Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature

BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Complex inferior vena cava reconstruction during ex vivo liver resection and autotransplantation:A case report

BACKGROUND Ex vivo liver resection and autotransplantation(ELRA)is an essential approach for treating patients with end-stage hepatic alveolar echinococcosis(AE),and its surgical indications involve severe invasion of important hepatic vessels,which makes in vivo resection impossible.Revascularization is a major step in the process of ELRA,which is extremely challenging when the invaded vessels have huge defects.CASE SUMMARY Herein,we have reported the case of a 26-year-old patient with hepatic AE in an autologous liver graft who underwent complex inferior vena cava(IVC)reconstruction using disease-free IVC,autologous portal vein fragments,and umbilical vein within the ligamentum teres hepatis.The patient showed good surgical recovery without vascular-related complications during the long-term follow-up.CONCLUSION We reviewed three studies that have reported complex revascularization of the IVC.This case report and systematic review showed that the use of autologous perihepatic vessels prevents donor-area trauma,immune rejection,and other adverse reactions.When the blood vessel is severely invaded and a single vascular material cannot repair and reconstruct the defect,ELRA may provide a safe and feasible surgical approach,which has good prospects for clinical application.

Clinical Outcomes of Ex Vivo Liver Resection and Liver Autotransplantation for Hepatic Alveolar Echinococcosis

The effectiveness of liver autotransplantation for patients with partial hepatic alveolar echinococcosis was analyzed.We retrospectively studied 6 patients with hepatic alveolar echinococcosis who underwent liver autotransplantation in our hospital from 2008 to 2010.We also summarized the surgical indications of liver autotransplantation for hepatic alveolar echinococcosis and our experience in the management of postoperative complications of liver autotransplantation.Of 6 patients,5 achieved good curative results,and one died of multiple organ failure caused by portal vein thrombosis.Main complications included postoperative bleeding,bile leak and small-for-size liver graft syndrome.Liver autotransplantation offers a new approach to cure hepatic alveolar echinococcosis with non-resectable lesions.It could be the most effective method to cure intractable hepatic alveolar echinococcosis if correct handling in operation and proper prevention of complications are performed.But the long-term outcomes are still needed to be confirmed in longer follow-up.

Ex vivo liver resection followed by autotransplantation in radical resection of gastric cancer liver metastases:A case report

BACKGROUND Radical resection of gastric cancer liver metastases(GCLM)can increase the 5-year survival rate of GCLM patients.However,patients may lose the theoretical feasibility of surgery due to the critical location of liver metastasis in some cases.CASE SUMMARY A 29-year-old woman had a chief complaint of chronic abdominal pain for 1 year.Abdominal computed tomography and magnetic resonance imaging examinations suggested a mass of unknown pathological nature located between the first and second hila and the margin of the lower segment of the right lobe of the liver.The anterior wall of the gastric antrum was unevenly thickened.The diagnosis of(gastric antrum)intramucosal well-differentiated adenocarcinoma was histopathologically confirmed by puncture biopsy with gastroscopy guidance.She underwent radical resection(excision of both gastric tumors and ex vivo liver resection followed by autotransplantation simultaneously)followed by XELOX adjuvant chemotherapy.Without serious postoperative complications,the patient was successfully discharged on the 20th day after the operation.Pathological examination of the excised specimen indicated that gastrectomy with D2 lymph node dissection for primary gastric tumors and R0 resection for liver metastases were achieved.The resected mass was confirmed to be poorly differentiated gastric carcinoma(hepatoid adenocarcinoma with neuroendocrine differentiation)with liver metastases in segments VIII.No recurrence or metastasis within the liver was found during a 7.5-year follow-up review that began 1 mo after surgery.CONCLUSION Application of ex vivo liver resection followed by autotransplantation in radical resection for GCLM can help selected patients with intrahepatic metastases located in complex sites obtain a favorable clinical outcome.

Approaches to reconstruction of inferior vena cava by ex vivo liver resection and autotransplantation in 114 patients with hepatic alveolar echinococcosis

BACKGROUND Hepatic alveolar echinococcosis(AE)is most commonly found in retrohepatic inferior vena cava(RHIVC).Ex vivo liver resection and autotransplantation(ELRA)can better realize the radical resection of end-stage hepatic AE with severely compromised hepatocaval confluences,and reconstruction of the affected vessels.Currently,there is a scarcity of information regarding RHIVC reconstruction in ELRA.AIM To propose reasonable RHICV reconstruction strategies for ex vivo liver resection and autotransplantation.METHODS We retrospectively summarized the clinical data of 114 patients diagnosed with hepatic AE who treated by ELRA in our department.A total of 114 patients were divided into three groups according to the different reconstruction methods of RHIVC:Group A with original RHIVC being repaired and reconstructed(n=64),group B with RHIVC being replaced(n=43),and group C with RHIVC being resected without reconstruction(n=7).The clinical data of patients,including the operation time,anhepatic phase,intraoperative blood loss,complications and postoperative hospital stay,were analyzed and the patients were routinely followed up.The normally distributed continuous variables were expressed as means±SD,whereas the abnormally distributed ones were expressed as median and analyzed by analysis of variance.Survival curve was plotted by the Kaplan-Meier method.RESULTS All patients were routinely followed up for a median duration of 52(range,12-125)mo.The 30 d mortality rate was 7.0%(8/114)and 7 patients died within 90 d.Among all subjects,the inferior vena cava(IVC)-related complication rates were 17.5%(11/63)in group A and 16.3%(7/43)in group B.IVC stenosis was found in 12 patients(10.5%),whereas thrombus was formed in 6 patients(5.3%).Twenty-two patients had grade III or higher complications,with the complication rates being 17.2%,16.3%,and 57.1%in the three groups.The average postoperative hospital stay in the three groups was 32.3±19.8,26.7±18.2,and 51.3±29.4 d(P=0.03),respectively.CONCLUSION ELRA can be considered a safe and feasible option for end-stage hepatic AE patients with RHIVC infiltration.The RHIVC reconstruction methods should be selected appropriately depending on the defect degree of AE lesions in IVC lumen.The RHIVC resection without any reconstruction method should be considered with caution.

A new veno-venous bypass type for ex-vivo liver resection in dogs

Ex-vivo liver resection is a procedure in which the liver is completely removed, perfused and after bench surgery, the liver is autotransplanted to the original site. Ex vivo liver resection is an important treatment for unresectable liver tumors. This surgical procedure requires long operation time, during which blood flow must be carefully maintained to avoid venous congestion. An effective veno-venous bypass (VVB) may meet this requirement. The present study was to test our new designed VVB device which comprised one heparinized polyvinylchloride tube and three magnetic rings The efficacy of this device was tested in five dogs. A VVB was established in 6-10 minutes. There was no leakage during the procedure. Hemodynamics was stable at anhepatic phase, which indicated that the bypass was successful. This newly-developed VVB device maintained circulation stability during ex-vivo liver resection in our dog model and thus, this VVB device significantly shortened the operation time.

Therapeutics administered during ex vivo liver machine perfusion:An overview

Although the use of extended criteria donors has increased the pool of available livers for transplant,it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury(IRI),as these"marginal"organs are particularly vulnerable to IRI during the process of procurement,preservation,surgery,and post-transplantation.In this review,we explore the current basic science research investigating therapeutics administered during ex vivo liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process.These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway,utilizing defatting cocktails,and administering classes of agents such as vasodilators,anti-inflammatory drugs,human liver stem cell-derived extracellular vesicles,and δ-opioid agonists in order to reduce the damage of IRI.Ex vivo machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ,effectively deliver substrates and oxygen required for cellular metabolism,therapeutically administer pharmacological or cytoprotective agents,and continuously monitor organ viability during perfusion.The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies.While novel therapeutic approaches to combat IRI are being developed through basic science research,their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.

Pediatric living donor liver transplantation using liver allograft after ex vivo backtable resection of hemangioma: A case report

BACKGROUND Use of liver allograft with hepatic hemangioma after in vivo resection of hemangioma in living donor liver transplantation(LDLT)has been previously reported.However,there are few reports describing ex vivo backtable resection of hemangioma from liver allografts in LDLT.CASE SUMMARY A 55-year-old male was evaluated as a donor for an 8-month-year old patient with acute hepatic failure due to biliary atresia.Pre-operative contrast enhanced computed tomography revealed a 9 cm hemangioma in segment 4 with vascular variations in the donor.During LDLT,an intra-operative intrahepatic cholangiography was performed to ensure no variation in the anatomy of the intrahepatic bile duct.After intra-operative pathological diagnosis,ex vivo backtable resection of the hemangioma was performed and the liver allograft was transplanted into the recipient.The donor’s and recipient’s post-operative course were uneventful.At the 2-year follow-up,the liver allograft showed good regeneration without any recurrence of hemangioma.CONCLUSION Liver allografts with hemangiomas are an acceptable alternative strategy for LDLT.Ex vivo backtable resection of hemangioma from the donor liver during pediatric LDLT is safe and feasible,and can effectively reduce the operative time and intra-operative bleeding for the donor.

终末期肝泡型包虫病的肝移植治疗

肝泡型包虫病(HAE)是我国西部地区常见的人畜共患地方性寄生虫病,早期缺乏典型临床表现,症状明显时常已进入终末期,具有极高的致死率。在终末期HAE(es-HAE)治疗中,因残余肝体积不足、无法控制的出血、脉管在体重建困难等,同种异体原位肝移植几乎成为唯一根治的方式。但因供肝短缺、术后需长期使用免疫抑制药等因素限制了其应用,离体肝切除联合自体肝移植术(ELRA)的出现打破了这一窘境,极大拓宽了es-HAE手术指征。此外,我国多中心对ELRA进行了诸多优化与改良,进一步完善es-HAE的治疗体系。目前,es-HAE的肝移植(包括ELRA)治疗仍是临床医师研究的热点。本文对原位肝移植、ELRA、辅助性ELRA等多种手段在es-HAE的外科治疗进行综述,旨在进一步提升es-HAE的诊治水平,改善患者临床预后。

Radiofrequency ablation during continuous saline infusion can extend ablation margins

AIM:To determine whether fluid injection during radiofrequency ablation(RFA) can increase the coagulation area.METHODS:Bovine liver(1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base,and the liver was punctured by an expandable electrode.During RFA,5% glucose;50% glucose;or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port.The area and volume of the thermocoagulated region of bovine liver were determined after RFA.The Joule heat generated was determined from the temporal change in output during the RFA experiment.RESULTS:No liquid infusion was 17.3 ± 1.6 mL,similar to the volume of a 3-cm diameter sphere(14.1 mL).Mean thermocoagulated volume was significantly larger with continuous infusion of saline(29.3 ± 3.3 mL) than with 5% glucose(21.4 ± 2.2 mL),50%glucose(16.5 ± 0.9 mL) or no liquid infusion(17.3 ± 1.6 mL).The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion,representing a significant difference between these two conditions.Total Joule heat generated during RFA was highest with saline,and lowest with 50% glucose.CONCLUSION:RFA with continuous saline infusion achieves a large ablation zone,and may help inhibit local recurrence by obtaining sufficient ablation margins.RFA during continuous saline infusion can extend ablation margins,and may be prevent local recurrence.

History,ethics,advantages and limitations of experimental models for hepatic ablation

Numerous techniques developed in medicine require careful evaluation to determine their indications,limitations and potential side effects prior to their clinical use.At present this generally involves the use of animal models which is undesirable from an ethical standpoint,requires complex and time-consuming authorization,and is very expensive.This process is exemplified in the development of hepatic ablation techniques,starting experiments on explanted livers and progressing to safety and efficacy studies in living animals prior to clinical studies.The two main approaches used are ex vivo isolated non-perfused liver models and in vivo animal models.Ex vivo non perfused models are less expensive,easier to obtain but not suitable to study the heat sink effect or experiments requiring several hours.In vivo animal models closely resemble clinical subjects but often are expensive and have small sample sizes due to ethical guidelines.Isolated perfused ex vivo liver models have been used to study drug toxicity,liver failure,organ transplantation and hepatic ablation and combine advantages of both previous models.

Concise review of machine perfusion in liver transplantation

With the advances and clinical growth in liver transplantation over the last four decades the focus on expanding deceased donor organs has been in need of scientific research.In the past ten years several researchers have looked at the domain of machine perfusion as it applies to deceased donor livers.The following review focuses on the clinical trials and recent advances that will likely have the earliest entrance into the clinical arena.

Adult human liver slice cultures:Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs

BACKGROUND Liver fibrosis can result in end-stage liver failure and death.AIM To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)model.METHODS Fibrotic liver samples(F0 to F4 fibrosis stage according to the METAVIR score)were collected from patients after liver resection.Human liver slices(HLS)were cultivated for up to 21 days.Hepatitis C virus(HCV)infection,alcohol(ethanol stimulation)and steatosis(palmitate stimulation)were examined in fibrotic(F2 to F4)liver slices infected(or not)with HCV.F0-F1 HLS were used as controls.At day 0,either ursodeoxycholic acid(choleretic and hepatoprotective properties)and/or α-tocopherol(antioxidant properties)were added to standard of care on HLS and fibrotic liver slices,infected(or not)with HCV.Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzymelinked immunosorbent assay.RESULTS The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs.Expression of the biomarkers of fibrosis and the progression to steatosis(estimated by triglycerides production)was increased with the addition of HCV and/or ethanol or palmitate.From day 15 of the follow-up studies,a significant decrease of both transforming growth factorβ-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.CONCLUSION These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver(viral,alcoholic,nonalcoholic steatohepatitis liver diseases)and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.

Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge

The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.

Ex vivo liver resection followed by autotransplantation for end-stage hepatic alveolar echinococcosis

Background For patients with end-stage hepatic alveolar echinococcosis （AE）, in vivo resection of the involved parts of the liver is usually very difficult, therefore, allogenic liver transplantation is indicated. However, we hypothesize that for selected patents, ex vivo liver resection for thorough elimination of the involved tissues and liver autotransplantation may offer a chance for clinical cure. Methods We presented a 24-year-old women with a giant hepatic AE lesion who was treated with hepatectomy, ex vivo resection of the involved tissue and hepatic autotransplantation. The patient had moderate jaundice and advanced hepatic AE lesion which involved segments I, IV, V, VI, VII, VIII and retrohepatic inferior vena cava. The lateral segments （II and III） of the left liver remained normal with over 1000 ml in its volume. No extrahepatic metastases （such as to the lung or brain） could be found. As the first step of treatment, X-ray guided percutaneous transhepatic cholangiodrainage （PTCD） was performed twice for bile drainage in segment III and II separately until her serum total bilirubin decreased gradually from 236 to 88 umol/L. Total liver resection was then performed, followed by extended right hepatic trisegmentectomy and the entire retrohepatic vena cava was surgically removed en bloc while her hemodynamics parameters were stable. Neither veino-veinous bypass nor temporary intracorporeal cavo-caval or porto-caval shunt was used during the 5.7-hour anhepatic phase. The remained AE-free lateral segments of the-left liver were re-implanted in situ. The left hepatic vein was directly anastomosed end-to-end to the suprahepatic inferior vena cava due to the lack of the retrohepatic inferior vena cava with AE total infiltration. Because compensatory retroperitoneal porto-caval collateral circulation developed, we enclosed remained infrahepatic inferior vena cava at renal vein level without any haemodynamics problems. Results During a 60-day following-up after operation, the patient had a good recovery except for a mildly elevated serum total bilirubin. Conclusions As a radical approach, ex vivo liver resection and liver autotransptantation in a case has shown a optimal potential for treatment of the end-stage hepatic AE. Strict compliance with its indications, evaluation of vessels of patients pre-operatively, and precise surgical techniques are the keys to improve the prognosis of patients.

离体猪肝微波消融固化范围与组织局部热沉积剂量的相关性研究

目的研究离体猪肝消融过程中实际到达微波天线末端的有效输出功率,并进一步研究组织热沉积剂量与消融固化范围之间的相关性。方法根据微波消融的工作原理,遵循能量守恒定律设计实验。以新鲜离体猪肝为模型,按实验设计图连接实验设备,主机输出功率从60、80、100、120 W共4个功率段,消融时间为10 min,离体猪肝每个功率消融10个位点,测定其有效输出功率与组织热沉积剂量;研究主机输出功率与有效输出功率的关系;并探讨组织热沉积剂量与消融体积的相关性。结果随着主机输出功率的增加,有效输出功率亦增加,组织热沉积剂量也相应增加,获得的消融体积也相应的增大。不同功率组消融体积的差异96.7%与组织热沉积剂量相关,两者有着极高的相关性。结论有效输出功率真实地反映组织接受的功率;组织热沉积剂量更真实地反映微波对组织的消融能量,两者有望成为量化消融范围一个新的标准。

水冷915MHz与2450MHz微波凝固离体猪肝的比较

目的比较水冷915MHz与2450MHz微波相同条件下凝固离体肝组织范围与焦化区体积方面的差别。方法在相同能量输出的条件下分别进行水冷915MHz与2450MHz微波的离体猪肝凝固实验,其中功率分别为50W、60W、70W、80W。结果915MHz比2450MHz微波在凝固区长、宽径、体积及焦化区范围均增大,其差异有统计学意义。结论在离体猪肝凝固实验中,在相同能量输出的条件下水冷915MHz比2450MHz微波有着更强的组织穿透与凝固能力,这一结果为915MHz微波进一步的研究及临床应用提供了依据。

溪黄草有效成分nodosin灌注对大鼠移植肝脏病理损伤的影响

目的探讨溪黄草有效成分nodosin体外保留灌注的方式对移植肝病理损伤的影响。方法建立nodosin体外保留灌注大鼠肝脏的实验模型。实验组分为nodosin高剂量组(200μg/ml)、中剂量组(20μg/ml)、低剂量组(10μg/ml)和空白对照组(乳酸林格注射液)进行体外灌注。采用Banff标准分级评价体外保留灌注的离体大鼠肝脏的病理损伤。电镜下评估nodosin高剂量组肝脏细微结构的损伤情况。建立使用nodosin(200μg/ml)保留灌注供肝行大鼠原位肝移植的实验模型,设立空白对照组,分别于移植术后1d、3d、7d、21d获取肝脏病理组织,采用Suzuki评分标准评价移植肝的病理损伤。结果 nodosin各剂量组Banff评分与空白对照组比较差异无统计学意义。电镜下,no-dosin高剂量组保留灌注2h的大鼠肝脏组织结构无明显破坏。移植模型中,移植术后1d、3d、7d两组的Suzuki评分比较差异无统计学意义,但术后21d两组的Suzuki评分比较差异有统计学意义(P<0.01)。结论使用200μg/ml剂量以下的nodosin体外直接灌注不会对肝脏组织结构和肝细胞造成直接的病理损伤,是安全的。