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

J Hepatol. 2001 Jun;34(6):895-902. doi: 10.1016/s0168-8278(01)00089-7.

Abstract

Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Motifs
  • Antiviral Agents / therapeutic use*
  • Female
  • Hepatitis B / prevention & control*
  • Hepatitis B / therapy
  • Hepatitis B / virology
  • Hepatitis B Antibodies / therapeutic use*
  • Hepatitis B virus / genetics
  • Humans
  • Immunoglobulins / therapeutic use*
  • Lamivudine / therapeutic use*
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Mutation
  • Recurrence
  • Risk Factors
  • Time Factors

Substances

  • Antiviral Agents
  • Hepatitis B Antibodies
  • Immunoglobulins
  • Lamivudine