Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease

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Abstract

The aims of this study are to assess the efficacy of hepatitis B virus (HBV) vaccination using an accelerated schedule and double dose of recombinant vaccine in liver transplant recipients and identify factors associated with seroconversion and persistence of antibody to hepatitis B surface antigen (anti-HBs). Three hundred fifty-six patients were enrolled. Exclusion criteria were previous HBV infection, fulminant liver failure, or less than 2 years of follow-up after orthotopic liver transplantation (OLT). The vaccination schedule was 0, 2 weeks, 4 weeks, and 6 months using double-dose recombinant vaccine. Seroconversion was evaluated prospectively by measuring anti-HBs on the day of OLT and 1 and 2 years after OLT. Quantitative analyses of anti-HBs were performed retrospectively on stored sera. Geometric mean concentrations (GMCs) were calculated using a standard formula. All patients completed the full vaccination schedule, and 129 patients (36%) completed the schedule before OLT. The overall prevalence of anti-HBs was 128 of 356 pre-OLT samples (36%) compared with 41 of 353 (11.6%) and 26 of 325 post-OLT samples (8%) 1 and 2 years after OLT, respectively (both P = .001). The pre-OLT GMC was 86.7 compared with 0.32 and 0.33 at 1 and 2 years after OLT, respectively (P = .001). Patients with high titers of anti-HBs before OLT were more likely to have persistence of antibodies 1 or 2 years after OLT. Younger age (P = .02), low Child-Pugh score (P = .02), underlying chronic hepatitis C (P= .03), and specific host HLA subtypes were most strongly associated with seroconversion and/or persistence of anti-HBs. Thus, (1) seroconversion before or after OLT using double-dose accelerated-schedule vaccination against HBV is low, (2) there is a rapid, significant decrease in antibody titer after OLT, (3) pre-OLT anti-HBs titer potentially may be useful in predicting persistence of protective antibodies after OLT, and (4) several factors (age, genetic predisposition, severity of liver disease, and underlying liver disease) may have a role in poor vaccine responsiveness.

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