Recurrence-Free Long-Term Survival After Liver Transplantation for Hepatitis B Using Interferon-Alpha Pretransplant and Hepatitis B Immune Globulin Posttransplant

Abstract

ObjectiveThe authors determined whether pretransplant reduction of hepatitis B virus (HBV) load using alpha-interferon-2b (IFN) and passive immunoprophylaxis using hepatitis B immunoglobulin (HBIg) posttransplantation can prevent HBV recurrence in patients undergoing liver transplantation (LT) for HBV cirrhosis. Summary Background DataLiver transplantation in patients with HBV cirrhosis is associated with a high rate of recurrence and reduced survival. In patients with evidence of replicating virus (HBV-DNA or hepatitis B e antigen [HBeAg]-positive serum or both), recurrence is nearly universal. Passive immunoprophylaxis with HBIg alone is not effective in preventing HBV recurrence posttransplant, especially in patients with evidence of active viral replication pretransplant. Higher doses of HBIg posttransplant has reduced recurrence rates to 30% to 50%.Lamivudine, a nucleoside analogue that has shown early promise, also is associated with significant HBV recurrence. The authors report a reliable method of preventing viral recurrence in patients even with evidence for active HBV replication pretransplant. MethodsPretransplant patients with evidence of replicating HBV were given IFN starting at 1 million IU 3 times per week subcutaneously. This dose was increased to 2 and then 3 million IU 3 times per week when patient's side effects permitted and was maintained until the patient underwent a LT. All patients were tested every 4 weeks for hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA. When patients became negative for HBeAg and HBV-DNA, they were listed for LT. Patients that were only HBsAg positive were listed immediately and received a LT without prior IFN treatment. Post-LT, all patients began receiving HBIg 2000 IU (10 mL) daily from days 1 to 20 and then weekly for the first 2 356

Assessing virologic efficacy of combination lamivudine and low-dose hepatitis B immune globulin posttransplantation with the ultrasensitive digene hybrid capture II assay

“…Our experience, as well as the experience of other centers, 2,3 continues to support the effectiveness of low-dose HBIG (in contrast to the standard high-dose protocol) in combination with lamivudine. Letters to the Editors…”

Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin

“…We found that even with reduced maintenance dosing of HBIG, our patients were subsequently able to achieve their target threshold serum titers of HBIG. This finding is supported by the experience of German investigators 26 who reported that crossing over to intramuscular HBIG injec- The feasibility of a low-dose induction protocol of intramuscular HBIG has also been suggested by the Montreal group, 27 which administered 2000 IU of HBIG. Our center' s protocol differs from that of our Canadian colleagues in the total dose of HBIG.…”

“…Our experience in this regard has also been confirmed by the Montreal group. 27 In conclusion, we found a combination lamivudine-low-dose HBIG protocol has been effective in the prophylaxis of allograft reinfection. Whether our patients will continue to remain free of recurrent HBV infection in the long term, a condition that hinges on the possible development of mutated strains of HBV resistant to both agents, remains to be seen.…”

Fulminant hepatitis B following bone marrow transplantation in an HBsAg-negative, HBsAb-positive recipient; reactivation of dormant virus during the immunosuppressive period

“…HB specific immunoglobulin infusions may be effective. 7,11 When active hepatitis does occur, ganciclovir or lamivudine may be effective. 12 Lamivudine inhibits the reverse transcriptase step in HBV replication.…”