Identifying a targeted population at high risk for infections after liver transplantation in the MELD era

Sun H‐Y, Cacciarelli TV, Singh N. Identifying a targeted population at high risk for infections after liver transplantation in the MELD era.
Clin Transplant 2011: 25: 420–425. © 2010 John Wiley & Sons A/S. Abstract: Impact of model for end‐stage liver disease (MELD) scoring system on post‐transplant infections and associated risk factors are unknown. Infections <90 d post‐transplant were assessed in 277 consecutive liver transplant recipients from 1999 to 2008. “High‐risk” factors for infections were pre‐defined as MELD score >30, ICU stay >48 h prior to transplant, intraoperative transfusion ≥15 units, retransplantation, post‐transplant dialysis, or reoperation. Of the 240 recipients in the MELD era (2002–2008), 48.5% had any high‐risk factor. The OR for infection was 1.69, 2.00, 18.00, and 4.50 in recipients with any 1, 2, 3, and ≥4 high‐risk factors, respectively (χ² for trend, p < 0.001). In logistic regression model, recipient age (OR 1.12, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) were associated with infections. Compared with 37 pre‐MELD recipients, the overall infections and mortality at 12 months did not differ in the two eras. In Cox regression model, recipient age (OR 1.09, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) remained associated with infections. The overall frequency of infections did not increase in the MELD era. Pre‐defined risk factors accurately predicted the risk of infections in these patients.     

When Living Donor Liver Allografts Fail: Exploring the Outcomes of Retransplantation Using Deceased Donors

Outcomes of retransplantation after initial living donor liver transplantation (LDLT) are poorly understood. The aim of this study is to better understand the indications, timing, and outcomes of retransplantation after initial LDLT when compared to after initial deceased donor transplantation (DDLT). From 2002 to 2013, 209 retransplant recipients after initial LDLT and 2893 after initial DDLT were identified in Organ Procurement and Transplantation Network/United Network for Organ Sharing. Multivariable logistic models evaluated the association between initial transplant type and 1‐year mortality. The most frequent reason for early graft failure (≤14 days) in LDLT recipients was vascular thrombosis (63.6%) versus primary graft failure in initial DDLT recipients (59.1%). LDLT recipients were more often acutely and/or critically ill with a greater proportion of Status 1 (42.6% vs. 27.3%; p < 0.001) and intensive care unit (52.2% vs. 39.9%; p = 0.001) recipients at the time of retransplantation. There was no difference in adjusted 1‐year mortality between retransplant recipients after initial LDLT versus DDLT (odds ratio 0.74; 95% confidence interval 0.51–1.08). The proportion of recipients who ultimately required retransplantation for a third time was not different between the two groups (4.8%). Retransplantation outcomes after LDLT are not different from other retransplant procedures, despite recipients having greater acuity of illness and different indications.     

Evolution of Causes and Risk Factors for Mortality Post‐Liver Transplant: Results of the NIDDK Long‐Term Follow‐Up Study

Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long‐term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow‐up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal‐related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre‐LT diabetes, post‐LT diabetes, post‐LT hypertension, post‐LT renal insufficiency, retransplantation >1 year, pre‐LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post‐LT diabetes, hypertension and renal insufficiency were significant risk factors for liver‐related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre‐LT hypertension and post‐LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post‐LT factors including diabetes, hypertension and renal insufficiency may impact long‐term mortality.     

Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation‐05 Study

Identification of biomarkers that assess posttransplant risk is needed to improve long‐term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)‐05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy‐proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti‐HLA‐ and auto‐antibodies, angiogenic proteins, peripheral blood allo‐reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti‐HLA antibody (p < 0.04). Recipient CMV‐negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor‐C (OR 20; 95%CI:1.9–218) combined with decreases in endothelin‐1 (OR 0.14; 95%CI:0.02–0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.     

Changing trends in the aetiology,treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single‐centre prospective cohort study

To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post‐transplant over the last 10‐year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post‐transplant from 2007 to 2016. Trends of factors were analysed by 2‐year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram‐positive BSI decreased over time (40.5–2.2%). In contrast, there was a steady increase in Gram‐negative bacilli (GNB) BSI (54.1–93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4–20.4%) and Klebsiella pneumoniae (7.1–26.5%). Multidrug‐resistant (MDR) GNB (4.8–38.8%; P < 0.001) rose dramatically, especially due to extended‐spectrum β‐lactamase (ESBL) production (7.1–34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9–55.3%; P < 0.001) and as targeted antibiotic treatment (11.9–46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL‐producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time.     

再次肝移植--挽救肝移植失败受体生命唯一的手段(附774例报告)

目的 评估肝移植，尤其是再次肝移植的长期随访结果及影响结果的因素。方法 对1981年2月至1998年4月期间进行的、存活时间大于2年的4000例肝移植进行随访，其中再次肝移植774例。根据首次肝移植的时间，分为A、B、C三期。结果 774例（19．4％）接受第2次肝移植，148例（3．7％）接受第3次肝移植，20例（0．5％）接受第4次肝移植，5例（0．13％）接受第5次及5次以上肝移植。第1次再移植原因主要为移植肝原发性无功能、肝动脉栓塞和排斥反应。C期再次肝移植率（13．4％）明显低于A期（33．4％）和B期（23．7％），P＝0．001。结论 掌握适当的再移植指征、再次手术时机、受体的选择和手术技巧，再次肝移植的长期生存率明显改善。     

Kidney transplant outcomes from older deceased donors: a paired kidney analysis by the European Renal Association–European Dialysis and Transplant Association Registry

As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor–recipient age groups is required. Using ERA‐EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor (55–70 years), and transplanted into one recipient younger and one recipient of similar age to the donor. The recipient pairs were divided into two groups: group 1; younger (median age: 52 years) and older (60 years) and group 2; younger (41 years) and older (60 years). A total of 1410 adults were transplanted during 2000–2007. Compared to the older recipients, the mean number of functioning graft years at 10 years was 6 months longer in the group 1 and group 2 younger recipients (P < 0.001). Ten‐year graft survival was 54% and 40% for the group 1 younger and older recipients, and 60% and 49% for the group 2 younger and older recipients. Paired Cox regression analyses showed a lower risk of graft failure (group 1 younger; adjusted relative risk [RRa]:0.57, 95% CI:0.41–0.79, and group 2 younger; RRa:0.63, 95% CI:0.47–0.85) in younger recipients. Outcomes from older deceased donor allografts transplanted into differing donor–recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar‐aged recipients.     

Cytomegalovirus viremia associated with death or retransplantation in pediatric lung-transplant recipients

BACKGROUND: Cytomegalovirus (CMV) infection is a frequent complication of lung transplantation. However, there is limited information regarding the incidence and sequelae of CMV infections in pediatric lung-transplant recipients. On the basis of case series suggesting that CMV infection was associated with excess morbidity and mortality in lung-transplant recipients, we hypothesize that CMV viremia increases the risk of bronchiolitis obliterans (BOS) or death and retransplantation in the first year following transplantation. METHODS: A case-cohort study of pediatric primary lung-transplant recipients was performed. Univariate analysis was used to assess whether CMV viremia was associated with BOS or death and retransplantation within 1 year after transplantation. Patients at high risk for CMV infection received ganciclovir prophylaxis for 42 days posttransplantation. RESULTS: From July 1990 to November 2000, 194 pediatric patients received primary lung transplants. Twenty-three percent of patients developed CMV viremia. Eighty percent of CMV viremia episodes occurred before 120 days posttransplant. A first episode of CMV viremia was associated with retransplantation or death between days 90 and 365 (RR=4.1, 95% confidence interval [CI] 1.1-14.5) and was not associated with BOS (RR=1.3, 95% CI 0.5-3.3). CONCLUSIONS: CMV viremia in the first year after pediatric primary lung transplantation is associated with increased risk of death or retransplantation between 90 and 365 days posttransplant, when CMV prophylaxis has stopped. A phase II pilot trial is warranted to assess safety and short-term efficacy of increasing the duration of CMV prophylaxis from 42 to 120 days.     

Preformed and De Novo Donor Specific Antibodies in Visceral Transplantation: Long‐Term Outcome With Special Reference to the Liver

Despite improvement in early outcome, rejection particularly chronic allograft enteropathy continues to be a major barrier to long‐term visceral engraftment. The potential role of donor specific antibodies (DSA) was examined in 194 primary adult recipients. All underwent complement‐dependent lymphocytotoxic crossmatch (CDC‐XM) with pre‐ and posttransplant solid phase HLA–DSA assay in 156 (80%). Grafts were ABO‐identical with random HLA‐match. Liver was included in 71 (37%) allografts. Immunosuppression was tacrolimus‐based with antilymphocyte recipient pretreatment in 150 (77%). CDC‐XM was positive in 55 (28%). HLA–DSA was detectable before transplant in 49 (31%) recipients with 19 continuing to have circulating antibodies. Another 19 (18%) developed de novo DSA. Ninety percent of patients with preformed DSA harbored HLA Class‐I whereas 74% of recipients with de novo antibodies had Class‐II. Gender, age, ABO blood‐type, cold ischemia, splenectomy and allograft type were significant DSA predictors. Preformed DSA significantly (p < 0.05) increased risk of acute rejection. Persistent and de novo HLA–DSA significantly (p < 0.001) increased risk of chronic rejection and associated graft loss. Inclusion of the liver was a significant predictor of better outcome (p = 0.004, HR = 0.347) with significant clearance of preformed antibodies (p = 0.04, OR = 56) and lower induction of de novo DSA (p = 0.07, OR = 24). Innovative multifaceted anti‐DSA strategies are required to further improve long‐term survival particularly of liver‐free allografts.     

Risk factors for and outcomes of delayed graft function in live donor kidney transplantation – a retrospective study

Delayed graft function (DGF) in deceased donor kidney transplantation is associated with worse outcomes. DGF has been less well studied in live donor transplantation. We aimed to examine the risk factors for DGF, and associations between DGF and short‐ and long‐term outcomes in live donor kidney transplant recipients. Using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included live donor kidney transplants performed in Australia and New Zealand over 2004–2015 and excluded pediatric recipients (n = 440), pathological donors (n = 97), grafts that failed in the first week (as a proxy for primary non function; n = 38), and grafts with missing DGF data (n = 46). We used multivariable logistic regression to identify the risk factors for DGF and the association between DGF and rejection at 6 months; Cox proportional hazards models to examine the relationship between DGF and patient and graft survival; and linear regression to examine the association between DGF and eGFR at 1 year. DGF occurred in 77 (2.3%) of 3358 transplants. Risk factors for DGF included right‐sided kidney [odds ratio (OR) 2.00 (95% CI 1.18, 3.40)], donor BMI [OR 1.06 per kg/m² (95% CI 1.01, 1.12)]; increasing time on dialysis and total ischemic time [OR 1.09 per hour (1.00, 1.17)]. DGF was associated with increased risk of rejection at 6 months [OR 2.37 (95% CI 1.41, 3.97)], worse patient survival [HR 2.14 (95% CI 1.21, 3.80)] and graft survival [HR 1.98 (95% CI 1.27, 3.10)], and worse renal function at 1 year [Coefficient ‐9.57 (95% CI ?13.5, ?5.64)]. DGF is uncommon after live donor kidney transplantation, but associated with significantly worse outcomes. The only modifiable risk factors identified were kidney side and total ischemic time.     

Long‐term outcomes of donation after cardiac death liver allografts from a single center

Abstract: Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non‐heart‐beating or donation after cardiac death (DCD) are encouraging. However, long‐term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow‐up >4.5 years. During 1998–2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart‐beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non‐function and biliary complications as compared with SCD and ECD. The overall one‐, two‐, and five‐yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long‐term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.     

A retrospective analysis of re‐exploration after living donor right lobe liver transplantation: incidence,causes, outcomes,and risk factors

Despite technical difficulties, right lobe liver grafting is preferred in living donor liver transplantation because of the graft size. Re‐exploration after living donor right lobe liver transplantation (LRLT) has never been separately analyzed. We aimed to analyze the incidence, causes, outcomes, and risk factors of re‐exploration after LRLT. We reviewed medical records of 1016 LRLT recipients from October 2003 to July 2017 and identified recipients who underwent re‐exploration within hospital stay. Separate analyses were also performed according to cause of re‐exploration. The overall incidence of re‐exploration was 17.0% (173/1016). The most common cause of re‐exploration was bleeding (50%). Overall re‐exploration was associated with clinical outcome, but different results were shown on analyses according to cause of re‐exploration. Risk factors of re‐exploration were underlying hepatocellular carcinoma and operative duration [Odds ratio (OR), 1.49; 95% confidence interval (CI), 1.05–2.12; P = 0.03, and OR, 1.002; 95% CI, 1.001–1.004; P = 0.0023, respectively]. Re‐exploration after LRLT is relatively common, and is strongly associated with mortality and graft failure.     

Recipient Outcomes Following Transplantation of Allografts From Live Kidney Donors Who Subsequently Developed End‐Stage Renal Disease

Live kidney donors have an increased risk of end‐stage renal disease (ESRD) compared with nondonors; however, it is unknown whether undetected, subclinical kidney disease exists at donation that subsequently contributes to this risk. To indirectly test this hypothesis, the authors followed the donated kidneys, by comparing the outcomes of 257 recipients whose donors subsequently developed ESRD with a matched cohort whose donors remained ESRD free. The compared recipients were matched on donor (age, sex, race/ethnicity, donor–recipient relationship), transplant (HLA mismatch, peak panel‐reactive antibody, previous transplantation, year of transplantation), and recipient (age, sex, race/ethnicity, body mass index, cause of ESRD, and time on dialysis) risk factors. Median recipient follow‐up was 12.5 years (interquartile range 7.4–17.9, maximum 20 years). Recipients of allografts from donors who developed ESRD had increased death‐censored graft loss (74% versus 56% at 20 years; adjusted hazard ratio [aHR] 1.7; 95% confidence interval [CI] 1.5–2.0; p < 0.001) and mortality (61% versus 46% at 20 years; aHR 1.5; 95% CI 1.2–1.8; p < 0.001) compared with matched recipients of allografts from donors who did not develop ESRD. This association was similar among related, spousal, and unrelated nonspousal donors. These findings support a novel view of the mechanisms underlying donor ESRD: that of pre‐donation kidney disease. However, biopsy data may be required to confirm this hypothesis.     

Multicentric evaluation of model for end‐stage liver disease‐based allocation and survival after liver transplantation in Germany – limitations of the ‘sickest first’‐concept

Since the introduction of model for end‐stage liver disease (MELD) in 2006, post‐orthotopic liver transplantation (OLT) survival in Germany has declined. The aim of this study was to evaluate risk factors and prognostic scores for outcome. All adult OLT recipients in seven German transplant centers after MELD implementation (December 2006–December 2007) were included. Recipient data were analyzed for their influence on 1‐year outcome. A total of 462 patients (mean calculated MELD = 20.5, follow‐up: 1 year) were transplanted for alcoholic cirrhosis (33.1%), hepatocellular carcinoma (26.6%), Hepatitis‐C (17.1%), Hepatitis‐B (9.5%), primary sclerosing cholangitis (5.6%) and late graft‐failure after first OLT before December 2006 (8.7%). 1‐year patient survival was 75.8% (graft survival 71.2%) correlating with MELD parameters and serum choline esterase. MELD score >30 [odds ratio (OR) = 4.17, confidence interval: 2.57–6.78, 12‐month survival = 52.6%, c‐statistic = 0.669], hyponatremia (OR = 2.07), and pre‐OLT hemodialysis (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153, mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum bilirubin and the survival after liver transplantation score were independent outcome parameters, respectively. MELD >30 currently represents a major risk factor for outcome. Risk factors differ in individual patient subgroups. In the current German practice of organ allocation to sicker patients, outcome prediction should be considered to prevent results below acceptable standards.     

A systematic review and meta‐analysis of donor ischaemic preconditioning in liver transplantation

Ischaemic preconditioning (IPC) is a strategy to reduce ischaemia–reperfusion (IR) injury. Its benefit in human liver transplantation is unclear. The aim of this study was to analyse the current evidence for donor IPC in liver transplantation. Systematic review and meta‐analysis of studies involving IPC of liver transplant donors. Ovid Medline, Embase and Cochrane CENTRAL were searched up until January 2015. Data retrieved included the primary outcomes of 1‐year mortality, incidence of primary graft non‐function (PGNF) and retransplantation. Secondary outcomes included aspartate aminotransferase (AST) levels on day 3 post‐op. Pooled odds ratios (ORs) were calculated for dichotomous data and mean weighted ratios for continuous data. Ten studies included 593 patients (286 IPC; 307 control). IPC was associated with a reduction in mortality at 1 year (6% vs. 11%) although this was not statistically significant (OR 0.54, 95% C.I. 0.28–1.04, P = 0.06). The IPC group had a significantly lower day 3 AST level (WMD ?66.41iU, P = 0.04). This meta‐analysis demonstrates that IPC reduces liver injury following transplantation and produces a large reduction in 1‐year mortality which was not statistically significant. Confirmation of clinical benefit from IPC requires an adequately powered prospective RCT.     

Donor predictors of allograft utilization for pediatric heart transplantation

Pediatric heart transplantations are limited by the supply of donor allografts. We sought to determine the cardiac allograft utilization rate for pediatric donors and identify donor factors that predict graft use for transplantation. The United Network for Organ Sharing deceased donor database was queried from April 30, 2006, to March 31, 2014. Donor risk factors that might affect graft use for cardiac transplantation were evaluated. The pediatric cardiac graft utilization rate was calculated, and logistic regression modeling was performed to determine the relationship of risk factors with graft use for transplantation. During the study period, 6682 eligible cardiac donors <18 years of age were identified, and 3758 (56.2%) grafts were utilized for transplantation. Grafts from male donors (OR 1.181) were significantly associated with graft utilization. Graft donor age >1 year (OR 0.363), non‐O blood type (OR 0.586), CDC ‘high‐risk’ donor status (OR 0.676), use of inotropes (OR 0.718), use of >2 inotropes (OR 0.328), and donor left ventricular ejection fraction <50% (OR 0.045) were significantly associated with graft nonutilization. The pediatric cardiac allograft utilization rate and risk factors for graft use for transplantation have been identified. Additional studies will be needed to assess the donor–recipient relationship on pediatric transplant outcomes.     

Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart–Liver Transplantation

When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart–liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune‐mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol‐ and indication‐specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell–mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor‐specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody‐mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0–0.02; p < 0.0001), antibody‐mediated rejection (OR 0.04, 95% CI 0–0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07–0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients.     

Dynamic changes of B‐cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection

B cells play an important role in the immune responses which affect the outcomes of kidney allografts. Dynamic changes of B‐cell compartments in clinical kidney transplantation are still poorly understood. B‐cell subsets were prospectively monitored using flow cytometry for 1 year in 98 kidney transplant recipients. Data were correlated with immunosuppression and clinical outcomes. An increase in the total population of B lymphocytes was observed during the first week after transplantation. The level of IgM^highCD38^highCD24^high transitional B cells reduced significantly up until the third month, with partial repopulation in the first year. Lower numbers of transitional B cells in the third month were associated with higher risk of graft rejection. IgM⁺IgD⁺CD27^? naive B cells did not change within follow‐up. IgM⁺CD27⁺ nonswitched memory B cells and IgM^?CD27⁺ switched memory B cells increased on post‐operative day 7. IgM^?CD38^highCD27^high plasmablasts showed similar kinetics during the first post‐transplant year, similar to transitional B cells. In conclusion, sensitized kidney transplant recipients as well as those with either acute or chronic rejection within the first post‐transplant year exhibited lower levels of transitional B cells. Therefore, these data further support the hypothesis that transitional B cells have a protective role in kidney transplantation.     

Invasive aspergillosis in the recipients of liver retransplantation.

Retransplantation is a major risk factor for invasive aspergillosis in liver transplant recipients. However, the risk for invasive aspergillosis with time elapsed since retransplantation, clinical characteristics, and outcome of patients who develop this infection after retransplantation of the liver has not been defined. Patients comprised 17 liver retransplant recipients with invasive aspergillosis between 1990 and 2004. Retransplantation was considered early if it was performed within 30 days and late if performed after 30 days of the first or primary transplant. Retransplant recipients comprised 25% of all cases of invasive aspergillosis after liver transplantation. Fifty-three percent of the Aspergillus infections occurred within 30 days, and 76% within 90 days of retransplantation. In all, 53% (9/17) of the patients were late retransplant recipients. Late compared to early retransplant recipients with invasive aspergillosis were more likely to have central nervous system involvement with invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late and 63% for early retransplant recipients with Aspergillus infections. In conclusion, time-varying risk for invasive aspergillosis after retransplantation has implications relevant for guiding antifungal prophylaxis. Given a greater risk for disseminated infection and poor outcome in late retransplant recipients with aspergillosis, potent and aggressive antifungal therapy should be considered upfront in these patients.