Case Report of Lamivudine-Resistant Hepatitis B Virus Infection Post Liver Transplantation from a Hepatitis B Core Antibody Donor

Abstract

The use of allografts from donors with hepatitis B core antibody in liver transplantation (LT) is associated with the risk of de novo hepatitis B virus (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and lamivudine alone or in combination has been reported. Yet, there are no standardized regimens and long-term efficacy is not known. We report a case of a patient who underwent LT for alcoholic liver disease who received an allograft from a donor with Hepatitis B core antibody. The patient had no previous exposure to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface antibody present in serum before and 6 months after transplantation. Prophylaxis with short-term HBIg (1 week) and indefinite lamivudine was given. De novo HBV infection developed more than 3 years after LT with a lamivudineresistant polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the risk of de novo post-LT HBV infection in recipients of livers from hepatitis B core antibody positive donors. High risk were HBV naïve recipients, moderate risk recipients had isolated hepatitis B surface antibody (anti-HBs) or hepatitis B core antibody (anti-HBc), while low-risk recipients had both anti-HBs and anti-HBc. We reviewed prophylaxis protocols reported in the literature and made recommendations for management.

Hepatitis B Immune Globulin in Liver Transplantation Prophylaxis: An Update

“…This is accompanied by subsequent graft failure, rapid progression to cirrhosis, fulminant hepatitis, and patient death. The frequency of HBV reinfection is the lowest in HBV-immune recipients (0%-18%) and is the highest in HBV-naive recipients (70%-80%) (2,(4)(5)(6)(7)(8)(9). Reinfection has been hypothesized to occur due to the presence of circulating virions at the time of LT, exposure to extrahepatic reservoirs of HBV, or the persistence of the HBV covalently closed circular DNA (cccDNA) as a replicative intermediate (8,10,11).…”

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers

“…Furthermore, prophylactic protocols may vary even within a center based on donor and recipient HBV serologic status. Table 2 summarizes published prophylactic protocols involving HBIG use at different transplant programs [15,18,20,21,24,26,27,29,[33][34][35][36][37][38][39][40][41][42][43]. There are a number of important questions that remain to be answered regarding prevention of DNH in anti-HBc-positive donor LT. We will address the following four questions.…”

“…Nevertheless, monotherapy appears not as good as combination therapy since there was no DNH in 43 naïve recipients treated with combination therapy (Tables 1, 3). HBIG monotherapy effectively prevents the occurrence of DNH in 22 and 12 recipients who were positive for either anti-HBs or anti-HBc alone, respectively (Table 3) [20,24,26,27,29,33,34,36,39,40,42,44]. This population has intermediate risk (20%) of developing DNH when receiving a liver from anti-HBcpositive donors (Table 1).…”

“…LAM monotherapy has the same efficacy as the combination therapy at far less cost [47,48]. However, drug-resistance HBV mutants have been reported as the cause of DNH in a case after being on LAM for more than 3 years [42]. To overcome this potential problem, nucleos(t)ide analogs with a high barrier of developing drug resistance is preferred either as a monotherapy or in combination with LAM, but without HBIG, for prophylaxis of DNH [47].…”

“…This finding suggests that IM HBIG may not be the best immediate postoperative prophylaxis especially for patients who have a high viral load before LT and hence require higher protective antibody level after LT. Nonetheless, low-dose IM or SC HBIG may be a good alternative for prevention of DNH since recipients receiving isolated anti-HBc-positive livers should not have detectable viremia immediately after LT. One patient dropped from the prophylaxis protocol due to poor compliance [33] } Five of six patients developed surface escape mutation [27] ¥ The patient developed surface escape mutation [27] § One patient dropped from the prophylaxis protocol due to poor compliance [33] £ One patient developed lamivudine-resistant polymerase mutant [42] and the other stopped prophylactic lamivudine 2 months prior to developing DNH [44] HBV hepatitis B, anti-HBs antibody against hepatitis B surface antigen, anti-HBc antibody against hepatitis B core antigen, DNH de novo hepatitis B * Single patient did not compliant with lamivudine prophylaxis [29] One patient was seroconverted for anti-HBc but remained negative for HBV DNA and hepatitis B surface antigen [31] } Single patient did not compliant with lamivudine prophylaxis [29] Hepatol Int (2011) 5:635-643 639…”