Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: Analysis of the US Multicenter HCC Transplant Consortium.

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

Liver Transplantation as a New Standard of Care in Patients With Perihilar Cholangiocarcinoma? Results From an International Benchmark Study.

OBJECTIVE: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

High-grade myelodysplastic syndrome in a pediatric multi-organ transplant recipient: A case report and literature review.

BACKGROUND: Pediatric myelodysplastic syndrome is a rare but life-threatening condition requiring prompt recognition and management. METHODS: We herein present the only reported case of a pediatric multi-organ transplant recipient developing myelodysplastic syndrome. RESULTS: The patient was a 14-year-old girl on chronic calcineurin inhibitor therapy who presented with peri-rectal pain approximately 13 years after liver, small bowel, and pancreas transplant. The initial workup revealed pancytopenia and parvovirus B19 viremia. Her definitive diagnosis was complicated by a lack of adequate bone marrow biopsy specimens and expert consultation that resulted in treatment for hemophagocytic lymphohistiocytosis. She was later diagnosed with high-grade myelodysplastic syndrome. Although curative treatment with chemotherapy and hematopoietic stem cell transplantation was strongly considered, it was not performed due to the child's rapid clinical progression, ventilator status, and active infections. The patient died approximately 6 months following symptom onset. CONCLUSIONS: This case emphasizes the importance of early recognition of myelodysplastic syndrome in multi-organ transplant recipients on chronic immunosuppression. Pancytopenia is a common presentation in the post-transplant period that requires thorough investigation. Multiple confounding considerations such as infection, immunosuppression, and systemic inflammation can delay the diagnosis of underlying hematological malignancies. Transplant care providers should be aware of myelodysplastic syndrome and advocate for a comprehensive evaluation, given early recognition and intervention can significantly improve outcomes.

Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria.

BACKGROUND AND AIMS: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma: Analysis From the US Multicenter HCC Transplant Consortium.

OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Including colon in intestinal transplantation: a focus on post-transplant renal function - a retrospective study.

Intestinal transplant recipients experience a high rate of renal complications secondary to dehydration due to increased ostomy output. It is hypothesized that inclusion of donor colon in the intestinal allograft may improve renal function in patients without functional native colon by improving fluid absorption. A single-center retrospective study of intestinal transplant recipients compared outcomes of patients receiving en bloc colon as part an intestinal allograft (ICTx), and those not receiving colon (CCNTx), as well as a control group of intestinal transplant recipients with functional native colon (ITx). Forty-seven patients (ICTx n = 17, CCNTx n = 15, ITx n = 15) were studied. One-year post-transplant renal function, as measured by change in glomerular filtration rate (GFR) and blood urea nitrogen (BUN) from baseline, was superior in ICTx (mean delta-GFR of -1.31 and delta-BUN of -1.46) compared to CCNTx (-6.54 and 17.54, P = 0.05 and P = 0.17, respectively) and similar to the ITx controls (0.55 and 2.09). Recipients of donor colon experienced a higher rate of ileostomy reversal when compared to CCNTx (62.5% vs. 20%, P = 0.0008), which was similar to the ITx controls (60%). These findings support the inclusion of en bloc donor colon in the intestinal allograft for recipients without functional native colon.

Viral enteritis in intestinal transplant recipients.

Intestinal transplant recipients (ITR) are at high risk for infections due to the high level of immunosuppression required to prevent rejection. There are limited data regarding viral enteritis post-intestinal transplantation. We retrospectively reviewed ITR transplanted between January 2008 and December 2016. Descriptive statistics, including mean (standard deviation) and median (range), were performed. Sixty-one (43.9%) of the 139 transplanted patients had viral enteritis: 26% norovirus, 25% adenovirus, and 9% each rotavirus and sapovirus. The median age of pediatric patients was 1.6 years (0.4-16.9) and for adults 36.3 years (27.1-48.2). Fifty-seven (58%) of 99 pediatric ITR had viral enteritis compared to 4 (10%) of 40 adult ITR. Median time-to-clinical resolution of enteritis for all patients was 5 days (1-92). Standard of care therapies administered: anti-motility agents (10%), anti-emetics agents (14%), and intravenous fluids (42%). There was a higher incidence of viral enteritis in pediatric compared to adults ITR. The majority of viral enteritis episodes resolved within 1 week and were treated with supportive therapy.

Failure of abdominal wall closure after intestinal transplantation: Identifying high-risk recipients.

Open abdomen and fascial dehiscence after intestinal transplantation increase morbidity. This study aims to identify recipient and donor factors associated with failure to achieve sustained primary closure (failed-SPC) of the abdomen after intestinal transplant. We conducted a single-center retrospective study of 96 intestinal transplants between 2013 and 2018. Thirty-eight (40%) were adult patients, and 58 were pediatric patients. Median age at transplantation was 36.0 and 5.8 years, respectively. Failed-SPC occurred in 31 (32%) patients. Identified risk factors of failed-SPC included preexisting enterocutaneous fistula (OR: 6.8, CI: 2.4-19.6, P = .0003), isolated intestinal graft (OR: 3.4, CI: 1.24-9.47, P = .02), male sex in adults (OR: 3.93, CI: 1.43-10.8, P = .009), and age over four years (OR: 6.22, CI: 1.7-22.7, P = .004). There was no association with primary diagnosis and prior transplant with failed-SPC. Donor-to-recipient size ratios did not predict failed-SPC. There was an association between failed-SPC and extended median hospital stay (100 vs 57 days, P = .007) and increased time to enteral autonomy in pediatric patients. There is a relationship between failed-SPC and a higher rate of laparotomy (OR: 21.4, CI: 2.78-178.2, P = .0003) and fistula formation posttransplant (OR: 11.4, CI: 2.83-45.84, P = .0005) in pediatric patients. Given inferior outcomes with failed-SPC, high-risk recipients require careful evaluation.

Invasive pneumococcal infections in pediatric liver-small bowel-pancreas transplant recipients.

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5 years (range: 1.5-7.1 years). The median time from transplant to first infection was 3 years (range: 0.8-5.8 years). Clinical presentation included as follows: pneumonia (n = 1), bacteremia/sepsis (n = 7), pneumonia with sepsis (n = 1), meningitis with sepsis (n = 2), pneumonia and meningitis with sepsis (n = 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23-valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients.

Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium.

OBJECTIVE: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013). RESULTS: Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044). CONCLUSIONS: Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

Serial transverse enteroplasty allows children with short bowel to wean from parenteral nutrition.

OBJECTIVE: To analyze the effects of serial transverse enteroplasty (STEP) on parenteral and enteral calories in children with short bowel syndrome, and examine short- and long-term complications. STUDY DESIGN: A retrospective analysis of prospectively-collected data from a large single center cohort of patients undergoing STEP procedure was analyzed. Baseline demographic and clinical information, operative data, and short- and long-term complications were recorded. Detailed growth and nutritional data were obtained for 6 months prior and 12 months following STEP procedure. RESULTS: Sixty-eight procedures were performed in 51 patients over a 68-month period. Median bowel length at first STEP was 51 cm with a median length gain of 54%. Repeat STEP patients had longer initial length (77 cm) and reduced length gain (20%). Operative times and blood loss were low, with few complications. Parenteral calorie requirement was stable or rising for 6 months prior to STEP, but decreased to median <20 kCal/kg/d at 1 year postop. Longer length gains were associated with higher risk of stricture formation. Seven children were transplanted, and 60% of nontransplanted children were enterally independent, with the remainder making ongoing progress; 48/51 children are alive at a median of 39 months follow-up. CONCLUSIONS: STEP is shown to be safe, well tolerated, and to have definitive benefit in reducing parenteral calorie requirements over the first year following the procedure. It has an important role in achieving enteral independence in children with short bowel syndrome.

Intestinal transplantation in children with multiple intestinal atresias and immunodeficiency.

GVHD has been reported in 8-10% of children after small bowel transplant (SBTx). Immunodeficient children may be predisposed to aggressive, steroid-resistant GVHD. There exists a unique association of immunodeficiency in children with MIA (MIAI). We report on our SBTx experience in patients with the diagnosis of MIAI, their high incidence of GVHD, and the possible role of stem cell transplantation in these patients. We performed a review of records from children that underwent SBTx or that we evaluated for SBTx at our institution. We focused on the diagnoses of atresia, multiple intestinal atresia, immunodeficiency, and GVHD in our patient population. Children with MIAI are likely to experience severe GVHD following SBTx. MIAI correlated with a 100% incidence of GVHD in these patients. Of the five patients with MIAI that underwent SBTx, three succumbed to severe GVHD within 1-6 months after SBTx. One patient received stem cell transplant prior to SBTx and did not develop severe GVHD, but died from influenza nine months after SBTx. Our unique patient survives long-term, with engraftment of donor γ δ T cells. He has mild, persistent chronic GVHD. Atresia is a common referral diagnosis for SBTx. Patients with multiple atresias, especially MIAI, are at significant risk for the complication of GVHD following SBTx. We recommend careful immunologic assessment and antecedent stem cell transplant in children with MIAI prior to SBTx.

Improved Early Post-Transplant Outcomes and Organ Use in Kidney Transplant Using Normothermic Regional Perfusion for Donation after Circulatory Death: National Experience in the US.

BACKGROUND: Normothermic regional perfusion (NRP) is a technique that is intended to enhance organ transplant outcomes from donation circulatory death (DCD) donors. STUDY DESIGN: A retrospective analysis of data from the Scientific Registry of Transplant Recipients was performed. DCD donors were screened for inclusion based on date of donation 2020 or later, and whether the heart was also recovered for transplantation. We grouped donors as either donation after brain death or DCD. DCD donors were further divided into groups including those in which the heart was not recovered for transplant (Non-Heart DCD) and those in which it was, based on recovery technique (thoracoabdominal-NRP [TA-NRP] Heart DCD and Super Rapid Recovery Heart DCD). RESULTS: A total of 219 kidney transplant recipients receiving organs from TA-NRP Heart DCD donors were compared to 436 SRR Super Rapid Recovery DCD, 10,630 Super Rapid Recovery non-heart DCD, and 27,820 donations after brain death recipients. Kidney transplant recipients of TA-NRP DCD allografts experienced shorter length of stay, lower rates of delayed graft function, and lower serum creatinine at the time of discharge when compared with recipients of other DCD allografts. CONCLUSIONS: Our analysis demonstrates superior early kidney allograft function when TA-NRP is used for DCD organ recovery.

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Successful rehabilitation in pediatric ultrashort small bowel syndrome.

OBJECTIVE: To examine treatment outcomes in pediatric patients with ultrashort small bowel (USSB) syndrome in an intestinal rehabilitation program (IRP). STUDY DESIGN: We reviewed IRP records for 2001-2011 and identified 28 children with USSB (≤ 20 cm of small bowel). We performed univariate analysis using the Fisher exact test and Wilcoxon rank-sum test to compare characteristics of children who achieved parenteral nutrition (PN) independence with intact native bowel and those who did not. Growth, nutritional status, and hepatic laboratory test results were compared from the time of enrollment to the most recent values using the Wilcoxon signed-rank test. RESULTS: Of the 28 patients identified, 27 (96%) survived. Almost one-half (48%) of these survivors achieved PN independence with their native bowel. The successfully rehabilitated patients were more likely to have an intact colon and ileocecal valve (P = .01). Significant improvements in PN kcal/kg, total bilirubin, and height and weight z-scores were seen in all patients, but serum hepatic transaminase levels did not improve in the nonrehabilitated patients. CONCLUSION: Enrollment in an IRP provides an excellent probability of survival for children with USSB. The presence of an intact ileocecal valve and colon are positively associated with rehabilitation in this population, but are not requisite. Approximately one-half of patients with USSB can achieve rehabilitation, with a median time to PN independence of less than 2 years. The USSB population can attain reduced PN dependence, improvement of PN-associated liver disease, and enhanced growth with the aid of an IRP.

Hepatic fibrosis persists and progresses despite biochemical improvement in children treated with intravenous fish oil emulsion.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) is a multifactorial process, which can culminate in cirrhosis and need for transplantation. Fish oil-based lipid emulsions (FOE) reportedly reverse hyperbilirubinemia, but there are little data on their effect on the histopathology of IFALD. METHODS: We blindly examined sequential liver biopsy data on 6 children receiving FOE, with scoring of cholestasis, inflammation, fibrosis, and ductal proliferation based on standardized systems. This information was correlated with biochemical and clinical data to determine any possible relations between biologic and histologic improvement. RESULTS: The median gestational age was 35 weeks, median birth weight 2064 g, and common most reason for intestinal loss was gastroschisis (5/6 children). Median intestinal length was 26 cm beyond the ligament of Treitz and most children had roughly 2 of 3 of their colonic length. It was observed that although hyperbilirubinemia reversed and hepatic synthetic function was preserved across timepoints, fibrosis was persistent in 2 cases, progressive in 3 cases, and regressed in only 1. It remained severe (grade 2 or higher) in 5 of 6 children at last biopsy. Histologic findings of cholestasis improved in all patients and inflammation improved in 5 of 6 children. There were mixed effects on ductal proliferation and steatosis. CONCLUSIONS: In children treated with FOE, reversal of hyperbilirubinemia is not reflected by a similar histologic regression of fibrosis at the timepoints studied. Children with IFALD should have active ongoing treatment and be considered for early referral to an Intestinal Failure Program even with a normalized bilirubin.

Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: a systematic review and meta-analysis.

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.