Prevention of lamivudine-resistant hepatitis B recurrence after liver transplantation with entecavir plus tenofovir combination therapy and perioperative hepatitis B immunoglobulin only

Combination therapy with antivirals plus hepatitis B immunoglobulin (HBIg) has become the standard treatment for prevention of post-liver transplant hepatitis B virus (HBV) recurrence. However, HBIg therapy is inconvenient and expensive. Alternative therapeutic approaches with modern nucleos(t)ide analogues are limited so far. The present case report describes prevention of HBV recurrence with entecavir and tenofovir. A 48-year-old male patient with hepatitis B-induced decompensated liver cirrhosis initially improved on lamivudine (LAM) until LAM resistance (rtL180M and rtM204V) emerged followed by renewed decompensation. Therefore, tenofovir was added to LAM leading to undetectable HBV DNA (<200 copies/mL). Six months later, low-level viremia (479 copies/mL) was detected. Treatment was escalated to tenofovir plus entecavir. HBV DNA became negative again, and the patient underwent orthotopic liver transplantation. HBIg was administered during transplantation (10,000 IU) and on the second and third postoperative days (total dose 26,000 IU). Subsequently, the anti-hepatitis B surface (HBs) titer rose to 1477 IU/L at day 4 post transplantation. Although HBIg should have been continued, the patient remained on combination therapy with tenofovir plus entecavir only. The anti-HBs titer decreased and became negative 4 months later. However, under continued combination therapy with oral antivirals, HBV DNA and hepatitis B surface antigen remained negative during the entire follow-up of 21 months after liver transplantation. Combination therapy with entecavir plus tenofovir may prevent post-liver transplant hepatitis B recurrence even without HBIg maintenance therapy. This case illustrates that combination oral antiviral therapy might substitute for HBIg as indefinite prophylactic regimen due to profound antiviral efficacy and low risk of viral resistance. Efficacy and safety must be further investigated in randomized controlled trials.