Management of HBV Infection in Liver Transplantation Patients

Abstract

A Ab bs st tr ra ac ct t In the absence of preventative therapy, reinfection of allografts with hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) resulted in dismal allograft and patient survival. Major advances in the management of HBVinfected recipients of OLT during the past 15 years have steadily reduced the rate of reinfection, resulting in improved outcomes. Initially, long-term use of hepatitis B immune globulin (HBIG) as a source of anti-HBs antibodies was effective in preventing or delaying reinfection. Lamivudine monotherapy made it possible to suppress HBV replication prior to OLT, markedly decreasing the risk of reinfection. Although lamivudine monotherapy used before and after OLT could prevent reinfection, its effectiveness was limited by progressive development of lamivudine-resistant mutant infections. Combination therapy with HBIG and lamivudine after OLT reduced both HBV recurrence and the risk of lamivudine resistance even in patients with active HBV replication. Introduction of adefovir provided a safe, alternative oral antiviral able to treat effectively lamivudine-resistant mutants HBV. Available strategies to prevent reinfection have resulted in OLT outcomes for HBV-infected patients comparable to those for patients transplanted for non-HBV indications. In the future, combination therapies of HBIG and both nucleoside and/or nucleotide agents will undoubtedly be optimized. Development of new drugs to treat HBV will increase opportunities to combine agents to enhance safety, efficacy and prevent emergence of HBV escape mutants. New vaccines and adjuvants may make it possible to generate anti-HBs in immunosuppressed patients, eliminating the need for HBIG. K

Posttransplantation Hepatitis B Prophylaxis with Combination Oral Nucleoside and Nucleotide Analog Therapy

“…patients on HBIg therapy (14,15). The use of a combination of oral drugs would result in potential cost savings of greater than $14 000 over 10 years, as compared to the standard regimens of HBIg with lamivudine (16,17).…”

Hepatitis B Immune Globulin in Liver Transplantation Prophylaxis: An Update

“…Moreover, hepatitis B infection in LT recipients who have received grafts from hepatitis B core antibody positive donors is a serious medical concern (16). Therefore, HBV-related liver disease was initially regarded as a contraindication to LT (17,18). The morbidity and mortality caused by recurrent Dindoost …”

“…Combination therapy appears to be an effective strategy for reducing HBV recurrence to 0 and 16% (Table 1) (6, 39-41, 44, 46, 51, 63), and for bringing about >90% long-term negativity for HBsAg (70,71). Further, combination therapy is more cost effective because the dosage of HBIg, which is expensive, can be reduced, making NA and HBIg combination therapy far more economically attractive and potentially more widely available (17,19,40,43,44,(72)(73)(74)(75)(76). Some stud- (Table 1) (25,39,67).…”

Liver transplantation for hepatitis B-related cirrhosis: recent advances

“…The effectiveness of LAM monotherapy before and after DDLT represents proof of the principle that combination antiviral therapies after DDLT prevent reinfection from extrahepatic reservoirs of HBV if escape mutants do not emerge . If effective oral therapies are developed, passive immunoprophylaxis with HBIG will likely be reserved for patients with residual circulating HBV DNA at the time of liver transplantation.…”