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

<div><p>Introduction</p><p>Prophylactic 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.</p><p>Methods</p><p>Recipients 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.</p><p>Results</p><p>Twenty-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).</p><p>Conclusions</p><p>Active 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.</p></div

Exogenous APN increases circulatory APN level and improves liver dysfunction during I/R.

<p>(A) Serum APN concentration was increased after APN injection. (B) Serum ALT and (C) AST levels in the sham group, I/R control group I/R+APN group and I/R+APN+bAMP group. (D) Representative photomicrograph of liver histology in the sham group, I/R control group I/R+APN group and I/R+APN+bAMP group at 24h after reperfusion. (E) Suzuki scores were presented in the sham group, I/R control group, I/R+APN group and I/R+APN+bAMP group.</p

Therapeutic window of APN after reperfusion.

<p>Therapeutic window of APN after reperfusion.</p

The dynamic changes of anti-HBs titers during the vaccination and follow-up periods.

<p>(A) Responders, (B) non-responders and (C) overall kinetics of both groups. *Mann–Whitney U-tests, P<0.01.</p

Hepatocyte apoptosis was diminished by APN treatment.

<p>(A) Representative liver sections for TUNEL staining of apoptotic cells (green cells) from each experimental group were shown at 24h after reperfusion. (B) Quantitative analysis of TUNEL-positive hepatocyte nuclei per total nuclei in each experimental group is presented. (C) expression levels of cleaved caspase-3, in the liver in each experimental group at 24h after reperfusion are shown.</p

APN inhibits macrophage and neutrophil infiltration.

<p>(A) Representative immunohistochemical staining showing CD68⁺ macrophages and MPO⁺ neutrophils in the sham group, I/R control group, I/R+APN group and I/R+APN+bAMP group at 24h after reperfusion. (B) Quantitative analysis of CD68⁺ macrophages and MPO+ neutrophils per high power field (HPF) in each experimental group.</p

Demographic, clinical and virological characteristics of individual patients.

<p>Demographic, clinical and virological characteristics of individual patients.</p

Distribution of LY/EO ratio in responders and non-responders.

<p>Distribution of LY/EO ratio in responders and non-responders.</p

Comparison between responders and non-responders.

<p>Comparison between responders and non-responders.</p