RECURRENCE-FREE LONG-TERM SURVIVAL AFTER LIVER-TRANSPLANTATION FOR HEPATITIS-B USING INTERFERON-ALPHA PRETRANSPLANT AND HEPATITIS-B IMMUNE GLOBULIN POSTTRANSPLANT

Objective The authors determined whether pretransplant reduction of he patitis B virus (HBV) load using alpha-interferon-2b (IFN) and passive immunoprophylaxis using hepatitis B immunoglobulin (HBIg) posttranspl antation can prevent HBV recurrence in patients undergoing liver trans plantation (LT) for HBV cirrhosis. Summary Background Data Liver trans plantation in patients with HBV cirrhosis is associated with a high ra te of recurrence and reduced survival. In patients with evidence of re plicating virus (HBV-DNA or hepatitis B e antigen [HBeAg]-positive ser um or both), recurrence is nearly universal. Passive immunoprophylaxis with HBIg alone is not effective in preventing HBV recurrence posttra nsplant, especially in patients with evidence of active viral replicat ion pretransplant. Higher doses of HBIg posttransplant has reduced rec urrence rates to 30% to 50%. Lamivudine, a nucleoside analogue that ha s shown early promise, also is associated with significant HBV recurre nce. The authors report a reliable method of preventing viral recurren ce in patients even with evidence for active HBV replication pretransp lant. Methods Pretransplant patients with evidence of replicating HBV were given IFN starting at 1 million IU 3 times per week subcutaneousl y. 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 pa tient underwent a LT. All patients were tested every 4 weeks for hepat itis B surface antigen (HBsAg), HBeAg, and HBV-DNA, When patients beca me negative for HBeAg and HBV-DNA, they were listed for LT. Patients t hat were only HBsAg positive were listed immediately and received a LT without prior IFN treatment. Post-LT, all patients began receiving HB Ig 2000 IU (10 mL) daily from days 1 to 20 and then weekly for the fir st 2 years. After 2 years, all patients received 2000 IU (10 mL) month ly. Additional HBIg immunoprophylaxis was given during intense immunos uppression for rejection. Posttransplant serum was tested for HBsAg, H BeAg, and HBV-DNA in all patients 1 week, 1 month, and every 3 months thereafter. Liver biopsies were done at least yearly and when liver en zymes were abnormal and were always tested for HBsAg and HBcAg by immu noperoxidase. Results Thirteen patients with decompensated HBV cirrhos is were transplanted. Pretransplant, eight patients had evidence of ac tive viral replication at the initial assessment (HBeAg or HBV-DNA-pos itive serum or both). Ail eight were successfully treated with IFN (me dian duration, 24 weeks; range, 8-53) and converted to a negative stat us before transplantation. Side effects from IFN were minimal and well tolerated, except in one patient who required 6 million IU to convert to a nonreplicating status. The five patients that were only HBsAg po sitive were not treated with IFN pretransplant. After surgery, HBIg gi ven as described achieved consistently serum levels greater than 1000 IU/L. Twelve of the 13 patients are alive with normal liver function a nd without serologic evidence of HBV recurrence at a median follow-up of 32 months (range, 9-56 months). None have evidence of HBV recurrenc e as measured by serum HBsAg/HBeAg/HBV-DNA at recent follow-up. The se ra of the seven longest survivors has tested negative for HBV-DNA usin g the polymerase chain reaction method. In addition, a liver biopsy wa s obtained in six of these patients, the results of which also tested negative for HBV-DNA using polymerase chain reaction. Liver biopsy spe cimens have been negative for the presence of HBsAg and HBcAg by immun operoxidase staining in all 12 patients. Conclusion A reduction of vir al load pretransplant with IFN and posttransplant HBIg prevents recurr ence of hepatitis B and permits LT for HBV cirrhosis, even in patients with evidence of replicating virus. The IFN pretransplant was well to lerated, and the small frequent dosing of HBIg posttransplant did not cause side effects while achieving serum levels >1000 IU/L.