Hepatitis B virus reactivation in kidney transplant patients with resolved hepatitis B virus infection: Risk factors and the safety and efficacy of preemptive therapy

Abstract

Background: Hepatitis B virus (HBV) reactivation is associated with complications and adverse outcomes in patients with clinically resolved HBV infection who are seronegative for hepatitis B surface antigen (HBs Ag), and seropositive for hepatitis B core antibody (HBc Ab) and/or hepatitis B surface antibody (HBs Ab) before kidney transplantation (KT). Methods:We retrospectively analyzed 52 patients with resolved HBV infection who were HBV-DNA negative. HBV-DNA after KT was evaluated, and the occurrence of HBV reactivation and outcomes were monitored. We defined HBV reactivation as seropositivity for HBV-DNA at or above the minimal detection level of 1.0 log IU/mL and treated preemptively (using entecavir) when the HBV-DNA level was at or above 1.3 log IU/mL, in accordance with the Japanese Guidelines for HBV treatment. Results:Among the 52 patients, the mean age was 57.2 ± 10.8 years. The median HBc Ab titer was 12.8 (interquartile range, 4.6-42.6) cutoff index, and five (9.6%) cases of HBV reactivation occurred. No patients developed graft loss and died due to HBV reactivation. Statistical analysis showed that age and HBc Ab titer were significant risk factors for HBV reactivation (P = .037 and P = .042, respectively). No significant differences were found between graft survival and the presence or absence of HBV reactivation. Conclusion:These results suggest that HBc Ab titer and age could be significant risk factors for HBV reactivation. Resolution of HBV infection did not appear to be associated with patient or graft survival, regardless of whether HBV reactivation occurred, when following our preemptive strategy. K E Y W O R D Skidney transplantation, preemptive strategy, resolved HBV infection

A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation

“…A group of Japanese investigators reviewed 52 patients with resolved HBV infection who underwent kidney transplantation and found that age and anti-HBc titer to be significant risk factors for HBV reactivation. 12 Our study did not evaluate anti-HBc titers, and we did not find age to be a significant risk factor for reactivation. However, we did find delayed graft function to be a significant predictor of HBV reactivation.…”

“…Age has been shown to be a factor associated with HBV reactivation based on a previous study; therefore, it was also included in our model. 12 Our multivariate logistic regression model demonstrated that the absence of HBV prophylaxis did not predict the development of HBV reactivation in our patient population.…”

“…16 Similarly, previous studies have demonstrated an HBV reactivation incidence ranging from 1% to 10% in this specific kidney transplant population. [10][11][12][13]17 Given the historical data and the results of our study, we suggest that standard maintenance immunosuppression post kidney transplantation may not significantly increase the risk for HBV reactivation. However, it is important to note that our multicenter retrospective study did not evaluate overall glucocorticoid exposure, which future studies should aim to report.…”

“…9 The risk of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients reported in the literature ranges between 1.4% and 9.6%. [10][11][12][13] Despite recovery from initial hepatitis B infection, there lies a risk of reactivation of the virus due to its dormant nature, and the role of antivirals becomes less clear. HBV reactivation is evidenced by loss of HBV immune control in HBsAg-positive, anti-HBc-positive or HBsAg-negative, anti-HBcpositive patients receiving immunosuppressive therapy, an increase in HBV DNA, compared to baseline, and reverse seroconversion of HBsAg negative to positive.…”

“…15 Data on HBV reactivation based on the use of antiviral prophylaxis and various patient risks such as lymphocyte-depleting agents and anti-HBs status is limited. 12,13 Therefore, this multicenter study was conducted to evaluate the prevalence of HBV reactivation in HBsAgnegative and anti-HBc-positive kidney transplant recipients who did or did not receive hepatitis B antiviral prophylaxis, and to identify risk factors associated with HBV reactivation.…”