Renal outcomes of simultaneous liver–kidney transplantation compared to liver transplant alone for candidates with renal dysfunction

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD‐LTA; n = 103) or simultaneous liver–kidney transplant (RD‐SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)–glomerular filtration rate (GFR) <25 mL/min/1.73 m². RD‐LTAs had worse one‐yr post‐transplant survival compared to RD‐SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD‐LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD‐LTA recipients died in the first post‐transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD‐LTA recipients might have derived survival benefit from RD‐SLKT. Overall, 87% of RD‐LTA patients recovered renal function within one month of transplant. One yr after RD‐LTA or RD‐SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD‐SLKT would have yielded substantial short‐term survival benefit to RD‐LTA recipients.     

Tumor biology and pre‐transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre‐transplant locoregional therapy (LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty‐five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha‐fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five‐yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre‐transplant LRT did not affect post‐transplant outcomes in patients meeting Milan criteria but did result in lower three‐yr HCC recurrence (7% vs. 75%, p < 0.001) and better three‐yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre‐transplant LRT are important factors that determine the post‐transplant outcomes in patients with HCC who meet R4T3 criteria.     

Influence of larger graft weight to recipient weight on the post‐liver transplantation course

Size matching between recipient and donor livers is an important factor in organ allocation in the context of liver transplantation (LT). The aim of this study was to determine whether a large graft for recipient size influenced the post‐transplant course. One hundred and sixty‐two successive LT recipients were included and retrospectively divided into two groups: 25 (15%) had a graft‐to‐recipient weight ratio (GWRW) ≥2.5% and 137 (85%) had a GWRW <2.5%. Postoperative complications and outcomes were recorded. In the GWRW >2.5% group, more end‐to‐end caval replacement (72% vs. 38%, p = 0.003) and veno‐venous bypass (48% vs. 23%, p = 0.01) were used. Peak AST/ALT values were higher in the GWRW >2.5% group (AST: 596 [70–5876] vs. 453 [29–5132] IU/l, p = 0.03; ALT: 773 [101–5025] vs. 383 [36–4921] IU/l, p = 0.02). Among postoperative complications, the rate of respiratory failure was higher in the GWRW >2.5% group (32% vs. 14%, p = 0.04). The rates of other complications did not differ between the two groups. Both groups had similar graft and patient survival rates at one yr. Using large grafts for recipient size did not impair liver function and did not modify graft and patient outcomes at one yr. However, a GWRW >2.5% appeared to be a determining factor for respiratory morbidity following LT.     

Impact of locoregional therapy and alpha‐fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis

Liver transplantation (LT) provides optimal long‐term disease‐free survival for hepatocellular carcinoma (HCC). High pre‐LT alpha‐fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT‐recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (2006–2009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease‐free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.038–0.14), normal peak AFP (29.6, 95% CI, 2.96–296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.03–0.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4–100.5). Twenty‐one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre‐transplant appears to positively influence outcomes in those who received locoregional therapy.     

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.     

Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.     

Screening colonoscopy in liver transplant candidates: risks and findings

The indication for mandatory screening colonoscopies in liver transplant candidates is controversial. Since the introduction of MELD‐based allocation, patients with advanced liver disease and often severe comorbidities are prioritized for liver transplantation (LT). This study evaluated safety and outcome of colonoscopy in this high‐risk patient group. During a two‐yr period, we performed 243 colonoscopies in potential LT candidates. Endoscopic findings were registered in a standardized form, and correlations with biochemical or clinical parameters were analyzed using Mann–Whitney U‐test and chi‐square test. Only 57 patients (23.5%) had an endoscopically normal colon. Main findings were polyps (45.7%), hypertensive colopathy (24.3%), diverticulosis (21%), rectal varices (19.8%), and hemorrhoids (13.6%). In 21% of all patients, the removed polyps were diagnosed as adenomas. The prevalence of neoplastic polyps increased significantly with age: 13.6% (patients <50 yr) vs. 25% (patients ≥50 yr) (p = 0.03). Advanced neoplasia was found only in patients older than 40 yr. No major complications were observed; post‐interventional hemorrhage was observed in 1.7% and controlled by clipping or injection therapy. In conclusion, lower gastrointestinal endoscopy is safe and effective in LT candidates. Due to the age dependency of neoplastic polyps, a screening colonoscopy should be performed in LT candidates older than 40 yr or with symptoms or additional risk factors.     

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.     

Comparing 10‐yr renal outcomes in deceased donor and living donor liver transplants

Few studies have explored whether the type of LT, deceased donor LT (DDLT) or living donor LT (LDLT), impacts long‐term renal outcomes. We performed a retrospective analysis of 220 LT recipients at our institution to study their renal outcomes at 10 yr. Exclusion criteria were age ≤ 18 yr, graft survival ≤6 months, and multiorgan transplants; 108 DDLTs and 62 LDLTs were eligible. At baseline, DDLTs had a lower eGFR than LDLTs and 10.2% of DDLTs were on dialysis as compared to 0% of LDLTs. At 10 yr, seven DDLT and three LDLT recipients required dialysis or renal transplant (p = 0.75). In recipients with graft survival >6 months, DDLTs had a slower decline in eGFR as compared to LDLTs (p < 0.01). Among LDLTs, the decline in eGFR continued over the entire 10‐yr period, whereas among DDLTs, the decline in eGFR slowed significantly after six months (p = 0.01). This difference between the two groups was not seen among patients in the highest quartile of baseline eGFR. Patient survival and graft survival were similar. In conclusion, the incidence of end‐stage renal disease was similar in both DDLT and LDLT patients, but LDLT recipients seem to have a more sustained decline in eGFR when compared with DDLT recipients.     

Clinical analysis of recurrent hepatocellular carcinoma after living donor liver transplantation

This study aimed to analyze the clinical outcomes and factors influencing the outcome in the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). Between October, 1997 and September, 2010, 25 (16.0%) of 156 patients who had undergone LDLT for HCC experienced recurrence. All patients with recurrence, with a single exception, were in the high‐risk group. Among patients with recurrence, 76.0% of patients experienced recurrence within one yr after LDLT. One‐ and five‐yr survival rates of recurred patients were 56.0% and 8.6%, respectively. Among them, 32% of patients were treated with curative‐intent treatment, and their one‐ and five‐yr survival rates were 62.5% and 25.0%, respectively. Beyond the Milan criteria at liver transplantation (LT) (p = 0.032), multiple recurrence (p = 0.001), and palliative treatment for recurrent tumors (p = 0.049) were related to poor survival after recurrence. Additionally, the independent prognostic factors included multiple recurrence (p = 0.005) and the Milan criteria at LT (p = 0.047). Because almost all recurrent cases belonged to the high‐risk group and recurred within two yr, the high‐risk group should undergo close follow‐up for early detection and be treated with liver‐directed therapies. Although the prognosis of recurrent HCC after LDLT is poor, long‐term survival can be expected on a single recurrence and curative treatment.     

Hepatocellular carcinoma in Child's A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention‐to‐treat principle

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre‐treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention‐to‐treat principle resulted in a better five‐yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five‐yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five‐yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis.     

Organ allocation in pediatric renal transplants: is there an optimal donor?

The 2005 revised allocation scheme for pediatric renal transplantation made the decision of whether to transplant an available living‐donor (LD) kidney or use a deceased‐donor (DD) kidney controversial. The aim of this study was to examine kidney allograft utilization, sensitization, and outcomes of pediatric transplant recipients. Between January 2000 and December 2009, 91 consecutive pediatric kidney recipients (<20 yr) were transplanted. The LD (n = 38) and DD (n = 53) groups were similar in age, gender, dialysis status at transplant, warm ischemia time, and overall patient survival. LD recipients were more likely to be Caucasian (92 vs. 69%), receive older allografts (39 ± 10 vs. 23 ± 9 yr), and have fewer human leukocyte antigen (HLA) mismatches (3.3 ± 1.6 vs. 4.4 ± 1.5, p < 0.01 for all). Graft survival at one, three, and five yr post‐transplant was longer for LD recipients (97%, 91%, 87% vs. DD 89%, 79%, 58%, respectively, p < 0.05). At the time of transplant, 17 (33%) DD recipients had an available LD (mean age 40 yr). A greater proportion of all patients were moderately (PRA 21–79%) sensitized post‐transplant (p < 0.05). A multivariable analysis of graft survival indicated that the advantage in LD organs was likely due to fewer HLA mismatched in this group. Nonetheless, LD organs appear to provide optimal outcomes in pediatric renal transplants when considering the risk of becoming sensitized post‐transplant complicating later use of the LD kidney.     

Medication adherence and rejection rates in older vs younger adult liver transplant recipients

A growing number of older adults are undergoing liver transplantation (LT) in the United States. In some settings, it is thought that adherence declines with age. This retrospective study examined adherence and clinical outcomes in older vs younger adult LT recipients. Medical records of adult LT recipients from 2009 to 2012 from a single urban center were reviewed. The medication level variability index (MLVI) was the predefined primary outcome, with nonadherence defined as MLVI >2.5. The secondary outcome was incidence of rejection. Outcomes were evaluated starting 1 year post‐LT until 2015. A total of 42 of 248 patients were ≥65 at transplant. Older adults had significantly better adherence than younger ones (65%≥65 were adherent vs 42% younger adults; chi‐square two‐tailed P=.02). Survival analyses of rejection between age groups censored by time since transplant showed no difference among the four age groups (χ²=0.84, P=.84). Older age was not found to be a risk factor for reduced adherence or graft rejection in patients surviving at least 1 year post‐LT.     

Histologically proven non‐alcoholic fatty liver disease and clinically related factors in recipients after liver transplantation

Non‐alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the world population, and its prevalence has been increasing. The study was aimed at evaluating the prevalence and peri‐transplant risk factors for post‐liver transplantation (LT) NAFLD. A retrospective review was performed for adult recipients who underwent late protocol biopsy (>1 yr after LT) between August 2010 and December 2012. Hepatic steatosis was reviewed and graded by hepatopathologists, and the peri‐transplant factors were analyzed for relationships to histologically proven NAFLD. Total 166 biopsies had been performed in 156 recipients. NAFLD was present in 27.1% at a mean period of 35.4 months between LT and biopsy, moderate and severe steatosis (≥33%) consisted of 28.9%. In multivariate analysis, pre‐LT alcoholic cirrhosis (odds ratio [OR] 8.031, p = 0.003), obesity at biopsy (OR 3.873, p = 0.001), and preexisting donor graft steatosis (OR 3.147, p = 0.022) were significant risk factors for post‐LT NAFLD. In conclusion, NAFLD represented a considerable portion of recipients, but this prevalence was not higher than those for general population. Three risk factors were significantly related to post‐LT NAFLD, and recipients with those factors should be monitored for NAFLD. Furthermore, possible progression to non‐alcoholic steatohepatitis (NASH) or fibrosis and metabolic syndrome should be considered in future studies.     

Living Donor Liver Transplantation for Patients Older Than Age 70 Years: A Single‐Center Experience

Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.     

Steroid‐free living donor liver transplantation for HCV – a multicenter prospective cohort study in Japan

This prospective, non‐randomized, multicenter cohort study analyzed the safety and efficacy of a steroid‐free immunosuppressive (IS) protocol for hepatitis C virus (HCV)‐positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assigned the steroid‐free IS protocol (Fr group) and 29 the traditional steroid‐containing IS protocol (St group). Serum HCV RNA levels increased over time and were higher in the St group until postoperative day 90 (POD 14, p = 0.013). Preemptive anti‐HCV therapy was started in a higher percentage of recipients (59.3%) in the Fr group than in the St group (31.0%, p = 0.031), mainly due to early HCV recurrence. The incidence of HCV recurrence at one yr was lower in the Fr group (22.2%) than in the St group (41.4%; p = 0.066). The incidence of acute cellular rejection was similar between groups. New onset diabetes after transplant, cytomegalovirus infection, and renal dysfunction were significantly less frequent in the Fr group than in the St group (p = 0.022, p < 0.0001, p = 0.012, respectively). The steroid‐free IS protocol safely reduced postoperative morbidity and effectively suppressed both the HCV viral load in the early post‐transplant period and HCV recurrence in HCV‐positive LDLT recipients.     

Conversion to everolimus dramatically improves the prognosis of de novo malignancies after liver transplantation for alcoholic liver disease

De novo malignancies are a main cause for late death after liver transplantation (LT). Everolimus (ERL) is an immunosuppressive agent with antitumoral properties. The aim of the present retrospective study was to identify prognostic factors, including conversion to ERL, for patients presenting non‐cutaneous de novo solid organ malignancy after LT for alcoholic cirrhosis. The study population consisted of 83 patients (presenting 100 tumors, including 75% of upper aerodigestive tract cancers), among the 398 patients who underwent LT for alcoholic cirrhosis in our center. After diagnosis, ERL was introduced in 38 patients and calcineurin‐inhibitor was discontinued in 64.1% of them. Tumor stage was a significant prognostic factor with a one‐yr survival at 82.6% for early stages, 63.4% for intermediate stages (N+) and 27.4% for disseminated diseases (p < 0.001). Associated relative risk factor was 2.202 (95% CI 1.044–4.644) for intermediate stages and 5.743 (95% CI 2.436–13.541) for metastatic stages. One‐ and five‐yr survival was 77.4% and 35.2% in ERL group vs. 47.2% and 19.4% in the non‐ERL group, respectively (p = 0.003). The relative risk factor for ERL was 0.447 (95%CI 0.257–0.778). Our results strongly suggest that conversion to ERL improves the prognosis of de novo malignancies after LT for alcoholic cirrhosis. Prospective studies are needed to confirm this benefit.     

Belatacept treatment for two yr after liver transplantation is not associated with operational tolerance

Belatacept was recently evaluated in liver transplantation (LT) in a phase II multicenter trial, which was terminated prematurely. Patients were more than two yr post‐LT at the time. As high rates of spontaneous tolerance after LT have been reported and as belatacept has marked immunomodulatory effects, we decided to maintain the belatacept patients enrolled at our center (n = 4) on MMF monotherapy. All belatacept patients on MMF monotherapy developed graft dysfunction consistent with acute rejection after a mean period of 10.3 (7–14) wk. Patients were therefore switched to triple therapy with CNI, MMF, and corticosteroids. Graft dysfunction resolved within 1–3 wk after switch. At the time of belatacept discontinuation, mean eGFR was 105.1 mL/min/1.73 m² (92.1–118.9) in belatacept patients compared to 58 mL/min/1.73 m² (36.1–98.2) in controls (p = 0.022). One yr after the switch to CNI therapy, eGFR had declined by 27.4 mL (19.2–39.3; p = 0.008). Thus, LT patients treated with belatacept show superior kidney function that declines upon institution of CNIs. MMF monotherapy following withdrawal of belatacept is associated with a high incidence of graft dysfunction. Belatacept has no obvious immunomodulatory effects in LT recipients that would be sufficient to allow drug withdrawal with a high rate of success.     

Re‐exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies

Re‐exposure to beta cell autoantigens and its relevance in the presence of donor‐specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty‐three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma‐associated antigen 2 (IA‐2), insulin (micro‐IAA [mIAA]), and islet‐specific zinc transporter isoform‐8 (ZnT8). Twenty‐five (75.7%) had pre‐transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA‐2 n = 2, GA65 + mIAA+IA‐2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA‐2 (>0.16), and ZnT8 (p > 0.07) were observed between pre‐transplant and post‐transplant at 6 or 12 months. A decrease in mIAA from pre‐ to post‐6 months (p < 0.0001), 12 months (p < 0.0001), and from post‐6 to post‐12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow‐up (three yr). Re‐exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.     

Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997–2010

This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post‐transplant cancers were diagnosed—including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10‐year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios ‐ SIR=4.7, 95% CI: 3.2–6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1–17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high‐risk recipients like those with ALD.