Small-for-size Syndrome Research Articles

Clinical Significance of Grade A Small-for-size Syndrome After Living Donor Liver Transplantation Utilizing the New Definition of Diagnostic Criteria: An International Multicenter Study.

New diagnostic criteria have recently been established to classify small-for-size syndrome (SFSS) after living donor liver transplantation into 3 groups based on severity. This study aimed to evaluate the clinical impact of grade A SFSS and identify the mortality risk. We collected data from 406 patients diagnosed with grade A SFSS after living donor liver transplantation. Grade A SFSS is characterized by total bilirubin >5 mg/dL on postoperative day (POD) 7 or total bilirubin >5 mg/dL or ascites >1 L/d on POD 14. After propensity score matching, 193 patients were categorized into the up-trend group, down-trend group, and ascites group, with 43 patients (22.3%) in the up-trend group (total bilirubin on POD 7 < POD 14), 107 patients (55.4%) in the down-trend group (total bilirubin on POD 7 > POD 14), and 43 patients (22.3%) in the ascites group (only satisfying ascites criteria). There was no significant difference in survival between patients with grade A SFSS and those without SFSS (P = 0.152). The up-trend group showed a higher 90-d mortality rate than the down-trend and ascites groups (P = 0.025). The 1-y survival rate differed significantly between the groups (87.6%, 91.9%, and 97.7%, respectively; P = 0.044). The independent risk factors for survival were up-trend of total bilirubin, recipient age (65 y and older), model for end-stage liver disease score (≥30), and ABO incompatibility. Patients with ≥2 risk factors had worse survival rates than those with none and only 1 risk factor (P < 0.001). Although the survival rate was comparable between the grade A SFSS and non-SFSS cohorts, the up-trend group showed worse survival. Aggressive interventions should be considered for up-trend patients with risk factors.

Graft Inflow Modulation by Splenic Artery Ligation for Portal Hyper Perfusion does not Decrease Rates of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation: A Randomized Control Trial.

The primary objective was to compare the rates of early allograft dysfunction (EAD) in patients undergoing elective adult live donor liver transplantation (ALDLT) with and without graft portal inflow modulation (GIM) for portal hyper-perfusion. The secondary objectives were to compare time to normalization of bilirubin and International Normalized Ratio (INR), day 14 ascitic output more than 1liter, small-for-size syndrome (SFSS), intensive care unit / high dependency unit and total hospital stay, and 90 day morbidity and mortality. GIM can prevent EAD in ALDLT patients with portal hyper-perfusion. A single-center randomized trial with and without GIM for portal hyper-perfusion by splenic artery ligation (SAL) in ALDLT was performed. After reperfusion, patients with portal venous pressure (PVP)>15mm Hg with a gradient (PVP - central venous pressure) of ≥ 7mm Hg and/or portal venous flow (PVF)>250mL/min/100 grams of liver were randomized into two groups: GIM and No GIM. 75 of 209 patients satisfied the inclusion criteria, and 38 underwent GIM. Baseline PVF and PVP were comparable between the GIM and no GIM groups. SAL significantly reduced the PVF and PVP (P<0.001). There were no differences in the primary and secondary outcomes between the two groups. In the subgroup analysis, with a Graft to Recipient Weight Ratio (GRWR)≤0.8, there were no significant differences in the primary and secondary outcomes. SAL significantly decreased PVP and PVF, but did not decrease rates of EAD in adult LDLT.

International multicenter study of ultralow graft-to-recipient weight ratio grafts in adult living donor liver transplantation

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient weight ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multicenter study, 92 adult LDLTs with a final GRWR ≤0.6 performed at 12 international liver transplant centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation, development of small for size syndrome (SFSS), morbidity, and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day, and 1-year mortality. The preoperative model for end-stage liver disease and inpatient status were independent predictors for SFSS (P < .05). Pre-liver transplant renal dysfunction was an independent predictor of survival (hazard ratio 3.1; 95% confidence intervals 1.1, 8.9, P = .035). PFH or portal flow modulation were not predictive of SFSS or survival. We report the largest ever multicenter study of LDLT outcomes using ultralow GRWR grafts and for the first time validate the International Liver Transplantation Society-International Living donor liver transplantation study group-Liver Transplantation Society of India consensus definition and grading of SFSS. Preoperative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Vascular damage and excessive proliferation compromise liver function after extended hepatectomy in mice.

Surgical resection remains the gold standard for liver tumor treatment, yet the emergence of post-operative liver failure, known as the small for size syndrome (SFSS), poses a significant challenge. The activation of hypoxia sensors in a SFSS liver remnant initiated early angiogenesis, improving vascular architecture, safeguarding against liver failure and reducing mortality. The study aimed to elucidate vascular remodeling mechanisms in SFSS, its impact on hepatocyte function and subsequent liver failure. Mice underwent extended partial hepatectomy to induce SFSS, with a subset exposed to hypoxia immediately after surgery. Hypoxia bolstered post-hepatectomy survival rates. Early proliferation of liver sinusoidal cells, coupled with recruitment of putative endothelial progenitor cells (EPC), increased vascular density, improved lobular perfusion, and limited hemorrhagic events in the regenerating liver under hypoxia. Administration of granulocyte colony stimulating factor (G-CSF) in hepatectomized mice mimicked the effects of hypoxia on vascular remodeling and EPC recruitment, but failed to rescue survival. Compared to normoxia, hypoxia favored hepatocyte function over proliferation, promoting functional preservation in the regenerating remnant. Injection of AAV8-TBG-HNF4α virus for hepatocyte-specific overexpression of HNF4α, the master regulator of hepatocyte function, enforced functionality in proliferating hepatocytes but did not rescue survival. The combination of HNF4α overexpression and G-CSF treatment rescued survival after SFSS-setting hepatectomy. In summary, SFSS arises from an imbalance and desynchronized interplay between functional regeneration and vascular restructuring. To improve survival following SFSS-hepatectomy, it is essential to adopt a two-pronged strategy aimed at preserving the function of proliferating parenchymal cells and simultaneously attenuating vascular damage.

Role of temporary portosystemic surgical shunt during liver resection to prevent a post-resection small for size-like syndrome

Liver resection stands as the gold-standard therapeutic approach for selected cases of hepatocellular carcinoma (HCC). The extent of resectable parenchyma hinges upon the underlying liver function and its regenerative potential. Consequently, cirrhosis may impede access to potentially curative interventions for HCC arising within this context. Cirrhotic patients undergoing liver resection face heightened susceptibility to post-hepatectomy liver failure (PHLF). The clinical profile of PHLF bears a resemblance to a well-documented syndrome within the liver transplant (LT) domain: Small-for-size syndrome (SFSS), a form of graft failure observed in the postoperative phase following LT with undersized or partial organs. Management of SFSS targets mitigating the overflow syndrome, achievable through diverse portal diversion techniques. Portal vein flow diversion encompasses procedures redirecting a variable proportion of portal vein flow towards systemic circulation. Consequently, derivative procedures aim to directly alleviate portal hypertension. Side-to-side portocaval shunts emerge as the most straightforward and efficacious means of decompressing the portal system. Furthermore, they afford flow calibration to diminish the incidence and severity of steal syndrome and hepatic encephalopathy, without compromising efficacy or hepatic function. Translating insights gleaned from LT complexities involving SFSS to liver resection, strategies involving portal flow diversion warrant consideration in efforts to forestall PHLF. This approach aims to extend the frontiers of liver surgery, broadening access to hepatectomy with curative intent, either as a standalone intervention or as part of a comprehensive treatment regimen where LT serves as a secondary option.

Outcomes of living donor liver transplant recipients receiving grafts with the Graft-to-Recipient weight ratio less than 0.6%: A matched pair analysis.

We sometimes experience living donor liver transplantation (LDLT) involving very small grafts with graft-to-recipient weight ratio (GRWR) <0.6% when the actual graft size is smaller than predicted. The outcomes in this situation have not been fully investigated. The present study aimed to determine the graft outcomes of LDLT with GRWR <0.6%. We retrospectively reviewed 280 cases of adult LDLT performed at our institution between January 2000 and March 2021. In our institution, the lower limit for graft volume/standard liver volume ratio was 30%. The patients were divided into two groups according to the cutoff value of 0.6% for actual GRWR. Graft survival and surgical outcomes including small-for-size syndrome (SFSS) were compared between the groups using propensity score matching (PSM) analysis. Risk factors associated with SFSS in recipients with GRWR <0.6% were also evaluated. Fifty-nine patients received grafts with GRWR <0.6%. After PSM, similar graft survival rates were observed for GRWR <0.6% (n=53) and GRWR ≥0.6% (n=53) (p=0.98). However, patients with GRWR <0.6% had a significantly worse 3-month graft survival rate (86.8% vs. 98.1%, p=0.03) and higher incidence of SFSS (p<0.001) than patients with GRWR ≥0.6%. On multivariate analysis, Model for End-Stage Liver Disease score and donor age were associated with SFSS in patients with GRWR <0.6%. The same factors were also associated with graft survival. In conclusions, although similar overall graft survival rates were observed for LDLT with GRWR <0.6% and GRWR ≥0.6%, GRWR <0.6% was associated with an increased risk of SFSS. Appropriate donor and recipient selection is important for successful LDLT with very small grafts.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

Management of Established Small-for-size Syndrome in Post Living Donor Liver Transplantation: Medical, Radiological, and Surgical Interventions: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) following living donor liver transplantation is a complication that can lead to devastating outcomes such as prolonged poor graft function and possibly graft loss. Because of the concern about the syndrome, some transplants of mismatched grafts may not be performed. Portal hyperperfusion of a small graft and hyperdynamic splanchnic circulation are recognized as main pathogenic factors for the syndrome. Management of established SFSS is guided by the severity of the presentation with the initial focus on pharmacological therapy to modulate portal flow and provide supportive care to the patient with the goal of facilitating graft regeneration and recovery. When medical management fails or condition progresses with impending dysfunction or even liver failure, interventional radiology (IR) and/or surgical interventions to reduce portal overperfusion should be considered. Although most patients have good outcomes with medical, IR, and/or surgical management that allow graft regeneration, the risk of graft loss increases dramatically in the setting of bilirubin >10 mg/dL and INR>1.6 on postoperative day 7 or isolated bilirubin >20 mg/dL on postoperative day 14. Retransplantation should be considered based on the overall clinical situation and the above postoperative laboratory parameters. The following recommendations focus on medical and IR/surgical management of SFSS as well as considerations and timing of retransplantation when other therapies fail.

Preventing Small-for-size Syndrome in Living Donor Liver Transplantation: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

Analysis of Outcome in Recipients with Different Graft-Recipient-Weight-Ratio (GRWR) Post Adult to Adult Living Donor Liver Transplant (LDLTx)

Abstract Background The problem of graft size is one of the critical factors limiting the expansion of adultto-adult living donor liver transplantation (LDLT). Graft-to-recipient weight ratio (GRWR) &amp;gt; 0.8% is perceived as the critical graft size to meet the metabolic demand of the recipient. Small-for-size graft (SFSG) is the graft with GRWR &amp;lt; 0.8 and when its unable to meet the recipients metabolic demands, small-for-size syndrome (SFSS) occurs which is a life-threatening condition with rapidly progressive liver failure. This lower limit of GRWR (0.8%) has been challenged over the last decade perhaps due to better understanding of the pathophysiology, coupled with technical refinements, particularly related to venous outflow reconstruction. Aim of Work Our aim was to analyse the different outcomes of patients undergoing Living donor liver transplantation using grafts with GRWR ≤ 0.8% with those &amp;gt;0.8% to evaluate the factors that affect the post-operative outcome and the overall one year Graft survival. Methods This is a retrospective cohort study on 100 adult patients with ESLD or HCC (mean age 54.16 ± 10.53 years old) who underwent adult LDLT in the period between 2018 and 2020 and follow up the patients for one year post transplant, Patients were divided into two groups, patients who received Graft with GRWR ≤ 0.8 (N = 22 patients with lower limit of GRWR = 0.58 and there is 7 patients with GRWR ≤ 0.7) and those with GRWR &amp;gt;0.8 (N = 78 patients). We compared the the Donor factors, preoperative patient factors, intraoperative factors, development of small for size syndrome and graft survival in patients received small-for-size grafts (GRWR ≤ 0.8) with patients received GRWR &amp;lt;0.8. Results We retrospectively evaluated the donor factors, recipient factors and operative factors through the medical records. Small-for-size syndrome (SFSS) occurred in 2 of 22 patients (9.1%) in patients with GRWR ≤ 0.8 and in 1 of 78 patients (1.3%) in patients with GRWR &amp;gt;0.8 which was statistically insignificant between two groups. There was No significant difference in the Donor age, Preoperative MELD, CHILD, Portal hypertension, cold and warm ischemia, operative time, presence of PVT and HCC in patients who received GRWR ≤ 0.8 and patients with GRWR &amp;gt;0.8. the mean overall survival for all the studied cases was found 43.35 months and the overall survival at 6 months and 1 year was 96.0% but there was statistically significant increase in the overall survival of cases with GRWR &amp;gt;0.8 than those with GRWR ≤ 0.8 with p-value = 0.009, as the overall 6 months and 1 year survival for patients with GRWR &amp;gt;0.8 was 98% and 98 % compared to 86 % and 86 % in thoses with GRWR ≤ 0.8 Conclusion There is no difference in the outcome in form of development of Small for size syndrome when we use Grafts with GRWR &amp;gt;0.8 or with GRWR ≤ 0.8, However the venous Outflow of SFSG (GRWR &amp;lt; 0.8) is very critical to maintain good graft function in the recipient.

Response to Comment on "Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts".

Response to Comment on "Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts".

Comment on "Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts".

We would like to congratulate the authors for publishing this important article on the outcome of utilizing left lobe grafts in their series of living donor liver transplantation (LDLT).1 Their study represents one of the largest series of utilizing left lobe grafts in the West and showed favorable 1-, 3-, and 5-year graft survival of 97%, 94%, and 89% comparable to the right lobe graft survival of 99%, 96%, and 93% (P = 0.97). This contrasts sharply from the European experience of 46 left lobe LDLTs from 4 centers showing a relatively poor 1-year graft survival of 59.4% due to a high rate of small for size syndrome (SFSS) and hepatic artery thrombosis.2 The key to their excellent outcomes was achieved by the use of venous outflow augmentation and liberal use of splenectomy to modulate portal inflow. From their series, 61 of 130 (47%) recipients received left lobe graft. Donor/recipient selection likely played a huge role to their highly favorable outcomes. The Kyoto group previously showed that the overall survival was significantly worse when using left lobe graft compared with right lobe graft in recipients who were considered high risk (at least 2 risk factors of: model for end-stage liver disease [MELD] score > 20; preoperative hospitalization; recent preoperative bacterial infection).3 In contrast, no difference in survival were found between left lobe or right lobe recipient if only 1 risk factor was present. The Kyushu group reported donor age ≥ 48 years, MELD score ≥ 19, and end portal venous pressure ≥ 19 mm Hg as the important factors for the development of SFSS.4 These factors reflect on the poor graft quality from higher donor age, poor clinical status of the recipient and excessive portal flow after reperfusion of the partial graft. To highlight the important of graft selection, the Kyushu group has also devised a scoring system that incorporates factors such as graft size, donor age, MELD score, and the presence of portosystemic shunts, which correlate well with graft survival and can be employed for graft selection.5 Although there is currently no consensus on the selection criteria when comes to choosing left lobe graft, most groups have demonstrated that donor age, and MELD score as crucial deciding factors as mentioned. In fact, the European cohort with poor outcome with left lobe grafts reported MELD score >14 as the most significant factor for the development of SFSS.2 Looking at the Cleveland cohort, it is very clear that this is a highly selected group of donors and recipients when considering for left lobe graft with a donor median age of 36 years (interquartile range, 31–41 years), low median MELD score of 12 (interquartile range, 10, 16), and less severe portal hypertension as evident by the low median splenic volume (611 mL for left lobe graft compared with 918 for right lobe graft). Their left lobe graft experience has been accumulated over 8 years from 2013 to 2020 sharing between the 2 centers ranging from 5 to 17 left lobe grafts per year (mean 7 to 8 per year). This likely represents only a fraction of their overall liver transplant activity and further suggests that the recipients chosen for left lobe graft were highly selected. As regards to the use of inflow modulation such as splenectomy in this series, a group from Tokyo has described in their series of 42 LDLTs using exclusively left lobe graft without the use of any inflow modulation technique with a very good 1-, 3-, and 5-year graft survival rate of 100%, 97%, and 91%, despite 38% of their recipients had graft-to-recipient weight ratio (GRWR) of less than 0.8%.6 Therefore, it is unclear how much contribution to current reported outcomes were related to patient selection or the use of splenectomy, the use of which has been shown to be a protective for graft dysfunction here. Although the reported morbidities with splenectomy were acceptable in this series, with sicker recipients, the added morbidity of splenectomy may become problematic and could lead to worse outcomes. It has been well established that the grafts are considered small for size when the GRWR is less than 0.8% or the standard liver volume is less than 35%.7 This article has also reported the graft outcome when actual size of the graft was smaller than the expected minimum GRWR of 0.6%. While the 5-year graft survival of 88% and only 1 mortality amongst the 9 left lobe recipients is impressive, this is still small numbers, from selected donors and recipients. Until there are more data and replication of this practice in other centers, we feel that the usage of small left lobe grafts remains an option for very few and not a promised land for the many.

Left liver graft in adult-to-adult living donor liver transplantation with an optimal portal flow modulation strategy to overcome the small-for-size syndrome – A retrospective cohort study

BackgroundAdult-to-adult living donor liver transplantation (LDLT) is a notable type of liver transplantation. Several centers prefer the right liver graft (RLG) over the left liver graft (LLG) for better recovery of recipients. We compared the outcomes of donors and recipients between LDLT using LLGs and RLGs. Materials and methodsThe study cohort comprised of 25 patients in the LLG group and 93 in the RLG group. When both hemiliver grafts met the selection criteria, an LLG was preferred. When portal flow (≥300 ml/min/100gLW) and hepatic venous pressure gradient (≥10 mmHg) were increased, intraoperative splenic artery ligation was performed for portal modulation. Postoperatively, somatostatin was administered when small-for-size syndrome (SFSS) was highly suspected. ResultsThe graft-to-recipient weight ratio was lower in the LLG group than in the RLG group. There was no significant complication above Clavien–Dindo grade IIIA in donors. Regarding recipient outcomes, SFSS occurred in four (16.0%) patients in the LLG group and three (3.2%) in the RLG group (P = 0.036). Splenic artery ligation was frequently performed in the LLG group than the RLG group (5 [20.0%] vs. 12 [12.9%], P = 0.035) and 5 patients received intravenous continuous somatostatin for 7 (5–12) days. SFSS-related hospital mortality did not occur. There was no significant difference in the short-term and long-term outcomes between the groups. ConclusionThis study demonstrates the comparable outcomes of donors and recipients between the LLG and RLG groups although with a higher risk of SFSS that needs high experience to avoid severe complications and graft loss. We expect LLG to be used more actively in adult-to-adult LDLT with portal flow modulation strategies to overcome fatal SFSS.

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.

Portal inflow modulation (PIM) aimed at reducing portal hyperperfusion is commonly used in 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. To identify whether modifications of portal pressures and flows enhance recovery after LDLT and to provide international expert panel recommendations. Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. CRD42021260997 RESULTS: 594 articles were identified through databases' search. Of the 24 included for a final review by the working group (WG), there were 5 randomized controls trials, 4 prospective studies and 15 retrospective series. Six outcomes 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. 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) This article is protected by copyright. All rights reserved.

Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts.

Living donor liver transplantation (LDLT) using small grafts, especially left lobe grafts (H1234-MHV) (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved. Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG (H1234-MHV) in a single Enterprise. The median graft-to-recipient weight ratio was 0.84%, with graft-to-recipient weight ratio <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right lobe graft (H5678) (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival. Graft survival rates at 1, 3, and 5 years were 94%, 90%, and 83%, respectively, with no differences between LLG (H1234-MHV) and RLG (H5678). Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed model for end-stage liver disease score and LLG (H1234-MHV) as independent risk factors for EAD and splenectomy as a protective factor (odds ratio: 0.09; P =0.03). For LLG (H1234-MHV)-LDLT, patients who underwent prereperfusion splenectomy tended to have better 1-year graft survival than those receiving postreperfusion splenectomy. LLG (H1234-MHV) are feasible in adult LDLT with excellent outcomes comparable to RLG (H5678). Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival.

Ascites post-living donor liver transplantation: Risk factors and outcome

Background and aimPersistent ascites post-liver transplantation is reported to be a rare event. This study aimed to determine the prevalence, risk factors, etiology and outcome of ascites post-living donor liver transplantation (LDLT). MethodsThis is a retrospective observational study on 347 recipients who underwent LDLT at our center from 2008 to 2018. We classify the ascites post-LDLT into either persistent (PA): present > four weeks post LT, or refractory (RA): new-onset ascites after the first-month post LT. ResultsThe prevalence of ascites post LDLT was 8.4% (n = 29), including PA, 4.9%, and RA, 3.45%. Idiopathic ascites (no specific cause) was the most common in the PA group, while vascular complications and graft failure were more common in the RA group. On regression analysis model, the presence of pre-LT PVT, small for size syndrome (SFSS) and vascular complications were the independent risk factors of PA (p value=0.017, 0.026, 0.011, respectively and Odds ratio (95% CI) = 4.25(1.290–13.97), 4.01(1.177–13.63) and 7.4(1.596–34.46), respectively. Pre-LT-HCV-related chronic liver disease, significant portal hypertension, donor overweight and vascular complications were the risk factors for the development of RA (p value= 0.04, 0.001, 0.031, <0.001, respectively and Odds ratio (95% CI) = 18.99 (1.1–315.14), 46.67 (4.51–483.08), 4.72 (1.15–19.31) & 67.23(6.38–708.72) respectively. Three- and five-year survival are not significantly reduced in patients who developed ascites post LDLT. ConclusionsAscites post-LDLT does not affect the 3- and 5-year survival rates. Idiopathic ascites pos-LDLT is common and has a good prognosis.

Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model

The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM). We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION". Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process. The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.

Prevention and Management of Small-for-Size Syndrome of Liver Transplantation

Small-for-size syndrome (SFSS) is a critical complication of partial liver transplantation, particularly in adult-to-adult living donor liver transplantation (ALDLT) using a small graft. Minimally required liver graft size for a successful ALDLT is classically 40% of a standard recipient’s liver volume or 0.8% of recipient body weight. Recent progress in perioperative care and technical improvement push the lower limit of safe graft size to 25% of the recipient’s standard liver volume or 0.6% of the graft versus recipient weight ratio although this is an ongoing debate. The clinical manifestations of SFSS include various symptoms and signs related to graft dysfunction and portal hypertension in patients with small grafts. The risk factors for SFSS include poor preoperative patient condition, including portal pressure, surgical techniques to reduce portal pressure, and graft quality and size. Hence, various approaches have been explored to modulate inflow and pressure to a small graft and to decrease the outflow block to alleviate this SFSS as well as the selection of a patient and graft. Additionally, recent research and efforts to prevent and treat SFSS are reviewed. (Ewha Med J 2022;45(2):29-34)

Liver Graft-to-Spleen Volume Ratio as a Useful Predictive Factor of the Outcomes in Living Donor Liver Transplantation: A Retrospective Study.

BackgroundIn living donor liver transplantation (LDLT), graft-to-recipient weight ratio (GRWR) <0. 8% is an important index for predicted portal hypertension, which may induce the graft small-for-size syndrome (SFSS). Recently, the value of graft-to-spleen volume ratio (GSVR) on predicted portal hypertension had been reported, whether without splenectomy prevent portal hypertension in transplantation remains disputed, we aimed to identify GSVR contributing to portal venous pressure (PVP) and outcomes without simultaneous splenectomy in LDLT.MethodsA retrospective study had been designed. Excluded patients with splenectomy, 246 recipients with LDLT between 2016 and 2020 were categorized into a low GSVR group and a normal GSVR group. Preoperative, intraoperative, and postoperative data were collected, then we explored different GSVR values contributing to portal hypertension after reperfusion.ResultsAccording to the first quartile of the distributed data, two groups were divided: low GSVR (<1.03 g/mL) and normal GSVR (>1.03 g/mL). For the donors, there were significant differences in donor age, graft type, liver size, GRWR, and GSVR (P < 0.05). Following the surgical factors, there were significant differences in blood loss and CRBC transfusion (P < 0.05). The low GSVR has demonstrated had a significant relationship with ascites drainage and portal venous flow after LDLT (P < 0.05). Meanwhile, low GSVR heralds worse results which covered platelet count, international normalized ratio (INR), and portal venous velocity. Kaplan–Meier analysis showed that there was a significant difference between the two groups, while the low GSVR group demonstrated worse recipients survival compared with the normal GSVR group (P < 0.05).ConclusionsWithout splenectomy, low GSVR was an important predictor of portal hypertension and impaired graft function after LDLT.