Decoding the Clavien-Dindo Classification: Artificial Intelligence (AI) as a Novel Tool to Grade Postoperative Complications.

OBJECTIVE: To assess ChatGPT's capability of grading postoperative complications using the Clavien-Dindo classification (CDC) via Artificial Intelligence (AI) with Natural Language Processing (NLP). BACKGROUND: The CDC standardizes grading of postoperative complications. However, consistent, and precise application in dynamic clinical settings is challenging. AI offers a potential solution for efficient automated grading. METHODS: ChatGPT's accuracy in defining the CDC, generating clinical examples, grading complications from existing scenarios, and interpreting complications from fictional clinical summaries, was tested. RESULTS: ChatGPT 4 precisely mirrored the CDC, outperforming version 3.5. In generating clinical examples, ChatGPT 4 showcased 99% agreement with minor errors in urinary catheterization. For single complications, it achieved 97% accuracy. ChatGPT was able to accurately extract, grade, and analyze complications from free text fictional discharge summaries. It demonstrated near perfect performance when confronted with real-world discharge summaries: comparison between the human and ChatGPT4 grading showed a κ value of 0.92 (95% CI 0.82-1) (P<0.001). CONCLUSIONS: ChatGPT 4 demonstrates promising proficiency and accuracy in applying the CDC. In the future, AI has the potential to become the mainstay tool to accurately capture, extract, and analyze CDC data from clinical datasets.

The role of preoperative psychosocial counseling on the improvement of the recipient compliance and speed of recovery after liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Psychosocial disorders ranging from anxiety to severe psychiatric diseases and active alcohol/substance abuse are frequent in liver transplant candidates and potentially associated with worse post- transplant outcomes. Therefore, psychosocial evaluation is mandatory to optimize success after liver transplantation. However, how to carry out this evaluation, the type of intervention needed and its potential impact on patient outcome remain unclear. OBJECTIVES: To investigate whether psychosocial assessment may help in predicting risks of poor outcome; and to investigate whether psychosocial interventions may mitigate these risks and improve posttransplant outcomes, in particular compliance and speed of recovery. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. The protocol was registered on PROSPERO CRD42021238361. Main outcomes assessed were mortality, alcohol relapse, rejection, and medication compliance. RESULTS: Fifteen studies were analyzed including five observational comparative and ten observational noncomparative studies. Preoperative psychosocial evaluation of LT candidates was associated with higher concordance with the treatment plan (i.e., higher adherence to treatment and lower alcohol relapse) and lower rates of rejection. Psychosocial assessment tools were used in some studies to guide the evaluation, but their predictive ability remains debated, and they should not be used in isolation. Most of the interventions were studied in patients with alcohol related issues. In this context, support by specialized teams was associated with better posttransplant outcome, especially through a decrease in post-transplant alcohol relapse. CONCLUSIONS: Preoperative psychosocial assessment should be provided in order to detect patients at increased risk of poorer post-transplant outcome, in particular in terms of concordance to the treatment plan (Quality of Evidence; Low | Grade of Recommendation; Strong/For). The experts suggest that, when possible, provision of preoperative psychological assessment and concomitant interventions aimed at improving the concordance to treatment plans will positively impact the success of liver transplantation. (Quality of Evidence; Very Low | Grade of Recommendation; Strong/For].

Early removal of drains and lines after liver transplantation to reduce the length of hospital stay and enhance recovery - A systematic review of the literature and expert panel recommendations.

BACKGROUND: The timing of removing abdominal drains, central venous catheters (CVC), and urinary catheters (UC) on post liver transplantation (LT) outcomes is not well elucidated. OBJECTIVES: To provide international expert panel recommendations and guidelines on time of drain and catheter removal as a part of an ERAS protocol to reduce the length of hospital stay and enhance recovery. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Papers considered were those reporting one or more outcomes of interest related to drainage and line removal in the setting of LT. POSPERO Protocol ID: CRD42021238349 RESULTS: On analyzing five relevant studies pertaining to drains in patients undergoing LT (four retrospectives and one prospective), the length of hospital and/or ICU stay was similar or shorter, and postoperative morbidity and mortality were lower in those without drains. No studies pertaining specifically to the time of removal of drains, CVC's, or UC's in LT were found. Studies in patients undergoing major abdominal surgery or hepatectomies recommend early removal of CVC and UC to reduce catheter-associated infections. CONCLUSIONS: Based more on expert recommendation, we propose that abdominal drains, if placed during LT, should be removed by postoperative day 5 after LT, based on quantity and fluid characteristics (Quality of Evidence; Low to Moderate | Grade of Recommendation; Strong). Larger studies are needed to more reliably determine indications for early drain and line removal in an ERAS protocol setting.

What is the optimal prophylaxis against postoperative deep vein thrombosis in the living donor to avoid complications and enhance recovery? - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Deep venous thrombosis (DVT) prophylaxis is often employed to prevent the potentially serious complication of pulmonary embolism (PE). However, little data exist regarding the optimal DVT prophylaxis strategy for living donors undergoing hepatectomy for living donor liver transplantation. Here we present our consensus statement on DVT prophylaxis for living donors undergoing hepatectomy. OBJECTIVES: To identify the optimal DVT prophylaxis strategy, which reduces, risk of complications in living liver donors, and enhances recovery. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Of interest was the impact of DVT prophylaxis or lack of prophylaxis on living donors undergoing hepatectomy and subsequent rates of DVT, PE, and hemorrhagic complications. PROSPERO ID: CRD42021260720 RESULTS: The review of the literature identified three studies, which directly addressed thrombogenesis following living donor hepatectomy. All studies were observational in nature without randomization into treatments. The rate of DVT-PE in unscreened living donors with chemoprophylaxis was 5%. Furthermore, thromboelastography of living donors demonstrated sustained hypercoagulability for 50% of donors 10 days postoperatively. In line with CHEST (The American College of Chest Physicians) guidelines of chemoprophylaxis for surgical procedures with 3% or greater risk of DVT-PE, we conclude that a minimum of 10 days of postoperative chemoprophylaxis with unfractionated heparin or low-molecular weight heparin is recommended for patients undergoing living donor hepatectomy. The quality of evidence (QOE) for these recommendations based on the GRADE criteria is low, with a Grade of Recommendation of Strong. CONCLUSIONS: Chemoprophylaxis for DVT following living donor hepatectomy is associated with reduced adverse thrombotic events, (Quality of Evidence; Low | Grade of Recommendation; Strong).

Which cava anastomotic techniques are optimal regarding immediate and short-term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations.

BACKGROUND: It has long been debated whether cava anastomosis should be performed with the piggyback technique or cava replacement, with or without veno-venous bypass (VVB), with or without temporary portocaval shunt (PCS) in the setting of liver transplantation. OBJECTIVES: To identify whether different cava anastomotic techniques and other maneuvers benefit the recipient regarding short-term outcomes and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021240979). RESULTS: Of 3205 records screened, 307 publications underwent full-text assessment for eligibility and 47 were included in qualitative synthesis. Four studies were randomized control trials. Eighteen studies were comparative. The remaining 25 were single-center retrospective noncomparative studies. CONCLUSION: Based on existing data and expert opinion, the panel cannot recommend one cava reconstruction technique over another, rather the surgical approach should be based on surgeon preference and center dependent, with special consideration toward patient circumstances (Quality of evidence: Low | Grade of Recommendation: Strong). The panel recommends against routine use of vevo-venous bypass (Quality of evidence: Very Low | Grade of Recommendation: Strong) and against the routine use of temporary porto-caval shunt (Quality of evidence: Very Low | Grade of Recommendation: Strong).

Optimal anesthetic conduct regarding immediate and short-term outcomes after liver transplantation - Systematic review of the literature and expert panel recommendations.

BACKGROUND: In the era of enhanced recovery after surgery, there is significant discussion regarding the impact of intraoperative anesthetic management on short-term outcomes following liver transplantation (LT), with no clear consensus in the literature. OBJECTIVES: To identify whether or not intraoperative anesthetic management affects short-term outcomes after liver transplantation. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review following PRISMA guidelines was undertaken. The systematic review was registered on PROSPERO (CRD42021239758). An international expert panel made recommendations for clinical practice using the GRADE approach. RESULTS: After screening, 14 studies were eligible for inclusion in this systematic review. Six were prospective randomized clinical trials, three were prospective nonrandomized clinical trials, and five were retrospective studies. These manuscripts were reviewed to look at five questions regarding anesthetic care and its impact on short term outcomes following liver transplant. After review of the literature, the quality of evidence according to the following outcomes was as follows: intraoperative and postoperative morbidity and mortality (low), early allograft dysfunction (low), and hospital and ICU length of stay (moderate). CONCLUSIONS: For optimal short term outcomes after liver transplantation, the panel recommends the use of volatile anesthetics in preference to total intravenous anesthesia (TIVA) (Level of Evidence: Very low; Strength of Recommendation: Weak) and minimum alveolar concentration (MAC) versus bispectral index (BIS) for depth of anesthesia monitoring (Level of Evidence: Very low; Strength of Recommendation: Weak). Regarding ventilation and oxygenation, the panel recommends a restrictive oxygenation strategy targeting a PaO2 of 70-120 mmHg (10-14 kPa), a tidal volume of 6-8 ml/kg ideal body weight (IBW), administration of positive end expiratory pressure (PEEP) tailored to patient intraoperative physiology, and recruitment maneuvers. (Level of evidence: Very low; Strength of Recommendation: Strong). Finally, the panel recommends the routine use of antiemetic prophylaxis. (Level of evidence: low; Strength of Recommendation: Strong).

What is the optimal anesthetic monitoring regarding immediate and short-term outcomes after liver transplantation?-A systematic review of the literature and expert panel recommendations.

BACKGROUND: Liver transplant centers vary in approach to intraoperative vascular accesses, monitoring of cardiac function and temperature management. Evidence is limited regarding impact of selected modalities on postoperative outcomes. OBJECTIVES: To review the literature and provide expert panel recommendations on optimal intraoperative arterial blood pressure (BP), central venous pressure (CVP), and vascular accesses, monitoring of cardiac function and intraoperative temperature management regarding immediate and short-term outcomes after orthotopic liver transplant (OLT). METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Recommendations made for: (1) Vascular accesses, arterial BP and CVP monitoring, (2) cardiac function monitoring, and (3) Intraoperative temperature management (CRD42021239908). RESULTS: Of 2619 articles screened 16 were included. Studies were small, retrospective, and observational. Vascular access studies demonstrated low rates of insertion complications. TEE studies demonstrated low rates of esophageal hemorrhage. One study found lower hospital-LOS and 30-day mortality in patients monitored with both PAC and TEE. Other monitoring studies were heterogenous in design and outcomes. Temperature studies showed increased blood transfusion and ventilation times in hypothermic groups. CONCLUSIONS: Recommendations were made for; routine arterial and CVP monitoring as a minimum standard of practice, consideration of discrepancy between peripheral and central arterial BP in patients with hemodynamic instability and high vasopressor requirements, and routine use of high flow cannulae while monitoring for extravasation and hematoma formation. Availability and expertise in PAC and/or TEE monitoring is strongly recommended particularly in hemodynamic instability, portopulmonary HT and/or cardiac dysfunction. TEE use is recommended as an acceptable risk in patients with treated esophageal varices and is an effective diagnostic tool for emergency cardiovascular collapse. Maintenance of intraoperative normothermia is strongly recommended.

Are short-term complications associated with poor allograft and patient survival after liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Maximizing patient and allograft survival after liver transplant (LT) is important from both a patient care and organ utilization perspective. Although individual studies have addressed the effects of short-term post-LT complications on a limited scale, there has not been a systematic review of the literature formally assessing the potential effects of early complications on long-term outcomes. OBJECTIVES: To identify whether short-term complications after LT affect allograft and overall survival, to identify short-term complications of particular clinical interest and significance, and to provide recommendations to improve post-LT graft and patient survival. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. RESULTS: The literature review and analysis provided show that short-term complications have a large impact on allograft and patient survival after LT. The complications with the strongest effect on survival are acute kidney injury (AKI), biliary complications, and early allograft dysfunction (EAD). CONCLUSION: This panel recommends taking measures to reduce the risk and incidence of short-term complications post-LT. Clinicians should pay particular attention to preventing or ameliorating AKI, biliary complications, and EAD (Quality of evidence; Moderate | Grade of Recommendation; Strong).

The role of prehabilitation on short-term outcomes after liver transplantation: A review of the literature and expert panel recommendations.

BACKGROUND: Prehabilitation programs as part of ERAS protocols are being increasingly used in multiple surgeries, improving postoperative outcomes. Data regarding prehabilitation programs in patients awaiting liver transplantation and their outcomes is scarce. OBJECTIVES: To identify whether prehabilitation programs based on exercise training conducted prior to liver transplantation improve short-term postoperative outcomes, and to provide expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies included those evaluating postoperative outcomes, as well as those evaluating functional outcomes. PROSPERO ID: CRD42021236305. RESULTS: Of the 170 studies screened, only one assessed the primary objective. Most studies focus on the preoperative impact of exercise training on aerobic capacity, muscle mass and/or strength, showing positive effects and no significant adverse events, but are underpowered and with heterogenous designs and interventions. The non-randomized observational study which assessed relevant postoperative outcomes, showed a non-significant trend towards reduced 90-day readmission rate and shorter length of stay in the prehabilitation group. CONCLUSIONS: Prehabilitation prior to liver transplantation is unlikely to be harmful, and likely to have short term benefits on functional status. We cautiously recommend prehabilitation on the basis of absence of harm and possibility of benefit (Quality of Evidence; Very Low | Grade of Recommendation; Low).

The role of acute in-patient rehabilitation on short-term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations.

BACKGROUND: The indication and surgical complexity of orthotopic liver transplantation underscore the need for strategies to optimize the recovery for transplant recipients. We conducted a systematic review aimed at identifying, evaluating, and synthesizing the evidence examining the effect of in-patient rehabilitation for liver transplant recipients and provide related practice recommendations. METHODS: Health research databases were systematically reviewed for studies that included adults who received liver transplantation and participated in acute, post-transplant rehabilitation. Postoperative morbidity, mortality, length of hospital stay, length of intensive care unit stay, and other markers of surgical recovery were extracted. Practice recommendations are provided by an international panel using GRADE. RESULTS: Twelve studies were included in the review (including 3901 participants). Rehabilitation interventions varied widely in design and composition; however, details regarding intervention delivery were poorly described in general. The quality of evidence was rated as very low largely owing to "very serious" imprecision, poor reporting, and limited data from comparative studies. Overall, the studies suggest that in-patient rehabilitation for recipients of liver transplantation is safe, tolerable, and feasible, and may benefit functional outcomes. CONCLUSION: Two practice recommendations related to in-patient rehabilitation following LT were yielded from this review: (1) it is safe, tolerable, and feasible; and (2) it improves postoperative functional outcomes. Each of the recommendations are weak and supported by low quality of evidence. No recommendation could be made related to benefits or harms for clinical, physiological, and other outcomes. Adequately powered and high quality randomized controlled trials are urgently needed in this area.

Does modification of portal pressure and flow enhance recovery of the recipient after living donor liver transplantation? A systematic review of literature and expert panel recommendations.

BACKGROUND: Portal inflow modulation (PIM) aimed at reducing portal hyperperfusion is commonly used in living donor liver transplantation (LDLT) to reduce the risk of small-for-size syndrome (SFSS). Many different techniques, both pharmacological and surgical have been used for this purpose. There is, however, little consensus on the best method of PIM, its exact role in preventing SFSS and on early post-LDLT recovery. OBJECTIVES: To identify whether modifications of portal pressures and flows enhance recovery after LDLT and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID: CRD42021260997. RESULTS: Five hundred and ninety four articles were identified through databases' search. Of the 24 included for a final review by the working group (WG), there were five randomized control trials, four prospective studies and 15 retrospective series. Six outcome measures which were likely to influence early recovery after LDLT, especially in small-for-size grafts (SFSG) were shortlisted. These included acute kidney injury, SFSS, morbidity including sepsis, length of ICU and hospital stay, morbidity of the PIM technique and overall mortality. The WG noted that PIM in this subset of LDLT recipients had a beneficial effect on all the outcomes measures. CONCLUSIONS: Considering all decision domains, the panel recommends pre- and intraoperative actual graft weight validation, portal pressure/flow measurements, and a comprehensive donor evaluation for the determination of potentially small-for-size/ small-for-flow grafts as mandatory. (Quality of Evidence: Moderate | Grade of Recommendation: Strong) Pharmacological PIM helps improve early renal function in LDLT recipients. (Quality of Evidence: High | Grade of Recommendation: Strong) In selected patients with SFSG, PIM helps reduce SFSS/EAD and sepsis. (Quality of Evidence: Moderate | Grade of Recommendation: Strong) PIM in the form of splenectomy has increased morbidity compared to splenic artery ligation (SAL). (Quality of Evidence: Low | Grade of Recommendation: Strong) In LDLT recipients with SFSG, PIM may help reduce morbidity/mortality. (Quality of Evidence: Low | Grade of Recommendation: Strong) In LDLT recipients with SFSG, modification of portal pressures and flows enhances recovery after LDLT. (Quality of Evidence: Moderate | Grade of Recommendation: Strong).

The role of T-tubes and abdominal drains on short-term outcomes in liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: This systematic review and expert panel recommendation aims to answer the question regarding the routine use of T-tubes or abdominal drains to better manage complications and thereby improve outcomes after liver transplantation. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel to assess the potential risks and benefits of T-tubes and intra-abdominal drainage in liver transplantation (CRD42021243036). RESULTS: Of the 2996 screened records, 33 studies were included in the systematic review, of which 29 (six RCTs) assessed the use of T-tubes and four regarding surgical drains. Although some studies reported less strictures when using a T-tube, there was a trend toward more biliary complications with T-tubes, mainly related to biliary leakage. Due to the small number of studies, there was a paucity of evidence on the effect of abdominal drains with no clear benefit for or against the use of drainage. However, one study investigating the open vs. closed circuit drains found a significantly higher incidence of intra-abdominal infections when open-circuit drains were used. CONCLUSIONS: Due to the potential risk of biliary leakage and infections, the routine intraoperative insertion of T-tubes is not recommended (Level of Evidence moderate - very low; grade of recommendation strong). However, a T-tube can be considered in cases at risk for biliary stenosis. Due to the scant evidence on abdominal drainage, no change in clinical practice in individual centers is recommended. (Level of Evidence very low; weak recommendation).

When is the optimal time to discharge patients after liver transplantation with respect to short-term outcomes? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Several factors associated with prolonged hospital stay have been described. A recent study demonstrated that hospital length of stay (LOS) is directly associated with an increased cost for liver transplantation (LT) and may be associated with greater mortality; however, the factors associated with post-LT mortality are also related to a prolonged hospital stay, that is, those factors are confounders. Thus, the actual impact of the length of post-LT hospital stay on both short-term and long-term patient and graft survival remains uncertain. OBJECTIVES: To identify the optimal time to discharge patients after LT with respect to short-term outcomes; readmission rate, 30-90-mortality and morbidity. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Initial search keywords for screening were as follows; ((discharge AND (time OR "time point" OR "time-point")) OR "length of hospital stay" OR "length of stay") AND ((liver OR hepatic) AND (transplant OR transplantation)). PROSPERO ID: CRD42021245598 RESULTS: The strength of recommendation was rated as Weak, and we did not identify the direction of recommendations regarding the optimal timing after LT concerning short-term outcomes, including "Readmission rate," six studies on 30- and/or 90-day mortality, and five studies on "30- and/or 90-day morbidity rate." CONCLUSIONS: Evidence is scarce to judge the optimal timing to discharge patients after LT with respect to short-term outcomes. In centers with robust outpatient follow-up, discharge can occur safely as early as post-transplant 6-8 days (Quality of Evidence [QOE]; Low | Grade of Recommendation; Weak).

Perioperative fluid management and outcomes in adult deceased donor liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Fluid management practices during and after liver transplantation vary widely among centers despite better understanding of the pathophysiology of end-stage liver disease and of the effects of commonly used fluids. This reflects a lack of high quality trials in this setting, but also provides a rationale for both systematic review of all relevant studies in liver recipients and evaluation of new evidence from closely related domains, including hepatology, non-transplant abdominal surgery, and critical care. OBJECTIVES: To develop evidence-based recommendations for perioperative fluid management to optimize immediate and short-term outcomes following liver transplantation. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies included those evaluating the following postoperative outcomes: acute kidney injury, respiratory complications, operative blood loss/red cell units required, and intensive care length of stay. PROSPERO protocol ID: CRD42021241392 RESULTS: Following expert panel review, 18 of 1624 screened studies met eligibility criteria for inclusion in the final quantitative synthesis. These included six single center RCTs, 11 single center observational studies, and one observational study comparing centers with different fluid management techniques. Definitions of interventions and outcomes varied between studies. Recommendations are therefore based substantially on expert opinion and evidence from other clinical settings. CONCLUSIONS: A moderately restrictive or "replacement only" fluid regime is recommended, especially during the dissection phase of the transplant procedure. Sustained hypervolemia, based on absence of fluid responsiveness, elevated filling pressures and/or echocardiographic findings, should be avoided (Quality of Evidence: Moderate | Grade of Recommendation: Weak for restrictive fluid regime. Strong for avoidance of hypervolemia). Mean Arterial Pressure (MAP) should be maintained at >60-65 mmHg in all cases (Quality of Evidence: Low | Grade of Recommendation: Strong). There is insufficient evidence in this population to support preferential use of any specific colloid or crystalloid for routine volume replacement. However, we recommend against the use of 130/.4 HES given the high incidence of AKI in this population.

The role of preoperative optimization of the nutritional status on the improvement of short-term outcomes after liver transplantation? A review of the literature and expert panel recommendations.

BACKGROUND: Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post-transplant outcomes for transplant recipients. OBJECTIVES: Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short-term outcomes after LT. SECONDARY OBJECTIVES: To determine if preoperative improvement of malnutrition improves short-term outcomes after LT, as well as if weight loss in obese patients affects short-term outcomes after LT. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 RESULTS: 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full-text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post-transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients. CONCLUSIONS: We have made a weak recommendation supporting pre-transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence.

Which preoperative assessment modalities best identify patients who are suitable for enhanced recovery after liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: To implement Enhanced Recovery After Surgery (ERAS) protocols for liver transplant (LT) candidates, it is essential to identify tools that can help risk stratify patients by their risk of early adverse post-LT outcomes. OBJECTIVE: We aimed to identify pre-LT tools that assess functional capacity, frailty, and muscle mass that can best risk stratify patients by their risk of adverse post-LT outcomes. METHODS: We first conducted a systematic review following PRISMA guidelines, expert panel review and recommendations using the GRADE approach (PROSPERO ID CRD42021237434). After confirming there are no studies evaluating assessment modalities for ERAS protocols for LT recipients specifically, the approach of the review focused on pre-LT modalities that identify LT recipients at higher risk of worse early post-LT outcomes (≤90 days), considering that this is particularly pertinent when evaluating candidates for ERAS. RESULTS: Twenty-two studies were included in the review, encompassing three different types of pre-LT modalities: evaluation of physical function (including frailty and general physical scores like the Karnofsky Performance Status (KPS), assessment of cardiopulmonary capacity, and estimation of muscle mass and composition. The majority of studies evaluated frailty assessment and muscle mass. Most studies, except for liver frailty index (LFI), were retrospective and single-center. All assessment modalities could identify, in different grade, LT recipients with higher risk of early post-LT mortality, length of stay or postoperative complications. CONCLUSIONS: We identified four pre-LT assessment tools that could be used to identify patients who are suitable for ERAS protocols: (1) KPS (quality of evidence moderate, grade of recommendation strong); (2) LFI (quality of evidence moderate, grade of recommendation strong); (3) abdominal muscle mass by CT (quality of evidence moderate, grade of recommendation strong); and (4) cardiopulmonary exercise testing (CPET) (quality of evidence moderate, grade of recommendation weak). We recommend that selection of the appropriate tool depends on the specific clinical setting and available resources to administer the tool, and that use of a tool be incorporated into the routine preoperative assessment when considering implementation of ERAS protocols for LT.

Intraoperative transfusion management, antifibrinolytic therapy, coagulation monitoring and the impact on short-term outcomes after liver transplantation-A systematic review of the literature and expert panel recommendations.

BACKGROUND: Liver transplantation (LT) is frequently complicated by coagulopathy associated with end-stage liver disease (ESLD), that is, often multifactorial. OBJECTIVES: The objective of this systematic review was to identify evidence based intraoperative transfusion and coagulation management strategies that improve immediate and short-term outcomes after LT. METHODS: PRISMA-guidelines and GRADE-approach were followed. Three subquestions were formulated. (Q); Q1: transfusion management; Q2: antifibrinolytic therapy; and Q3: coagulation monitoring. RESULTS: Sixteen studies were included for Q1, six for Q2, and 10 for Q3. Q1: PRBC and platelet transfusions were associated with higher mortality. The use of prothrombin complex concentrate (PCC) and fibrinogen concentrate (FC) were not associated with reductions in intraoperative transfusion or increased thrombotic events. The use of cell salvage was not associated with hepatocellular carcinoma (HCC) recurrence or mortality. Cell salvage and transfusion education significantly decreased blood product transfusions. Q2: Epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA) were not associated with decreased blood product transfusion, improvements in patient or graft survival, or increases in thrombotic events. Q3: Viscoelastic testing (VET) was associated with decreased allogeneic blood product transfusion compared to conventional coagulation tests (CCT) and is likely to be cost-effective. Coagulation management guided by VET may be associated with increases in FC and PCC use. CONCLUSION: Q1: A specific blood product transfusion practice is not recommended (QOE; low | Recommendation; weak). Cell salvage and educational interventions are recommended (QOE: low | Grade of Recommendation: moderate). Q2: The routine use of antifibrinolytics is not recommended (QOE; low | Recommendation; weak). Q3: The use of VET is recommended (QOE; low-moderate | Recommendation; strong).

What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery, or portal vein thrombosis? A systematic review of the literature and expert panel recommendations.

BACKGROUND: A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding (CRD42021244288). RESULTS: Of the 2478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS: Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT.

Does machine perfusion improve immediate and short-term outcomes by enhancing graft function and recipient recovery after liver transplantation? A systematic review of the literature, meta-analysis and expert panel recommendations.

BACKGROUND: Recent evidence supports the use of machine perfusion technologies (MP) for marginal liver grafts. Their effect on enhanced recovery, however, remains uncertain. OBJECTIVES: To identify areas in which MP might contribute to an ERAS program and to provide expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach. CRD42021237713 RESULTS: Both hypothermic (HMP) and normothermic (NMP) machine perfusion demonstrated significant benefits in preventing postreperfusion syndrome (PRS) (HMP OR .33, .15-.75 CI; NMP OR .51, .29-.90 CI) and early allograft dysfunction (EAD) (HMP OR .51, .35-.75 CI; NMP OR .66, .45-.97 CI), while shortening LOS (HMP MD -3.9; NMP MD -12.41). Only NMP showed a significant decrease in the length of ICU stay (L-ICU) (MD -7.07, -8.76; -5.38 CI), while only HMP diminishes the likelihood of major complications. Normothermic regional perfusion (NRP) reduces EAD (OR .52, .38-.70 CI) and primary nonfunction (PNF) (OR .51, .27-.98 CI) without effect on L-ICU and LOS. CONCLUSIONS: The use of HMP decreases PRS and EAD, specifically for marginal grafts. This is supported by a shorter LOS and a lower rate of major postoperative complications (QOE; moderate | Recommendation; Strong). NMP reduces the incidence of PRS and EAD with associated shortening in L-ICU for both DBD and DCD grafts (QOE; moderate | Recommendation; High) This technology also shortens the length of hospital stay (QOE; low | Recommendation; Strong). NRP decreases the likelihood of EAD (QOE; moderate) and the risk of PNF (QOE; low) when compared to both DBD and SRR-DCD grafts preserved in SCS. (Recommendation; Strong).

What is the optimal antimicrobial prophylaxis to prevent postoperative infectious complications after liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Antimicrobial prophylaxis is well-accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined. OBJECTIVES: To identify the optimal antimicrobial prophylaxis to prevent post-LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short-term outcomes, and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID: CRD42021244976. RESULTS: Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included. CONCLUSIONS: Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong).