dence of active viral replication at the time of transplantation Prophylactic hepatitis B immunoglobulin (HBIg) re-(hepatitis B e antigen [HBeAg]-positive or HBV DNA-posiduces the risk of reinfection in hepatitis B surface anti-
tive by hybridization assay) seem to have the greatest risk gen (HBsAg)-positive liver transplant recipients. In the of recurrent infection. 3,4 Prophylactic hepatitis B immunomedical center of this study, high-dose HBIg immunoglobulin (HBIg) has been shown to reduce the incidence of prophylaxis is administered at a fixed dose of 10,000 IU recurrent HBV infection and improve survival in HBsAg-posmonthly, and in this study, the long-term efficacy of this itive transplant recipients. 5 Previously reported studies have treatment regimen was examined. Of 52 HBsAg-positive used target antibody to HBsAg (anti-HBs) titers to determine liver transplant recipients, 24 were administered HBIg the frequency of HBIg administration. [6][7][8][9] Using trough antiimmunoprophylaxis, and 28 were administered no spe-HBs levels of 100-300 mIU/mL, recurrent HBV infection has cific therapy; the 2-year recurrence rates (defined by the reappearance of HBsAg) were 19% and 76%, respectively. developed in 10%-50% of patients, and rates of reinfection Fifty-four percent of the HBIg-treated patients were posmay be as high as 80% in patients with indices of active viral itive for HBeAg or hepatitis B virus (HBV) DNA (by hyreplication pretransplantation. 3,[6][7][8][9] The optimal schedule of bridization assay) pretransplantation. In patients ad-HBIg administration is yet to be defined, and the long-term ministered monthly HBIg, intrapatient and interpatient consequences of HBIg administration are unknown.
variability in trough antibody to HBsAg (anti-HBs) titer
The HBIg protocol used at our institution provides intravewas significant, highlighting the potential difficulties of nous HBIg daily during the first week posttransplantation using anti-HBs titer to guide therapy. Trough anti-HBs and then on a fixed schedule of 10,000 IU monthly until titers were less in patients who became HBsAg positive recurrence of infection is documented. This regimen offers than in patients who remained HBsAg-negative (490 vs. the advantage of ease of administration and monitoring. This 1290 mIU/mL) (P Γ
.0001), reflecting either the cause or study focuses on the long-term efficacy and safety of this effect of HBV reinfection. Of 9 patients who remained treatment protocol and seeks to define appropriate treatment HBsAg-negative and who were administered monthly end points.
HBIg for at least 1 year, HBV DNA by polymerase chain reaction amplification was detectable in
the sera of 67%, PATIENTS AND METHODS the lymphocytes of 50%, and the liver of 57%. In conclusion, a fixed monthly dose of HBIg reduces the recur-Patients rence of HBs antigenemia, even in patients with indices Fifty-eight transplantations were performed in 55 HBsAg-positive of active viral replication pretransplantation. The prespatients at the University of California at San Francisco between ence of residual virus in the majority of patients admin-October 1988 and June 1995. Six transplantations that were peristered HBIg suggests that long-term HBIg administraformed using prophylactic treatment with ribavirin were excluded tion may be necessary. (HEPATOLOGY 1996;24:1327-1333.) from the analysis. One patient was treated with prophylactic ribavi- rin therapy with the first transplantation and prophylactic HBIg
In patients undergoing liver transplantation for hepatitis therapy with the second transplantation; data from the second trans- plantation were included in the analysis. Three patients with HBV B virus (HBV) infection, recurrent disease is common in the infection underwent retransplantation for recurrent HBV disease.
absence of immunoprophylaxis and leads to reduced graft and All patients had HBsAg detectable in the serum at the time of transpatient survival compared with hepatitis B surface antigen plantation. Patients with fulminant hepatitis and chronic end-stage (HBsAg)-negative transplant recipients. 1,2 Patients with evicirrhosis were included. The following were obtained for each patient: 1) clinical data including date, age, and diagnosis at transplantation; gender; use of HBV prophylaxis; time of retransplantation; time to recurrence of HBV infection; and duration of survival and cause of Abbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBIg, hepatitis B immunoglobulin; anti-HBs, antibody to hepatitis death; and 2) serological and virological data including pretrans-B surface antigen; anti-HDV, antibody to hepatitis delta virus; HDV, hepatitis delta virus; plantation HBsAg, HBeAg, antibody to hepatitis B core antigen imanti-HCV, antibody to hepatitis C virus; HCV, hepatitis C virus; PCR, polymerase chain munoglobulins M and G, antibody to hepatitis delta virus (antireaction; HBcAg, hepatitis B core antigen.
HDV), hepatitis delta virus (HDV) RNA, and HBV DNA in serum;