Safety of hematopoietic stem cell transplantation from hepatitis B core antibodies-positive donors with low/undetectable viremia in HBV-naïve children

Frange, Pierre; Leruez‐Ville, Marianne; Neven, Bénédicte; Mascard, L.; Moshous, Despina; Touzot, Fabien; Héritier, Sébastien; Chaix, Marie‐Laure; Cavazzana, Marina; Casanova, Jean‐Laurent; Fischer, Alain; Blanche, Stéphane

doi:10.1007/s10096-013-1982-x

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…[27] However, the current recommendations by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group suggest 5000 IU of HBIG should be administered intravenously to lowrisk patients and 10 000 IU should be administered to high-risk patients while NA monoprophylaxis without HBIG administration is not recommended in the early periods following LT. [6] Among HBIG-free protocol, lamivudine monotherapy is associated with the emergence of escape mutation, while lamivudine/adefovir combination had no HBV recurrence at 22-month follow-up. [28] With the advent of more potent antivirals with lower resistance, more patients have undetectable HBV DNA prior to LT, thereby decreasing posttransplant reinfection rates. Similar arguments can be made to explain the variability in prophylactic recommendations in different parts of the world.…”

Section: Discussionmentioning

confidence: 99%

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective

Edwards¹

2023

Hepatology Forum

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Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods:HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/ without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed.Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion:Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

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Section: Discussionmentioning

confidence: 99%

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective

Edwards¹

2023

Hepatology Forum

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“…In statistical analysis there were no significant associations between anti‐HBc and anti‐HBs serostatus and the presence of occult HBV infection. In a study conducted in France 20 there were no cases of HBV infection after allogeneic HSCT from 17 anti‐HBc‐positive donors between 2006 and 2012. The ECIL‐5 has stated that HBsAg‐negative and anti‐HBc‐positive donors might transmit HBV to recipients.…”

Section: Discussionmentioning

confidence: 99%

“…Follow‐up anti‐HBc assessment in this patient may help to clarify the likelihood of this possibility. Another observation that should be noted was that 7 recipients of 20 anti‐HBc‐positive donors received intravenous immunoglobulin after HSCT, which might help to prevent HBV reactivation 20 . More data are needed to clarify whether anti‐viral prophylaxis is necessary in patients whose donors are anti‐HBc‐positive but HBV viral load is undetectable.…”

Section: Discussionmentioning

confidence: 99%

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients

Chaichotjinda

Anurathapan

Boonsathorn

et al. 2020

Clinical Transplantation

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Background Hematopoietic stem cell transplantation (HSCT) recipients require hepatitis B (HBV) revaccination. Hepatitis B surface antibody (anti‐HBs) seroconversion rates after revaccination range from 64% to 79% in these patients. The seroconversion rate and factors associated with non‐seroconversion have not been clearly elucidated in pediatric and young adult recipients after HSCT. Objectives To evaluate anti‐HBs seroconversion rates in pediatric and young adult patients revaccinated after HSCT, and to identify factors associated with non‐seroconversion. Method The current study was prospective and cross‐sectional. Post‐HSCT recipients aged ≤25 years who had completed a course of three HBV revaccinations were recruited, and their anti‐HBs titers were assessed. Non‐seroconverted patients were administered a fourth vaccination. Those who subsequently remained seronegative were administered two additional vaccinations. Those who remained seronegative after all six vaccinations were defined as non‐responders. Results A total of 118 patients were enrolled. The HBV‐containing vaccines used included DTaP‐IPV‐HBV‐Hib, DTwP‐HBV‐Hib, and monovalent vaccines. The anti‐HBs seroconversion rate after three revaccinations was 82% (95% confidence interval [CI], 73.7‐89.2). One patient (0.8%) was classified as non‐responder. Factors associated with non‐seroconversion after three revaccinations included cytomegalovirus (CMV) reactivation (odds ratio [OR] 10.63, 95% CI 1.16‐97.00), anti‐HBs seronegativity before HSCT (OR 7.01, 95% CI 1.55‐31.78) and three DTwP‐HBV‐Hib revaccinations (OR 11.71, 95% CI 1.43‐96.26). Conclusion In the current study the anti‐HBs seroconversion rate after three HBV revaccinations was excellent. CMV reactivation, anti‐HBs seronegativity before HSCT, and three DTwP‐HBV‐Hib revaccinations were associated with non‐seroconversion, but the non‐responder rate was low.

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“…Conversely, little is known about the effects of anti-HBc-positive donors on HBV-negative HSCT recipients. Recent reports documented the absence of HBV transmission in HBV-naïve children undergoing prophylaxis with vaccination and/or immunoglobulins when receiving HSCs from an anti-HBc-positive donor [45]. Another study demonstrated a protective role of HBV-immune/ exposed HBV donors for anti-HBc-positive HSCT recipients who did not receive LMV prophylaxis [21].…”

Section: Discussionmentioning

confidence: 99%

Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor

Cerva

Colagrossi

Maffongelli

et al. 2016

Clinical Microbiology and Infection

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The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.

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Safety of hematopoietic stem cell transplantation from hepatitis B core antibodies-positive donors with low/undetectable viremia in HBV-naïve children

Cited by 7 publications

References 15 publications

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients

Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor

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