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.
OBJECTIVE
Reinfection with hepatitis B virus (HBV) after liver transplantation (OLT) is associated with an unfavourable clinical course. Lamivudine/hepatitis B immune globulin (HBIG) combination treatment reduces reinfection rates. However, it is unclear at what time point lamivudine should be 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 thereafter. HBIG was started intraoperatively and continued according to anti-HBs-titers. 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 above 10 pg/ml prior to OLT. Both had developed mutations in the YMDD motif and suffered from HBV reinfection 13 and 75 days postoperatively. Individual HBIG consumption was highly variable (range 787-4,766 lU/month). Twenty-two percent of anti-HBs titers measured before HBIG administration were below 100 IU/l.


CONCLUSIONS
Combined reinfection prophylaxis with lamivudine and HBIG is effective in patients with controlled viral replication at the time of OLT. However, pretransplantation lamivudine resistance is a risk factor for reinfection. Low dose HBIG maintenance therapy individualized according to anti-HBs-titers appears to be tenable.
Rosenau
J
J
Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany.
Bahr
M J
MJ
Tillmann
H L
HL
Trautwein
C
C
Klempnauer
J
J
Manns
M P
MP
Böker KHW
D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control* / Q000628:therapy / Q000821:virology; D006510:Hepatitis B Antibodies / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors
D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D007136:Immunoglobulins; D019259:Lamivudine