Small-for-size syndrome in liver transplantation:Definition,pathophysiology and management

Background: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.Data sources: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-forsize 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.Results: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.Conclusions: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.

Outcome of patients undergoing right lobe living donor liver transplantation with small-for-size grafts

AIM: To investigate the outcome of living donor liver transplantation (LDLT) recipients transplanted with small-for-size grafts (SFSGs). METHODS: Between November 2001 and December 2010, 196 patients underwent LDLT with right lobe liver grafts at our center. Recipients were divided into 2 treatment groups: group A with an actuarial graft-to-recipient weight ratio (aGRWR) < 0.8% (n = 45) and group B with an aGRWR = 0.8% (n = 151). We evaluated serum liver function markers within 4 wk after transplantation. We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients, the donors and the transplantation procedures based upon a review of their medical records. RESULTS: Small-for-size syndrome (SFSS) developed in 7 of 45 patients (15.56%) in group A and 9 of 151 patients (5.96%) in group B (P = 0.080). The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation, albeit not sig-nificantly. The cumulative 1-, 3-and 5-year liver graft survival rates were 82.22%, 71.11% and 71.11% for group A and 81.46%, 76.82%, and 75.50% for group B patients, respectively (P = 0.623). However, univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival (P < 0.001). Furthermore, multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival. CONCLUSION: Our study suggests that LDLT recipients with an aGRWR < 0.8% may have liver graft outcomes comparable to those who received larger size grafts. Further studies are required to ascertain the safety of using SFSGs. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Small-for-size syndrome in adult-to-adult living-related liver transplantation

Small-for-size syndrome (SFSS) in adult-to-adult living-related donor liver transplantation (LRLT) remains the greatest limiting factor for the expansion of segmental liver transplantation from either cadaveric or living donors. Portal hyperperfusion, venous pathology, and the arterial buffer response signif icantly contribute to clinical and histopathological manifestations of SFSS. Here, we review the technical aspects of surgical and radiological procedures developed to treat SFSS in LRLT, along with the pathophysiology of this condition.

Excessive portal flow causes graft failure in extremely small-for-size liver transplantation in pigs

AIM： To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely smallfor-size liver transplantation in pigs. METHODS： The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups： graft without portocaval shunt （n = 11） and graft with portocaval shunt （n = 11）. Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated. RESULTS： In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h afcer transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2±26.9 mL/min/100 g liver tissue and 270.5±72.9 ml./min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2±27.8 ml./ min/100 g liver tissue and 42.7±32.3 mL/min/100 g liver tissue, respectively （P〈0.01）. As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed afl：er reperfusion, but these findings were not recognized in the group with portocaval shunt. CONCLUSION： These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts

AIM： To investigate the tacrolimus dosage requirements and blood concentrations in adult-to-adult right lobe living donor liver transplantation （AALDLT） recipients with small-for-size （SFS） grafts. METHODS： During January 2007 and October 2008, a total of 54 cases of AALDLT with an observation period of 6 mo were enrolled in this study. The 54 patients were divided into two groups according to graftrecipient body weight ratio （GRBW）： SFS grafts group （Group S, GRBW 〈 0.8%, n = 8） and non-SFS grafts group （Group N, GRBW ≥ 0.8%, n = 46）. Tacrolimus 12-hour blood levels and doses were recorded during weeks 1, 2, 3 and 4 and months 2, 3, 4, 5 and 6 in group S and group N. Meanwhile, acute rejection rates, liver and renal function test results, and the number of potentially interacting medications were determined at each interval in the two groups. A comparison of tacrolimus dosage requirements and blood levels were made weekly in the first month post-surgery, and monthly from months 2 to 6. RESULTS： There were no differences in the demo-graphic characteristics, acute rejection rates, liver and renal function test results, or the number of potentially interacting medications administered between the two groups. The tacrolimus dosage requirements in group S were significantly lower than group N at 2 wk （2.8 ± 0.4 mg/d vs 3.6 ± 0.7 mg/d, P = 0.006）, 3 wk （2.9± 0.7 mg/d vs 3.9±0.8 rag/d, P = 0.008）, 4 wk （2.9 ± 0.8 mg/d vs 3.9 ± 1.0 mg/d, P = 0.023） and 2 mo （2.8 ±0.7 mg/d vs 3.8±1.1 mg/d, P = 0.033）. Tacrolimus 12-h trough concentrations were similar between the two groups at all times except for 2 wk post-transplantation, when the concentrations were significantly greater in group S recipients than in group N recipients （11.3 ± 4.8 ng/mL vs 7.0 ± 3.8 ng/mL, P = 0.026）. CONCLUSION： SFS grafts recipients have significantly decreased tacrolimus dosage requirements compared with non-SFS grafts recipients in AALDLT during the first 2 mo post-surgery.

Extracorporeal continuous portal diversion plus temporal plasmapheresis for “small-for-size” syndrome

AIM:To investigate the effect of plasmapheresis via the portal vein for"small-for-size"syndrome(SFSS)aided by extracorporeal continuous portal diversion(ECPD).METHODS:Extensive or total hepatectomy in the pig is usually adopted as a postoperative liver failure(PLF)or SFSS model.In this study,animals which underwent85%-90%hepatectomy were randomized into either the Systemic group(n=7)or the Portal group(n=7).In the Systemic group,all pigs received temporal plasmapheresis(PP)via the extracorporeal catheter circuit(systemic to systemic circulation)from 24 to 30 h posthepatectomy(PH);in the Portal group,all pigs received ECPD to divert partial portal vein flow(PVF)to the systemic circulation after hepatectomy,then converted to temporal PP from 24 to 30 h PH,and subsequently converted to ECPD again until 48 h PH.In the Portal group,the PVF was preserved at 3.0-3.3 times that of the baseline value,similar to that following 70%hepatectomy,which was regarded as the optimal PVF to the hypertrophic liver remnant.At 48 h PH,all pigs were re-opened and the portal vein pressure(PVP),PVF,and HAF(hepatic artery flow)were measured,and then diversion of the portal venous flow was terminated.After1 h the PVP,PVF,and HAF were re-measured.The portal hemodynamic changes,liver injury,liver regeneration and bacterial/lipopolysaccharide(LPS)translocation were evaluated in the two groups.RESULTS:The PVP in the Portal group was significantly lower than that in the Systemic group during the time period from 2 to 49 h PH(P<0.05).Serum alanine aminotransferase(ALT),total bilirubin(TB)and ammonia were significantly reduced in the Portal group compared with the Systemic group from 24 to 48 h PH(P<0.05).The Portal group may have attenuated sinusoidal endothelial injury and decreased the level of HA compared with the Systemic group.In the Systemic group,there was significant sinusoidal dilation,hydropic changes in hepatocytes and hemorrhage into the hepatic parenchyma,and the sinusoidal endothelial lining was partially destroyed and detached into the sinusoidal space.CD31immunostaining revealed significant destruction of the endothelial lining.In the Portal group,there was no intraparenchymal hemorrhage and the sinusoidal endothelial cells and hepatocytes were well preserved.CD31immunostaining was mild which indicated less destruction of the endothelial lining.HA was significantly decreased in the Portal group compared with the Systemic group from 2 to 48 h PH.The rate of liver remnant regeneration was elevated,while apoptosis was attenuated in the Portal group compared with the Systemic group.Thymidine kinase activity was much higher in the Portal group than in the Systemic group at 48 h PH.The PCNA index was significantly increased and the apoptotic index was significantly decreased in the Portal group compared with the Systemic group.Bacterial translocation and endotoxin,as well as the inflammatory response,were significantly attenuated in the Portal group compared with the Systemic group.LPS,tumor necrosis factor-and interleukin-6 levels were all significantly decreased in the Portal group compared with the Systemic group from 24 to48 h PH,while bacterial DNA level was significantly decreased from 2 to 48 h PH.CONCLUSION:PP plus ECPD via the portal vein can attenuate toxic load and hyperperfusion injury,and should be undertaken instead of PP via the systemic circulation in SFSS or PLF.

Impact of small-for-size liver grafts on medium-term and long-term graft survival in living donor liver transplantation: A meta-analysis

BACKGROUND Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking. AIM To evaluate the impact of small-for-size liver grafts on medium-term and longterm graft survival in adult to adult LDLT. METHODS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted. RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies. CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation.

Expression of iNOS in early injury in a rat model of small-for-size liver transplantation

BACKGROUND: Living donor liver transplantation has been widely accepted as the treatment of choice for end-stage liver disease. Large amounts of nitric oxide generated by inducible nitric oxide synthase (iNOS) have been shown to play an important role in many inflammatory and immune reactions, but expression of iNOS in small-for-size liver transplantation is unknown. The aims of this study were to determine the time course of iNOS mRNA and protein as well as the redox state of liver biopsies in a rat model of small-for-size liver transplantation. METHODS: Male Sprague-Dawley rats were divided into a control group, a warm ischemia-reperfusion (IR) group, and a small-for-size liver graft group. Real-time RT-PCR and Western blotting were used to characterize the time course of the expression of iNOS mRNA and protein, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) were used as markers to characterize the redox state of liver tissues, and the time courses of MDA and SOD levels were also measured. RESULTS: The expression of iNOS mRNA and protein levels in the warm IR and small-for-size graft groups both significantly increased after reperfusion, and peaked at 3 hours. Moreover, the increase in MDA was accompanied by increased iNOS in the period of 1-24 hours after reperfusion. The MDA levels in the warm IR and small-for-size graft groups significantly increased after reperfusion, peaked at 3 hours, and decreased thereafter. The direction of change in SOD was opposite that of the change in MDA. CONCLUSIONS: The expression of iNOS mRNA and protein is activated after reperfusion both in hepatic warm IR injury and small-for-size liver graft. Furthermore, the results of this study suggest that iNOS contributes to the damage in warm IR injury and small-for-size grafts via free oxygen radicals.

Small-for-size syndrome in living donor liver transplantation

When the graft volume is too small to satisfy the recipient’s metabolic demand, the recipient may thus experience small-for-size syndrome (SFSS). Because the occurrence of SFSS is determined by not only the liver graft volume but also a combination of multiple negative factors, the definitions of small-for-size graft (SFSG) and SFSS are different in each institute and at each time. In the clinical setting, surgical inflow modulation and maximizing the graft outflow are keys to overcoming SFSS. Accordingly, relatively smaller-sized grafts can be used with surgical modification and pharmacological manipulation targeting portal circulation and liver graft quality. Therefore, the focus of the SFSG issue is now shifting from how to obtain a larger graft from the living donor to how to manage the use of a smaller graft to save the recipient, considering donor safety to be a priority.

Should temporary extracorporeal continuous portal diversion replace meso/porta-caval shunts in “small-for-size” syndrome in porcine hepatectomy?

AIM:To investigate the feasibility of temporary extracorporeal continuous porta-caval diversion(ECPD) to relieve portal hyperperfusion in "small-for-size" syndrome following massive hepatectomy in pigs.METHODS:Fourteen pigs underwent 85%-90% liver resection and were then randomly divided into thecontrol group(n = 7) and diversion group(n = 7).In the diversion group,portal venous blood was aspirated through the portal catheter and into a tube connected to a centrifugal pump.After filtration,the blood was returned to the pig through a double-lumen catheter inserted into the internal jugular or subclavian vein.With the conversion pump,portal venous inflow was partially diverted to the inferior vena cava through a catheter inserted via the gastroduodenal vein at 100-130 m L/min.Portal hemodynamics,injury,and regeneration in the liver remnant were compared between the two groups.RESULTS:Compared to the control group,porta-caval diversion via ECPD significantly mitigated excessive portal venous flow and portal vein pressure(PVP); the portal vein flow(PVF),hepatic artery flow(HAF),and PVP in the two groups were not significantly different at baseline; however,the PVF(431.8 ± 36.6 vs 238.8 ± 29.3,P < 0.01; 210.3 ± 23.4 vs 122.3 ± 20.6,P < 0.01) and PVP(13.8 ± 2.6 vs 8.7 ± 1.4,P < 0.01; 15.6 ± 2.1 vs 10.1 ± 1.3,P < 0.05) in the control group were significantly higher than those in the diversion group,respectively.The HAF in the control group was significantly lower than that in the diversion group at 2 h and 48 h post hepatectomy,and ECPD significantly attenuated injury to the sinusoidal lining and hepatocytes,increased the regeneration index of the liver remnant,and relieved damage that the liver remnant suffered due to endotoxin and bacterial translocation.CONCLUSION:ECPD,which can dynamically modulate portal inflow,can reduce injury to the liver remnant and facilitate liver regeneration,and therefore should replace permanent meso/porta-caval shunts in "smallfor-size" syndrome.

Minimizing the risk of small-for-size syndrome after liver surgery

Background: Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant(FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-forsize syndrome(SFSS). Data sources: This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specifc modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. Results: Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. Conclusions: With those techniques the indications of radical treatment for patients with liver tumors have signifcantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modifcation of interventions and the right timing of surgery.

Extended hepatectomy with segments Ⅰand Ⅶ as resection remnant:a simple model for small-for-size injuries in pigs

BACKGROUND:Small-for-size(SFS)syndrome is an important clinical problem after living donor liver transplantation,split liver transplantation or extended hepatectomy.The uncertainty of the mechanisms and treatments of SFS syndrome urges surgeons to establish effective models for SFS syndrome. METHODS:A new porcine model for SFS syndrome based on extended hepatectomy was established.Portal pressure gradient was observed before and after the surgery,and venous sampling for estimation of alanine aminotransferase, total bilirubin,and international normalized ratio was continued on a daily basis. RESULTS:Although the external morphology of the porcine liver differs from that of human being,segmental anatomy is remarkably similar in term of its vascularity and biliary tree.Extended hepatectomy with segmentsⅠand Ⅶas resection remnant(about 20%of total liver volume) resulted in similar survival rates,blood liver function tests,and elevated portal pressure gradient as clinical SFS syndrome. CONCLUSIONS:The extended hepatectomy based new model can easily be reproduced,with few costs and surgical complications.Clinical SFS syndrome can easily be simulated by this new model,which is a useful tool for studying SFS syndrome-related liver injuries,especially portal overperfusion and hypertension.

Outcomes of adult patients adopting small-for-size grafts in living donor liver transplantation: A systematic review and meta-analysis

Background: Small-for-size graft(SFSG) has emerged as one of the very contentions in adult-to-adult living donor liver transplantation(LDLT) as a certain graft size is related to recipients’ prognosis. Graftto-recipient weight ratio(GRWR)≥0.8% was considered as a threshold to conduct LDLT. However, this also has been challenged over decades as a result of technique refinements. For a better understanding of SFSG in practice, we conducted this meta-analysis to compare the perioperative outcomes and long-term outcomes between patients adopting the grafts with a lower volume(GRWR < 0.8%, SFSG group) and sufficient volume(GRWR ≥ 0.8%, non-SFSG group) in adult-to-adult LDLT. Data sources: The studies comparing recipients adopting graft with a GRWR < 0.8% and ≥ 0.8% were searched by three authors independently in Pub Med, Web of Science, Embase, the Cochrane Library, MEDLINE and Google Scholar databases until September 2018 and data were analyzed by RevMan 5.3.5. Results: Sixteen studies with a total of 3272 subjects were included in this meta-analysis. In terms of small-for-size syndrome(SFSS), no significant difference was found in subjects enrolled after year 2010(before 2010, OR = 3.00, 95% CI: 1.69–5.35, P = 0.0002;after 2010, OR = 1.23, 95% CI: 0.79–1.90, P = 0.36;P for interaction: 0.02). There was no significant difference in operative duration, blood loss, cold ischemia time, biliary complications, acute rejection, postoperative bleeding, hospitalization time, perioperative mortality, and 1-, 3-and 5-year overall survival rates between two groups. Conclusions: This meta-analysis suggested that adopting SFSG in adult LDLT has comparable outcomes to those with non-SFSG counterparts since 2010.

Portal inflow preservation during portal diversion in small-for-size syndrome

AIM: To investigate the impact of portal inflow on liver remnants in a stable pig model of small-for-size syndrome.

Computed tomography perfusion study of hemodynamic changes and portal hyperperfusion in a rabbit model of small-for-size liver

BACKGROUND:Portal hyperperfusion in the small-for-size (SFS) liver can threaten survival of rabbits.Therefore,it is important to understand the hemodynamic changes in the SFS liver.METHODS:Twenty rabbits were divided into two groups:a control group and a modulation group.The control group underwent an extended hepatectomy.The modulation group underwent the same procedure plus splenectomy to reduce portal blood flow.CT perfusion examinations were performed on all rabbits before and after operation.Perfusion parameter values,especially portal vein perfusion (PVP),were analyzed.RESULTS:PVP in the modulation group was lower than in the control group after operation (P=0.002).In the control group,postoperative PVP increased by 193.7±55.1% compared with preoperative PVP.A weak correlation was found between the increased percentage of PVP and resected liver-to-body weight ratio (RLBWR) (r=0.465,P=0.033).In the modulation group,postoperative PVP increased by 101.4±32.5%.No correlation was found between the increased percentage of PVP and RLBWR (r=0.167,P=0.644).Correlations were found between PVP and serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin after surgery (P<0.05).CONCLUSION:We successfully evaluated the characteristics of hemodynamic changes as well as the effects of splenectomy in the SFS liver in rabbits by the CT technique.

Hemi-portocaval shunt： A simple salvage maneuver for small-for-size graft during living donor liver transplantation： a case report

Since the fast expansion of living donor liver transplantation （LDLT） over last few decades, small-for-size syndrome （SFSS） has emerged as a tough problem. Herein the first case of LDLT combined hemi-portocaval shunt in the mainland of China was reported. Portal venous overperfusion was well modulated and the recipient recovered uneventfully. LDLT combined hemi-portocaval shunt was a feasible procedure for preventing SFSS in LDLT.

A better way to do small-for-size liver transplantation in rats

Establishing a model for small-for-size liver transplantation is the basis for this study of partial and living donor graft liver transplantation.This study aims to explore a simpler and more effective way of establishing a 30%small-for-size liver transplantation in rats.Sprague-Dawley rats were selected as the donors and recipients.Small-for-size orthotopic liver transplantation was performed using Kamada’s two-cuff method.The donor’s liver was flushed via the abdominal aorta and hepatectomy was performed in situ.The animals were divided into three groups depending on the graft selected,with 40 pairs of rats in each group.In group Ⅰ,the median lobe of the liver was used as graft;in group Ⅱ,the right half of the median lobe and the right lobe were used as graft;and in group Ⅲ,the median and right lobes were used as graft.In groups Ⅰ and Ⅱ,the bodyweights of donors were the same as those of recipients;however,in group Ⅲ the bodyweights of donors were 100–120 g less than those of the recipients.The duration needed for transplantation,the 7-day survival rates,and the technical complication rates were compared among these three groups.The time required for hepatectomy was shorter in group Ⅲ compared with groups Ⅰ and II(8.8±0.7 min vs.11.5±1.1 min and 10.1±1.0 min,P=0.001).The cold ischemia time for the grafts,the anhepatic times,and the transplantation times for the recipients were not significantly different among the three groups.Compared with groups Ⅰ and Ⅱ,the incidence of bleeding,bile leakage,and inferior vena caval strictures were significantly decreased in group Ⅲ(P<0.05).No significant differences between the three groups were found based on other complications after the operation(P>0.05).Group Ⅲ had better 7-day survival rates and longer median survival times but the differences were not statistically significant.The method of small for donor bodyweight using the median and right lobes for grafting may be a more effective and simpler way of establishing a 30%small-for-size liver transplantation in rats,as shown by the shorter hepatectomy time and the occurrence of fewer complications after the operation.

Graft-to-recipient weight ratio lower to 0.7% is safe without portal pressure modulation in right-lobe living donor liver transplantation with favorable conditions

BACKGROUND: The low graft-to-recipient weight ratio(GRWR) in adult-to-adult living donor liver transplantation(LDLT) is one of the major risk factors affecting graft survival. The goal of this study was to evaluate whether the lower limit of the GRWR can be safely reduced without portal pressure modulation in right-lobe LDLT. METHODS: From 2005 to 2011, 317 consecutive patients from a single institute underwent LDLT with right-lobe grafts without portal pressure modulation. Of these, 23 had a GRWR of less than 0.7%(group A), 27 had a GRWR of ≥0.7%, 【0.8%(group B), and 267 had a GRWR of more than and equal to 0.8%(group C). Medical records, including recipient, donor, operation factors, laboratory findings and complications were reviewed retrospectively. RESULTS: The baseline demographics showed low model for end-stage liver disease score(mean 16.3±8.9) and high percentage of hepatocellular carcinoma(231 patients, 72.9%). Three groups by GRWR demonstrated similar characteristics except recipient body mass index and donor gender. For smallforsize syndrome, there were 3(13.0%) in group A, 1(3.7%) in group B, and 2 patients(0.7%) in group C(P【0.001). Hepatic artery thrombosis was more frequently observed in group A than in groups B and C(8.7% vs 3.7% vs 1.9%, P=0.047). However, among the three groups, graft survival rates at 1 year(100% vs 96.3% vs 93.6%) and 3 years(91.7% vs 73.2% vs 88.1%) were not different(P=0.539). In laboratory measurements,there was no group difference in total bilirubin and albumin. However, prothrombin time was longer in group A within postoperative 1 week and platelet count was lower in groups A and B within postoperative 1 month. CONCLUSION: A GRWR lower to 0.7% is safe and does not need to modulate portal pressure in adult-to-adult LDLT using the right-lobe in favorable conditions including low model for end-stage liver disease score.

Adult-to-adult living-donor liver transplantation: The experience of the Université catholique de Louvain

Background: Liver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation(LDLT) is presented. Methods: A retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29(45.3%) females and 35(54.7%) males was 50.2 years(interquartile range, IQR 32.9–57.5). Twenty-two(34.4%) recipients had no portal hypertension. Three(4.7%) patients had a benign and 33(51.6%) a malignant tumor [19(29.7%) hepatocellular cancer, 11(17.2%) secondary cancer and one(1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months(IQR 41–159) and 39 months(22–91), respectively. Results: Right and left hemi-livers were implanted in 39(60.9%) and 25(39.1%) cases, respectively. Median weights of right-and left-liver were 810 g(IQR 730–940) and 454 g(IQR 394–534), respectively. Graft-to-recipient weight ratios(GRWRs) were 1.17%(right, IQR 0.98%-1.4%) and 0.77%(left, 0.59%-0.95%). One-and five-year patient survivals were 85% and 71%(right) vs. 84% and 58%(left), respectively. Oneand five-year graft survivals were 74% and 61%(right) vs. 76% and 53%(left), respectively. The patient and graft survival of right and left grafts and of very small( < 0.6%), small(0.6%–0.79%) and large( ≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3-and 12-month. No donor died while five(7.8%) developed a Clavien–Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three(4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. Conclusions: Adult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely with low morbidity. The recipient operation carries a major morbidity indicating an important learning curve. Shifting the risk from the donor to the recipient, by moving from the larger right-liver to the smaller left-liver grafts, should be further explored as this policy makes donor hepatectomy safer and may stimulate the development of transplant oncology.

Liver function impairment in liver transplantation and after extended hepatectomy

Extended hepatectomy,or liver transplantation of reduced-size graft,can lead to a pattern of clinical manifestations,namely"post-hepatectomy liver failure"and"small-for-size syndrome"respectively,that can range from mild cholestasis to irreversible organ non-function and death of the patient.Many mechanisms are involved in their occurrence but in the recent past,high portal blood flow through a relatively small liver vascular bed has taken a central role.Therefore,several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation,such as portocaval shunt,mesocaval shunt,splenorenal shunt,splenectomy or ligation of the splenic artery.However,high portal flow is not the only factor responsible,and before major liver resections,preoperative assessment of the residual liver function is necessary.Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume,preventing posthepatectomy liver failure.More recently,a new surgical procedure,that combines in situ splitting of the liver and portal vein ligation,has gradually come to light,inducing remarkable hypertrophy of the healthy liver in just a few days.Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.