Comparison of different immunoprophylaxis regimens after liver transplantation with hepatitis B core antibody-positive donors: A systematic review

Abstract

Orthotopic liver transplantation (OLT) recipients without hepatitis B virus (HBV) infection who receive liver grafts from antibody to hepatitis B core antigen-positive [HBcAb(þ)], hepatitis B surface antigen-negative [HBsAg(À)] donors have an increased risk of developing de novo hepatitis B infection. We compared the 2 most commonly employed prophylactic regimens-lamivudine (LAM) monotherapy and hepatitis B immunoglobulin (HBIG)þLAM combination therapy-to determine the relative efficacies of these 2 protocols in preventing de novo hepatitis B infection. A comprehensive search of the Cochrane Database of Systematic Reviews, MEDLINE (1966 to June 2009), and bibliographies of retrieved trials was conducted. Eligible studies included OLT recipients who received HBcAb(þ) liver grafts and were treated prophylactically with either LAM monotherapy or HBIGþLAM combination therapy. 13 studies were identified as meeting the eligibility criteria. The rates of de novo hepatitis B infection, mortality, and mortality due to de novo hepatitis B infection were assessed. The incidence of de novo hepatitis B infection was 2.7% (n ¼ 73) in patients receiving LAM-only prophylaxis versus 3.6% (n ¼ 110) in patients receiving HBIGþLAM combination therapy. In the HBIGþLAM group, the dose and duration of HBIG therapy were highly variable. The median follow-up time for the LAM monotherapy group was 25.4 months with a range of 14.78 to 27.6 months, whereas the median follow-up time for the LAMþHBIG group was 31.1 months with a range of 15.3 to 38.5 months. The risk of developing de novo hepatitis B infection based on the pretransplant recipient HBV serology in each treatment group could not be calculated because of incomplete data and the limited number of de novo hepatitis B infection cases in the series reviewed. In conclusion, on the basis of these findings, we conclude that published studies have not shown HBIGþLAM combination therapy to be more effective than LAM-only treatment. Nucleoside analogue monotherapy should therefore be considered when one is treating HBV(À) patients who have received liver allografts from HBcAb(þ) donors. Liver Transpl 16:300-307,

Natural history of hepatitis B virus infection: pediatric perspective

“…It is also very important to utilize prophylaxis regimens to prevent the reactivation of HBV infection in patients who receive organ transplants, especially due to HBV-related liver diseases [67]. Nowadays, pediatric liver transplantation is mainly indicated for biliary atresia, metabolic diseases, genetic diseases, and so on [68].…”

Impfen und prophylaktisches Infektionsmanagement

“…Das Risiko nimmt zu, wenn der Spender HBsAg-("hepatitis B surface antigen") oder sogar HBeAg-positiv (HBeAg: "hepatitis B envelope antigen") ist. Entschließt man sich trotzdem zur Transplantation, sollte der Empfänger mit Lamivudin prophylaktisch behandelt werden [14].…”

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers

“…9 2 years Chang [37] HBIG 100 IU/Kg IV intraoperatively and then daily 9 3 days, followed by booster to maintain anti-HBs [20 IU/L plus vaccination based on anti-HBs titer Fabrega [38] HBIG 10,000 IU IV during anhepatic phase and then daily 9 7 days plus LAM 100 mg daily ¥ Nery [29] HBIG 10,000 IU IV intraoperatively and then daily 9 7 days, weekly 9 1 month, and monthly 9 6 months and/or LAM 150 mg daily lifelong } Lee [15] HBIG (100 IU/Kg for children and 10,000 IU for adults) IV daily 9 7 days, followed by booster to maintain antiHBs [ 200 IU/L Suehiro [39] HBIG 10,000 IU IV during anhepatic phase and then 2,000 IU IV daily 9 7 days, followed by 2,000 IU IV every 2 months to maintain anti-HBs [ 100 IU/L plus LAM 100 mg daily Donataccio [24] HBIG 10,000 IU IV during anhepatic phase and then daily that current available studies do not support prophylactic use of the combination therapy over LAM monotherapy in HBV DNA negative patients receiving anti-HBcpositive liver grafts. LAM monotherapy has the same efficacy as the combination therapy at far less cost [47,48]. However, drug-resistance HBV mutants have been reported as the cause of DNH in a case after being on LAM for more than 3 years [42].…”

“…These findings argue that HBIG may be a dispensable part of prophylaxis. In a recent systemic review, Saab et al [47] reported the incidence of DNH was 2.7% in patients receiving LAM-only prophylaxis versus 3.6% in those receiving HBIG plus LAM combination therapy. In another systemic review, Cholongitas reported that DNH rates were 19, 2.6, and 2.8% in HBsAg-negative recipients under HBIG, LAM, and their combination, respectively.…”

“…However, drug-resistance HBV mutants have been reported as the cause of DNH in a case after being on LAM for more than 3 years [42]. To overcome this potential problem, nucleos(t)ide analogs with a high barrier of developing drug resistance is preferred either as a monotherapy or in combination with LAM, but without HBIG, for prophylaxis of DNH [47]. There is no study published to date comparing LAM monotherapy with other nucleos(t)ide analogs, either as monotherapy or in combination with LAM, in prevention of DNH.…”