Exacerbated ischemia-reperfusion injury in fatty livers is mediated by lipid peroxidation stress and ferroptosis.

BACKGROUND: Ischemia-reperfusion injury is a common problem in liver surgery and transplantation. Although ischemia-reperfusion injury is known to be more pronounced in fatty livers, the underlying mechanisms for this difference remain poorly understood. We hypothesized that ferroptosis plays a significant role in fatty liver ischemia-reperfusion injury due to increased lipid peroxidation in the presence of stored iron in the fatty liver. To test this hypothesis, the ferroptosis pathway was evaluated in a murine fatty liver ischemia-reperfusion injury model. METHODS: C57BL6 mice were fed with a normal diet or a high fat, high sucrose diet for 12 weeks. At 22 weeks of age, liver ischemia-reperfusion injury was induced through partial (70%) hepatic pedicle clamping for 60 minutes, followed by 24 hours of reperfusion before tissue harvest. Acyl-coenzyme A synthetase long-chain family member 4 and 4-hydroxynonenal were quantified in the liver tissues. In separate experiments, liproxstatin-1 or vehicle control was administered for 7 consecutive days before liver ischemia-reperfusion injury. RESULTS: Exacerbated ischemia-reperfusion injury was observed in the livers of high fat, high sucrose diet fed mice. High fat, high sucrose diet + ischemia-reperfusion injury (HDF+IRI) livers had a significantly greater abundance of acyl-coenzyme A synthetase long-chain family member 4 and 4-hydroxynonenal compared with normal diet + ischemia-reperfusion injury (ND+IRI) livers or sham fatty livers, which indicated an increase of ferroptosis. HFD fed animals receiving liproxstatin-1 injections had a significant reduction in serum aspartate transaminase and alanine transaminase after ischemia-reperfusion injury, consistent with attenuation of ischemia-reperfusion injury in the liver. CONCLUSION: Ferroptosis plays a significant role in ischemia-reperfusion injury in fatty livers. Inhibiting ferroptotic pathways in the liver may serve as a novel therapeutic strategy to protect the fatty liver in the setting of ischemia-reperfusion injury.

Successful Sequential Liver and Isolated Intestine Transplantation for Mitochondrial Neurogastrointestinal Encephalopathy Syndrome: A Case Report.

BACKGROUND Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is an autosomal recessive disease caused by thymidine phosphorylase deficiency leading to progressive gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Although liver transplantation corrects thymidine phosphorylase deficiency, intestinal deficiency of the enzyme persists. Retrospective chart review was carried out to obtain clinical, biochemical, and pathological details. CASE REPORT We present a case of liver and subsequent intestine transplant in a 28-year-old man with MNGIE syndrome with gastrointestinal dysmotility, inability to walk, leukoencephalopathy, ptosis, cachexia, and elevated serum thymidine. To halt progression of neurologic deficit, he first received a left-lobe partial liver transplantation. Although his motor deficit improved, gastrointestinal dysmotility persisted, requiring total parenteral nutrition. After exhaustive intestinal rehabilitation, he was listed for intestine transplantation. Two-and-half years after liver transplantation, he received an intestine transplant. At 4 years after LT and 20 months after the intestine transplant, he remains off parenteral nutrition and is slowly gaining weight. CONCLUSIONS This is the first reported case of mitochondrial neurogastrointestinal encephalomyopathy to undergo successful sequential liver and intestine transplantation.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. METHODS: All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. RESULTS: Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. CONCLUSIONS: Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

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.

Assessment of Vascular and Valvular Calcification Improves Screening for Coronary Artery Disease Before Liver Transplantation.

Coronary artery disease (CAD) is common in patients with cirrhosis who underwent orthotopic liver transplantation (OLT) evaluation and stress echocardiogram (echo) has a low sensitivity in these patients. This study aimed to assess the impact of vascular and valvular calcification on the ability to identify CAD before OLT. We performed a case-control study of 88 patients with and 97 without obstructive CAD who underwent OLT evaluation. All patients had a preoperative stress echo, abdominal computed tomography, and cardiac catheterization. A series of nested logistic regression models of CAD were fit by adding independent variables of vascular (including coronary) calcification, aortic and mitral valve calcification, age, gender, and history of diabetes mellitus requiring insulin to a baseline model of abnormal stress echo. Compared with stress echo alone, identification of the presence or absence of vascular and valvular calcification on routine preoperative computed tomography and echo improved the diagnostic performance for the detection of CAD based on coronary angiogram when combined with stress echo in patients with cirrhosis who underwent OLT evaluation (area under the curve 0.58 vs 0.73, p <0.001), which is even further improved when age, gender, and history of diabetes mellitus requiring insulin are considered (area under the curve 0.58 vs 0.80, p <0.001). Achieving target heart rate (p = 0.92) or rate-pressure product >25,000 (p = 0.63) did not improve the ability of stress echo to identify CAD. In conclusion, the use of abdominal vascular, coronary artery, and valvular calcification, along with stress echo, improves the ability to identify and rule out obstructive CAD before OLT compared with stress echo alone.

Intestinal Gpr17 deficiency improves glucose metabolism by promoting GLP-1 secretion.

G protein-coupled receptors (GPCRs) in intestinal enteroendocrine cells (EECs) respond to nutritional, neural, and microbial cues and modulate the release of gut hormones. Here we show that Gpr17, an orphan GPCR, is co-expressed in glucagon-like peptide-1 (GLP-1)-expressing EECs in human and rodent intestinal epithelium. Acute genetic ablation of Gpr17 in intestinal epithelium improves glucose tolerance and glucose-stimulated insulin secretion (GSIS). Importantly, inducible knockout (iKO) mice and Gpr17 null intestinal organoids respond to glucose or lipid ingestion with increased secretion of GLP-1, but not the other incretin glucose-dependent insulinotropic polypeptide (GIP). In an in vitro EEC model, overexpression or agonism of Gpr17 reduces voltage-gated calcium currents and decreases cyclic AMP (cAMP) production, and these are two critical factors regulating GLP-1 secretion. Together, our work shows that intestinal Gpr17 signaling functions as an inhibitory pathway for GLP-1 secretion in EECs, suggesting intestinal GPR17 is a potential target for diabetes and obesity intervention.

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.

Combined liver-kidney transplantation with positive crossmatch: Role of delayed kidney transplantation.

BACKGROUND: Positive crossmatch (XM+) combined liver-kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver-kidney transplantations. METHODS: XM+ combined liver-kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. RESULTS: Of 183 combined liver-kidney transplantations performed (2002-2019), 114 (62%) were with "delayed" kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver-kidney transplantations, kidney transplant was "delayed" in 14 by an average of 47 hours (range 24-64 hours) from liver transplant. There was a significant reduction in both class I (mean pre-liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post-liver transplant and pre-delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre-liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre-liver transplant MFI 17,899 versus post-liver transplant and pre-delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver-kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM- combined liver-kidney transplantation. Whereas patient survival in recipients before "delayed" approach ("simultaneous"; n = 5) was 40% when liver-kidney transplants were performed simultaneously (P = .06). CONCLUSION: In sensitized combined liver-kidney transplantation recipients, the "delayed" kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

Oncologic indications of liver transplantation and deceased donor liver allocation in the United States.

PURPOSE OF REVIEW: Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy. RECENT FINDINGS: Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT). SUMMARY: With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.

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.

Allograft Necrosis in Liver Biopsy Is Predictive for Organ Outcome and Patient Survival.

AIM: To evaluate if any association existed between the extent of allograft necrosis in liver biopsy and patient survival. METHODS: Sixty-nine patients who had 70 liver transplantations with allograft necrosis were included in the study. Correlations of necrosis, the Model for End-Stage Liver Disease (MELD) score, and allograft survival were analyzed. RESULTS: Allograft failure rate within 1 month after index biopsy was worse in patients with a higher extent of necrosis (2.5%, 12.5%, 25%, and 40% in groups with allograft necrosis of 1-25%, 26-50%, 51-75%, and >75%, respectively). Adequate biopsy with more than 50% necrosis is associated with significant allograft failure (P <.001). The MELD scores did not always accurately predict fatality that was caused by massive necrosis. In the absence of substantial clinical changes, repetition of allograft biopsy within a short period of time did not provide additional value. Among patients with more than 75% allograft necrosis, one who received an immediate second transplantation survived and 3 out of 9 patients who had not received those deceased within 1 month. CONCLUSIONS: Allograft necrosis demonstrates strong predictive power in organ and patient survival. Additionally, biopsy-proven allograft necrosis unequivocally pinpoints ischemia as the direct cause of allograft failure, which facilitates clinical management. Immediate retransplantation is crucial for patients with substantial allograft necrosis.

Tracheostomy Post Liver Transplant: Predictors, Complications, and Outcomes.

BACKGROUND Liver transplant (LT) patients have an increased risk of postoperative respiratory failure requiring tracheostomy. This study sought to characterize objective clinical predictors of tracheostomy. MATERIAL AND METHODS The records for 2017 LT patients at a single institution were reviewed. Patients requiring tracheostomy were first compared with all other patients. A case-control subgroup analysis was conducted in which 98 tracheostomy patients were matched with 98 non-tracheostomy LT patients. For the case-control study, muscle mass was assessed using preoperative computed tomography scans. RESULTS Among 2017 LT patients, 98 required tracheostomy (5%), with a 19% complication rate. Tracheostomy patients were older and had a higher model for end-stage liver disease score, a lower body mass index (BMI), and a greater smoking history. Tracheostomy patients had a longer hospital stay (45 vs. 10 days, P<0.001) and worse 1-year survival (65% vs. 91%, P<0.001). Ten-year Cox regression patient survival for tracheostomy patients was significantly worse (32% vs. 68%, P<0.001). In the case-control analysis, respiratory failure patients were older (P<0.01) and had a lower BMI (P=0.05). They also had a muscle mass deficit of -39% compared with matched LT controls (P<0.001). No significant differences were seen with pre-LT total protein or albumin or with forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) values. CONCLUSIONS Predictors for respiratory failure requiring post-LT tracheostomy include higher model for end-stage liver disease score, older age, lower BMI, greater smoking history, and worse sarcopenia. Patients requiring tracheostomy have dramatically longer hospital stays and worse survival.

Complex Abdominal Wound Healing After Multivisceral Retransplant: A Case Report on the Importance of Nutrition.

BACKGROUND: Intestinal transplantation (ITx) is performed as an isolated ITx or as a part of multivisceral transplantation for intestinal failure secondary to short gut syndrome, inflammatory bowel disease, trauma, and sequelae of chronic parenteral nutrition dependence. Wound complications after ITx are very common, and abdominal wound closure cannot be immediately achieved in half of cases. CASE PRESENTATION: A 25-year-old man sustained an abdominal crush injury causing complete loss of his small intestine, requiring an isolated ITx in March 2016. He lost his graft because of early exfoliative rejection in November 2016. Five months after enterectomy and the immunosuppression-free period, he underwent multivisceral retransplantation in April 2017. His post-transplant course was complicated by wound healing problems that improved with treatment of his malnutrition, quantified by increasing albumin, total protein, prealbumin, weight, body mass index, and total psoas muscle area over a period of 19 months after retransplant. CONCLUSION: To our knowledge, this is the first case described of long-term wound follow-up after a multivisceral (re)transplantation, with corresponding nutrition information and images of the wound.

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.

Specialized care improves outcomes for patients with cirrhosis who require general surgical operations.

BACKGROUND: General surgical operations on patients with cirrhosis have historically been associated with high morbidity and mortality rates. This study examines a contemporary series of patients with cirrhosis undergoing general surgical procedures. METHODS: A retrospective evaluation of 358 cirrhotic patients undergoing general surgical operations at a single institution between 2004-2015 was performed. Thirty- and 90-day mortality along with complications and subsequent transplantation rates were examined. RESULTS: 358 cirrhotic patients were identified. The majority were Child-Turcotte-Pugh class (CTP) A (55.9%) followed by class B (32.4%) and class C (11.7%). Mean MELD score differed significantly between the groups (8.7 vs. 12.1 vs. 20.1; p<0.001). The most common operations were herniorrhaphy (29.9%), cholecystectomy (19.3%), and liver resection (14.5%). The majority of cases were performed semi-electively (68.4%), however, within the CTP C patients most cases were performed emergently (73.8%). Thirty and 90-day mortality for all patients were 5% and 6%, respectively. Mortality rates increased from CTP A to CTP C (30 day: 3.0% vs. 5.2% vs. 14.3%; p = 0.01; 90 day: 4.5% vs. 6.9% vs. 16.7%; p = 0.016). Additionally, 30-day mortality (12.8% vs. 2.3%; p<0.001), 90 day mortality (16.0% vs. 3.4%; p<0.001) were higher for emergent compared to elective cases. A total of 13 (3.6%) patients underwent transplantation ≤ 90 days from surgery. No elective cases resulted in an urgent transplantation. CONCLUSION: Performing general surgical operations on cirrhotic patients carries a significant morbidity and mortality. This contemporary series from a specialized liver center demonstrates improved outcomes compared to historical series. These data strongly support early referral of cirrhotic patients needing general surgical operation to centers with liver expertise to minimize morbidity and mortality.

Postoperative renal impairment is associated with increased length of stay for incisional hernia repair after liver transplantation.

BACKGROUND: Incisional hernia repair is the most common procedure after orthotopic liver transplantation. Although enhanced recovery protocols are increasingly employed, the post-orthotopic liver transplantation patient may not benefit from all aspects of these models. The aim of the present study is to assess which perioperative interventions and patient factors affect hospital length of stay in a cohort of post-orthotopic liver transplantation patients undergoing incisional hernia repair. METHODS: We conducted a retrospective review of a series of adult patients undergoing incisional hernia repair after orthotopic liver transplantation. The primary endpoint was length of stay. Results were stratified by demographic, intraoperative, and postoperative variables. RESULTS: Eleven percent (172/1523) of patients who received orthotopic liver transplantation during the study period underwent subsequent incisional hernia repair. Median length of stay was 5 days (range 2-50). The strongest predictor of length of stay was postoperative renal function. Despite liberal intraoperative administration of volume (median 642 mL/h) and brisk intraoperative urine output (median 72 mL/h), postoperative acute kidney injury occurred in 48% of patients. Those that developed acute kidney injury received less intraoperative volume (6 vs 8.5 mL/kg/h; P = .031) and the severity of postoperative renal injury was inversely related to the amount intraoperative volume given. CONCLUSIONS: In patients undergoing incisional hernia repair after orthotopic liver transplantation, postoperative renal function is frequently impaired. Although many aspects of current ERAS protocols may be applied to post-transplant patients, restrictive intraoperative fluid administration strategies should be employed with caution given a high propensity for the development of post-operative acute kidney injury in this complex population.

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.