Active immunization in patients transplanted for hepatitis B virus related liver diseases: A prospective study

Abstract

IntroductionProphylactic administration of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs) is the standard treatment for controlling hepatitis B virus (HBV) recurrence after liver transplantation (LT). Since lifelong use of HBIG is expensive and inconvenient and the antibodies level in anti-hepatitis B surface (HBs) is not sustainable and stable, an alternative strategy is to produce anti-HBs antibodies by active immunization. Our present study aimed to prospectively investigate the efficacy and safety of procedural HBV vaccination in transplanted patients.MethodsRecipients who had undergone LT for hepatitis B related liver diseases more than one year before, with no evidence of HBV recurrence or rejection and normal liver function were enrolled. All subjects received the hepatitis B vaccine (40 μg) by intramuscular injection at months 0, 1, 2, 6 and 12 after enrollment with continuous administration of NAs. The liver function and anti-HBs titers were measured before each vaccination and HBIG (400U) was administrated intramuscularly when anti-HBs titer was lower than 30 IU/L during the course. The results of routine blood tests, liver function, concentration of immunosuppressant, and HBV-DNA copies were monitored during the research. After completion of the vaccination procedure, recipients were regarded as responders if their anti-HBs greater than 30 IU/L were maintained for up to six months without using HBIG and vaccine.ResultsTwenty-seven patients were enrolled in this study and the average anti-HBs titer before vaccination was 19.86±14.80 IU/L. The average anti-HBs titer of the nine responders at the end of the follow-up was 57.14±22.75 IU/L, giving an overall response rate of 33.3% (9/27). There were no reports of reactivation of HBV, rejection, severe anaphylaxis or other adverse events. Responders and non-responders showed their significant difference in anti-HBs titers after the fourth vaccination (P<0.01). Moreover, the majority of non-responders (11/18, 63.64%) had high LY/EO rates (lymphocyte number/eosinophil number>15) while most responders (8/9, 88.89%) had low LY/EO rates at the beginning of vaccination (P = 0.019).ConclusionsActive immunization is an effective, cost-saving, and safe method for the prevention of HBV reactivation in patients transplanted for hepatitis B virus related liver diseases. The LY/EO rate may be a valuable indicator in selecting potential recipients for vaccination.

An immunogenomic signature for molecular classification in hepatocellular carcinoma

“…As the biggest immune organ, the liver plays an important role in immune responses. 18 C-reactive protein (CRP) is an acute phase reactant protein considered as a diagnostic indicator of early inflammation, which is synthesized by the liver. 19 Furthermore, the liver is engaged in inflammation, and elevated inflammation will cause liver damage.…”

Prevention of HBV Recurrence after Liver Transplant: A Review

“…A single-center prospective study to investigate the efficacy and safety of active vaccination in patients was conducted, in which each patient was given double doses of the intramuscular vaccine at 0, 1, 2, 6 and 12 months of enrollment, with a follow up period of 6 months after completion of the vaccine protocol. 59 Out of 27 men included in this study, 9 were responders (33.3%). All the patients in this study were at least 1-year post-LT and were HBsAg-and HBV DNA-negative, with normal liver functions.…”

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

“…Patients’ response to HBV vaccination is influenced by their immune status. In their prospective study, Yang et al suggested baseline lymphocyte‐to‐eosinophil (LY/EO) ratio as a potential biomarker in identifying best candidates among HBV transplant recipients for HBV vaccination, as it was negatively correlated with patients’ immune system status 82 . Of 27 patients transplanted for HBV‐related liver disease, low (<15) LY/EO ratio was observed in the majority of nine responders to HBV vaccination (8/9, 89%), whereas the majority of non‐responders (11/18, 63.64%) had high LY/EO ratio 82 .…”

“…In their prospective study, Yang et al suggested baseline lymphocyte‐to‐eosinophil (LY/EO) ratio as a potential biomarker in identifying best candidates among HBV transplant recipients for HBV vaccination, as it was negatively correlated with patients’ immune system status 82 . Of 27 patients transplanted for HBV‐related liver disease, low (<15) LY/EO ratio was observed in the majority of nine responders to HBV vaccination (8/9, 89%), whereas the majority of non‐responders (11/18, 63.64%) had high LY/EO ratio 82 . Owing to immunosuppression, LT recipients have different levels of innate or acquired tolerance to HBsAg, therefore, long‐term and repetitive antigenic stimulation is often required, in order to develop adequate immune response, which can be reinforced with booster vaccination if necessary 83 …”