Current guidelines lack consensus on whether antiviral prophylaxes should be administered after kidney transplantation from HBcAb+ donors. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of de novo HBV (DNH) infection, as well as graft and patient survival.

We searched PubMed, Embase, and the Cochrane Library up to December 31, 2023. We included relevant studies that assessed clinical outcomes following transplantation utilizing HBcAb+ kidneys. Summary measures of effect and 95% confidence intervals (CI) for prevalence, risk factors, as well as graft and patient survival were estimated using random-effects meta-analysis.

Thirteen studies were included for the final analysis. The DNH incidence was at 0.36% (9/2516) with low heterogeneity (I2 = 6%). HBsAb+ recipients (OR: 0.78, 95%CI: 0.25-2.38), HBcAb+ recipients (OR: 3.11, 95%CI: 0.91-10.66, P = 0.071), and recipients not receiving any antiviral prophylaxis (OR: 1.26, 95%CI: 0.15-10.58) were not associated with higher DNH risk. Specifically, HBsAb-/HBcAb+ recipients had the highest DNH incidence (4.65%), followed by HBsAb-/HBcAb- (0.49%), HBsAb+/HBcAb- recipients (0.45%), and HBsAb+/HBcAb+ (0%). Furthermore, recipients receiving HBcAb+ kidneys had comparable graft survival (HR: 1.06, 95%CI: 0.94-1.19, P = 0.55) and patient survival (HR:1.16, 95%CI: 0.98-1.38, P = 0.090) compared with recipients receiving HBcAb- kidneys.

Kidney transplantation utilizing HBcAb+ kidneys contributed to comparable graft and patient survival with an extremely low risk of HBV transmission. Antiviral prophylaxes may only be administered in HBsAb-/HBcAb+ recipients.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.

Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.

Utilizing kidneys from donors with hepatitis B is one way to alleviate the current organ shortage situation. However, the risk of hepatitis B virus (HBV) transmission remains a challenge that undermines the chance of organs being used. This is particularly true with hepatitis B surface antigen (HBsAg) positive donors despite the comparable long-term outcomes when compared with standard donors. To reduce the risk of HBV transmission, a comprehensive approach is needed. This includes assessment of donor risk, optimal allocation to the proper recipient, appropriate immunosuppressive regimen, optimizing the prophylactic therapy, and post-transplant monitoring. This review provides an overview of current evidence of kidney transplants from donors with HBsAg positivity and outlines the challenge of this treatment. The topics include donor risk assessment by adopting the nucleic acid test coupled with HBV DNA as the HBV screening, optimal recipient selection, importance of hepatitis B immunity, role of nucleos(t)ide analogues, and hepatitis B immunoglobulin. A summary of reported long-term outcomes after kidney transplantation and proposed criteria to utilize kidneys from this group of donors was also defined and discussed.

Lack of availability of donor organs is a constant challenge that patients and providers face in transplantation. To address this shortage, donors that test positive for hepatitis B, in particular those with resolved infection, have been increasingly utilized in clinical practice. We review here the potential risks for the recipient and the advances in hepatitis B management that have made use of these donors a well tolerated and advisable proposition.

As routine administration of antiviral prophylaxis in the posttransplant setting among those deemed high risk for transmission, outcomes for recipients of hepatitis B donors, including liver transplant recipients, have been comparable to uninfected donors. Universal hepatitis B nucleic acid testing of donors has also enhanced our ability to accurately inform recipients regarding transmission risk. Appropriate use of prophylaxis and careful monitoring for transmission posttransplant is key to ensuring no adverse outcomes occur.

Treatment of hepatitis B has evolved over the past two decades. Expanding the donor pool with hepatitis B donors is now well tolerated, ethical, and advantageous to the transplant community at large. A clear discussion with recipients on the substantial benefit and low harm of using hepatitis B donors will lead to greater acceptance and utilization of these organs.

Patients on regular dialysis show a poor response to hepatitis B vaccine due to uremia. A recombinant HB vaccine (containing an improved adjuvant system AS04, HBV-AS04) has been licensed but the evidence on its efficacy and safety in dialysis population over the long term is extremely limited.

We have measured antibody (anti-HBs) persistence for up to 72 months in a large cohort of patients on long-term dialysis (with susceptibility to HBV infection) who underwent vaccination with HBV-AS04 vaccine.

Patients were prospectively recruited to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle). Two vaccine schedules were adopted: 0,1,2, and 3 month (n=217 patients) and 0,1,2, and 6 month (n=31 patients). Anti-HBs antibody concentrations were tested at 1,2,3, 4, 7 and 12 months and then every year up to 72 months. Multivariate analysis was made to find the baseline parameters that were associated with the immune response to HBV-AS04 vaccine.

Two hundred and seventy-two patients were included and 248 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 81.5% (202/248) (mean anti-HBs antibody titers, 384.9±391.9mIU/mL), according to per-protocol analysis. On the grounds of univariate analysis, age was lower in responder than non- responder patients to HBV AS04 even if no statistical significance was achieved (P=0.09). The sero-protection rate at month 72 was 77% (7/9) (anti-HBs antibody titers, 184.9±360.1mIU/mL, P=0.001). Multivariate analysis found a relationship between sero-response rate and age (P=0.04). No major side effects and no de novo HBV episodes were observed.

Our open-label nonrandomized trial performed in a 'real-world' practice showed the persistence of anti-HBs antibody among responder patients over a very long follow-up. Studies with longer observation periods are under way.

Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD.

To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection).

Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine.

One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9±385mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non- or low-responder patients to HBV-AS04 (P=0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5±269.6mIU/mL, P=0.001). No major side effects were observed.

Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders.