Recurrence of Hepatitis B Infection in Liver Transplant Patients Receiving Long-Term Hepatitis B Immunoglobulin Prophylaxis

Abstract

BackgroundLong-term real-world data are relatively sparse regarding recurrence of chronic hepatitis B virus (HBV) infection after liver transplantation using hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogue (NUC) prophylaxis.Material/MethodsData from 371 adults transplanted for HBV-related disease at 20 European centers and given HBIg for ≥12 months ± NUC therapy were analyzed retrospectively.ResultsHBIg comprised Hepatect® (iv HBIgB; n=299), subcutaneous Zutectra® (sc HBIg, n=236), and other HBIg preparations (n=130); 93.5% received NUC therapy. Mean follow-up was 6.8±3.5 years. The primary efficacy variable, freedom from HBV recurrence, occurred in 95.7% of patients (95% CI [93.1%, 97.5%]). The observed incidence of recurrence was 16/371 (4.3%) (annual rate 0.65%); 5/16 patients with recurrence had discontinued HBIg and 7/16 had anti-HBs <100 IU/l. Excluding these 7 patients, the HBV recurrence rate was 2.4%. The recurrence rate while on HBIg therapy was 1 per 2069 months. In patients who discontinued HBIg, risk of HBV recurrence versus sc HBIg users was increased by 5.2-fold (1 per 1 603 versus 1 per 8379 treatment months). The annual rate of HBV-related hepatocellular carcinoma (HCC) recurrence was 1.7%.ConclusionsThese results support the long-term use of HBIg with NUC therapy as an effective management strategy to minimize risk of HBV recurrence and virus-related complications after liver transplantation.

Synchronized infection identifies early rate-limiting steps in the hepatitis B virus life cycle

“…To assess the specificity of our viral internalization assay we evaluated the effect of known HBV entry inhibitors: heparin that competes for virus attachment to cellular HSPGs 10 ; MyrB 30 and Hepatect a polyclonal anti-HBV Ig that neutralizes viral infection 31 . All of the entry inhibitors were used at a concentration that neutralized >90% of HBV infection (judged by HBeAg expression at 5d post-infection) and significantly reduced intracellular HBV DNA levels by more than 80% after 6h post inoculation ( Fig.3b ).…”

Antiviral prophylaxis against hepatitis B recurrence after liver transplantation: Current concepts

“…Likewise, a Chinese registry indicated that low‐dose IM HBIG in combination with a NA (mainly ETV) was an effective prophylactic option against HBV recurrence 54 . In the same concept, the efficacy of SC HBIG has been evaluated in a recent European multicentre retrospective study of 371 patients who received long‐term routine prophylaxis with IV or SC HBIG for a minimum of 1 year in combination with LAM or a newer NA 39 . Of the 16 patients who experienced HBV recurrence, 11 were receiving HBIG at the time of recurrence, but only one patient was under SC HBIG, with anti‐HBs levels <100 IU/L 39 .…”

“…In the same concept, the efficacy of SC HBIG has been evaluated in a recent European multicentre retrospective study of 371 patients who received long‐term routine prophylaxis with IV or SC HBIG for a minimum of 1 year in combination with LAM or a newer NA 39 . Of the 16 patients who experienced HBV recurrence, 11 were receiving HBIG at the time of recurrence, but only one patient was under SC HBIG, with anti‐HBs levels <100 IU/L 39 . Another multicentre study evidenced that the early introduction of SC HBIG by week 3 after LT, in combination with NA, effectively prevented HBV recurrence, with no treatment failures reported 38 .…”

Nucleos(t)ide analogues and Hepatitis B virus-related hepatocellular carcinoma: A literature review

“…56 In these cases, prophylaxis with HBV immunoglobulin is recommended. 57 However, data from several meta-analyses have revealed the benefits of adding lamivudine to the HBV immunoglobulin with regard to HBV, HCC recurrence and survival rates. [58][59][60] Nevertheless, adding adefovir to the HBV immunoglobulin was found to be superior to lamivudine plus HBV immunoglobulin.…”