Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

CAD-LT score effectively predicts risk of significant coronary artery disease in liver transplant candidates.

BACKGROUND & AIMS: Patients with cirrhosis and significant coronary artery disease (CAD) are at risk of peri-liver transplantation (LT) cardiac events. The coronary artery disease in liver transplantation (CAD-LT) score and algorithm aim to predict the risk of significant CAD in LT candidates and guide pre-LT cardiac evaluation. METHODS: Patients who underwent pre-LT evaluation at Indiana University (2010-2019) were studied retrospectively. Stress echocardiography (SE) and cardiac catheterization (CATH) reports were reviewed. CATH was performed for predefined CAD risk factors, irrespective of normal SE. Significant CAD was defined as CAD requiring percutaneous or surgical intervention. A multivariate regression model was constructed to assess risk factors. Receiver-operating curve analysis was used to compute a point-based risk score and a stratified testing algorithm. RESULTS: A total of 1,771 pre-LT patients underwent cardiac evaluation, including results from 1,634 SE and 1,266 CATH assessments. Risk-adjusted predictors of significant CAD at CATH were older age (adjusted odds ratio 1.05; 95% CI 1.03-1.08), male sex (1.69; 1.16-2.50), diabetes (1.57; 1.12-2.22), hypertension (1.61; 1.14-2.28), tobacco use (pack years) (1.01; 1.00-1.02), family history of CAD (1.63; 1.16-2.28), and personal history of CAD (6.55; 4.33-9.90). The CAD-LT score stratified significant CAD risk as low (≤2%), intermediate (3% to 9%), and high (≥10%). Among patients who underwent CATH, a risk-based testing algorithm (low: no testing; intermediate: non-invasive testing vs. CATH; high: CATH) would have identified 97% of all significant CAD and potentially avoided unnecessary testing (669 SE [57%] and 561 CATH [44%]). CONCLUSIONS: The CAD-LT score and algorithm (available at www.cad-lt.com) effectively stratify pre-LT risk for significant CAD. This may guide more targeted testing of candidates with fewer tests and faster time to waitlist. LAY SUMMARY: The coronary artery disease in liver transplantation (CAD-LT) score and algorithm effectively stratify patients based on their risk of significant coronary artery disease. The CAD-LT algorithm can be used to guide a more targeted cardiac evaluation prior to liver transplantation.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Pre-Liver Transplant Cardiac Catheterization Is Associated With Low Rate of Myocardial Infarction and Cardiac Mortality.

BACKGROUND AND AIMS: A study at Indiana University demonstrated a reduction in myocardial infarction (MI) incidence with increased frequency of cardiac catheterization (CATH) in liver transplant (LT) candidates. A strict protocol for performing CATH based upon predefined risk factors, rather than noninvasive testing alone, was applied to a subgroup (2009-2010) from that study. CATH was followed by percutaneous coronary intervention (PCI) in cases of significant coronary artery disease (CAD; ≥50% stenosis). The current study applies this screening protocol to a larger cohort (2010-2016) to assess post-LT clinical outcomes. APPROACH AND RESULTS: Among 811 LT patients, 766 underwent stress testing (94%) and 559 underwent CATH (69%), of whom 10% had CAD requiring PCI. The sensitivity of stress echocardiography in detecting significant CAD was 37%. Predictors of PCI included increasing age, male gender, and personal history of CAD (P < 0.05 for all). Compared to patients who had no CATH, patients who underwent CATH had higher mortality (P = 0.07), and the hazard rates (HR) for mortality increased with CAD severity (normal CATH, HR, 1.35; 95% confidence interval [CI], 0.79-2.33; P = 0.298; nonobstructive CAD, HR, 1.53; 95% CI, 0.84-2.77; P = 0.161; and significant CAD, HR, 1.96; 95% CI, 0.93-4.15; P = 0.080). Post-LT outcomes were compared to the 2009-2010 subgroup from the previous study and showed similar 1-year overall mortality (8% and 6%, P = 0.48), 1-year MI incidence (<1% and <1%, P = 0.8), and MI deaths as a portion of all deaths (3% and 9%, P = 0.35). CONCLUSIONS: Stress echocardiography alone is not reliable in screening LT patients for CAD. Aggressive CAD screening with CATH is associated with low rate of MI and cardiac mortality and validates the previously published protocol when extrapolated over a larger sample and longer follow-up period.

Donor-recipient body size mismatch has no impact on outcomes after deceased donor whole liver transplantation: Role of donor liver size measurement.

The role of donor-recipient body size mismatch (DRSM) on outcomes after whole liver transplantation (LT) is not clearly defined. At our center, in presence of considerable DRSM, objective assessment of the donor liver by a radiology or intraoperative evaluation by procuring surgeon was incorporated. To evaluate the impact of DRSM on graft outcomes with this approach, adult deceased donor whole liver transplants between July 2001 and December 2017 at our center were studied. DRSM was considered when the donor-recipient body surface area (BSA) ratio (DR-BSAr) was either <0.69 or >1.25. There were 54 (3.2%) transplants with DR-BSAr <0.69 and 61 (3.6%) with DR-BSAr >1.25. One-year graft survival was 85% vs. 89% vs. 89%; (p = .64) for transplants with DR-BSArs of <0.69, 0.69-1.25, and >1.25, respectively. Early allograft dysfunction (EAD) (28% vs. 27% vs. 37%; p = .07), post-transplant coagulopathy, bilirubinemia, and renal function were also comparable. In conclusion, with the actual measurement of the donor liver and recipient abdominal cavity, significant DRSM did not have a negative impact on early and long-term outcomes. Routine measurement of donor liver size by radiology may be incorporated in liver allocation to improve utilization.

Admission Factor V Predicts Transplant-Free Survival in Acute Liver Failure.

BACKGROUND AND AIMS: Traditional laboratory markers are insensitive in distinguishing between patients with acute liver failure (ALF) who will require urgent liver transplantation (LT) from those who will recover spontaneously, particularly within 24 h of presentation. Coagulation factor-V (FV) may improve the accuracy of outcome prediction in ALF due to its predominant synthesis in the liver and short half-life in plasma. METHODS: Patients enrolled in the ALF Study Group Registry from a single site had FV determined within 24 h of presentation (Derivation-Cohort). Area under the receiver operating characteristic curves (AUROC) dichotomized by ALF etiology [acetaminophen (APAP) or non-APAP] were constructed to evaluate the diagnostic performance of FV for transplant-free-survival (TFS). Multivariate logistic regression modeling was performed using FV and other clinical variables to predict TFS. Accuracy of FV and multivariable model were performed in a Validation-Cohort from a different site. RESULTS: 90-patients (56% with APAP) were included in the Derivation-Cohort. Median FV was significantly higher in TFS versus those who died/LT (31% vs. 15%, respectively; p = 0.001). When dichotomized by etiology, AUROC for FV was 0.77 for APAP (cutoff, sensitivity, specificity 10.5%, 79%, 69%, respectively) and 0.77 for non-APAP (22%, 85%, 67%, respectively). When the optimal cutoffs for FV in the Derivation-Cohort were applied to the Validation-Cohort (N = 51; 59% with APAP), AUROC for FV was 0.75 for APAP (sensitivity/specificity 81/44) and 0.95 for non-APAP (sensitivity/specificity 90/73). In multivariate analyses, AUROC for FV model was 0.86 in the Derivation-Cohort and 0.90 in the Validation-Cohort. CONCLUSION: Admission FV may improve selection of patients who are likely to improve without LT.

Postoperative Atrial Fibrillation and Flutter in Liver Transplantation: An Important Predictor of Early and Late Morbidity and Mortality.

Postoperative atrial fibrillation/flutter (POAF) is the most common perioperative arrhythmia and may be particularly problematic after liver transplantation (LT). This study is a single-center retrospective analysis of POAF to determine its incidence following LT, to identify risk factors, to assess its impact on clinical outcomes, and to summarize management strategies. The records of all patients who underwent LT between 2010 and 2018 were reviewed. Extracted data included pre-LT demographics and cardiac evaluation, in-hospital post-LT cardiac events, early and late complications, and survival. Among 1011 patients, the incidence of post-LT POAF was 10%. Using binary logistic regression, pre-LT history of atrial fibrillation was the strongest predictor of POAF (odds ratio [OR], 6.72; 95% confidence interval [CI], 2.00-22.57; P < 0.001), followed by history of coronary artery disease (CAD; OR, 2.52; 95% CI, 1.10-5.81; P = 0.03). Cardiac stress testing abnormality and CAD on cardiac catheterization were also associated with higher risk. Median time to POAF onset after LT was 3 days with 72% of cases resolving within 48 hours. POAF patients had greater hospital length of stay, death during the LT admission, and 90-day and 1-year mortality. POAF was an independent risk factor for post-LT mortality (OR, 2.0; 95% CI, 1.3-3.0; P < 0.01). Amiodarone was administered to 73% of POAF patients with no evidence of increased serum alanine aminotransferase levels. POAF occurred in 10% of post-LT patients with early onset and rapid resolution in most affected patients. POAF patients, however, had significant morbidity and mortality, suggesting that POAF is an important marker for worse early and late post-LT outcomes.

Impact of donor preprocurement cardiac arrest on clinical outcomes in pediatric deceased donor liver transplantation.

PPCA has historically been considered detrimental to donor quality in LT, but transplantation of grafts from this group of donors is now routine. Our study aims to evaluate the outcomes associated with use of donors with a history of PPCA in the pediatric population. This study is a single-center retrospective analysis of all pediatric LTs performed over an 18-year period. Donors and recipients were stratified by the presence and length of donor PPCA time. Preprocurement donor and post-transplant recipient laboratory values were collected to assess the degree of ischemic liver injury associated with each donor group. Cox regression analysis was used to compare survival. The records for 130 deceased pediatric LT donors and corresponding recipients were reviewed. There were 73 (56%) non-PPCA donors and 57 (44%) PPCA donors. Donors that experienced a PPCA event demonstrated a higher median, pretransplant peak alanine aminotransferase (ALT) level (P < .001). When comparing post-transplant recipient median ALT levels, donors with any PPCA had lower median peak ALT (P = .15) and day 3 ALT (P = .43) levels than the non-PPCA group. Rates of early graft loss did not differ. The PPCA group with >40 minutes of ischemia had markedly lower survival at 10 years, but this finding did not reach statistical significance. Liver grafts from donors with or without PPCA demonstrated no statistically significant differences in function or survival. A history of donor PPCA alone should not be used as an exclusionary criterion in pediatric liver transplantation.

Expanding the Donor Pool With the Use of Extended Criteria Donation After Circulatory Death Livers.

Use of donation after circulatory death (DCD) donor livers for transplantation has remained cautious in the United States. The aim of this study was to demonstrate the expansion of a DCD liver transplantation (LT) program with the use of extended criteria donor (ECD) DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with 1 of the following factors: donor age >50 years, donor body mass index >35 kg/m2 , donor functional warm ischemia time >30 minutes, and donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush and efforts to minimize ischemia times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC), and change in DCD LT volume. Of 135 consecutive DCD LTs, 62 were ECD DCDs. In total, 24 ECD DCD LTs were performed before (era 1) and 38 after the institution of optimization protocol (era 2), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in era 2, with a significantly lower incidence of IC (5% versus 17% in era 1; P = 0.03) and better 1-year graft survival (93% versus 75% in era 1; P = 0.07). Survival outcomes for ECD DCD LT in era 2 were comparable to matched deceased donor LT. With the expansion of the DCD donor pool, the number of DCD LTs performed at our center gradually increased in era 2 to account for >20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.

Post-intestine transplant graft-vs-host disease associated with inclusion of a liver graft and with a high mortality risk.

INTRODUCTION: This study reports the incidence, anatomic location, and outcomes of graft-vs-host disease (GVHD) at a single active intestine transplant center. METHODS: Records were reviewed for all patients receiving an intestine transplant from 2003 to 2015. Pathology reports and pharmacy records were reviewed to establish the diagnosis, location, and therapeutic interventions for GVHD. RESULTS: A total of 236 intestine transplants were performed during the study period, with 37 patients (16%) developing GVHD. The median time to onset of disease was 83 days, with 89% of affected patients diagnosed in the first year post-transplant. Mortality for affected patients was 54% in the 1 year after GVHD diagnosis. Skin lesions were the most common manifestation of GVHD. Other sites of disease included lungs, bone marrow, oral mucosa, large intestine, and brain. The incidence of GVHD was 16% in adult patients, and slightly lower in pediatric recipients (13%). In adults, increasing graft volume (isolated vs multi-organ) and liver inclusion were associated with increasing risk of GVHD, though this was not seen in pediatric patients. CONCLUSION: Overall, 16% of intestine transplant recipients developed GVHD. GVHD is associated with high mortality, and disease in the lungs, brain, and bone marrow was universally fatal.

Excellent outcomes in combined liver-kidney transplantation: Impact of kidney donor profile index and delayed kidney transplantation.

The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver-kidney transplantation (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on kidney donor profile index [KDPI]) or the delayed approach KT contributes to improved patient survival. In total, 130 CLKTs were performed between 2002 and 2015, 69 with simultaneous KT (group S) and 61 with delayed KT (group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50 ± 15 hours). All patients were categorized according to the KDPI score: 1%-33%, 34%-66%, and 67%-99%. Recipient and donor characteristics were comparable within groups S and D. Transplant outcomes were comparable within groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. The combination of delayed KT and KDPI 1%-33% resulted in 100% patient survival at 3 years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3 years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more extended criteria donor and donation after circulatory death kidneys. Liver Transplantation 24 222-232 2018 AASLD.

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor-Specific Antibody Formation After Liver Transplantation.

Formation of de novo donor-specific antibodies (dn-DSAs) has been associated with longterm immunologic complications after liver transplantation (LT). We hypothesized that human leukocyte antigen (HLA) epitope/eplet mismatch (MM) is a marker of immunogenicity and a risk factor for dn-DSA formation. Sera from 80 LT recipients were prospectively screened for dn-DSA by a Luminex single-antigen test (One Lambda, Inc., Canoga Park, CA) at 1, 2, 3, 6, 12, 18, 24, and 36 months after LT. HLA typing of the recipients and donors was performed using polymerase chain reaction (PCR)-SSP and PCR-SSOP Luminex low-resolution methods (One Lambda, Inc.). The HLAMatchmaker computer algorithm was used for identification of MM eplets at HLA-DRB1 and -DQA1/B1 loci. Luminex single-antigen bead solid phase assay was used for antibody analysis. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus maintenance. There were 27 (34%) patients who developed dn-DSA. There were no episodes of antibody-mediated rejection, and 9 (11%) developed acute cellular rejection (ACR). A positive crossmatch status and a higher number of HLA-A, -B, -DR, and -ABDR MMs were not associated with dn-DSA formation. Patients developing dn-DSA had a significantly higher number of total (38 ± 2.7 versus 28 ± 2.3; P = 0.01) and antibody-verified (AbVer; 14 ± 1.1 versus 10 ± 1; P = 0.015) class II MM eplets. By a multivariate regression analysis, the number of class II MM eplets was strongly associated with risk of class II dn-DSA formation (odds ratio [OR], 1.2; P < 0.01). Patients with ACR had a significantly higher number of total (20.2 ± 1.3 versus 13.9 ± 0.9; P < 0.01) as well as AbVer (10.7 ± 1.1 versus 7.5 ± 0.6; P = 0.03) class I MM eplets. In conclusion, donor-recipient HLA epitope MM is associated with a risk of dn-DSA formation and rejection after LT. However, further studies are required to evaluate the clinical utility of epitope matching in LT.

Posttransplant complications in adult recipients of intestine grafts without bowel decontamination.

BACKGROUND: Selective digestive decontamination is commonly used to decrease lumenal bacterial flora. Preoperative bowel decontamination may be associated with a lower wound infection rate but has not been shown to decrease risk of intra-abdominal abscess or lower leak rate for enteric anastomoses. Alternatively, the decontamination disrupts the normal flora of the gastrointestinal tract and may affect normal physiology, including immunologic function. This study reports complication rates of an intestine transplant program that has never used bowel decontamination. METHODS: All adult patients who underwent intestine transplant from 2003 to 2015 at a single center were reviewed. Posttransplant complications included intra-abdominal abscess, enteric fistula, and leak from the enteric anastomosis. Viral, fungal, and bacterial infections in the first year after transplant are reported. RESULTS: There were 184 adult patients who underwent deceased donor intestine transplant during the study period. Among these patients, 30% developed an infected postoperative fluid collection, 4 developed an enteric fistula (2%), and 16 had an enteric or anastomotic leak (8%). The rate of any bacterial infection was 91% in the first year, with a wound infection rate of 25%. Fungal infection occurred in 47% of patients. Rejection rates were 55% at 1 y for isolated intestine patients and 17% for multivisceral (liver inclusive) patients. CONCLUSIONS: Among this population of intestine transplant patients in which no bowel decontamination was used, rates of surgical complications, infections, and rejection were similar to those reported by other centers. Bowel decontamination provides no identifiable benefit in intestine transplantation.

Comparable outcomes in intestinal retransplantation: Single-center cohort study.

BACKGROUND: Graft loss in intestinal transplantation (ITx) is close to 25% in the first year and 50% at 5-year post-transplantation. Although technically and immunologically challenging, intestinal retransplantation is now the 4th most common indication for ITx. METHODS: The aim of this study was to review and compare the outcomes of intestinal retransplantation with primary ITx, which included isolated ITx, modified multivisceral transplantation (mMVTx), and full MVTx, between 2003 and 2014 at Indiana University. RESULTS: Of 218 ITx, 18 (8.3%) were retransplantation. Causes of graft loss were rejection(78%), pancreatitis (11%), and severe intestine dismotility (11%). MVTx (16/18, 89%) was the preferred retransplantation option. In 7 (39%) patients, graftectomy was performed between primary and intestinal retransplantation. Median interval between primary ITx and retransplantation was 421 days. Although patient and graft survival rates at 1 year, 3 years, and 5 years were comparable between primary and retransplants, the number of retransplants was limited in the follow-up after post-transplant year 3. CONCLUSIONS: We identified that timing of retransplantation, graftectomy prior to retransplant allowing an immunosuppression free state, inclusion of the liver, and preserved renal function are important factors in the consideration of intestinal retransplantation. Immunological aspects remain challenging in the decision making and for short- and long-term outcomes.

Multivisceral transplant is a viable treatment option for patients with non-resectable intra-abdominal fibromatosis.

BACKGROUND: Intra-abdominal fibromatosis often involves the mesentery root which is non-resectable by conventional surgery. Multivisceral transplant (MVT), as a potential cure to non-resectable fibromatosis, has rarely been reported and the prognosis is unknown. METHODS: Six patients who underwent MVT for intra-abdominal fibromatosis were reviewed. Clinicopathological features, immunohistochemistry for ß-catenin, p53, and Ki67, and outcomes were evaluated. Appropriate data for comparative analysis were obtained from a cohort of 24 patients who underwent conventional resection for intra-abdominal fibromatosis. RESULTS: Among six MVT patients, four had familial adenomatous polyposis (FAP). Two patients had an initial intestinal transplantation, three had multiple prior surgeries, and two had adjuvant therapy. One patient died of hemorrhagic stroke shortly after MVT, and five patients (83%) survived with a median follow-up of 64 months. The 1-year and 5-year survival rates were 67% for all five patients. Two patients had recurrences after MVT and one of them had FAP. In comparison, six of 24 patients who underwent conventional surgery had FAP; six (25%) had recurrences and three had FAP. For FAP patients; the mean recurrence time was 13 months for MVT versus 6 months for conventional surgery. Ki67 proliferative index, ß-catenin, and p53 expression did not significantly correlate to recurrence. CONCLUSIONS: Multivisceral transplant (MVT) is a viable option for patients who have non-resectable intra-abdominal fibromatosis with promising surviving rates, although recurrence still occurs. Surgical margin, Ki67 proliferative index, ß-catenin, and p53 expression are not predicative for recurrence of fibromatosis.

Complications in pediatric intestine transplantation in the absence of peri-operative donor or recipient bowel decontamination.

This study reports the clinical complication and infection rates of an active pediatric IT program that has never utilized bowel decontamination in either the donor or the recipient. All patients undergoing IT from 2003 to 2015 at a single pediatric IT center were reviewed. Post-transplant surgical, infectious, and immunosuppressive complications are reported. There were 52 patients who underwent IT during the study period. Among these patients, 4% developed a postoperative abscess, one developed an enteric fistula (2%), and one had an enteric or anastomotic leak (2%). The rate of any bacterial infection was 90% in the first year, with a wound infection rate of 23%. Any fungal infection occurred in 25% of patients. Any viral infection occurred in 75% of patients. Gastrointestinal viruses were diagnosed in 52% of patients, and cytomegalovirus infections occurred in 17%. Rejection rates were 39% at any time post-transplant (isolated 44% and 35% for multivisceral patients). At this center in which no bowel decontamination was used, rates of surgical complications, infections, and rejection were similar to those reported by other centers. These findings suggest bowel decontamination may provide no significant benefit in this population of high-risk transplant patients.

Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin preservation solutions in pediatric liver transplantation.

UW and HTK solutions are the two primary organ preservation solutions most used in the United States. This study analyzes use of the two solutions in all pediatric liver transplants performed at a single center between 2001and 2017. Outcome measures included early graft function, as well as graft and patient survival. Bile duct complications were reviewed. Operative technique, immunosuppressive protocols, and donor acceptance criteria remained uniform among participating surgeons throughout the study period. There were 104 pediatric liver transplants with complete data during the study period, 75 preserved with HTK (68%) and 29 with UW (26%). Demographics were similar. Cold and warm ischemia times were similar. Peak ALT post-transplant was higher in the UW group at both peak and post-transplant day 3. The peak TB levels were similar. Bile duct strictures were more common in the UW group (44% vs 16%, P < .01). Early graft survival was statistically similar at 7-, 90- and 365-days post-transplant. Cox regression graft survival was similar at 10-years. This study suggests that use of HTK in pediatric liver transplantation is safe with outcomes similar to UW, though bile duct stricture rates may be lower with HTK.

A Novel Approach in Combined Liver and Kidney Transplantation With Long-term Outcomes.

OBJECTIVE: The aim of this study was to compare the outcomes of simultaneous and delayed implantation of kidney grafts in combined liver-kidney transplantation (CLKT). BACKGROUND DATA: Delayed function of the renal graft (DGF), which can result from hypotension and pressor use related to the liver transplantation (LT), may cause worse outcomes in CLKT. METHODS: A total of 130 CLKTs were performed at Indiana University between 2002 and 2015 and studied in an observational cohort study. All kidneys underwent continuous hypothermic pulsatile machine perfusion until transplant: 69 with simultaneous kidney transplantation (KT) (at time of LT, group 1) and 61 with delayed KT (performed at a later time as a second operation, group 2). All patients received continuous veno-venous hemodialysis during the LT. Propensity score match analysis in a 1:1 case-match was performed. RESULTS: Mean kidney cold ischemia time was 10 ± 3 and 50 ± 15 hours, for groups 1 and 2 (P < 0.0001), respectively. The rate of DGF was 7.3% in group 1, but no DGF was seen in group 2 (P = 0.0600). Kidney function was significantly better in group 2, if the implantation of kidneys was delayed >48 hours (P < 0.01). Patient survival was greater in group 2 at 1 year (91%), and 5 year (87%) post-transplantation (P = 0.0019). On multivariate analysis, DGF [hazard ratio (HR), 165.7; 95% confidence interval (CI), 9.4-2926], extended criteria donor kidneys (HR, 15.9; 95% CI 1.8-145.2), and recipient hepatitis C (HR, 5.5; 95% CI 1.7-17.8) were significant independent risk factors for patient survival. CONCLUSIONS: Delayed KT in CLKT (especially if delayed >48 h) is associated with improved kidney function with no DGF post-KT, and improved patient and graft survival.