Advent of hepatitis B immunoglobulin (HBIG) as the mainstay of prophylaxis against hepatitis B recurrence after liver transplantation with antiviral drugs has resulted in excellent outcomes for liver transplantation in hepatitis B virus (HBV)-related cirrhosis in the last two decades. However, there is no consensus on a gold standard prophylaxis protocol and several controversies over the duration, dose, and route of administration of HBIG with or without different antivirals exist among liver transplantation centers. We present this review of different prophylaxis regimens including HBIG and antiviral monotherapy, combination of HBIG with antivirals, and withdrawal of HBIG and whole prophylaxis. HBIG monotherapy in either the intramuscular or the subcutaneous form is an accepted choice for prevention of HBV re-infection after liver transplantation in low risk patients. Withdrawal of HBIG monotherapy may be considered but should only occur after transitioning to an oral antiviral therapy such as adefovir, tenofovir, or entecavir. Lamivudine monotherapy may be associated with a higher recurrence rate compared to more potent antivirals. In high risk patients, intramuscular or subcutaneous HBIG in combination with an antiviral, most commonly lamivudine, is currently considered the standard of care. Complete discontinuation of all preventative therapy cannot be recommended at this time and should only be performed in the setting of a clinical trial.
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