Asystolic donor warm ischemia time is associated with development of postreperfusion syndrome in donation after circulatory death liver transplant.

BACKGROUND: Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor warm ischemia time (dWIT), and may have differing effects on the outcome of the liver graft. This study aimed to identify risk factors for postreperfusion syndrome (PRS), a state of severe hemodynamic derangement following graft reperfusion, and its impact on DCD liver transplantation (LT) outcomes. METHODS: This was a retrospective analysis using 106 DCD LT. Detailed information for events during procurement (withdrawal of life support; systolic blood pressure < 80 mmHg; oxygen saturation < 80%; circulatory arrest; aortic cold perfusion) and their association with the development of PRS were examined using logistic regression. RESULTS: The overall incidence of PRS was 26.4%, occurring in 28 patients. Independent risk factors for PRS were asystolic dWIT (odds ratio (OR) 3.65, 95% confidence interval (CI) 1.38-9.66) and MELD score (OR 1.06, 95% CI 1.01-1.10). Total bilirubin was significantly higher in the PRS group at postoperative day (POD) 1 (p = .02; 5.2 mg/dL vs. 3.4 mg/dL), POD 3 (p = .049; 4.5 mg/dL vs. 2.8 mg/dL), and POD 7 (p = .04; 3.1 mg/dL vs. 1.9 mg/dL). Renal replacement therapy after LT was more likely to be required in the PRS group (p = .01; 48.2% vs. 23.1%). CONCLUSION: Asystolic dWIT is a risk factor for the development of PRS in DCD LT. Our results suggest that asystolic dWIT should be considered when selecting DCD liver donors.

Balancing immunosuppression in pediatric liver transplantation: Playing the long game.

The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long-term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune-mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression-free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health.

A 3-Decade, Single-Center Experience of Liver Transplantation for Cholangiocarcinoma: Impact of Era, Tumor Size, Location, and Neoadjuvant Therapy.

Liver transplantation (LT) for cholangiocarcinoma (CCA) remains limited to a small number of centers. Although the role of neoadjuvant therapy (NAT) has been explored over time, an in-depth analysis of NAT strategies remains limited. Furthermore, controversy exists regarding acceptable tumor size during patient selection for LT. This study explores the impact of era, tumor size, and NAT strategy on LT outcomes for CCA. We conducted a retrospective review of 53 patients with CCA treated with LT from 1985 to 2019; 19 hilar CCA (hCCA) and 30 intrahepatic CCA (iCCA) were included. The relative contributions of varying NAT (neoadjuvant chemotherapy [NAC], neoadjuvant local therapy [NALT], and combined NAC and NALT [NACLT]) as well as the implication of tumor size and era were analyzed. The primary endpoint was overall survival (OS). Compared with the old era (1985-2007), 5-year OS in patients who underwent LT in the recent era (2008-2019) showed a superior trend. The 5-year OS from initial treatment in patients receiving NACLT for hCCA and iCCA were 88% and 100% versus 9% and 41% in patients without it, respectively (P = 0.01 for hCCA; P = 0.02 for iCCA), whereas NAC or NALT alone did not show significant differences in OS versus no NAT (P > 0.05). Although 33 patients had large-size tumors (hCCA ≥ 30 mm, n = 12, or iCCA ≥ 50 mm, n = 21), tumor size had no impact on survival outcomes. Outcomes of LT for CCA seem to have improved over time. Multimodal NAT is associated with improved survival in LT for both iCCA and hCCA regardless of tumor size.

Perioperative Skeletal Muscle Fluctuations in High-Acuity Liver Transplantation.

BACKGROUND: Frailty has been implicated as a negative predictor of Liver Transplant (LT) outcomes. However, an understanding of changes in patient muscle mass peri-LT, and their effect in high-acuity patients remains lacking. We examined the impact of perioperative muscle mass changes (ΔSMI) on high-acuity (MELD ≥35) LT recipients. MATERIALS AND METHODS: Skeletal muscle index (SMI) was calculated using CT imaging. Patients were divided into two groups, based on severity of peri-operative SMI decrease. LT recipients with chronic end-stage liver disease, MELD ≥35, and abdominal CT ≤30 days prior, and 30-90 days post LT were included. [1011 adult LT recipients reviewed, 2012-2018]. RESULTS: Of 1011 patients reviewed, 88 met inclusion criteria (median MELD 41.1). The median ΔSMI was -5.0 (-29.4 - +21.1 cm2/m2) (fig A). Patients were classified into two groups: ΔSMI<-5.0 (median ΔSMI: -0.4, n = 44) and ΔSMI>-5.0 (median ΔSMI: -9.2, n = 44). Recipients with ΔSMI<-5.0 had higher pre-LT SMI (35.4 versus 31.2 cm2/m2, P <0.001) and lower post-LT SMI (26.0 versus 30.8 cm2/m2, P <0.001). The ΔSMI<-5.0 group had higher early allograft dysfunction (40.9 versus 20.5%, P = 0.037), and inferior patient and graft survival (P = 0.015, 0.017, respectively). Multivariate analysis identified ΔSMI<-5.0 (HR: 2.938, P = 0.048), long cold-ischemia time (≥9h, HR: 7.332, P = 0.008), HCV (HR: 5.614, p = 0.001), and tracheostomy after LT (HR:9.218, P <0.001) as negative prognostic factors for patient survival . CONCLUSIONS: Progressive perioperative sarcopenic deterioration was associated with inferior patient and graft survival in high acuity LT. These findings may guide pre and post-operative patient care and rehabilitation efforts in this challenging patient population.

Sarcopenia in high acuity liver transplantation: Does it predict outcomes?

BACKGROUND: Sarcopenia has gained momentum as a potential risk-stratification tool in liver transplantation (LT). While LT recipients recently have more advanced end-stage liver disease, the impact of sarcopenia in high acuity recipients with a high model for end-stage liver disease (MELD) score remains unclear. METHODS: We retrospectively assessed sarcopenia by calculating skeletal muscle index (SMI) from cross-sectional area at third lumbar vertebra (cm2 ) and height (m2 ) in 296 patients with a CT ≤ 30 days prior to LT. Sex-specific SMI cut-offs were developed, and its impact was assessed in patients with MELD ≥ 35. RESULTS: In patients with MELD ≥ 35 (n = 217), men with a SMI < 30 cm2 /m2 had significantly higher rates of bacteremia (P = .021) and a longer hospital stay (P < .001). Women with a SMI < 34 cm2 /m2 had a longer hospital stay (P = .032). There were no relationships between SMI and survival in men and women with MELD ≥ 35. CONCLUSIONS: This series examined sarcopenia with a focus on high MELD patients. Although decreased SMI contributed to higher post-LT hospital stay, it did not impact patient survival, suggesting that while SMI alone may not aid in patient selection for LT, it certainly may guide perioperative care-planning in this challenging patient population.

Postoperative Trapped Lung After Orthotopic Liver Transplantation is a Predictor of Increased Mortality.

Pleural effusions are a common complication of orthotopic liver transplantation (OLT), and chronic post-OLT pleural effusions have been associated with worse outcomes. Furthermore, "trapped lung" (TL), defined as a restrictive fibrous visceral pleural peel preventing lung re-expansion, may have prognostic significance. We performed a retrospective analysis of adult OLT recipients over a 9-year period at UCLA Medical Center. Post-OLT patients with persistent pleural effusions, defined by the presence of pleural fluid requiring drainage one to 12 months after OLT, were included for analysis. Outcomes for patients with and without TL were compared using univariate and multivariate analysis. Of the 1722 patients who underwent OLT, 117 (7%) patients met our criteria for persistent postoperative pleural effusion, and the incidence of TL was 21.4% (25/117). Compared to patients without TL, those with TL required more surgical pleural procedures (OR 59.8, 95%CI 19.7-181.4, p < 0.001), spent more days in the hospital (IRR 1.56, 95%CI 1.09-2.23, p = 0.015), and had a higher risk of mortality (HR 2.47, 95%CI 1.59-3.82, p < 0.001) following transplant. In sum, we found that post-OLT TL was associated with higher morbidity, mortality, and healthcare utilization. Future prospective investigation is warranted to further clarify the risk factors for developing postoperative pleural effusions and TL.

Ischemia-reperfusion injury and its relationship with early allograft dysfunction in liver transplant patients.

Ischemia-reperfusion injury (IRI) is believed to contribute to graft dysfunction after liver transplantation (LT). However, studies on IRI and the impact of early allograft dysfunction (EAD) in IRI grafts are limited. Histological IRI was graded in 506 grafts from patients who had undergone LT and classified based on IRI severity (no, minimal, mild, moderate, and severe). Of the 506 grafts, 87.4% had IRI (no: 12.6%, minimal: 38.1%, mild: 35.4%, moderate: 13.0%, and severe: 0.8%). IRI severity correlated with the incidence of EAD and graft survival at 6 months. Longer cold/warm ischemia time, recipient/donor hypertension, and having a male donor were identified as independent risk factors for moderate to severe IRI. Among 70 grafts with moderate to severe IRI, 42.9% of grafts developed EAD, and grafts with EAD had significantly inferior survival compared to grafts without EAD. Longer cold ischemia time and large droplet macrovesicular steatosis (≥20%) were identified as independent risk factors for EAD. Our study demonstrated that increased IRI severity was correlated with inferior short-term graft outcomes. Careful consideration of IRI risk factors during donor-recipient matching may assist in optimizing graft utilization and LT outcomes. Furthermore, identification of risk factors of IRI-associated EAD may guide patient management and possible timely graft replacement.

Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. Previously we reported that the liver graft assessment following transplantation (L-GrAFT7) risk score was superior to binary EAD or the model for early allograft function (MEAF) score for estimating 3-month graft failure-free survival in a single-center derivation cohort. Herein, we sought to externally validate L-GrAFT7, and compare its prognostic performance to EAD and MEAF. METHODS: Accuracies of L-GrAFT7, EAD, and MEAF were compared in a 3-center US validation cohort (n = 3,201), and a Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion (NMP) trial cohort (n = 222); characteristics were compared to assess generalizability. RESULTS: Compared to the derivation cohort, patients in the validation and NMP trial cohort had lower recipient median MELD scores; were less likely to require pretransplant hospitalization, renal replacement therapy or mechanical ventilation; and had superior 1-year overall (90% and 95% vs. 84%) and graft failure-free (88% and 93% vs. 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; p <0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT7 maintained an excellent validation AUROC of 0.78, significantly superior to binary EAD (AUROC 0.68, p = 0.001) and MEAF scores (AUROC 0.72, p <0.001). In post hoc analysis of the COPE NMP trial, the highest tertile of L-GrAFT7 was significantly associated with time to liver allograft (hazard ratio [HR] 2.17, p = 0.016), Clavien ≥IIIB (HR 2.60, p = 0.034) and ≥IVa (HR 4.99, p = 0.011) complications; post-LT length of hospitalization (p = 0.002); and renal replacement therapy (odds ratio 3.62, p = 0.016). CONCLUSIONS: We have validated the L-GrAFT7 risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to existing scores. L-GrAFT7 may standardize grading of early hepatic allograft function and serve as a clinical endpoint in translational studies (www.lgraft.com). LAY SUMMARY: Early allograft dysfunction negatively affects outcomes following liver transplantation. In independent multicenter US and European cohorts totaling 3,423 patients undergoing liver transplantation, the liver graft assessment following transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure-free survival and post-liver transplantation complications.

How to Handle Arterial Conduits in Liver Transplantation? Evidence From the First Multicenter Risk Analysis.

OBJECTIVE: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective. BACKGROUND: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature. STUDY DESIGN: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival. RESULTS: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT. CONCLUSION: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC.

Impact of Payer Status on Delisting Among Liver Transplant Candidates in the United States.

Although socioeconomic disparities persist both pre- and post-transplantation, the impact of payer status has not been studied at the national level. We examined the association between public insurance coverage and waitlist outcomes among candidates listed for liver transplantation (LT) in the United States. All adults (age ≥18 years) listed for LT between 2002 and 2018 in the United Network for Organ Sharing database were included. The primary outcome was waitlist removal because of death or clinical deterioration. Continuous and categorical variables were compared using the Kruskal-Wallis and chi-square tests, respectively. Fine and Gray competing-risks regression was used to estimate the subdistribution hazard ratios (HRs) for risk factors associated with delisting. Of 131,839 patients listed for LT, 61.2% were covered by private insurance, 22.9% by Medicare, and 15.9% by Medicaid. The 1-year cumulative incidence of delisting was 9.0% (95% confidence interval [CI], 8.3%-9.8%) for patients with private insurance, 10.7% (95% CI, 9.9%-11.6%) for Medicare, and 10.7% (95% CI, 9.8%-11.6%) for Medicaid. In multivariable competing-risks analysis, Medicare (HR, 1.20; 95% CI, 1.17-1.24; P < 0.001) and Medicaid (HR, 1.20; 95% CI, 1.16-1.24; P < 0.001) were independently associated with an increased hazard of death or deterioration compared with private insurance. Additional predictors of delisting included Black race and Hispanic ethnicity, whereas college education and employment were associated with a decreased hazard of delisting. In this study, LT candidates with Medicare or Medicaid had a 20% increased risk of delisting because of death or clinical deterioration compared with those with private insurance. As more patients use public insurance to cover the cost of LT, targeted waitlist management protocols may mitigate the increased risk of delisting in this population.

The Impact of Previous Abdominal Surgery in a High-Acuity Liver Transplant Population.

BACKGROUND: It is not uncommon for liver transplant (LT) recipients to have had previous abdominal surgery (PAS) preceding transplant. The impact of PAS on morbidity and mortality in LT patients remains unclear. In this study, we investigated the correlation between PAS and LT outcomes in a high-acuity patient population. MATERIALS AND METHODS: This is a single-center retrospective review of 936 adult primary LT recipients between 2012 and 2018. Patients were divided based on PAS history. PAS was subdivided into upper abdominal surgery (UAS) and lower abdominal surgery (LAS). UAS was separated into high-impact UAS and low-impact UAS. Finally, we studied patients with PAS ≤90 d versus PAS >90 d. RESULTS: Extensive adhesiolysis was the only significant perioperative factor between the PAS group (n = 367) and the non-PAS group (n = 569) (P < 0.001). Red blood cell (RBC) transfusion (20U versus 17U, P = 0.044) and abdominal packing (24.2% versus 13.3%, P = 0.008) were significantly higher in the UAS group (n = 186) versus the LAS group (n = 181). Patients with high-impact UAS required greater RBC (P = 0.021) and fresh frozen plasma transfusion (P = 0.005), and arterial conduits (P = 0.016) during LT. Compared with recipients with PAS >90 d (n = 338), recipients with PAS ≤90 d (n = 29) had significantly higher RBC transfusion (P = 0.046), fresh frozen plasma transfusion (P = 0.022), and abdominal packing (P = 0.025). No differences in patient and graft survival was observed. CONCLUSIONS: These findings suggest that, with appropriate care in the perioperative setting, PAS is not a contraindication to successful LT. Careful consideration is warranted when risk stratifying patients with multiple comorbidities who had PAS, especially those with UAS or PAS ≤90 d.

Outcomes and resource use for liver transplantation in the United States: Insights from the 2009-2017 National Inpatient Sample.

INTRODUCTION: Liver transplantation (LT) is a life-saving treatment for end-stage liver disease patients that requires significant resources. We used national data to evaluate LT outcomes and factors associated with hospital resource use. METHODS: Using the National Inpatient Sample, we identified all patients undergoing LT from 2009 to 2017 and defined high-resource use (HRU) as having costs ≥ 90th percentile. Hierarchical regression models were used to assess factors associated with length of stay (LOS) and HRU. RESULTS: Over the study period, approximately 53,000 patients underwent LT, increasing from 5,582 in 2009 to 7,095 in 2017 (nptrend < 0.001). Morbidity and mortality were 42.2% and 3.9%, respectively, with a median post-LT LOS of 10 days. Hospitalization costs increased from $106,866 to $145,868 (nptrend < 0.001). Acute kidney injury (ß:4.7 days, P < .001) and end-stage renal disease (ESRD) with dialysis (ß:4.3 days, P < .001) were associated with greater LOS while the Northeast region (AOR:5.2, P < .001), ESRD with dialysis (AOR:3.4, P < .001), heart failure (AOR:2.5, P < .001), and fulminant liver disease (AOR:1.8, P = .01) were associated with HRU. CONCLUSION: The cost of LT has increased over time. Renal dysfunction, regional practice patterns, and patient acuity were associated with greater resource use. Transplanting patients before health deterioration may help contain costs, mitigate resource use, and improve LT outcomes.

The impact of marijuana use on liver transplant recipients: A 900 patient single center experience.

INTRODUCTION: Increased societal prevalence of marijuana continues to challenge liver transplant (LT) programs. This study aimed to examine the potential effects of marijuana use on outcomes. METHODS: This retrospective study included recipients who underwent LT between 1/2012 and 6/2018. According to pre-LT marijuana use, patients were classified into recent (≤6 months of LT), former (chronic use but not ≤6 months), or non-users. Additionally, the impact of post-LT marijuana use on survival was assessed. RESULTS: Of 926 eligible patients, 184 were pre-LT marijuana users (42 recent; 142 former) (median follow-up: 30.3 months). Pre-users were more likely to be male, White, and have histories of tobacco, alcohol, and illicit drug use. Additionally, recent users were of higher acuity, with higher MELD and requiring ICU admission. Patient survival at 1-year was 89% in non-users, 94% (HR: 0.494, 95% CI: 0.239-1.022 vs. non-users) in former users, and 83% (HR: 1.516, 95% CI: 0.701-3.282) in recent users. Post-operative complications in pre-LT users and the survival analysis for post-LT marijuana users vs. non-users did not show significance. CONCLUSIONS: Our results demonstrated that marijuana use did not have an adverse impact on post-LT outcomes; however, further studies utilizing larger cohorts are warranted.

Yttrium-90 radiation segmentectomy for hepatic metastases: A multi-institutional study of safety and efficacy.

BACKGROUND AND OBJECTIVES: This study assessed the outcomes of Yttrium-90 (90 Y) radiation segmentectomy for hepatic metastases unamenable to resection or ablation. MATERIALS AND METHODS: Over 6 years, 36 patients with 53 tumors underwent segmental radioembolization. Patients were not candidates for surgical resection or thermal ablation. Malignancies included metastases from colorectal cancer (31%), neuroendocrine tumors (28%), sarcoma (19%), and others (22%). Eighty-one percent of patients had undergone prior treatment with systemic chemotherapy. Ongoing systemic chemotherapy was continued. Toxicity, tumor response, tumor progression, and survival were assessed. RESULTS: The median tumor size was 3.6 cm (range 1.2-6.1 cm). Adverse event rates were low, with no hepatic-related Common Terminology Criteria for Adverse Events Grade 3 or 4 toxicity. Target tumor Response Evaluation Criteria in Solid Tumors disease control rate was 92% (28% partial response, 64% stable disease). For patients with enhancing tumors (n = 14), modified Response Evaluation Criteria in Solid Tumors target tumor objective response rate was 100%. During a median follow-up of 12 months, target tumor progression occurred in 28% of treated tumors. Overall survival was 96% and 83% at 6 and 12 months, respectively. CONCLUSIONS: 90 Y radiation segmentectomy for hepatic metastases demonstrates high rates of tumor control and minimal toxicity. Radiation segmentectomy should be considered for patients with metastatic hepatic malignancy who are not candidates for surgical resection.

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.

Impact of Rifaximin Therapy on Ischemia/Reperfusion Injury in Liver Transplantation: A Propensity Score-Matched Analysis.

Intestinal microbiota is thought to play an important role in hepatic ischemia/reperfusion injury (IRI) after liver transplantation (LT). Rifaximin, a nonabsorbable antibiotic used to treat encephalopathy, exhibits antibacterial activity within the gut. We report the first study examining the impact of pre-LT rifaximin use on reducing hepatic IRI and inflammatory cell infiltration after LT. This retrospective single-center study included adult LT recipients from January 2013 through June 2016. Patients were divided into 2 groups based on duration of rifaximin use before LT: rifaximin group (≥28 days) and control group (none or <28 days). Patients receiving other antibiotics within 28 days of LT and re-LTs were excluded. Outcomes and messenger RNA (mRNA) expression in the graft were compared by 1:1 propensity score-matching and multivariate analyses. On 1:1 matching (n = 39/group), rifaximin patients had lower postoperative serum transaminase levels and lower early allograft dysfunction (EAD; 10.3% versus 33.3%; P = 0.014). Of the matched patients, 8 patients (n = 4/group) had postreperfusion liver biopsies (approximately 2 hours after reperfusion) available for mRNA analysis. Hepatic expression of CD86 (macrophage marker) and cathepsin G (neutrophil marker) was significantly lower in rifaximin patients than controls (P < 0.05). The multivariate analysis included 458 patients. Rifaximin treatment <28 days was identified as an independent risk factor EAD in all patients and those with high Model for End-Stage Liver Disease (MELD) score (MELD ≥35; n = 230). In conclusion, the propensity score-matched and multivariate analyses suggest a therapeutic role of rifaximin in reducing EAD. Pre-LT rifaximin administration exerted a protective function against early liver injury, potentially by suppressing inflammatory cell activation in the graft.

The devil is in the detail: current management of perioperative surgical complications after liver transplantation.

PURPOSE OF REVIEW: Despite advances in the field, perioperative morbidity is common after liver transplantation. This review examines the current literature to provide up-to-date management of common surgical complications associated with liver transplantation. RECENT FINDINGS: Research focuses on problems with anastomoses of the vena cava, portal vein, hepatic artery, and bile ducts. Interventional endoscopic and radiological techniques are used more frequently to avoid reoperation. SUMMARY: Advances in the management of perioperative surgical complications have focused on minimally invasive measures that successfully treat technical problems with implantation of liver allografts from both living and deceased donors.

Coil-Assisted Retrograde Transvenous Obliteration (CARTO): An Alternative Treatment Option for Refractory Hepatic Encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (OHE) is a serious complication of liver dysfunction, which is associated with severe morbidity/mortality and healthcare resource utilization. OHE can be medically refractory due to spontaneous portosystemic shunts (SPSSs) and therefore a new treatment option for these SPSSs is critical. METHODS: This is a retrospective study of 43 patients with medically refractory OHE, who underwent CARTO (Coil-Assisted Retrograde Transvenous Obliteration) procedures between June 2012 and October 2016. The patient demographic characteristics, technical and clinical outcomes with an emphasis on HE improvement, and complications are reviewed and analyzed. RESULTS: The overall clinical success rate was 91% with a significant HE improvement. Eighty-one percent of patients had clinically significant improvement from OHE and 67% of patients had complete resolution of their HE symptoms during our follow-up period of 893 ± 585 days (range 36-1881 days, median 755.0 days). The median WH score improved from 3 (range 2-4) pre-CARTO to 1 (range 0-4) post-CARTO (p < 0.001). The median ammonia level significantly decreased from 134.5 pre-CARTO to 70.0 post-CARTO (p < 0.001) in 3 days. The overall mean survival was 1465.5 days (95% CI of 1243.0 and 1688.0 days). Only three patients had recurrent HE symptoms. There were 39.6% minor complication rate including new or worsened ascites and esophageal varices, and only 2.3% major complication rate requiring additional treatment (one patient with bleeding esophageal varices requiring treatment). No procedure-related death is noted. CONCLUSIONS: CARTO appears to be a safe and effective treatment option for refractory overt hepatic encephalopathy (OHE) due to spontaneous portosystemic shunts. CARTO could be an excellent addition to currently available treatment options for these patients.

Balanced blood product transfusion during liver transplantation.

INTRODUCTION: This study was conducted to determine whether an intra-operative ratio of at least 1:1:2 of fresh frozen plasma (FFP):platelets (PLTs):packed red blood cells (pRBCs) improves outcomes in orthotopic liver transplantation (OLT). METHODS: A single-center, retrospective study of deceased donor OLT recipients (MELD ≥15) requiring intra-operative pRBC transfusion (years 2013-2016). Patients were grouped into those receiving an intra-operative ratio of ≥1:1:2 of FFP:PLTs:pRBCs vs ratios <1:1:2. RESULTS: Patients in ≥1:1:2 group (n = 150) and patients in <1:1:2 group (n = 80) were matched for baseline characteristics (P > .05). Patients in the ≥1:1:2 group had lower pRBC and intra-operative blood product requirements (11 ± 0.5 vs 19 ± 1.4 units, P < .001, and 33 ± 1.3 vs 43 ± 3.3 units, P = .006, respectively), improved 1-month mortality (0 vs 8%, P = .002), improved 1-year survival (P = .004), less intra-operative cardiac arrest (3% vs 10%, P = .03), and shorter operating room time (389 ± 7.2 vs 431 ± 17.2 minutes, P = .03). After multivariate adjustment for baseline and intra-operative variables, balanced blood product transfusion (BBPT) was significantly associated with less intra-operative pRBC transfusion (95% confidence interval: 0.60-0.72). CONCLUSION: Balanced blood product transfusion is associated with reduced transfusion requirements in OLT.