Defining causes of death-censored kidney allograft failure: A 5-year multicentre ANZDATA and clinical cross-sectional study.

AIM: Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody-mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN). METHODS: All death-censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the "most likely" cause assigned. RESULTS: There were 642 death-censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5-39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody-mediated rejection (37.4%) and chronic T-cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody-mediated rejection. CONCLUSION: To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit.

Prolonged immunosuppression does not improve risk of sensitization or likelihood of retransplantation after kidney transplant graft failure.

The optimum approach towards immunosuppression withdrawal following kidney transplant failure is unclear. Prolonged weaning may be associated with reduced sensitization, less graft nephrectomy and greater likelihood of retransplantation, but conversely increased risk of infection, malignancy and death. We conducted a single-centre retrospective analysis of patients experiencing graft failure between 2007 and 2017, comparing rates of sensitization, retransplantation, nephrectomy, infection, malignancy and death between patients who had immunosuppression weaned over <90 vs. 90-180 vs. >180 days. Patient survival after immunosuppression withdrawal over <90 vs. 90-180 vs. >180 days was 73.3%, 72.1% and 80.4%, respectively (P = 0.35), with no differences in cPRA (80.06 vs. 81.21 vs. 85.42, P = 0.66) or retransplantation rate [24/31 (77.4%) vs. 21/35 (60.0%) vs. 22/36 (61.1%), P = 0.13]. There was significantly less nephrectomy after late immunosuppression cessation [10/42 (23.8%) vs. 7/42 (16.7%) vs. 3/43 (7.0%), P = 0.01] but no differences in infections or malignancy. On competing risk regression (death as competing risk) controlling for cofactors including age, nephrectomy and rejection, prolonged immunosuppression did not predict likelihood of retransplantation (SHR 1.000, P = 0.88). Prolonged immunosuppression withdrawal does not reduce sensitization or improve retransplantation rates but is associated with less nephrectomy. Immunosuppression withdrawal should be tailored to individual circumstances after graft failure.

Paediatric deceased donor kidney transplant in Australia: A 30-year review-What have paediatric bonuses achieved and where to from here?

BACKGROUND: In this 30-year national review, we describe trends in DD transplantation for paediatric recipients, assess the impact of paediatric allocation bonuses and identify outstanding areas of need for this population. METHODS: A retrospective review of all DD kidney only transplants to paediatric recipients (<18 years old) in Australia between 1989 and 2018 was conducted using deidentified extracts from the ANZDATA. RESULTS: Of the 1011 kidney only transplants performed in paediatric recipients during the study period, 426 (42%) were from deceased donors. Paediatric candidates on the DD waiting list had consistently higher rates of transplantation and shorter time from dialysis initiation to transplantation compared with adult candidates (median 372 vs 832 days in 2018, for example). Donor characteristics remained more favourable for paediatric recipients, despite a decline in the overall quality of the donor pool. The mean number of HLA antigen mismatches for paediatric recipients of DD transplants increased each decade (2.86 [1989-1998], 3.85 [1999-2008], 4.01 [2009-2018]). Both patient and graft survival have improved for paediatric DD transplant recipients in the most recent era (5-year graft and patient survival 85% vs 65% and 99% vs 94%, respectively, for 2009-2018 vs 1999-2008). CONCLUSIONS: The current DD kidney allocation system in Australia provides rapid access to high-quality organs for paediatric recipients, and early graft loss has decreased significantly in recent years; however, additional targeted interventions to address HLA matching may improve long-term outcomes in this population.

Frequency and outcomes of kidney donation from intensive care patients with acute renal failure requiring renal replacement therapy.

BACKGROUND: Kidney transplantation is the preferred treatment for end-stage renal failure. Unfortunately, donor organ shortages prevent many individuals receiving a renal transplant and there is a need to increase the pool of appropriate donors. The presence of acute kidney injury (AKI) in deceased donors has traditionally been a relative contraindication to renal transplantation, even though renal recovery may be favorable in the absence of chronic renal disease. METHODS: We undertook an 8 years retrospective observational study of potential deceased organ donors with AKI requiring renal replacement therapy (RRT). We evaluated the rate of successful transplantation as well as short term and outcomes at a median of 19.5 (13.0-52.7) months after donation. RESULTS: Amongst 1058 consented potential organ donors, 39 patients had AKI requiring RRT, of which 19 became donors (13 not medically suitable, 7 did not proceed to donation). The median (interquartile range (IQR)) donor age was 41 (34-50) years and norepinephrine, epinephrine and vasopressin were given to 18, 14 and 9 donors, respectively. From the 38 donated kidneys 34 were transplanted. The median (IQR) age of recipients was 53 (42.8-58.5) years and they were dialysis free in a median (IQR) of 5.5 (2.3-10.8) days. Only minor abnormalities were found at 3 and 6 months renal biopsies, and two patients experienced graft failure in the first 12 months. CONCLUSION: Amongst deceased donors with AKI receiving RRT and vasoactive medications outcomes of renal transplantation seems acceptable in the absence of pre-existing renal failure and other donor co-morbidity. Such patients may be an important additional source of kidney donation.

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Mineral adaptations following kidney transplantation.

Klotho is predominantly expressed in the kidney and reported to have antioxidant and antifibrotic properties. Soluble Klotho (sKl), the circulating protein cleaved from membrane-bound Klotho, is reduced significantly with kidney disease and inversely associated with mortality. sKl has not been thoroughly evaluated prospectively after kidney transplantation. Incident kidney transplant recipients (KTRs) were prospectively evaluated pretransplantation, 1, 12 and 52 weeks post-transplantation. Basic biochemistry, sKl and intact FGF23 were measured. Within-subject comparisons were evaluated using repeat-measure anova or Friedman's analysis. Effects of immunosuppression and biochemical parameters on sKl and FGF-23 over time were analysed using mixed-effects modelling. Median serum creatinine (sCr) at 1 week was 116 (92-142) µmol/l, and at 52 weeks, all 29 KTRs had a functioning graft with median sCr of 111 (97-131) µmol/l. Compared with baseline, sKl was increased at 52 weeks following an initial decline at 1 week (P < 0.005 and P < 0.01, respectively), while FGF23 was considerably reduced at 52 weeks (P < 0.001). In a mixed-effects model, an increased sKl was not associated with reduction in immunosuppression or evaluated biochemical parameters. Modest increase in sKl is observed one-year postkidney transplantation with excellent early graft function suggesting factors beyond renal capacity may influence circulating sKl. FGF23 normalization was observed. Longer term evaluation in transplantation, specifically addressing the effects of immunosuppression, is required to understand the pathophysiology of the sKl/FGF23 axis and potential for modification.

Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients.

BACKGROUND: Owing to limited availability of donor organs, previous solid organ transplant (SOT) recipients are increasingly considered as potential organ donors. We report donor-derived transmission of herpes simplex virus type-2 (HSV-2) to two clusters of SOT recipients with transmission from the original donor and an HSV-2-infected recipient who subsequently became a donor. METHODS: We reviewed medical records of the donors and recipients in both clusters. Pre-transplant serology and virological features of HSV-2 were characterized. Genotyping of HSV-2 isolates to determine potential for donor transmission of HSV-2 through transplantation of organs from prior organ recipients was performed. RESULTS: A kidney-pancreas recipient died day 9 post transplant. Following confirmation of brain death, the lungs and recently transplanted kidney were donated to two further recipients. The liver was not retrieved, but biopsy confirmed HSV-2 infection. Testing on the original donor showed negative HSV-2 polymerase chain reaction and HSV immunoglobulin (Ig)M, but positive HSV-2 IgG. The liver recipient from the original donor developed HSV-2 hepatitis and cutaneous infection that responded to treatment with intravenous acyclovir. In the second cluster, lung and kidney recipients both developed HSV-2 viremia that was successfully treated with antiviral therapy. Genotyping of all HSV-2-positive samples showed 100% sequence homology for three recipients. CONCLUSIONS: Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis.

Impact of cinacalcet pre-transplantation on mineral metabolism in renal transplant recipients.

AIM: Cinacalcet is effective in reducing parathyroid hormone (PTH) in patients on dialysis. Reports of biochemical profiles and other clinical outcomes in patients discontinuing cinacalcet at time of renal transplantation are limited. METHODS: A retrospective study assessing markers of mineral metabolism, graft and patient outcomes in renal transplant recipients to determine differences in patients discontinuing cinacalcet (C+) compared with patients not treated with cinacalcet (C-) at time of transplantation. To allow for differences between groups in pre-transplant biochemical parameters, we also analysed a matched cohort of C- with C+ recipients (2:1), matched for age, calcium and PTH levels at transplantation. RESULTS: Five hundred thirty-two recipients (460 C-, 72 C+), transplanted January 2006-December 2012, were analysed, mean age 48.0 ± 12.7 years and 64.3% were men. At a median 42.9 months follow up, there were 10 deaths (1.9%), 56 allograft loss (10.6%) and 5 parathyroidectomies post-transplant (0.8%). Median PTH immediately pre-transplant was higher in C+ versus C- (50.7(25.4-75.2) versus 28.3(13.9-49.7) pmol/L, P < 0.001). Twelve-month post-transplant PTH was reduced but higher in C+ (11.7(6.9-21.2) vs 7.2(4.6-11.2) pmol/L, P < 0.001). Mean calcium was higher for C+ versus C- at 12 months (2.50 ± 0.19 vs 2.43 ± 0.17 mmol/L, P < 0.001), with differences to 4 years post-transplant. No difference was seen in renal function, graft loss, post-transplant parathyroidectomy rate and mortality. In the matched cohort (144 C- vs 72 C+), similar findings were also seen. CONCLUSION: Differences in mineral metabolism post-transplant are seen with cinacalcet pre-transplant compared with no cinacalcet. Transplant recipients discontinuing cinacalcet had higher post-transplant PTH and calcium although the clinical significance is unclear.

Renal allograft re-use and herpetic re-infection.

A middle-aged man received a kidney transplant from a deceased multi-organ donor. The recipient suffered cardiac arrest several days post-operatively and sustained hypoxic brain injury and was declared brain dead. Following the family's consent, the allograft kidney was retrieved and re-transplanted into a man with end-stage renal failure secondary to reflux nephropathy. The liver was not transplanted due to suspicion of fatty changes based on macroscopic appearance. After transplantation of other organs, liver histology revealed coagulative parenchymal necrosis with nuclear inclusions and moderate parenchymal cholestasis, suggestive of herpes viral hepatitis. Renal implantation biopsy showed histiocytes with enlarged nuclei containing viral inclusions in the capsular fibrous tissue, with positive immunostaining for herpes simplex virus (HSV). Anti-viral therapy was commenced immediately after obtaining histological evidence of donor HSV infection. Our recipient had pre-formed immunoglobulin G antibodies to HSV-1 and HSV-2, and was immunoglobulin M negative pre-transplant. HSV viraemia was detected day 5 post-transplant with a viral load of 7688 copies/mL by polymerase chain reaction assay. The recipient completed a 30 day course of intravenous ganciclovir before switching to oral valganciclovir as standard cytomegalovirus prophylaxis. The HSV polymerase chain reaction became undetectable on day 7 of intravenous ganciclovir and has remained undetectable. The patient remains well 9 months post-transplant with an estimated glomerular filtration rate of 61 mL/min per 1.73 m(2). Although renal allograft re-use has been shown to be technically possible with a good outcome in this recipient, this does raise issues including assessment of allografts that have undergone repeated severe ischaemic insults and the potential of transmission of infections.

Antiphospholipid syndrome in renal transplantation.

Antiphospholipid syndrome (APS) may occur in isolation or in association with systemic lupus erythematosus (SLE), with the potential to cause renal failure via several distinct pathologies. Renal transplantation in the presence of APS carries a risk of early graft loss from arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Whilst perioperative anticoagulation reduces the risk of large vessel thrombosis, it may result in significant haemorrhage, and its efficacy in preventing post-transplant TMA is uncertain. Here, we report a patient with end-stage kidney disease (ESKD) due to lupus nephritis and APS, in whom allograft TMA developed soon after transplantation despite partial anticoagulation. TMA resolved with plasma exchange-based therapy albeit with some irreversible graft damage and renal impairment. We discuss the differential diagnosis of post-transplant TMA, and current treatment options.

Beyond Graft Survivl: A National Cohort Study Quantifying the Impact of Increasing Kidney Donor Profile Index on Recipient Outcomes 1 Year Post-transplantation.

Background: The reporting of a locally validated kidney donor profile index (KDPI) began in Australia in 2016. Across diverse populations, KDPI has demonstrated utility in predicting allograft survival and function. A metric that incorporates both elements may provide a more comprehensive picture of suboptimal recipient outcomes. Methods: A retrospective cohort study of adult kidney transplant recipients in Australia (January 2009 to December 2014) was conducted. Conventional recipient outcomes and a composite measure of suboptimal outcome (1-y allograft failure or estimated glomerular filtration rate [eGFR] <30 mL/min) were evaluated across KDPI intervals (KDPI quintiles and 5-point increments in the KDPI 81-100 cohort). The impact of increasing KDPI on allograft function (1-y eGFR) and a suboptimal outcome was explored using multivariable regression models, adjusting for potential confounding factors. Results: In 2923 donor kidneys eligible for analysis, median KDPI was 54 (interquartile range [IQR], 31-77), and Kidney Donor Risk Index was 1.39 (IQR, 1.03-1.67). The median 1-y eGFR was 52.74 mL/min (IQR, 40.79-66.41 mL/min). Compared with the first quintile reference group, progressive reductions in eGFR were observed with increasing KDPI and were maximal in the fifth quintile (adjusted ß-coefficient: -27.43 mL/min; 95% confidence interval, -29.44 to -25.42; P < 0.001). A suboptimal outcome was observed in 359 recipients (12.3%). The adjusted odds for this outcome increased across quintiles from a baseline of odds ratio of 1.00 (first quintile) to odds ratio of 11.68 (95% confidence interval, 6.33-21.54, P < 0.001) in the fifth quintile cohort. Conclusions: Increases in donor KDPI were associated with higher probabilities of a suboptimal outcome and poorer baseline allograft function, particularly in the KDPI > 80 cohort. These findings may inform pretransplant discussions with potential recipients of high-KDPI allografts.

Modifiers of complement activation for prevention of antibody-mediated injury to allografts.

PURPOSE OF REVIEW: Improvements in prevention and management of cellular rejection of solid organ transplants, coupled with increasing numbers of sensitized patients, have focused attention on antibody-mediated rejection (AbMR). Complement is a critical component of AbMR, in addition to interfacing between innate and adaptive immunity and the coagulation cascade. This article reviews complement biology and strategies to overcome complement in AbMR, cognisant that antibody can act independently of complement. RECENT FINDINGS: The past decade has witnessed an improvement in the prevention and treatment of AbMR as a result of solid-phase assays to determine antibody specificity, definition of histopathological criteria, and use of plasmapheresis and/or intravenous immunoglobulin (IVIG). Nonetheless, AbMR continues to impact adversely on short- and long-term graft survival. Use of B and/or T-lymphocyte-depleting therapies has not shown measurable benefit, and the need remains for therapies that deplete antibody, or provide better protection from complement-mediated damage. Disordered complement activity in human diseases such as paroxysmal nocturnal haemoglobinuria, has provided additional impetus to pursuing therapeutic complement inhibition. Preliminary data from C5 inhibition with eculizumab in the treatment and prevention of AbMR have shown promise. Trials with recombinant human inhibitors of C1 (effective in angioedema) to prevent or treat AbMR are beginning. SUMMARY: Despite current limitations, 'protection' of the transplant through plasmapheresis and/or IVIG enables many allografts to survive in sensitized recipients. Elucidating the pathways mediating graft acceptance, by constitutive antibody deletion, or 'accommodation' (wherein donor organ remains uninjured despite antibody binding), or other local protective mechanism(s), is an equally important challenge in the quest to overcome AbMR.

Successful Implementation of an Increased Viral Risk Donor Waiting List for Preconsented Kidney Transplant Candidates in Victoria, Australia.

Increased viral risk donors (IVRDs) with increased risk behaviors for blood-borne virus infection and negative nucleic acid testing have a low absolute risk of "window period" infection. Utilization and allocation of IVRD organs differ between jurisdictions. METHODS: We examined the characteristics and utilization of deceased donor IVRD kidneys and recipient outcomes within a 2-y period (July 31, 2018-July 31, 2020) postimplementation of a new opt-in allocation pathway for preconsented recipients in Victoria, Australia. RESULTS: Fifty-six kidneys from 31 IVRDs were utilized, comprising 13% of donors. Preconsent rate to accept IVRD kidneys increased to 41% of the waitlist in the 2 y postimplementation, and IVRDs having no kidneys utilized reduced to 0%. Compared with non-IVRD kidneys, kidney offer declines >10 per donor were less likely from IVRDs (3% vs 19%; P < 0.05). IVRDs were younger (median age 36 [IQR 30-44] vs 51 [35-60] y; P < 0.0001), with lower kidney donor profile index (25% [13-40%] vs 57% [29-75%]; P < 0.0001), and less hypertension (0% vs 22%; P < 0.01). Estimated glomerular filtration rate 3 mo post-transplant was superior (P < 0.01). Injecting drug use (61%) was the most common increased risk behavior. 29% of IVRDs were hepatitis C antibody positive but nucleic acid testing negative. No active infection was detected in any recipient post-transplant. CONCLUSIONS: The described opt-in system permits efficient allocation and utilization of kidneys from IVRDs, with superior quality and graft function. Education is crucial to facilitate informed consent and equity of access to this donor pool.

Telehealth model of care for routine follow up of renal transplant recipients in a tertiary centre: A case study.

Royal Melbourne Hospital (RMH) performs over 140 kidney transplant operations annually. Kidney transplant recipients require regular medical review, which results in loss of time and costs from travel, particularly for regional patients, and places high demand on the hospital outpatient service. The RMH renal transplant unit initiated a telehealth service in 2016 to provide cost effective, patient-centred clinical care for regional patients. To date, 263 clinical reviews have been conducted via telehealth, potentially saving 203,202 kilometres in travel distance; 2771 hours in car travel time; an estimated AUD $31,048 in petrol savings and 51 tonnes CO2 equivalents of greenhouse gas emissions. Lessons learnt have included the importance of using technology that allows patients to access telehealth from their place of choice. The option of a joint consultation with local healthcare providers has facilitated the development of extended care networks for our patients. Incorporation of telehealth into our outpatient system has been achieved with the existing nephrology workforce, making it a sustainable long-term review option. Our renal transplant telehealth outpatient clinic has been a successful change in the way we provide care to regional patients. Formal comparison of clinical outcomes and the patient experience of telehealth versus in person reviews are underway.

Examining the Increased Rates of Deceased Donor Kidney Nonutilization in Australia: What Has Changed?

BACKGROUND: From 2013, Australia has experienced a sustained increase in the proportion of deceased donor kidneys that are retrieved but not utilized for transplantation. We aimed to determine whether this could be explained by changes in donor characteristics over time. METHODS: Registry data were used to examine predictors of kidney nonutilization over the period 2005-2017. Multilevel mixed effect logistic regression modeling and propensity score analysis were used to determine whether era of donation (2013-2017 versus 2005-2012) was an independent predictor of organ nonutilization after controlling for donor characteristics. RESULTS: A total of 7810 kidneys were retrieved for the purpose of transplantation with 334 (4.3%) not utilized. The nonutilization rate was 5.8% in 2013-2017 compared to 2.7% in 2005-2012. Despite adjustment for donor characteristics, donation in the more recent era remained a significant predictor of kidney nonutilization (adjusted odds ratio, 1.98; 95% confidence interval, 1.54-2.54; P < 0.001). This finding was confirmed in the propensity score analysis. CONCLUSIONS: Kidneys retrieved in Australia since 2013 were more likely not to be utilized for transplantation even after adjusting for changes in donor characteristics. The abrupt increase may be explained by increased clinical risk aversion, changes in unmeasured donor factors or logistical issues. Although nonutilization rates in Australia remain low by international standards, further clinical auditing of the reasons for offer decline may help to optimize resource utilization and maximize transplant opportunities.

Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Introduction and Immunology.

Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.

Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Transplant Recipients.

Organ transplantation is a lifesaving procedure for many patients. To prevent rejection or graft-versus-host disease, recipients require long-term immunosuppression. In patients who have ever been exposed to hepatitis B, it is possible for reactivation to occur; this includes patients who are anti-hepatitis B core antibody-positive only or both anti-hepatitis B core antibody-positive and hepatitis B surface antibody-positive. The susceptibility to this varies with the nature of the transplant. Hepatitis B can be transmitted from donor to recipient. It is important to assess the hepatitis B status and formulate a strategy to prevent transmission and prevent reactivation.

Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Patients with Hematological and Solid Tumor Malignancies.

Patients with malignancies require chemotherapy and other immunosuppressive therapies for treatment. Because of this immunosuppression, in patients who have ever been exposed to hepatitis B it is possible for reactivation to occur. This reactivation can be fatal. Reactivation is particularly likely in patients who receive B cell-active agents such as rituximab. The occurrence of reactivation flares may also delay further chemotherapy, which can negatively affect the outcome of the underlying malignancy. Accordingly, it is important to screen patients for markers of hepatitis B and institute antiviral prophylaxis to prevent reactivation.

Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Other Populations and Newer Agents.

Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.