Hemodynamics and coagulation in experimental auxiliary liver transplantation during fulminant hepatic failure.

In pigs, ischemic liver cell necrosis was induced by 6 hours' occlusion of the hepatic artery and the portal vein 3 days after construction of a side-to-side portacaval shunt and division of the hepatic ligaments. Two thirds of the liver of an MLC-compatible donor was heterotopically transplanted 13 hours (group I), and 3 hours (group II) after induction of liver failure. In group I (N = 11), three animals died of liver failure before or shortly after induction of anesthesia. Of the remaining pigs, two animals survived more than 2 weeks. In group II (N = 10), intraoperative hypotension was prevented by reduction of the interval between liver failure and transplantation and by thermodilution catheter monitored fluid replacement. A significant decrease in cardiac output and an increase of pulmonary and systemic vascular resistance were observed during auxiliary partial liver transplantation (APLT). In the immediate postoperative period, six pigs died of deficiencies in hemostasis that were caused by consumptive coagulopathy related to severe host liver damage rather than fibrinolysis. Two pigs in group II survived in good condition 12 and 42 days after APLT. In the longer surviving pigs of both groups, either the graft or the host liver recovered. Processes that might be responsible for the observed hemodynamic changes and coagulation disorders are discussed. These results indicate that APLT is technically feasible in severely ill pigs with acute hepatic failure.     

Suppression of liver allograft rejection by administration of 15-deoxyspergualin

In this experiment, the effect of the administration route-the hepatic artery, portal vein, or systemic circulation-of the immunosuppressive drug 15-deoxyspergualin (DSG) on the suppression of liver allograft rejection is investigated. A 3-day injection of DSG at a dose of 0.32–1.28 mg/kg per day into the systemic circulation of a rat that had received a liver transplant was not effective in prolonging liver graft survival (14.3±2.9 days vs. 14.1±2.5 days for controls). However, the administration of DSG into the portal vein following liver transplantation markedly prolonged survival for up to 24.9±10.0 days. Survival times were prolonged even more when the DSG was administered via the hepatic artery for 3 successive days after liver grafting (30.9±9.6 days). The concentration of DSG in the blood following the one-shot injection of DSG was highest when DSG was administered via the hepatic artery, intermediate when injected into the portal vein, and lowest when injected into the systemic vein. In conclusion, DSG can inhibit liver graft rejection more effectively via the hepatic arterial route than via the portal vein or systemic circulation.     

猪急性缺血性肝衰模型的建立和辅助性异位部分肝移植的作用

目的: 探讨急性缺血性肝衰模型的制备、辅助性异位部分肝移植的作用. 方法: 用家猪配对开展辅助性异位部分肝移植.分三组,A组:受体肝脏和肝动脉保持原状,其门静脉缩窄;供肝植入受体右肝下,仅建立门静脉血供,不建立动脉血供.B组:受体肝动脉结扎,其他手术内容与A组相同.C组:受体肝动脉结扎,供肝动脉和门静脉血供均建立,其他手术内容与A组相同.监测各组受体存活情况,肝功能和肝脏血流情况,病理及供肝胆汁分泌情况. 结果: A组、C组受体3 d以上成活率显著高于B组.A组、C组手术前后胆红素无显著改变,B组术后胆红素显著高于术前,术后第二天B组胆红素显著高于A组、C组.C组供肝胆汁分泌和血供良好,肝细胞存活并有活跃的代偿性增生;A组、B组供肝无或仅有少量胆汁分泌,肝细胞大片坏死. 结论: 受体肝动脉结扎、门静脉缩窄足以造成急性肝衰模型;保留受体肝脏动脉血供、减少门静脉血供对受体肝脏功能无严重影响;辅助性异位部分肝移植能取得良好的效果,足以纠正急性肝衰.     

可量化的受体门静脉干预调节猪辅助性部分肝移植两肝门静脉血流竞争

目的 观察不同程度的受体肝门静脉缩窄对猪辅助性部分肝移植(APLT)受体肝和移植肝门静脉血流竞争的防治作用,探讨一种可量化的受体肝门静脉干预标准.方法 32头健康幼猪按体重相近原则配对,取右半肝作为供肝,切除受体肝左叶,共行16次APLT.根据移植后受体门静脉缩窄程度,将其分为4组:对照组(n=5,门静脉未行处理),缩窄1/4组(n=4,受体门静脉宽度缩窄1/4),缩窄1/3组(n=4,缩窄1/3)和结扎组(n=3,门静脉结扎).定期观察各组受体肝和移植肝的体积大小、血流状况及组织结构的变化.结果 术中电解质变化各组基本相似,血流动力学变化以对照组和缩窄1/4组较为平稳;各组存活率和最长存活时间均以缩窄1/4组最优;门静脉造影示缩窄1/4组两肝之门静脉均得到较好显影,未见明显造影剂淤积和血管扩张;多普勒超声示各组移植肝门静脉依次增宽,流速分别为0.220、0.293、0.336和0.400 m/s,受体门静脉流速分别为0.275、0.294、0.328和0 m/s;两肝体积、充盈度和包膜紧张度以缩窄1/4组最为适中,坏死程度亦以缩窄1/4组最轻.结论 在供受体体重相近且无明显肝硬化时,为防治APLT门静脉血流竞争,以受体门静脉宽度缩窄1/4较为适宜.     

猪辅助性部分肝移植模型制作及比较

目的建立猪的辅助性部分肝移植模型,观察其肝功能和术中血流动力学变化。方法 24头健康良种家猪,体质量23-30 kg,被随机分为供体(n=12)和受体(n=12)。气管插管 全麻,硫喷妥钠静脉维持。移植前切除受体肝左叶,供肝右叶作为植入肝。预实验2例行经体位转流的原位辅助性部分肝移植,对照组(5例)行简易转流下的原位辅助性部分肝移植。模型组(5例)行异位辅助性部分肝移植, 供肝被植入受体肝下间隙,供肝肝上下腔静脉与受体肝下下腔静脉端侧吻合,供肝门静脉与受体门静脉行端侧吻合,供肝肝动脉与受体脾动脉行端端吻合。供肝胆总管置管外引流。结果预实验中行体位静脉转流的原位辅助性部分肝移植的2例受体在肝上下腔静脉阻断后很快陷入血流动力学紊乱死亡。5例行简易静脉转流的原位辅助性部分肝移植的受体,2例在24 h内死亡,1例28 h,2侧超过48 h。而模型组受体 5例中有4例存活超过24 h。AST,ALT指标手术开始至术后24 h呈持续升高。模型组术中血流动力学较其他组稳定。结论该辅助性肝移植模型简明易建且具有不需静脉转流等优点,为研究辅助性部分肝移植原肝和供肝功能及血流变化提供了理想的平台。     

Portal vein pressure is the key for successful liver transplantation of an extremely small graft in the pig model

In partial-liver transplantation, the use of small grafts sometimes results in graft failure, usually caused by portal hypertension after transplantation (Tx). Portal hypertension after Tx can be decreased with a porto-caval shunt (PCS). The purpose of this study is to clarify the effect of the PCS on extremely reduced-size liver Tx. In a pig model, the posterior segment of 25% of a whole liver was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS ( n=7), and group B, graft without PCS ( n=7). The PCS was made by means of side-to-side anastomosis of the portal vein and the inferior vena cava. We examined the portal vein pressure, survival rate, regeneration rate of the graft, Ki-67 as an index of cell proliferation, and histological findings, and carried out liver-function tests. In group A, five pigs survived for more than 4 days and the remaining two died of a perforated gastric ulcer on post-operative day (POD) 2. In group B, all pigs except one died of graft failure within 24 h. Portal vein pressure after reperfusion in group A and group B was of statistically significant difference ( P<0.05), 14.2+/-3.2 and 18.9+/-4.7 cmH(2)O, respectively. In group A, the regeneration rate of the graft was 94%, 4 days after Tx, and Ki-67 stained remarkably in the parenchymal hepatocytes. In TEM finding, structure of the sinusoid was also well maintained after Tx. From these results we can conclude that the key to success in liver Tx with extremely small grafts lies in the control of the portal vein pressure.     

肝移植治疗晚期肝硬化

目的 肝移植治疗肝脏终末期病变。方法 采用改良的背驮式肝移植技术即保留肝后下腔静脉的全病肝切除,将供肝植于受肝原位,供、受体肝上下腔静脉,供、受体门静脉,供、受肝动脉行对端吻合;结扎供肝肝下下腔静脉。用ＦＫ５０６、晓翻和强的松三联免疫抑制剂抗排斥反应,加强术后监护和感染的控制。结果 例１、例２目前分别存活１１个月、８个月余,生活自理,例３因术后并发急性肾功能衰竭死亡,存活１４d。结论 肝移植是治愈肝脏终末期病谱的可靠方法。     

Simultaneous hepatic artery and portal vein thrombosis after living donor liver transplantation

Simultaneous hepatic artery and portal vein thrombosis rarely occurs after liver transplantation. The etiology is unknown. Of 213 patients (72 children and 141 adults) that underwent living donor liver transplantation (LDLT) from January 1996 to March 2003, 4 (2%) developed simultaneous thrombosis at 3 hours to 7 days (median, 4 days) after the operation. Emergent thrombectomy was performed in three patients; the remaining patient was registered in the Japan organ transplant network. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). Portal vein, hepatic artery, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography for 2 weeks after liver transplantation. These parameters were stable until just before the simultaneous thrombosis. These findings indicate that protocol Doppler ultrasonography can diagnose, but not predict, this fatal complication.     

Hepatocellular transplantation for experimental ischemic acute liver failure in dogs

Recovery from acute liver failure is possible if metabolic support can be provided during the period of exogenous liver regeneration. The ability of transplanted dispersed autologous hepatocytes to alter the course of experimental ischemic acute liver failure in dogs was tested. Liver failure was induced by occlusion of blood flow in the proximal portal vein and hepatic artery(s) 48 hr after creation of a side to side portacaval shunt and immediately after a left lateral hepatic lobectomy. Dogs in Group 1 had ischemic injury with no treatment. Dogs in Group II received intrasplenic autotransplants of hepatocytes (26 ± 4x × 10⁸ intact cells) after the ischemic period. Cells for transplantation were prepared from the excised lobe during the period of liver ischemia. Dogs in Group III received intrasplenic transplants of autologous hepatocytes (26 = 3 × 10⁸ intact cells) after liver ischemia and after ligation of the main splenic artery. Serum bilirubin, serum glutamic oxalocetic transaminase, lactate dehydrogenase, and alkaline phosphatase were measured before and serially after ischemia, and showed that the degree of liver injury in all three groups was similar, although survival in Group III was better. Only 20% of nontransplanted animals (Group I) survived 10 days. Liver histology in animals that died showed hemorrhagic necrosis situation around the terminal hepatic central veins. Transplantation did not improve survival in dogs with arterialized spleens and histological examination of dogs that died showed pulmonary infarcts and additional liver injury from embolization of hepatocytes. In contrast, 70% of the animals undergoing splenic artery ligation before intrasplenic transplantation of hepatocytes were alive at 10 days. Ligation of the splenic artery reduced the tendency for hepatocytes to escape into the splenic vein and the spleen remained viable due to collateral circulation. On histological examination, hepatocytes were readily identified in the splenic parenchyma at 24 hr. 2 and 4 weeks after transplantation. In conclusion, intrasplenic hepatocytes provide sufficient metabolic support for dogs to recover from otherwise lethal ischemically induced, acute liver failure.     

Native Portal Vein Embolization for Persistent Hyperoxaluria Following Kidney and Auxiliary Partial Liver Transplantation

Type 1 primary hyperoxaluria (PH1) causes renal failure, for which isolated kidney transplantation (KT) is usually unsuccessful treatment due to early oxalate stone recurrence. Although hepatectomy and liver transplantation (LT) corrects PH1 enzymatic defect, simultaneous auxiliary partial liver transplantation (APLT) and KT have been suggested as an alternative approach. APLT advantages include preservation of the donor pool and retention of native liver function in the event of liver graft loss. However, APLT relative mass may be inadequate to correct the defect. We here report the first case of native portal vein embolization (PVE) to increase APLT to native liver mass ratio (APLT/NLM‐R). Following initial combined APLT‐KT, both allografts functioned well, but oxalate plasma levels did not normalize. We postulated the inadequate APLT/NLM‐R could be corrected by trans‐hepatic native PVE. The resulting increased APLT/NLM‐R decreased serum oxalate to normal levels within 1 month following PVE. We conclude that persistently elevated oxalate levels after combined APLT‐KT for PH1 treatment, results from inadequate relative functional capacity. This can be reversed by partial native PVE to decrease portal flow to the native liver. This approach might be applicable to other scenarios where partial grafts have been transplanted to replace native liver function.     

First case of cadaveric liver transplantation in Japan

The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation. Received for publication on July 31, 1999; accepted on Sept. 8, 1999     

Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation

In split-liver transplantation, the entire portal flow is redirected through relatively small-for-size grafts. It has been postulated that excessive portal blood flow leads to graft injury. In order to elucidate the mechanisms of this injury, we studied the hemodynamic interactions between portal vein- and hepatic artery flow in an experimental model in pigs. Six whole pig liver grafts were implanted in Group 1 ( n=6) and six whole liver grafts were split into right and left grafts and transplanted to Groups 2 ( n=6) and 3 ( n=6), respectively. The graft-to-recipient liver volume ratio was 1:1, 2:3 and 1:3 in Groups 1, 2 and 3, respectively. Portal vein- and hepatic artery flows were measured with an ultrasonic flow meter at 60,120 and 180 min after graft reperfusion. Portal vein pressure was also recorded at the same time intervals. Graft function was assessed at 3,6h and 12h, and morphological changes at 12h after reperfusion. Following reperfusion, portal vein flow showed an inverse relationship to graft size, while hepatic artery flow was reduced proportionately to graft size. The difference was significant among the three groups ( P<0.05). Portal vein pressure was significantly higher in group 3, compared to groups 1 and 2 ( P<0.05). Hepatic artery buffer response was significantly higher in Group 3, compared to Groups 1 and 2 in relation to pre-occlusion values ( P<0.05). Split-liver transplantation, when resulting in small-for-size grafts, is associated with portal hypertension, diminished arterial flow, and graft dysfunction. Arterial flow impairment appears to be related to increased portal vein flow.     

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.     

Effect of total enterectomy, pancreatectomy, and portal vein ligation on liver function and histology: a case report

Impaired hepatic function and histology have been observed in experimental models of diversion of the portal vein blood inflow from the liver and among patients with intestinal failure. Survival after total enterectomy, pancreatectomy, and portal vein ligation, and the effect of such a condition on liver function have never been reported in humans. Herein a 32-year-old woman with familial adenomatous polyposis and multiple desmoid tumors involving the mesentery and the retroperitoneum underwent total enterectomy and pancreatectomy followed by en bloc transplantation of the stomach, small bowel, and pancreas. Due to early graft failure, the patient underwent graftectomy, ligation of the portal vein, and external drainage of the common bile duct. Liver function tests were checked daily and a liver biopsy performed 15 days after graftectomy. The patient died of a ruptured mycotic aneurysm of the abdominal aorta at 27 days after the graftectomy. Liver function tests remained normal throughout the postoperative period; liver biopsy showed normal hepatic architecture with mild portal inflammation and cholestasis and spotty necrosis. Total enterectomy with pancreatectomy and ligation of the portal vein are compatible with survival in humans (at least in the short term), allowing normal hepatic function with minimal histological alterations to the liver.     

Auxiliary partial liver grafting in rats: effect of host hepatectomy on graft regeneration,and review of literature on surgical technique

Auxiliary partial liver transplantation (APLT) is beneficial for fulminant liver failure when there is potential for recovery of the diseased liver. However, the impact of host hepatectomy on regeneration of the grafted liver is unclear. In this study, we modified a previous rat model of auxiliary whole liver transplantation without portal vein reconstruction, and studied the effect of host hepatectomy on regeneration of the cut liver graft. Thirty percent of the liver was heterotopically transplanted, to connect the recipient's left renal artery and vein with the graft's aortic cuff of the hepatic artery and inferior vena cava, respectively, using a cuff technique; 30% of the recipient liver then was cut. The control group was left intact. The liver grafts were weighed preoperatively and 2 weeks postoperatively. This procedure prevented congestion of the graft liver and achieved a high success rate, even when performed by a surgeon who was relatively inexperienced with the technique. The weight of the grafted liver in the host hepatectomized group significantly increased (P < 0.05) compared with that of the control group. We developed an experimental model of APLT and reviewed the literature on rat heterotopic liver transplantation, and compared the surgical techniques.     

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     

异位辅助性分肝移植供肝切取与植入体会

目的　为临床辅助性肝移植的开展,探索供肝切取及植入方法。　方法　猪异位辅助性部分肝移植13例,供肝切取按预分离方法分为A、B两组,A组标准法5例,B组快速灌注法8例。　结果　A组供肝质量优良为100%,B组供肝质量优良占88%。辅肝移植手术时间为122±28min,腔静脉和门静脉吻合时间为40±12min。　结论　如条件允许应首选标准法预分离,血流动力学不稳定时,可行快速灌注法预分离。     

A Novel Technique for Auxiliary Partial Liver Transplantation With Reno-Portal Anastomosis and Avoidance of the Hepatoduodenal Ligament

Auxiliary liver transplantation (ALT) is a treatment for acute liver failure when regeneration of the native liver is possible or for metabolic disorders. In selected cases ALT and orthotopic liver transplantation (OLT) have similar survival when ALT is performed in the orthotopic position (auxiliary partial orthotopic liver transplantation, APOLT). Drawback of ALT with portal vein to portal vein anastomosis is the frequent occurrence of thrombosis, compromising both graft and native liver, and the necessity of a significant resection. To avoid division of portal flow we performed ALT with an end-to-end anastomosis between the graft portal vein and the left renal vein of the recipient (reno-portal ALT, REPALT). The hepatic artery was anastomosed to the aorta using an iliac arterial graft conduit. The bile duct was anastomosed to the stomach. In the two cases presented here excellent immediate graft function occurred with rapid regeneration of the graft and without early vascular complications.     

Auxiliary transplantation of part of the liver improves survival and provides metabolic support in pigs with acute liver failure

In pigs subtotal ischemic liver cell necrosis was induced 4 days after auxiliary transplantation of 60% of the liver of an MLC-compatible donor (ATPL group, n = 13). In control animals (n = 14) temporary liver ischemia was preceded by division of the hepatic ligaments and creation of an end-to-side portacaval shunt. In the ATPL group six animals died of gastric hemorrhage, intestinal strangulation, or sepsis. The remaining seven animals survived in excellent condition until sacrifice 26 days after the induction of liver ischemia. Excellent graft function was demonstrated by uptake and excretion of 99mTc-HIDA at cholescintigraphy, ammonia detoxification, synthesis of clotting factors and glucohomeostasis. EEG recordings in the animals that underwent transplantation did not change from preischemic levels. Evidence of hepatic regeneration was found in the transplanted livers but could not be demonstrated in the damaged host livers. The control animals died in coma within 72 hours. These results indicate that auxiliary transplantation of a partial liver provides metabolic support and improves survival in animals with induced acute liver failure.     

A new animal model for split liver transplantation using an infrahepatic IVC graft

An animal model of split liver transplantation using pigs is described herein. The donor liver was divided into two grafts, the right graft consisting of the right medial and lateral segments with the caudate lobe, and the left graft consisting of the left lateral and medial segments. To make implantation easier, a distal part of the donor's inferior vena cava (IVC) was isolated and attached to the left graft with an anastomosis between the orifice of the renal vein and the graft's hepatic vein. The left graft thereby contained a newly constructed retrohepatic IVC for anastomosis to the recipient. During the anhepatic phase, no conventional bypass procedure was used, but an abdominal aortic clamp in combination with general hypothermia was employed. Ten pigs were used as donors and a total 20 liver transplantations performed. No immunosuppressive drugs were given in this series. Ten of the 20 recipients survived for more than 2 days, the mean survival time being 4.7 days, with a range of 2–14 days. The mean survival time of the left grafts was much longer than that of the right grafts, although no technical problems such as kinking of the graft or occlusion of the hepatic vein were encountered in either. This model is the first report of split liver transplantation in animals. The advantages of using the infrahepatic IVC graft include stability of the graft and safe hepatectomy. This model will therefore be useful for the experimental study of split liver transplantation and may also be employed for clinical use in the future.