Cervical human papillomavirus infection in the early postoperative period after liver transplantation: Prevalence,risk factors,and concordance with anal infections

Solid organ transplant recipients are at increased risk of developing several human papillomavirus (HPV)‐related malignancies, including cervical and anal cancers. The purpose of this prospective study was to assess the initial prevalence and risk factors for high‐risk HPV (HR‐HPV) cervical infections in liver transplant recipients, as well as their concordance with anal infections. A total of 50 female patients were enrolled in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw (center with >1600 liver transplantations). The initial prevalence of cervical HR‐HPV infection was 10.0% (5/50). The only significant risk factor for cervical HR‐HPV infection was ≥4 lifetime sexual partners (P=.037). Statistical tendencies toward higher prevalence of cervical HR‐HPV infections were found for patients with hepatitis B virus (HBV, P=.082) and with model for end‐stage liver disease (MELD) score ≤8 (P=.064). Cervical cytology was abnormal in 10 patients, including three with HR‐HPV. Out of 12 patients with available data on anal HR‐HPV, one had concordant HPV 16 infection. In conclusion, the initial prevalence of high‐risk HPV infection is relatively low, except for patients with ≥4 previous sexual partners and potentially in those with HBV and/or low MELD score.     

Liver transplantation for critically ill cirrhotic patients: Stratifying utility based on pretransplant factors

The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade‐3 acute‐on‐chronic liver failure (ACLF‐3). Patients with ACLF‐3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1‐year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1‐year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre‐LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO₂/FiO₂ ≤ 200 mm Hg (P = .026), and pre‐LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf‐3 model (TAM) score. A cut‐off at 2 points distinguished a high‐risk group (score >2) from a low‐risk group (score ≤2) with 1‐year survival of 8.3% vs 83.9% respectively (P < .001). This model was subsequently validated in the independent multicenter cohort. The TAM score can help stratify posttransplant survival and identify an optimal transplantation window for patients with ACLF‐3.     

Interactions between virus‐related factors and post‐transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia

Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post‐transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1‐year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0–F1 in 36% and F2–F3 in 57%. Factors independently associated with post‐transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV‐related ascites.     

Impact of MBL2 gene polymorphisms on the risk of infection in solid organ transplant recipients: A systematic review and meta‐analysis

Mannose‐binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have been associated with susceptibility to infection, although data in solid organ transplant recipients remains inconclusive. This meta‐analysis was primarily aimed at investigating the association between posttransplant bacterial and fungal infection and variant alleles of MBL2 gene SNPs in the promoter/5’ untranslated region and exon 1. Cytomegalovirus (CMV) infection and/or disease were considered secondary outcomes. PubMed, EMBASE, and Web of Knowledge were searched for relevant articles up to August 2018. Eleven studies (comprising 1858 patients) were included, with liver transplant (LT) recipients accounting for 80.4% of the pooled population. As compared to high‐MBL expression haplotypes (YA/YA, YA/XA), any MBL‐deficient haplotype was associated with an increased risk of posttransplant bacterial and fungal infections (risk ratio [RR]: 1.30; P = .04). Low/null‐MBL expression haplotypes (XA/O, O/O) also increased the risk of primary outcome (RR: 1.51; P = .008) and CMV events (RR: 1.50; P = .006). No effect was observed for individual promoter SNPs. In conclusion, MBL‐deficient haplotypes are associated with a significant, albeit moderate, increase in the risk of posttransplant infection, with this association being mainly restricted to LT recipients.     

Donation after cardiac death liver transplantation is associated with increased risk of end‐stage renal disease

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end‐stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty‐three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow‐up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long‐term renal outcomes in liver transplant recipients.     

Outcome comparison of liver transplantation for hepatitis A‐related versus hepatitis B‐related acute liver failure in adult recipients

Hepatitis A virus (HAV) can cause acute liver failure (ALF). This study compares outcomes between liver transplantation (LT) for HAV‐related ALF (HAV‐ALF) and LT for hepatitis B virus (HBV)‐related ALF (HBV‐ALF). Of 3616 adult LTs performed between January 2005 and December 2014, we performed LT for HAV‐ALF recipients (n = 29) and LT for HBV‐ALF recipients (n = 34). HAV‐ALF group included 18 males and 11 females with mean age of 33.1 years. Graft survival rates in HAV‐ALF and HBV‐ALF were 65.5% and 88.0% (1 year) and 65.5% and 84.0% (5 years) (P = .048). Patient survival rates in HAV‐ALF and HBV‐ALF were 69.0% and 88.0% (1 year) and 69.0% and 84.0% (5 years) (P = .09). Multivariate analyses demonstrated that acute pancreatitis and HAV recurrence were independent risk factors of graft and patient survival. Post‐transplant outcome was poorer in patients with HAV‐ALF than in those with HBV‐ALF. This weakens LT's appropriateness in HAV‐ALF patients with pancreatitis. HAV recurrence after LT for HAV‐ALF is common and often fatal; thus, HAV recurrence should be monitored vigilantly, beginning early post‐transplant.     

Physical frailty after liver transplantation

Frailty is prevalent in liver transplant candidates, but little is known of what happens to frailty after liver transplantation. We analyzed data for 214 adult liver transplant recipients who had ≥1 frailty assessment using the Liver Frailty Index (LFI) at 3‐ (n = 178), 6‐ (n = 139), or 12‐ (n = 107) months posttransplant (higher values=more frail). “Frail” and “robust” were defined as LFI ≥4.5 and <3.2. Median pre–liver transplant LFI was 3.7, and was worse at 3 months (3.9; P = .02), similar at 6 months (3.7; P = .07), and improved at 12 months (3.4; P < .001). The percentage who were robust pre‐ and 3‐, 6‐, and 12‐months posttransplant were 25%, 14%, 28%, and 37%; the percentage frail were 21%, 21%, 10%, and 7%. In univariable analysis, each 0.1 pretransplant LFI point more frail was associated with a decreased odds of being robust at 3‐ (odds ratio [OR] 0.75), 6‐ (OR 0.77), and 12‐months (OR 0.90) posttransplant (P ≤ .001), which did not change substantially with multivariable adjustment. In conclusion, frailty worsens 3 months posttransplant and improves modestly by 12 months, but fewer than 2 of 5 patients achieve robustness. Pretransplant LFI was a potent predictor of posttransplant robustness. Aggressive interventions aimed at preventing frailty pretransplant are urgently needed to maximize physical health after liver transplantation.     

Durability of the hepatitis B vaccination in pediatric renal transplant recipients

Since hepatitis B virus (HBV) vaccine implementation, HBV infection has significantly decreased. However, adult renal transplant recipients show a higher rate of seroreversion compared to the general population, leading to HBV infection risk. Data are limited in pediatric renal transplant recipients. Retrospective data were collected to determine the seroprotection and durability of HBV vaccination in pediatric renal transplant patients from 2004 to 2014. One hundred subjects were categorized based on pre‐ and post‐transplant hepatitis B surface antibody (HBsAb). Pretransplant, 85 recipients (85%) had a positive HBsAb compared to 15 (15%) with negative HBsAb. In univariable analyses, other than age (P < .05) no significant differences existed pretransplant by demographics, pretransplantation dialysis, or number of vaccinations. Of the 85 pretransplantation responders, 53 (62%) remained HBsAb positive post‐transplantation, 28 (32%) seroreverted, and 4 developed indeterminate titers. All seroreversions occurred within 5 years post‐transplant. Receipt of a living donor organ had higher risk of reversion (P = .005). No significant differences were found in demographics, pretransplantation dialysis, vaccination number, or acute rejection. Despite vaccination, 15% of pediatric renal transplant candidates were seronegative, and an additional 32% lost seroprotection within 5 years post‐transplantation leaving nearly half of transplant recipients at risk for HBV infection.     

Hepatic ischemia reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia‐reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single‐center study was to determine if hepatic ischemia‐reperfusion injury, estimated by peak peri‐operative serum amino‐transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500–2999 and ≥3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia‐reperfusion injury demonstrates a strong relationship with peri‐operative AKI in DBD liver transplant recipients.     

Prevalence of anal HPV infection in solid-organ transplant patients prior to immunosuppression

Patients that undergo organ transplantation have a high risk of developing various malignancies, depending on the duration and magnitude of immunosuppressive therapy. Among others, a 10-fold increased relative risk has been reported for the development of anal cancer. There is a strong association between persistent infection with high-risk mucosal types of human papillomavirus (HPV) and anogenital neoplasia. In this study we analysed the prevalence of anal HPV infection in organ transplant patients before starting immunosuppressive therapy. In a university transplant unit, patients (n=60, 40 male, 20 female) that were undergoing solid-organ transplantation (kidney, liver) for the first time were routinely screened for anal HPV infection. Anal swabs were obtained within 24 h after transplantation and analysed for the presence of mucosal-type HPV DNA by liquid DNA/RNA hybridization [hybrid capture (HC) 2 test]. Overall, some type of HPV DNA was detected in 14/60 (23.3%) patients; 9/60 (15%) were positive for high-risk HPV and 8/60 (13.4%) were positive for low-risk HPV, and 3/60 (5%) were positive for both types. Prevalence of HPV infection tended to be higher in patients that were receiving liver transplants than in those receiving kidney transplants (29.4% vs. 20.9%), but the difference did not reach statistical significance. In our series of organ transplant patients the prevalence of previous HPV infection (23.3%) before immunosuppressive therapy was started was higher than that found in previous epidemiological studies or in a control group. In particular, there was a high rate (15%) of infection with oncogenic HPV types. These findings have important implications on screening and surveillance policies in this patient group at risk of developing neoplasias, including anal cancer.     

Organ donor screening for carbapenem‐resistant gram‐negative bacteria in Italian intensive care units: the DRIn study

The 759 cases of brain death declaration (BDD [Italian law, 6 hours of observation time]) that occurred in 190 Italian intensive care units (ICUs) between May and September 2012 were studied to quantify carbapenem‐resistant gram‐negative bacteria (CR‐GN) isolated in organ donors, to evaluate adherence to national screening guidelines, and to identify risk factors for CR‐GN isolation. Mandatory blood, bronchoalveolar lavage, and urine cultures were performed on the BDD day in 99% of used donors. Because results were rarely made available before transplant, >20% of transplants were performed before obtaining any microbiological information, and organs from 15 of 22 CR‐GN cases were used. Two (lung–liver) of the 37 recipients died, likely because of donor‐derived early CR‐GN sepsis. ICU stay >3 days (odds ratio [OR] = 7.49, P = .004), fever (OR = 3.11, P = .04), age <60 years (OR = 2.80, P = .06), and positive ICU epidemiology (OR = 8.77, P = .07) were associated with CR‐GN isolation. An association between single ICU and risk of CR‐GN was observed, as a result of differences across ICUs (ICC = 29%; 95% confidence interval [CI] 6.5%‐72%) probably related to inadequate practices of infection control. Continuous education aimed at implementing priority actions, including stewardship programs for a rational use of antimicrobials, is a priority in healthcare systems and transplant networks. Improved awareness among ICU personnel regarding the importance of early CR‐GN detection and timely alert systems might facilitate decisions regarding organ suitability and eventually save recipient lives.     

Clinical Analysis of Factors Affecting Hospital Mortality After Liver Transplant in Patients With High Model for End-Stage Liver Disease Score

BackgroundThis study was undertaken to identify poor prognostic factors in patients with high Model for End-Stage Liver Disease (MELD) scores.MethodsFrom September 2001 to December 2017, living donor liver transplant and deceased donor liver transplant were performed in 851 (84.4%) and 157 patients (15.6%), respectively, in our center. Eighty-one patients (8.0%) with MELD scores ≥ 35 were classified as patients with high MELD scores.ResultsThe overall survival rates in patients with high MELD scores were significantly worse than those in patients with low MELD scores (P = .005). However, no significant difference in survival was found between the 2 groups when in-hospital mortality was excluded. In-hospital mortality occurred in 18 patients (22.2%), and the main cause of death was sepsis (n = 14, 77.8%). On univariate analysis, the risk factors for in-hospital mortality were mean age (P = .028), mean MELD score (P = .045), intubation status (P < .001), culture positivity (P = .042), and encephalopathy grade 3 or 4 (P = .014). On multivariate analysis, age (P = .006), intubation status (P = .042), and culture positivity (P = .036) were significant.ConclusionsThe main cause of in-hospital mortality was sepsis, and the risk factors for in-hospital mortality of patients with high MELD score were older age, preoperative intubation, and culture positivity. Special attention should be paid to the prevention and treatment of infection in the liver transplant of patient with high MELD scores.     

Inferior graft survival of hepatitis B core positive grafts is not influenced by post‐transplant hepatitis B infection in liver recipients—A 35‐year single‐center experience

Nonoptimal liver grafts, and among them organs from anti‐HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long‐term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti‐HBc+ graft. The 10‐year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti‐HBc‐ grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti‐HCV+ recipients (P = 0.005), and anti‐HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti‐HBc+ grafts developed post‐transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long‐term survival (P = 0.008). Development of post‐transplant HBV infection did not affect adjusted 10‐year graft survival (100% vs. 100%; P = 1). Anti‐HBc+ liver grafts can be transplanted with reasonable but inferior long‐term patient and graft survival. The inferior graft survival is not, however, related with post‐transplant HBV infection as long as early diagnosis and treatment take place.     

Cytomegalovirus mismatch still negatively affects patient and graft survival in the era of routine prophylactic and preemptive therapy: A paired kidney analysis

The impact of cytomegalovirus (CMV) serostatus on kidney transplant outcomes in an era when CMV prophylactic and preemptive strategies are used routinely is not clearly established. Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, recipients with first deceased donor kidney transplant (≥18 years, 2010‐2015) were stratified into 4 groups in the main cohort: CMV‐seronegative donor (D?)/CMV‐seronegative recipient (R?), CMV‐seropositive donor (D+)/R?, D+/CMV‐seropositive recipient (R+), and D?/R+. In a paired kidney cohort, we identified 2899 pairs of D? kidney transplant with discordance of recipient serostatus (D?/R? vs D?/R+) and 4567 pairs of D+ kidney transplant with discordance of recipient serostatus (D+/R? vs D+/R+). In the main cohort, D+/R? was associated with a higher risk of graft failure (hazard ratio [HR] = 1.17, P = .01), all‐cause mortality (HR = 1.18, P < .001), and infection‐related mortality (HR = 1.38, P = .03) compared with D?/R?. In the paired kidney analysis, D+/R? was an independent risk factor for all‐cause mortality (HR = 1.21, P = .003) and infection‐related mortality (HR = 1.47, P = .04) compared with D+/R+. No difference in graft loss between D+/R? and D+/R+. CMV mismatch is still an independent risk factor for graft loss and patient mortality. The negative impact of D+/R? serostatus on mortality persists after fully matching for donor factors.     

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.     

Impact of the new MELD‐based allocation system on waiting list and post‐transplant survival—a cohort analysis using the French national CRISTAL database

Concerns related to equity and efficacy of our previous center‐based allocation system have led us to introduce a patient‐based allocation system called the “Liver Score” that incorporates the model for end‐stage liver disease (MELD) score. The main objective of this study was to compare waitlist and post‐transplant survivals before and after implementation of the “Liver Score” using the French transplant registry (period before: 2004–2006 and period after: 2007–2012). Patients transplanted during the second period were sicker and had a higher MELD. One‐year waitlist survival (74% vs. 76%; P = 0.8) and 1‐year post‐transplant survival (86.3% vs. 85.7%; P = 0.5) were similar between the 2 periods. Cirrhotic recipients with MELD > 35 had lower 1‐year post‐transplant survival compared to those with MELD <35 (74.8% vs. 86.3%; P < 0.01), mainly explained by their higher intubation and renal failure rates. The MELD showed a poor discriminative capacity. In cirrhotic recipients with MELD > 35, patients presenting 2 or 3 risk factors (dialysis, intubation, or infection) had a lower 1‐year survival compared to those with none of these risk factors (61.2% vs. 92%; P < 0.01). The implementation of the MELD‐based allocation system has led to transplant sicker patients with no impact on waitlist and post‐transplant survivals. Nevertheless, selection of patients with MELD > 35 should be completed to allow safe transplantation.     

Characteristics of Epstein–Barr viraemia in adult liver transplant patients: A retrospective cohort study

Therapeutic immunosuppression following solid organ transplantation increases the risk of Epstein–Barr (EBV) viraemia, which is implicated in post‐transplant lymphoproliferative disease (PTLD). We retrospectively analysed the incidence of EBV viraemia and clinical outcomes in 98 liver transplant recipients. Patients underwent EBV DNA monitoring by whole‐blood PCR: EBV levels were correlated with clinical parameters and outcomes for a median of 249 days. 67% patients developed EBV viraemia (EBV DNA ≥100 copies/ml) and 30% had sustained viraemia. There was a trend towards higher hazard ratios for viraemia with exposure to aciclovir (HR 1.57, P = 0.12) or in recipients of a poorly HLA‐matched graft (HR 1.62, P = 0.10). These associations became significant in the subgroup with >90 days surveillance; HR 2.54 (P = 0.0015) for aciclovir and HR 1.99 (P = 0.03) for poorly matched grafts. The converse was true with ganciclovir (HR 0.56 P = 0.13). Viraemia was more prolonged in men (median duration 7 days vs 1; P = 0.01) and in those with lower UKELD scores (11 days vs 1 day; P = 0.001) but shortened with ganciclovir exposure (P = 0.06). Younger patients were more likely to have high peak viral loads (P = 0.07). No clinical signs or symptoms or adverse outcomes were associated with EBV reactivation.     

HLA‐DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity

Alloimmune risk stratification in renal transplantation has lacked the necessary prognostic biomarkers to personalize recipient care or optimize clinical trials. HLA molecular mismatch improves precision compared to traditional antigen mismatch but has not been studied in detail at the individual molecule level. This study evaluated 664 renal transplant recipients and correlated HLA‐DR/DQ single molecule eplet mismatch with serologic, histologic, and clinical outcomes. Compared to traditional HLA‐DR/DQ whole antigen mismatch, HLA‐DR/DQ single molecule eplet mismatch improved the correlation with de novo donor‐specific antibody development (area under the curve 0.54 vs 0.84) and allowed recipients to be stratified into low, intermediate, and high alloimmune risk categories. These risk categories were significantly correlated with primary alloimmune events including Banff ≥1A T cell–mediated rejection (P = .0006), HLA‐DR/DQ de novo donor‐specific antibody development (P < .0001), antibody‐mediated rejection (P < .0001), as well as all‐cause graft loss (P = .0012) and each of these correlations persisted in multivariate models. Thus, HLA‐DR/DQ single molecule eplet mismatch may represent a precise, reproducible, and widely available prognostic biomarker that can be applied to tailor immunosuppression or design clinical trials based on individual patient risk.     

The association of pretransplant ferritin level with waiting list and post‐transplant survival. Does ferritin actually predict outcome?

Recent data suggest an association of serum ferritin (SF) with waiting list (WL) and postliver transplant (LT) outcomes. To assess the predictive capacity of SF on pre‐ and post‐LT outcomes, and to identify whether recipient or donor liver siderosis is associated with post‐LT survival; a retrospective analysis of 1079 patients assessed for first LT, 2000–2007 was performed. Iron deposition in the liver tissue was assessed using a semi‐quantitative grading system. Median age was 54 (18–82) years and 67% were male. Seventeen per cent had hepatocellular carcinoma (HCC). Median Model for End‐stage Liver Disease MELD score was 14 (6–40), ferritin was 174 μg/l (4–4597) with 36.5% had a SF ≥ μg/l. Age (OR = 1.028) and MELD score (OR = 1.158) were independently associated with WL mortality (P < 0.001), whilst SF was not (P = NS). Age (OR = 1.018), HCC (OR = 1.542) and cold ischemia time (CIT) ≥ 10 h (OR = 1.418) were independently associated with post‐LT survival (P < 0.05). Explant siderosis grade <2 was seen in 376 (71.7%) patients. Patients with explant siderosis grade ≥2 had inferior 12‐month post‐LT survival (P = 0.030). Presence of graft siderosis (15.8% of patients) was not associated with survival. In conclusion, we found a limited role for SF as a prognostic indicator for pre‐ or post‐transplant survival.