Nucleoside analogues and other antivirals for treatment of hepatitis B in the peritransplant period.
Chronic HBV infection is a common cause of advanced liver disease that is associated with substantial mortality. Furthermore, chronic hepatitis B was historically a controversial indication for liver transplantation because of a low post-transplant survival, with graft infection being the major contributor to adverse outcomes. The initial use of hepatitis B immune globulin as prophylaxis, followed later by combined therapy with lamivudine, markedly reduced viral recurrence and improved the survival of patients transplanted for acute or chronic hepatitis B with liver failure. Lamivudine alone can also be used for long-term prophylaxis against de novo HBV infection that can be transmitted by organs from donors positive for anti-HBc or anti-HBs. When used in patients with decompensated chronic hepatitis B with cirrhosis, lamivudine has been shown to improve clinical manifestations, prolong pretransplant survival, and defer, or even obviate, the need for transplantation. Despite prophylaxis, viral mutations with breakthrough reinfection may occur and lead to liver failure. The recently approved adefovir dipivoxil, which is active against lamivudine-resistant mutation, and other nucleoside analogs that are in various phases of development, offer hope as rescue therapy for viral recurrence. Other therapeutic alternatives in the future may include gene therapy and immune interventions.
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation; D009705:Nucleosides / Q000627:therapeutic use*; D063065:Organophosphonates; D011300:Preoperative Care; D012008:Recurrence; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007136:Immunoglobulins; D009705:Nucleosides; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil; C045213:hepatitis B hyperimmune globulin