Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis

Abstract

Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIgH BV reinfection after liver transplantation for HBVrelated cirrhosis is frequent in the absence of immunoprophylaxis and is associated with poor prognosis, resulting from the development of cirrhosis, fibrosing hepatitis, or fulminant hepatitis. 1-2 The introduction of the long-term use of anti-HBs immune globulins (HBIg) has allowed the reduction of graft reinfection to acceptable levels, resulting in survival rates comparable with, or even better than, those of other indications. [3][4][5] This passive immunoprophylaxis strategy is therefore currently considered the standard treatment to prevent HBV reinfection after liver transplantation for HBV-related cirrhosis. 6 Yet, using this approach, posttransplant HBV recurrence still occurs in 10% to 30% of cases, possibly depending on a variety of factors, such as the amount of HBIg infused, the route and frequency of administration, and the minimum trough levels of anti-HBs maintained during various periods after transplant. 6 According to current recommendations, HBIg should be administered indefinitely after transplant. This is associated with a number of problems, including the limited availability of HBIg, the possible emergence of HBV envelope protein mutations, 7,8 and/or other adverse events, 9,10 and, most importantly, the extremely high costs. 6 Whatever is the prophylactic regimen used (which varies remarkably from one Center to another) and the cost differences of HBIg preparations between U.S. and most Western European countries, the expenses of post-transplant HBIg administration range between $25,000 and $120,000 per year, thus exceeding in a few years those of an uncomplicated transplant.New prophylactic strategies to prevent posttransplant HBV recurrence are therefore needed. New approaches under evaluation include the combination of lower doses of HBIg with antivirals, such as lamivudine, 11,12 and HBV vaccination, as proposed in the recent provocative study of Sanchez-Fueyo et al. 13 from Spain.

Treatment of hepatitis�B and C after liver transplantation. Part 1, hepatitis�B

“…These results were confirmed with a longer follow-up time [54] and in another study [55]. Conflicting results were reported by Angelico et al using a triple course of hepatitis B vaccination in 17 patients that had undergone transplantation for HBV cirrhosis after cessation of HBIG [56]. Anti-HBs>100 IU/l was observed in only two patients (12%).…”

Induction and maintenance of anti-HBs in immunosuppressed murine hepatitis B virus carriers by a novel vaccination approach: implications for use in hepatitis B virus-infected subjects with liver transplantation

“…Sanchez-Fueyo et al 9 have reported that, in selected patients, post-transplantation vaccination with conventional vaccine would allow the discontinuation of lifelong HBIg treatment. However, Angelico et al 10 did not find a favorable results from reinforced vaccination in OLT patients, although some of their patients developed anti-HBs due to this approach. It is an open debate as to why patients in the Spanish group (reported by Sanchez-Fueyo et at.…”

Prevention of Hepatitis B Virus Reinfection in Liver Transplant Recipients

“…Studies of hepatitis B vaccination as an alternative to long-term HBIG in LT recipients have shown that successful hepatitis B vaccination and discontinuation of HBIG are feasible only in a small group of selected patients; however, the optimal vaccine protocol has not been established [25,26]. …”