significantly increases HBV reactivation. [10][11][12][13] Indeed, antiHBsAg antibodies (HBsAb) can neutralize circulating HBsAg and clear infectious HBV particles in vivo, and the presence of HBsAb in serum is considered an indicator of the resolution of chronic HBV infection.…”

HBsAg Seroclearance in Chinese Patients Receiving Lamivudine Therapy for Chronic Hepatitis B Virus Infection

“…However, HBsAg seroclearance in Chinese nontransplant patients receiving lamivudine has never been described. HBsAg seroclearance in Chinese patients receiving lamivudine has been reported only for patients with either bone marrow or liver transplantation (5,7,8). In these patients, the HBsAg seroclearance is most likely not related to lamivudine but due to adoptive immunity transfer from the donors (5,7,8).…”