Small-for-size syndrome (SFSS) remains a critical challenge in living donor liver transplantation (LDLT), characterized by graft insufficiency due to inadequate liver volume, leading to significant postoperative morbidity and mortality. As the global adoption of LDLT increases, the ability to predict and manage SFSS has become paramount in optimizing recipient outcomes. This review provides a comprehensive examination of the pathophysiology, risk factors, and strategies for managing SFSS across the pre-, intra-, and postoperative phases. The pathophysiology of SFSS has evolved from being solely volume-based to incorporating portal hemodynamics, now recognized as small-for-flow syndrome. Key risk factors include donor-related parameters like age and graft volume, recipient-related factors such as MELD score and portal hypertension, and intraoperative factors related to venous outflow and portal inflow modulation. Current strategies to mitigate SFSS include careful graft selection based on graft-to-recipient weight ratio and liver volumetry, surgical techniques to optimize portal hemodynamics, and novel interventions such as splenic artery ligation and hemiportocaval shunts. Pharmacological agents like somatostatin and terlipressin have also shown promise in modulating portal pressure. Advances in 3D imaging and artificial intelligence-based volumetry further aid in preoperative planning. This review emphasizes the importance of a multifaceted approach to prevent and manage SFSS, advocating for standardized definitions and grading systems. Through an integrated approach to surgical techniques, hemodynamic monitoring, and perioperative management, significant strides can be made in improving the outcomes of LDLT recipients. Further research is necessary to refine these strategies and expand the application of LDLT, especially in challenging cases involving small-for-size grafts.

The extension of liver transplantation to new oncologic indications might exacerbate the shortage of grafts. Living donor liver transplantation (LDLT) may emerge as a viable resource, although its diffusion in the Western world is still very limited. Several groups have advocated for minimizing the impact on donors by reducing the extent of donor hepatectomy, i.e., shifting from right-lobe to left-lobe or left-lateral segment donation ("shift-to-left"). This is particularly relevant when dealing with non-established indications and could make it more acceptable both for potential donors and for the recipients. Left grafts can be transplanted straightforward, despite a higher risk of small-for-size syndrome, or they can be used in the setting of dual-graft LDLT or RAPID procedures, despite technical complexity. This review will expose the most relevant features of each technique, highlighting their strengths and pitfalls and focusing on outcomes. This wide set of tools should be available at high-volume transplant centers, to propose the best technique to adapt to donor-recipient matching.

The shortage of deceased liver donor organs over the years has always posed the need to expand the donor pool. A viable alternative to deceased donors is that of the living donor. Indeed, the living donor in liver transplantation, initially in pediatric transplantation, but for several years now also in adult transplantation, is a more than viable alternative to deceased liver donation. In fact, right liver lobe donation has proven to be a surgical procedure with low impact on the donor's life in terms of morbidity and mortality, with excellent results in recipients of such organs. In recent years, an increasing number of studies have been published that show excellent results in right-lobe living donor liver transplantation, encouraging this practice not only in countries that have historically had a shortage of deceased donor organs, such as Asian countries, but making it a practice of increasing use in Western countries as well. In addition, thanks to improvements in surgical technique and the experience of high-volume centers, this surgery has also begun to be performed using minimally invasive surgical techniques, allowing us to envision ever better outcomes for both donor and recipient in the coming years.

A standard graft-to-recipient weight ratio (GRWR) ≥0.8% is widely accepted in living-donor liver transplantation (LDLT); however, the potential donor pool is expanded to patients adopting small-for-size graft (SFSGs) with GRWR <0.8%. This study aimed to investigate the effect of SFSG on short- and long-term outcomes following LDLT.

Electronic databases were searched from January 1995 to January 2022 for studies comparing short- or long-term outcomes between patients with SFSG (GRWR <0.8%, SFSG group) and sufficient volume graft (GRWR ≥0.8%, non-SFSG group). The primary outcomes were one-, three-, and five-year overall survival (OS) and graft survival (GS), while the secondary outcome was postoperative complications.

Twenty-four studies comprising 7996 patients were included. In terms of OS, SFSG group had poor three-year OS (HR: 1.48, 95% CI [1.01, 2.15], p = 0.04), but there were no significant differences between two groups in one-year OS (HR: 1.50, 95% CI [0.98, 2.29], p = 0.06) and five-year OS (HR: 1.40, 95% CI [0.95, 2.08], p = 0.02). In GS, there were no significant differences in one-year (HR 1.31, 95% CI [1.00, 1.72], p = 0.05), three-year (HR 1.33, 95% CI [0.97, 1.82], p = 0.07), and five-year GS (HR 1.17, 95% CI [0.95, 1.44], p = 0.13). The SFSG group had comparable postoperative complications, except for a high incidence of vascular complications and small-for-size syndromes.

Expanding the potential donor pool in LDLT to SFSG with GRWR <0.8% can be acceptable in terms of comparable long-term OS and GS, despite the risk for vascular complications and small-for-size syndrome.

Partial liver transplantation has recently been proposed to alleviate organ shortages. However, transplantation of a small-for-size graft is associated with an increased risk of posttransplant hepatic dysfunction, commonly referred to as small-for-size syndrome (SFSS). This review describes the etiology, pathological features, clinical manifestations, and diagnostic criteria of SFSS. Moreover, we summarize strategies to improve graft function, focusing on graft inflow modulation techniques. Finally, unmet needs and future perspectives are discussed.

In fact, posttransplant SFSS can be attributed to various factors such as preoperative status of the recipients, surgical techniques, donor age, and graft quality, except for graft size. With targeted improvement measures, satisfactory clinical outcomes can be achieved in recipients at increased risk of SFSS. Given the critical role of relative portal hyperperfusion in the pathogenesis of SFSS, various pharmacological and surgical treatments have been established to reduce or partially divert excessive portal inflow, and recipients will benefit from individualized therapeutic regimens after careful evaluation of benefits against potential risks. However, there remain unmet needs for further research into different aspects of SFSS to better understand the correlation between portal hemodynamics and patient outcomes.

Contemporary transplant surgeons should consider various donor and recipient factors and develop case-specific prevention and treatment strategies to improve graft and recipient survival rates.

Biliary complications (BCs) after liver transplantation (LT) remain a considerable cause of morbidity, mortality, increased cost, and graft loss.

To investigate the impact of BCs on chronic graft rejection, graft failure and mortality.

From 2011 to 2016, 215 adult recipients underwent right-lobe living-donor liver transplantation (RT-LDLT) at our centre. We excluded 46 recipients who met the exclusion criteria, and 169 recipients were included in the final analysis. Donors' and recipients' demographic data, clinical data, operative details and postoperative course information were collected. We also reviewed the management and outcomes of BCs. Recipients were followed for at least 12 mo post-LT until December 2017 or graft or patient loss.

The overall incidence rate of BCs including biliary leakage, biliary infection and biliary stricture was 57.4%. Twenty-seven (16%) patients experienced chronic graft rejection. Graft failure developed in 20 (11.8%) patients. A total of 28 (16.6%) deaths occurred during follow-up. BCs were a risk factor for the occurrence of chronic graft rejection and failure; however, mortality was determined by recurrent hepatitis C virus infection.

Biliary complications after RT-LDLT represent an independent risk factor for chronic graft rejection and graft failure; nonetheless, effective management of these complications can improve patient and graft survival.

Maximizing liver graft volume benefits the living donor liver recipient. Whether maximizing graft volume negatively impacts living donor recovery and outcomes remains controversial. Patient randomization between right and left hepatectomy has not been possible due to anatomic constraints; however, a number of published, nonrandomized observational studies summarize donor outcomes between 2 anatomic living donor hepatectomies. This meta-analysis compares donor-specific outcomes after right versus left living donor hepatectomy. Systematic searches were performed via PubMed, Cochrane, ResearchGate, and Google Scholar databases to identify relevant studies between January 2005 and November 2019. The primary outcomes compared overall morbidity and incidence of severe complications (Clavien-Dindo >III) between right and left hepatectomy in donors after liver donation. Random effects meta-analysis was performed to derive summary risk estimates of outcomes. A total of 33 studies (3 prospective and 30 retrospective cohort) were used to identify 7649 pooled patients (5993 right hepatectomy and 1027 left hepatectomy). Proportion of donors who developed postoperative complications did not significantly differ after right hepatectomy (0.33; 95% confidence interval [CI], 0.27-0.40) and left hepatectomy (0.23; 95% CI, 0.17-0.29; P = 0.19). The overall risk ratio (RR) did not differ between right and left hepatectomy (RR, 1.16; 95% CI, 0.83-1.63; P = 0.36). The relative risk for a donor to develop severe complications showed no differences by hepatectomy side (Incidence rate ratio, 0.97; 95% CI, 0.67-1.40; P = 0.86). There is no evidence that the overall morbidity differs between right and left lobe donors. Publication bias reflects institutional and surgeon variation. A prospective, standardized, multi-institutional study would help quantify the burden of donor complications after liver donation.

The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.

Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC).

To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription.

This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020.

Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created.

A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated.

This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

Studies indicate that low graft-to-recipient weight ratio (GRWR) affect graft survival in adult-to-adult living donor liver transplantation. However, the potential role of GRWR in the prognosis of patients following living donor liver transplantation according to patient characteristics remains controversial. This study aimed to update the role of GRWR in patients following living donor liver transplantation.

PubMed, Embase, and Cochrane Library were comprehensively searched for studies comparing low GRWR (< 0.8%) with normal GRWR (≥ 0.8%) in the prognosis following living donor liver transplantation from inception to March 2019. The 1-, 3-, and 5-year summary survival rates, small-for-size syndrome (SFSS), perioperative mortality, biliary complications, postoperative bleeding, and acute rejection were calculated using the random-effects model.

Eighteen studies comprising 4001 patients were included. Patients with low GRWR were associated with lower 1-year and 3-year survival rates compared to patients with normal GRWR, while no significant difference was found in the association of 5-year survival rate with low and normal GRWRs. Moreover, the risk of SFSS significantly increased in patients with low GRWR. Finally, no significant differences were observed in the association of low and normal GRWRs with the risk of perioperative mortality, biliary complications, postoperative bleeding, and acute rejection.

The results of this study indicated that low GRWR was associated with poor prognosis for patients following living donor liver transplantation, especially in terms of 1- and 3-year survival rates and SFSS.

Since the first success in an adult patient, living donor liver transplantation (LDLT) has become an universally used procedure. Small-for-size syndrome (SFSS) is a well-known complication after partial LT, especially in cases of adult-to-adult LDLT. The definition of SFSS slightly varies among transplant physicians. The use of a partial liver graft has risks of SFSS development. Persistent portal vein (PV) hypertension and PV hyper-perfusion after LT were identified as the main factors. Hence, various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome. Herein, the definition, clinical symptoms, pathophysiology, basic research, as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences.

The articles were collected through PubMed using search terms "liver transplantation", "living donor liver transplantation", "living liver donation", "partial graft", "small-for-size graft", "small-for-size syndrome", "graft volume", "remnant liver", "standard liver volume", "graft to recipient body weight ratio", "sarcopenia", "porcine", "swine", and "rat". English publications published before March 31, 2020 were included in this review.

Many transplant surgeons performed PV flow modulation, including portocaval shunt, splenic artery ligation and splenectomy. With these techniques, patient outcome has been improved even when using a "small" graft. Other factors, such as preoperative recipients' nutritional and skeletal muscle status, graft congestion, and donor factors, were also identified as risk factors which all have been addressed using various strategies.

The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients. In the absence of efficacious medications to resolve SFSS, conservative treatments, including aggressive fluid balance correction for massive ascites, anti-microbiological therapy to prevent or control sepsis and intensive nutritional therapy, are all required if SFSS could not be prevented.

During the last decades, deceased-donor liver transplantation (DDLT) has gained a place in the therapeutic algorithm of well-selected patients harbouring non-resectable secondary liver tumors. Living-donor LT (LDLT) might represent a valuable means to further expand this indication for LT.

Between 1985 and 2016, twenty-two adults were transplanted because of neuroendocrine (n = 18, 82%) and colorectal metastases (n = 4, 18%); 50% received DDLT and 50% LDLT. In LDLT, 4 (36%) right and 7 (64%) left grafts were used; the median graft-to-recipient-weight ratios (GRWR) were 1.03% (IQR 0.86%-1.30%) and 0.59% (IQR 0.51%-0.91%), respectively. Median post-LT follow-up was 64 months (IQR 17-107) in the DDLT group and 40 months (IQR 35-116) in the LDLT group. DDLT and LDLT recipients were compared in terms of overall survival, graft survival, postoperative complications and recurrence.

The 1- and 5-year actuarial patient survivals were 82% and 55% after DDLT, 100% and 100% after LDLT, respectively (P < 0.01). One- and 5-year actuarial graft survivals were 73% and 36% after DDLT, 91% and 91% after LDLT (P < 0.01). The outcomes of right or left LDLT were comparable. Donor hepatectomy proved safe, and one donor experienced a Clavien IIIb complication. Bilirubin peak was significantly lower after left hepatectomy compared with that after right hepatectomy [1.3 (IQR 1.2-2.2) vs. 3.3 (IQR 2.3-5.2) mg/dL; P = 0.02].

The more recent LDLT series compared favorably to our DDLT series in the treatment of secondary liver malignancies. The absence of portal hypertension and the use of smaller left grafts make recipient and donor surgeries safe. The safety of the procedures and lack of interference with the scarce allograft pool are expected to lead to a more frequent use of LDLT in the field of transplant oncology.