Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation - possible role of mutations in the YMDD motif prior to transplantation as a risk factor for reinfection

Background/Aims: Reinfection with hepatitis B virus (HBV) after liver trans plantation (OLT) is associated with an unfavourable clinical course. Lamivu dine/hepatitis B immune globulin (HBIG) combination treatment reduces reinf ection rates. However, it is unclear at what time point lamivudine should b e started and which HBIG doses are sufficient. Methods: Twenty-one patients receiving combination treatment,were studied. Lamivudine was started up to 16.5 months before OLT and continued thereafte r. HBIG was started intraoperatively and continued according to anti-HBs-ti ters. Median follow-up after OLT was 20 months. Results: Eleven patients received lamivudine pretreatment for >2 (median 6) months due to initial HBV-DNA-positivity (median 749 pg/ml), After initial lamivudine response HBV-DNA increased in two of them to concentrations abo ve 10 pg/ml prior to OLT. Both had developed mutations in the YMDD motif an d suffered from HBV reinfection 13 and 75 days postoperatively, Individual HBIG consumption was highly variable (range 787-4766 IU/month). Twenty-two percent of anti-HBs titers measured before HBIG administration were below 1 00 IU/I. Conclusion: Combined reinfection prophylaxis with lamivudine and HBIG is ef fective in patients with controlled viral replication at the time of OLT, H owever, pretransplantation lamivudine resistance is a risk factor for reinf ection. Low dose HBIG maintenance therapy individualized according to anti- HBs-titers appears to be tenable. (C) 2001 European Association for the Stu dy of the Liver. Published by Elsevier Science B.V. All rights reserved.