Rat auxiliary liver transplantation without portal vein reconstruction: comparison with the portal vein-arterialized model

Auxiliary liver transplantation (ALT) has been reintroduced in clinical cases recently and is now believed to be a viable alternative to orthotopic liver transplantation. To provide a simple rat ALT model for studying the physiological and immunological aspects of the ALT graft, a new ALT was performed, and the comparison between this new model and the portal arterialized one that was reported by other investigators was carried out. At first, we confirmed that liver could tolerate the deprivation of its portal flow well, using a portosystemic shunted rat model. The new rat ALT model, in which the ALT graft obtained its blood inflow only from the hepatic artery, was then performed. Our results demonstrated that 50% of the hepatic artery-alone ALT graft showed almost normal structure histologically at 1 month after grafting, with bile secretion preserved. By contrast, only 8% 1-month graft survival was noted in the portal arterialized group, and all grafts stopped bile secretion 1 week after operation. In conclusion, with arterial blood supply alone, the ALT graft survived and demonstrated normal bile secretion function for more than 1 month. Portal vein arterialization is not an appropriate way to establish the graft's blood supply if no pressure adjustment measures were taken in advance.     

Outcome and Hepatic Hemodynamics in Liver Transplant Patients with Portal Vein Arterialization

Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.     

Improved technique of heterotopic auxiliary rat liver transplantation with portal vein arterialization

BACKGROUND AND AIMS: In acute, potentially reversible hepatic failure, auxiliary liver transplantation is a promising alternative approach. Using the auxiliary partial orthotopic liver transplantation (APOLT) method--the orthotopic implantation of auxiliary segments--most of the technical problems (lack of space for the additional liver mass, the portal vein reconstruction, and the venous outflow) are avoided, but extensive resections of the native liver and the graft are necessary. Erhard described the heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA). Initial clinical results demonstrated that an adequate liver function can be achieved using this technique. We developed and improved a technique of HALT with flow-regulated PVA in the rat to perform further investigations. The aim of this paper is to explain in detail this improved experimental surgical technique. MATERIALS AND METHODS: Liver transplantations were performed in 122 male Lewis rats: After a right nephrectomy, the liver graft, which was reduced to about 30% of the original size, was implanted into the right upper quadrant of the recipient's abdomen. The infrahepatic caval vein was anastomosed end-to-side. The donor's portal vein was completely arterialized to the recipient's right renal artery in stent technique. Using a stent with an internal diameter of 0.3 mm, the flow in the arterialized portal vein was regulated to achieve physiologic parameters. The celiac trunk of the graft was anastomosed to the recipient's aorta, end-to-side. The bile duct was implanted into the duodenum. RESULTS: After improvements of the surgical technique, we achieved a perioperative survival of 90% and a 6-week survival of 80% in the last 112 transplantations. CONCLUSION: We developed a standardized and improved technique, which can be used for experiments of regeneration and inter-liver competition in auxiliary liver transplantation. Furthermore, this technique is suitable for the investigation of the influence of portal vein arterialization and portal hyperperfusion on liver microcirculation, function, and morphology.     

Primary permanent arterialization of the portal vein in liver transplantation

Permanent total arterialization of the portal vein in liver transplantation has been described as a method of providing portal inflow after insufficient thrombectomy due to chronic occlusion of the portal-vein system. A specific problem is the restriction of the arterial inflow and its long-term adaptation after transplantation. We describe here the surgical techniques and clinical course of three patients who underwent portal-vein arterialization for liver transplantation. Two patients had an uneventful course. In one patient, a flow reduction by means of coil embolization of one arterial inflow branch was performed; thereafter, the patient recuperated well. Analysing the microcirculation of an arterialized graft in comparison with liver grafts with normal non-arterialized portal-vein inflow, we observed an increase in inter-sinusoidal distance and a decrease in sinusoidal red blood cell velocity. From a technical point of view, we recommend permanent portal-vein arterialization by an iliac artery graft interposition from the subdiaphragmatic aorta. The inflow to the portal vein can easily be reduced by the banding of the arterial graft interposition.     

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver. Received: 15 September 1997 Received after revision: 4 February 1998 Accepted: 2 March 1998     

Improved microcirculation of a liver graft by controlled portal vein arterialization

BACKGROUND: The clinical results of portal vein arterialization (PVA) in liver transplantation are controversial without a standardized portal flow regulation. The aim of these experiments was to perform a flow-regulated PVA in liver transplantation, to examine the microcirculation and early graft function after heterotopic auxiliary liver transplantation (HALT) with flow-regulated PVA, and to compare this technique with HALT with porto-portal anastomosis. Using the recently developed orthogonal polarization spectral (OPS) imaging, for the first time the microcirculation of liver grafts with PVA was visualized. MATERIALS AND METHODS: HALT was performed in Lewis rats. The portal vein was either completely arterialized via the right renal artery in a standardized splint-technique (Group I, n = 8) or anastomosed end-to-end to the recipient's portal vein (Group II, n = 8). RESULTS: After reperfusion, the average blood flow in the portal vein was within the normal range in Group I (1.7 +/- 0.4 ml/min/g liver weight) and significantly higher than in Group II (1.2 +/- 0.2 ml/min/g liver weight). The functional sinusoidal density in Group I (335 +/- 48/microm) was significantly higher than in Group II (232 +/- 58/microm), whereas the diameter of the sinusoids and the postsinusoidal venules yielded no significant differences between both groups. The bile production was comparable (27 +/- 8 versus 29 +/- 11 microl/h/g liver weight). CONCLUSIONS: In our experiments it was possible to achieve an adequate flow regulation in the arterialized portal vein with good results concerning microcirculation and early graft function. We recommend that further investigations on liver transplantation with PVA should be performed with portal flow regulation, before PVA is employed in clinical transplantation.     

Experimental study of partial arterialization of the portal vein on the dearterialized liver

The influence of hepatic arterial obstruction on the hepatic circulation and tissue metabolism was studied between animals with and without partial arterialization of the portal vein. Mongrel dogs were divided into these groups: a group in which the collaterals to the liver were obstructed and the hepatic artery was dissected (hepatic artery ligated group); two groups in which an extracorporeal femoral artery-portal vein shunt was produced, and blood was sent by a Biopump at a rate of 100 or 200 ml/min (100 ml/min and 200 ml/min portal arterialized groups). The hepatic artery ligated group showed CO2 accumulation and acidosis in hepatic venous blood, reduction of oxygen supply, increase of oxygen consumption and marked increase of GOT and GPT. In the portal arterialized groups, sufficient oxygenation of portal blood was noted, and the oxygen demand and supply and tissue metabolism were kept approximately normal. The optimum flow rate for partial arterialization of the portal vein seemed to be 100 ml/min. At the flow rate of 200 ml/min, the original portal blood was reduced, leading to portal hypertension and increase of GOT and GPT. These results indicate that partial arterialization of the portal vein effectively preserves the liver function during the operation and in the early period after dissection of the hepatic artery.     

Description of a new auxiliary heterotopic partial liver transplantation technique with portal vein arteriolization of applicability in heterotopic liver xenotransplantation

OBJECTIVE: The aim of this study was to describe a new model of auxiliary heterotopic partial liver transplantation with portal vein arterialization. MATERIALS AND METHODS: Three standard hepatectomies were performed in pigs. The left lateral lobe was surgically resected and portal vein arteriolization constructed by an end-to-side "Y" anastomoses between the distal to the celiac axis aorta and the portal vein. RESULTS: The graft was placed in the left iliaca fossa using anastomoses of the donor infrahepatic inferior cava vein end-to-side to the host infrarenal inferior vein and the donor aortic stump with portal vein arteriolization end-to-side to the left iliac artery. After graft reperfusion, the 3 recipients showed intraoperative hypotension, which was treated with fluid administration and vasoactive drugs. At the end of the operation, the graft displayed normal arterial blood flow and good venous drainage. The donor liver graft appeared more red than the host liver, which was due to the increased arterial blood flow. One pig of 3 died at 24 hours after surgery, probably due to hypothermia. However, the other 2 pigs survived the procedure and remained stable. Echographic monitoring showed intrahepatic arterial expansion, which may be the result of high blood pressure due to the arteriolization procedure. CONCLUSIONS: We have developed a novel and easy to perform technique that diminishes the number of anastomoses and does not involve vessels from other organs.     

门静脉动脉化在肝脏外科的应用

门静脉动脉化是一种为防止肝脏缺血导致的肝损害而将动脉血灌注入门静脉的方法.本文就其在肝移植、肝门部肿瘤和门脉高压症外科治疗、急性肝功能衰竭治疗中的临床应用情况及存在的问题做一综述.     

Outcome of patients with pre-existing portal vein thrombosis undergoing arterialization of the portal vein during liver transplantation

Arterialization of the portal vein is being propagated as a technical possibility in liver transplant recipients with pre-existing portal vein thrombosis. In our own small series, portal vein arterialization (PVA) was carried out in four patients undergoing orthotopic liver transplantation. In three of these cases, the portal vein was anastomosed to the aorta via an interposed iliac artery, and in one case, directly to the hepatic artery. After PVA, all transplants showed regular initial function. Two patients died postoperatively after 19 and 50 days, of intra-abdominal haemorrhage and liver necrosis with thrombosis of the portal vein, respectively. A further patient had previously developed fibrosis of the liver, which led to the death of the patient 11 months after PVA. In the remaining patient, chronic rejection requiring re-transplantation developed 24 months after PVA had been performed. These unfavourable results prompt the conclusion that PVA cannot be recommended as a standard clinical procedure.     

Auxiliary liver transplantation with portal arterialization in the rat: description of a new model

In recent years, portal arterialization has been used in liver transplantation to increase the portal flow, as a solution for singular technical problems. We have developed a new auxiliary liver transplantation model in the rat with portal arterialization, so the native hepatic hilium remains untouched, consisting on a graft with a previous 70% hepatectomy. It is sited on the right renal bed, joining the infrahepatic inferior vena cava (IVC) of the graft with the recipient IVC. With an abdominal aortic graft, we connect the recipient aorta with the portal vein from the auxiliary liver. All the animals survived at the seventh day. No thrombosis was seen in any graft and an important rejection was observed in all the fields. We have developed a new experimental model of an auxiliary liver with portal arterialization, avoiding the utilisation of the native hepatic hilium, necessary for the possible recovering of the proper liver in the case of a reversible fulminant hepatitis.     

Successful Living Donor Liver Transplantation in Portomesenteric Thrombosis

Chronic portal vein thrombosis (PVT) is often considered a relative contraindication for living donor liver transplantation due to the risks involved and higher morbidity. In this report, we describe a surgical strategy for living donor liver transplant in patient with complete PVT using venovenous bypass from the inferior mesenteric vein (IMV) and then using a jump graft from the IMV for portal inflow into the graft. IMV is a potential source for portal inflow in orthotopic liver transplant.     

Liver transplantation with renoportal anastomosis after distal splenorenal shunt

BACKGROUND: The distal splenorenal shunt (DSRS) is designed to maintain hepatopetal portal vein flow while decompressing gastroesophageal varices. However, over time, as the underlying liver disease progresses, the DSRS loses its selectivity. The most common method of addressing this issue during orthotopic liver transplantation is shunt ligation with or without splenectomy. Dismantling the shunt increases the complexity of the transplantation, and splenectomy may increase the risk of infection. HYPOTHESIS: Anastomosis of the donor portal vein to the left renal vein without dismantling the shunt is an effective method of portal vein reconstruction for patients with a patent DSRS. DESIGN: Retrospective analysis. SETTING: University-based teaching hospital, Miami, Fla. PATIENTS: Five liver transplant recipients with patent DSRS who received an orthotopic liver transplant between September 1996 and August 1999. INTERVENTIONS: The donor portal vein was anastomosed end-to-end to the left renal vein during liver transplantation. MAIN OUTCOME MEASURES: Perioperatve morbidity, portal vein flow by Doppler study, patient survival, and graft survival. RESULTS: In all patients, the graft liver reperfused promptly via flow through the left renal vein with adequate decompression of the bowel. Normal portal venous flow was demonstrated by intraoperative and postoperative Doppler ultrasound studies. At the mean follow-up of 16 months, 4 patients were alive with well-functioning grafts. CONCLUSIONS: This novel technique has the advantage of decreasing the complexity of the procedure, without requiring splenectomy, while securing adequate portal perfusion. Additionally, it can be applied without modifications in patients with portal vein thrombosis.     

Application of cryopreserved vein grafts as a conduit between the coronary vein and liver graft to reconstruct portal flow in adult living liver transplantation

Abstract:  Adult-to-adult living donor liver transplantation is an alternative to donation from a deceased individual, and can help relieve the shortage of liver donations available for adult patients in Asian countries. When transplant candidates have thrombosis and deterioration of the portal vein, living donor liver transplantation is relatively contraindicated because portal veins in the grafts are short and vein grafts may not be available to reconstruct the portal vein. From June 2003 to May 2007, 82 adult living donor liver transplantations were performed at Chang-Gung Memorial Hospital. Three patients had portal vein thrombosis and marked fibrosis of the portal vein and cryopreserved vein grafts were used to reconstruct portal flow from the engorged coronary vein to the graft portal vein. All vein grafts are patent and all patients have normal liver function at 21–36 months after transplantation. When cryopreserved vein grafts are available, adult living donor liver transplantation can be successfully performed in patients with marked deterioration of the portal vein. The short distance from the engorged coronary vein to the graft portal vein may decrease the incidence of re-thrombosis of the venous conduit.     

Cervical heterotopic arterialized liver transplantation in the mouse

BACKGROUND: Orthotopic liver transplantation in the mouse is an extremely demanding procedure. Since the mouse, however, would be a good model for the study of various transplantation-related problems, we designed a new surgical technique for cervical heterotopic arterialized reduced-size liver transplantation. METHODS: Eighty percent hepatectomy was performed ex vivo and the remaining liver segment was transplanted to the neck of the recipient. The donor aorta was anastomosed to the right common carotid artery, the portal vein to the distal right external jugular vein, and the donor suprahepatic vena cava to the proximal right external jugular vein using a cuff technique. The bile duct was brought out as a cutaneous stoma. RESULTS: This relatively simple technique was performed in 22 BALB/C mice and associated with a high success rate: three mice died within 5 days due to surgical complications. All grafts in survivors were structurally normal until postoperative day 7 and began to show histological signs of atrophy around day 14. CONCLUSIONS: It is concluded that this technique may be useful for preservation, regeneration and reperfusion studies, and factors responsible for the maintenance of hepatocyte integrity in heterotopic liver transplantation.     

An improved model for rat liver transplantation including arterial reconstruction and simplified microvascular suture techniques.

For experimental liver transplantation in the rat, the models that have been used most frequently do not include reconstruction of the arterial blood supply to the liver. In these procedures, specially developed cuff anastomoses rather than the conventional microvascular suture technique are used almost exclusively in the recipient operation, so that the anhepatic time is minimized. In this study the technical details of an improved rat model for orthotopic liver transplantation are described. During the donor operation in this experimental method, the liver is prepared with an arterial pedicle that includes the abdominal segment of the aorta, permitting perfusion in situ of the portal vein as well as the hepatic artery. The transplantation of the excised donor organ into the recipient site is carried out with simplified microvascular suture techniques and includes reconstruction of the arterial supply to the liver. Anastomosis of the bile duct is accomplished by choledocho-choledochostomy with a splint technique and supplemental suturing. For the entire procedure, magnifying glasses with 2- to 2.5-fold magnification are sufficient. When this technique has been mastered, the average duration of the anhepatic phase is about 20 min, well below the critical 30-min limit for survival of the experimental animals. As proficiency increased, the perioperative mortality was reduced to 9.2% (n = 130). With the combination of portal and arterial in situ flushing during the donor operation and the rearterialization of the transplant during the recipient operation, the clinical conditions can be approximated more closely than is possible when the transplanted rat liver is supplied only by the portal vein. Use of microvascular suture techniques, without cuff anastomoses, reduces the need for ex situ handling of the donor organ.     

A new method for rat accessory hepatic transplantation — the cervical approach

Current methods for accessory liver transplantation in the rat require a high degree of microsurgical expertise and long training before success is achieved. We present a simpler method of arterialized accessory liver transplantation using the cervical vessels for revascularization of the transplanted liver with the cuff technique, which is useful for studies of liver preservation, reperfusion injury, and liver regeneration. After classical 70% hepatectomy is performed on the graft, the right common carotid artery is anastomosed to the donor aorta, the distal right external jugular vein is anastomosed to the donor portal vein, and the proximal right external jugular vein is anastomosed to the donor supradiaphragmatic inferior vena cava. The skin is not closed over the cervically transplanted liver (CTL). This method was used 30 times for periods of up to 6 h with a 90% success rate. CTL structure and function, as revealed by histology, bile flow rates, biliary bilirubin concentrating capacity, membrane potential, enzyme activity and distribution, have shown the CTL to be a structurally normal and metabolically active graft. In conclusion, the cervical approach to arterialized accessory liver transplantation is simple, and should prove useful for studies of liver preservation, reperfusion, regeneration, physiology, and toxicology.     

Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary.     

A new bioabsorbable material for rat orthotopic liver transplantation.

Rat orthotopic liver transplantation was performed using a newly synthesized bioabsorbable material (LA-GA copolymer) cuffs and the ordinary polyethylene cuffs. The LA-GA copolymer cuff which anastomosed the portal vein was patent and developed no collateral veins even after 6 months, keeping the transplanted liver normal. By contrast, the polyethylene cuff-anastomosed portal vein was completely occluded and the collateral veins were highly developed, with the transplanted liver showing the fatty degeneration of hepatocytes and numerous regenerative nodules. It is concluded that the LA-GA copolymer cuff is a suitable material for the short- and long-term study of rat orthotopic liver transplantation.