基质金属蛋白酶-9 与小体积移植肝早期损伤的相关性研究

目的 观察不同体积肝移植术后早期移植肝内基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达及活化特点,探讨MMP-2和MMP-9在小体积移植肝早期损伤中的作用机制. 方法 随机将108只SD大鼠分成3组,每组36只.分别为:全肝(100%肝体积)移植组、半肝(50%肝体积)移植组和小体积肝(25%肝体积)移植组.分别检测移植肝再灌注后0.5、6、12、24、48、72 h的肝功能及移植肝组织中丙二醛(MDA)和髓过氧化物酶(MPO)浓度,观察移植肝组织病理学特征,并运用双抗夹心酶联免疫吸附试验(ELISA)、实时定量聚合酶链反应(PCR)、明胶酶谱和免疫组织化学方法检查移植肝中MMP-2和MMP-9的表达情况. 结果 与全肝和半肝移植组比较,小体积肝移植组再灌注后6～24 h MMP-9表达明显升高;而且MMP-9活化和表达增高伴随着移植肝功能损害和严重的缺血再灌注损伤.MMP-9早期表达都集中在移植肝门静脉周围,与门静脉高灌注密切相关. 结论 MMP-9表达升高是小体积移植肝早期重要的致损伤因素;肝移植术后门静脉高灌注可能是触发MMP-9活化和表达的重要原因.     

Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival.

The major concern of living donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be developed. To investigate the protective effect of somatostatin related to hemodynamic stress on small-for-size liver graft injury, we applied a treatment regimen of low-dose somatostatin in a rat orthotopic liver transplantation model using small-for-size grafts (median, 38.7%; range, 35-42%). Somatostatin was given at 5 minutes before total hepatectomy and immediately after reperfusion in the recipient (20 microg/kg). Graft survival, portal hemodynamics, intragraft gene expression and hepatic ultrastructural changes were compared between the rats with or without somatostatin treatment. Seven-day graft survival rates in the somatostatin treatment group were significantly improved compared to the control group (66.7% vs. 16.7%, P = 0.036). In the treatment group, portal pressure and hepatic surface blood flow were significantly decreased within the first 30 minutes after reperfusion, whereas in the control group, transient portal hypertension and excessive hepatic blood flow were observed. Intragraft expression (both messenger RNA and protein) of endothelin-1 was significantly downregulated accompanied with upregulation of heme oxygenase-1 and A20. Better preservation of liver function was found in the treatment group. Hepatic ultrastructure, especially the integrity of sinusoids, was well protected in the treatment group. In conclusion, low-dose somatostatin rescues small-for-size grafts from acute phase injury in liver transplantation by attenuation of acute-phase shear stress that resulted from transient portal hypertension.     

Venous hemodynamics in living donor right lobe liver transplantation

We evaluated the influence of portal and hepatic venous hemodynamics on the immediate and 3-month postoperative function of living donor right lobe grafts. Portal velocity was measured prospectively by ultrasound in 14 consecutive donor/recipient pairs. Velocity was converted to flow with the Moriyasu formula. Measurements were taken in donors in the operating room and in recipients at 1 hour after reperfusion and 3 months after transplant. Recipient liver function tests were measured postoperatively. Prereperfusion and postreperfusion liver biopsies were evaluated and correlated with the hemodynamic and biochemical results. There were 11 male (78.6%) and 3 female donors (mean age, 38.9 ± 9.8 years) for 10 male (71.4%) and 4 female recipients (mean age, 49.3 ± 14 years). The mean graft/recipient weight ratio was 1.22 ± 0.3. The mean right portal vein pressure was 8 ± 1.8 mm Hg in donors versus 13 ± 4.7 mm Hg in recipients (P < .05). The mean peak flow velocity (Vmax) in the portal vein in donors was 47.6 ± 12.8 cm/sec (normal, 44 cm/sec). One hour after graft reperfusion in the recipient, the mean portal Vmax was significantly higher at 94.7 ± 28.4 cm/sec (P = .004), but by 3 months follow-up, mean portal Vmax had fallen to 58.8 ± 37.8 (P = .01). Recipient portal vein Vmax highly correlated with portal flow (r = 0.7, P = .01). Increased recipient total bilirubin on postoperative day 2 correlated highly with higher recipient portal flow one hour after transplant (r = 0.6; P = .03). Portal vein velocity/flow dramatically increases after reperfusion, returning to baseline about 3 months after transplant. Evaluation of hepatic and portal venous flow is a relatively easy skill to acquire. Intraoperative ultrasound may enable the surgeon to predict graft dysfunction and possibly, may be used to implement pre-emptive therapies. (Liver Transpl 2002;8:809-813.)     

Surgical procedures for decompression of excessive shear stress in small-for-size living donor liver transplantation--new hepatic vein reconstruction

We have reported that acute elevation of portal pressure, reflecting wall shear stress of sinusoidal endothelial cells, triggers liver regeneration after partial hepatectomy and that excessive portal hypertension induces liver failure. For prevention of excessive shear stress in small-for-size living donor liver transplantation (LDLT), we developed a new hepatic vein reconstruction to expand the anastomotic site. Fourteen adult patients, who underwent LDLT, were divided into two groups: previous end-to-end hepatic vein reconstruction in nine patients (group P) and the new method in five patients (group N). The outside middle and left hepatic veins of the graft were incised and enlarged to 40 mm. The vena cava was cut 40 mm longitudinally. The graft was positioned a quarter turn counterclockwise with the hepatic vein of the graft anastomosed end-to-side to the vena cava longitudinally. Postoperative portal pressures and serum total bilirubin levels of these two groups showed portal pressure in group N to rapidly decrease below 25 cm H2O following LDLT. No cases showed posttransplanted hyperbilirubinemia above 10 mg/dL in group N; however, all cases were small-for-size grafts. Moreover, serum total bilirubin levels in group N were significantly lower than those in group P. This procedure is simple despite not using a venous patch. If the hepatic vein is narrow or obstructed, such as in Budd-Chiari syndrome, the procedure is applicable. Even in small-for-size grafts, excessive tension did not occurred at the portal vein or hepatic artery anastomoses. Moreover, it is possible to avoid outflow block and posttransplanted hyperbilirubinemia.     

Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes

BACKGROUND: Damage to a small-for-size liver graft after reperfusion is frequently observed but the mechanism of injury remains unclear. HYPOTHESIS: Injury to a small-for-size liver graft is related to the changes of portal pressure and blood flow. MAIN OUTCOME MEASURES: Survival rates, portal hemodynamics, microcirculatory changes, and morphological changes (by light microscopy and electron microscopy). SETTING: A rat model of nonarterialized orthotopic liver transplantation comparing 2 groups of rats transplanted with whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of recipient liver weight). RESULTS: Median survival of the rats with small-for-size grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after reperfusion, mean arterial pressure of the small-for-size graft group was significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm Hg, P =.04; 15-minute: 96 vs 127 mm Hg, P =.04). Portal pressure (in centimeters of water) of the small-for-size graft group was significantly higher in the first 20 minutes after reperfusion than the level before the anhepatic phase (5-minute: 15.1 vs 9.3, P =.02; 10-minute: 16.1 vs 9.3, P =.03; 15-minute, 13.5 vs 9.3, P =.03; 20-minute: 13.4 vs 9.3, P =.03) and was significantly higher than that of the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1 vs 9.6, P =.02; 10-minute: 16.1 vs 10.3, P =.04). Hepatic microcirculatory blood flow (in milliliters per minute per 100 g) was also significantly higher in the small-for-size graft group during the first 40 minutes after reperfusion (5-minute: 16.3 vs 9.3, P =.02; 10-minute: 14.9 vs 6.6, P =.02; 15-minute: 14.8 vs 5.5, P =.02; 20-minute: 13.1 vs 7.0, P =.02; 30-minute: 13.2 vs 8.8, P =.04; 40-minute: 14.6 vs 7.1, P =.02). Light and electron microscopy showed normal morphological features of whole graft up to 24 hours after reperfusion. The small-for-size graft, however, showed sinusoidal congestion, tremendous swelling of mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and collapse of the space of Disse. CONCLUSIONS: In a rat model, the portal hemodynamic changes in small-for-size grafts are transient. Progressive damage of the graft may result from microcirculatory failure due to irreversible endothelial injury after reperfusion.     

Intraoperative measurement of graft blood flow - a necessity in liver transplantation

Abstract Portal venous and hepatic arterial flow was measured intraop-eratively in the 70 most recent patients undergoing liver transplantation in our institution. Impaired graft flow due to vascular abnormalities was detected in six patients. One patient suffered from arterial steal due to stenosis of the recipient celiac trunk with blood shunting from the hepatic to the splenic artery. Ligation of the recipient hepatic artery restored the arterial graft flow. In two patients we found reduced portal venous flow due to large portosystemic collaterals. The collaterals accountable for the impaired portal flow were identified and ligated, which restored portal venous graft flow. Excessive sensitivity of the portal venous flow to the position of the graft was found in a 6-month-old boy. Portal venous flow varied considerably, depending upon the position of the graft, and intraoperative flow measurement allowed the best position of the graft to be identified. Two patients developed arterial thrombosis in the early postoperative course. Immediate laparatomy with thrombectomy resulted in good, palpable pulsation in the graft artery in both patients. Intraoperative flow measurement demonstrated satisfactory arterial flow in one patient, whereas there was no net flow in the other patient's graft artery. Pulsation in this patient was caused by blood oscillating in and out of the liver. In conclusion, we find that causes of primary graft dysfunction due to technically flawed reperfusion of the graft can be identified and alleviated by intraoperative measurement of the flow in the graft vessels.     

Intraoperative measurement of graft blood flow — a necessity in liver transplantation

Portal venous and hepatic arterial flow was measured intraoperatively in the 70 most recent patients undergoing liver transplantation in our institution. Impaired graft flow due to vascular abnormalities was detected in six patients. One patient suffered from arterial steal due to stenosis of the recipient celiac trunk with blood shunting from the hepatic to the splenic artery. Ligation of the recipient hepatic artery restored the arterial graft flow. In two patients we found reduced portal venous flow due to large portosystemic collaterals. The collaterals accountable for the impaired portal flow were identified and ligated, which restored portal venous graft flow. Excessive sensitivity of the portal venous flow to the position of the graft was found in a 6-month-old boy. Portal venous flow varied considerably, depending upon the position of the graft, and intraoperative flow measurement allowed the best position of the graft to be identified. Two patients developed arterial thrombosis in the early postoperative course. Immediate laparatomy with thrombectomy resulted in good, palpable pulsation in the graft artery in both patients. Intraoperative flow measurement demonstrated satisfactory arterial flow in one patient, whereas there was no net flow in the other patient's graft artery. Pulsation in this patient was caused by blood oscillating in and out of the liver. In conclusion, we find that causes of primary graft dysfunction due to technically flawed reperfusion of the graft can be identified and alleviated by intraoperative measurement of the flow in the graft vessels.     

肝缺血再灌注后肝内血流动力学的变化

目的探讨肝脏缺血再灌注（I／R）后肝内分流（IHSF）和功能性肝血流（FHBF）的变化。方法健康雄性SD大鼠l2只，作右侧颈动脉、颈静脉插管；开腹后，经回结肠静脉作门静脉插管，分别用以输血、输液、给药、留样、检测等。大鼠经部分肝I／R制模后，随机分为2组（每组6只）：（1）正常对照组（对照组），术中只分离肝周围韧带，不作肝门阻断及再灌注。（2）缺血再灌注组（1／R组，实验组），进行45min的肝门阻断及60min的再灌注。然后两组均经门静脉输注D一山梨醇（10mmol／L，0．2mL／min），2min后同时取颈动脉、门静脉、肝静脉血各1mL。测定门静脉血流量（PVF）、肝动脉血流量（HAF）。计算肝脏山梨醇摄取率、FHBF和IHSF。结果两组PVF，HAF及总肝血流量（THBF）无明显统计学差异；与对照组比较，I／R组肝脏山梨醇摄取率和FHBF减少，IHSF增加（P〈0．01）。结论肝I／R后，肝内血流动力学变化表现为肝内门一体分流开放，功能性肝血流减少。     

Modulation of portal graft inflow: a necessity in adult living-donor liver transplantation?

OBJECTIVE: To evaluate the clinical significance of modulating the recipient portal inflow (rPVF) through perioperative ligation of the splenic artery in adult living-donor liver transplantation (ALDLTx) by focusing on vascular complications, intractable ascites production, and the prevention of small-for-size syndrome (SFSS). SUMMARY BACKGROUND DATA: In ALDLTx, portal graft flow is enhanced to at least twice the donor value, raising the total liver inflow. Recipient hepatic arterial flow (rHAF) is lower than expected. Portal hyperperfusion of small grafts in larger recipients is thought to be one of the main causes of posttransplant graft dysfunction/SFSS. METHODS: Seventeen ALDLTx were reviewed for a minimum of 2 months. Patients were divided retrospectively into two groups: G1 (n = 7), without modulation of rPVF, and G2 (n = 10), with splenic artery ligation to decrease rPVF perioperatively. Donor and recipient hepatic hemodynamics were evaluated against graft function and outcome, including correlations between rPVF, graft weight, graft:recipient body weight ratio, and recipient weight. RESULTS: Following portal and arterial reperfusion, mean rPVF and rPVF/graft weight were much higher than in the donors, whereas mean rHAF and rHAF/graft weight were much lower. No differences were found between groups, except for rPVF and rHAF, which were much more higher and lower, respectively, before splenic artery ligation. In G1 patients, SFSS was seen in two patients and vascular complications occurred in two others. In G2 patients, splenic artery ligation permitted a significant decrease in rPVF, an improvement in rHAF, and the resolution of refractory ascites. Neither SFSS nor vascular complications were seen in G2 patients. CONCLUSIONS: When a suboptimal graft:recipient body weight ratio is accompanied by high rPVF in ALDLTx, the portal flow should be modulated perioperatively; splenic artery ligation is a simple and safe method that is sufficient to allow this modulation in most patients.     

Living Donor Liver Transplantation with Left Liver Graft

Small-for-size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year-old patient underwent to LDLT at our institution. During the anhepatic phase a porto-systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post-operative course was characterized by good graft function. Small-for-size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult-to-adult living donor liver transplantation.     

FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway

OBJECTIVE: To investigate whether low-dose nitric oxide donor FK 409 could attenuate small-for-size graft injury in liver transplantation using small-for-size grafts. SUMMARY BACKGROUND DATA: The major concern of live donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be investigated. METHODS: We employed a rat orthotopic liver transplantation model using small-for-size (40%) graft. FK 409 was given at 30 minutes before graft harvesting (2 mg/kg) to the donor and immediately after reperfusion (1 mg/kg) to the recipient (FK group). Graft survival, intragraft genes expression, portal hemodynamics, and hepatic ultrastructural changes were compared between the 2 groups. RESULTS: Seven-day graft survival rates in the FK group were significantly improved compared with those of rats not receiving FK 409 (control group; 80% versus 28.6%, P = 0.018). In the FK group, portal pressure was significantly decreased within the first 60 minutes after reperfusion whereas in the control group, transient portal hypertension was observed. Intragraft expression (both mRNA and protein) of early growth response-1, endothelin-1, endothelin-1 receptor A, tumor necrosis factor-alpha, macrophage-inflammatory protein-2, and inducible nitric oxide synthase was significantly down-regulated accompanied with up-regulation of heme oxygenase-1, A20, interferon-gamma-inducible protein-10, and interleukin-10 during the first 24 hours after reperfusion. Hepatic ultrastructure, especially the integrity of sinusoids was well protected in the FK group. CONCLUSIONS: Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins.     

Norepinephrine in small-for-size liver grafts: an experimental study in pigs

BACKGROUND: Norepinephrine plasma levels may play a role in small-for-size grafts dysfunction at the early posttransplant period. MATERIALS AND METHODS: The 18 pigs used as recipients were assigned to group 1 (n = 6), group 2 (n = 6), and group 3 (n = 6) and given grafts with graft-to-recipient volume ratios of 1:1, 2:3, and 1:3, respectively. Blood serum norepinephrine was measured by high-performance liquid chromatography with electrochemical detection at the following time points: pre-anhepatic period (baseline); anhepatic period; and 30, 60, 180, and 360 min after reperfusion. Graft arterial and portal vein flows were obtained 30, 60, 180, and 360 min after reperfusion by the aid of an ultrasonic flowmeter. Aspartate transferase (AST) and international normalized ratio (INR) were measured before the procedure (baseline), and at 180 and 360 min after reperfusion. RESULTS: Anhepatic phase was characterized by a significant increase (6- to 8-fold) of norepinephrine in all groups (P < 0.05). In groups 1 and 2 plasma norepinephrine returned to normal values 30 min after reperfusion. In group 3, plasma norepinephrine remained significantly increased at every time point of the study compared to groups 1 and 2 (P < 0.001). Hepatic artery and portal vein flows in group 3 were significantly (P < 0.05) reduced and increased, respectively, compared to groups 1 and 2 at all times measured. Liver function tests (AST and INR) 360 min after reperfusion were significantly higher in group 3 compared to groups 1 and 2. CONCLUSIONS: Norepinephrine levels are increased in very small-for-size grafts and this increase may be associated with early graft dysfunction.     

Critical progressive small-graft injury caused by intrasinusoidal pressure elevation following living donor liver transplantation

In adult-to-adult living liver transplantation, small-for-size graft syndrome sometimes occurs. The relationship between the hemodynamic changes and histologic findings has not been studied in patients with failure of small-for-size grafts. We analyzed the relationship between the postoperative hemodynamic changes and pathologic findings in patients with small-for-size grafts that ended in graft failure. From March 1999 to December 2002, adult-to-adult living-donor liver transplantation with small-size grafts (graft volume/standard liver volume less than 40%) was performed in eight patients. Three patients died from graft failure caused by overperfusion, which was diagnosed from pathologic findings. We analyzed the relation between hepatic hemodynamic parameters, such as portal venous blood velocity or splenic arterial pulsatility index, and histologic changes in patients with graft failure. Severe portal hyperperfusion (90 cm/sec at the umbilical portion) was observed on postoperative day 1. Among patients with graft failure, critical hemodynamic changes, such as sudden onset of extremely deteriorated portal venous blood flow, occurred during the early postoperative period (postoperative day 5, 3, 6, respectively). Histologic examination revealed vacuolar changes in the cytoplasm of hepatocytes, and submassive necrosis indicated intrasinusoidal pressure elevation. These changes were not observed in the biopsy obtained soon after reperfusion. In conclusion, critically decreased vascular beds may cause intrasinusoidal pressure elevation and sinusoidal circulatory disturbances.     

Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression

OBJECTIVE: To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes in right lobe live donor liver transplantation (LDLT). SUMMARY BACKGROUND DATA: Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft injury after reperfusion is common, but the mechanism and degree of injury remain unclear. The hepatic sinusoidal injury in different graft sizes and its relationship with portal hemodynamics and intragraft gene response at the early phase after reperfusion have not been studied in right lobe LDLT. METHODS: From May 2000 to November 2001, 40 adults receiving right lobe LDLT had portal pressure measured continuously before and after reperfusion. Liver biopsies were taken before and after reperfusion for detection of vasoregulatory genes (endothelin-1 and endothelial nitric oxide synthase) and heat shock genes (heat shock protein 70 and heme oxygenase-1), and electron microscope examination. Blood samples from the portal vein and suprahepatic inferior vena cava were taken for the measurement of plasma nitric oxide level. RESULTS: The recipients were grouped according to the ratio of graft weight to estimated standard liver weight: group 1 (n = 10), less than 40%; group 2 (n = 21), 40% to 60%; and group 3 (n = 9), more than 60%. The portal pressures recorded after reperfusion in group 1 were significantly higher within 30 minutes of reperfusion than those in groups 2 and 3. After reperfusion, the intragraft endothelin-1 mRNA level in group 1 increased by 161% of the basal level but decreased by 31.5% and 62% of the basal level in groups 2 and 3, respectively. The intragraft mRNA level of heme oxygenase-1 in groups 1 and 2 decreased by 75.5% and 25.3% of the basal level respectively but increased by 41% of basal level in group 3. The intragraft protein level of heat shock protein 70 decreased by 50 ng/mL after reperfusion in group 1 but increased by 12.4 ng/mL and 0.6 ng/mL in groups 2 and 3, respectively. The portal vein plasma nitric oxide level decreased more significantly after reperfusion in group 1 than in group 2. Electron microscope examination of liver biopsies in group 1 showed tremendous mitochondrial swelling as well as irregular large gaps between the sinusoidal lining cells. There were two hospital deaths in group 1 and none in the other two groups. CONCLUSIONS: Patients implanted with grafts less than 40% of standard liver weight suffered from transient portal hypertension early after reperfusion. The phenomenon was accompanied by intragraft upregulation of endothelin-1 and ultrastructural evidence of sinusoidal damage. The transient portal hypertension after reperfusion, subsequent endothelin-1 overexpression, and plasma nitric oxide level reduction, together with downregulation of heme oxygenase-1 and heat shock protein 70, may account for the small-for-size graft injury.     

小体积肝移植的基础研究进展

目的介绍小体积肝移植术后移植物损伤机理及移植物保护措施。方法复习和总结了相关文献资料并作综述。结果小体积肝移植术后过高的门静脉压力导致移植物机械性损伤,并通过改变肝窦微循环状态及激活各类细胞因子使移植物损伤进一步加重。通过手术或药物的方法降低门静脉压力可对移植物起一定的保护作用。结论了解小体积肝移植术后移植物损伤机理对于临床提高活体肝移植的效果具有积极的意义。     

Hepatic venous outflow reconstruction in adult living donor liver transplants without portal hypertension

Graft congestion is one of the causes of poor graft function in segmental liver transplantation. Three factors are implicated in segmental graft congestion: graft size, hepatic venous outflow and portal inflow. The graft size must be matched to the body weight, which is conventionally done by using graft to body weight ratio. Hepatic blood outflow must be optimized by hepatic vein reconstruction, which can be complicated. High portal blood flow has been shown to be detrimental to small-for-size grafts. These factors are strictly connected to each other. They can all contribute to graft congestion and poor function, while one factor can compensate for the others and decrease congestion. Ideally, all the accessory veins should be reconstructed, if possible, to maximize the outflow. In the absence of portal hypertension and with an adequate sized graft, complex venous reconstruction may not be necessary. We present a case report of an adult living donor liver transplant with the favorable conditions of normal portal pressure and a large sized graft, but complicated by the presence of several accessory hepatic veins. A simple hepatic vein anastomosis was sufficient for adequate outflow and prompt graft function.     

A single-center experience with retrograde reperfusion in liver transplantation

Poor graft function secondary to injury by ischemia and reperfusion remains a major problem with regard to morbidity and mortality in clinical liver transplantation (LTX). Up to one fifth of patients suffer from poor initial liver function due to severe damage to hepatocytes. This situation leads either to primary nonfunction described in approximately 6% of LTX or to slow recovery. We present a new method of reperfusion during LTX. From July 1998 to July 2002, 42 LTX in 39 recipients, (10 female, 52 years old (26–70) were performed. LTX was carried out in piggy-back technique. After completing the piggy-back anastomosis, the caval vein was declamped immediately, and retrograde low pressure reperfusion of the graft with low oxygenated venous blood was established. Portal anastomosis was performed using a running suture. In order to provide optimal retrograde liver perfusion, no clamping of the donor portal vein was done. After completing portal anastomosis, the recipient portal vein was declamped immediately. During arterial anastomosis, the transplanted liver was antegradely perfused via the portal vein. After completing hepatic artery anastomosis, declamping of the hepatic artery was done and arterial perfusion started. No backtable or in-situ-flushing except the described reperfusion technique was performed. Forty-two LTX in 39 recipients using piggy-back technique and retrograde reperfusion via the caval vein followed by antegrade reperfusion via the portal vein were performed; 38 out of 39 patients (97.44%) were alive and well at day 8 after LTX. One patient (2.56%) died of a pre-existing portal vein thrombosis on day 2 after LTX. Three patients had to undergo retransplantation for hepatic artery thrombosis (7.14%). Liver enzymes, bilirubine, prothrombine time and AT III on day 1, 3, 5 and 8 after LTX showed favourable values. Median aspartate aminotransferase (ASAT) was 219 U/l on day 1 after LTX. One-month survival rate was 95.23%, and 1-year survival rate 87.88%. Two patients died of liver-associated causes (5.12%). One patient died of a late hepatic artery thrombosis, and one more of rejection. No other severe case of rejection appeared. We can conclude that retrograde reperfusion might be highly sufficient method of removing perfusion fluid from the transplanted liver. Low pressure perfusion with low oxygenated blood might reduce the production of free oxygen radicals. Retrograde reperfusion via the caval vein and antegrade reperfusion via the portal vein seemed to lower postoperative liver enzyme values and to improve initial liver function after LTX.     

采用不含肝中静脉的右半肝行成人间活体肝移植

目的探讨采用不含肝中静脉的右半肝行成人间活体肝移植的可行性及安全性。方法2002年1月至2005年8月,我院施行了16例成人间右半肝活体肝移植,术中采用了不含肝中静脉的右半肝移植物,同时进行了一系列改良的手术技术包括肝右静脉的重建,右肝下静脉的重建,肝中静脉分支的搭桥等改进。结果全组供者无严重并发症及死亡。前2例受者中,1例发生肝静脉吻合口狭窄,1例因发生小肝综合征,死于肝功进行性恶化。后14例受者中发生并发症5例:急性排斥反应,肝动脉栓塞,胆漏,左膈下脓肿及肺部感染各1例;1例再移植术后肺部感染死于MODS。14例中除肝右静脉与下腔静脉(IVC)直接吻合外,其中5例加行右肝下静脉重建,另5例采用自体大隐静脉搭桥行肝中静脉分支与IVC重建,保证了右肝的流出道通畅。移植物与受者重量比(GRWR)为0.72%~1.15%,11例<1.0%,其中2例<0.8%,无小肝综合征发生。结论采用了改进的手术技术,特别是肝静脉流出道的充分重建可有效的避免小肝综合征,从而使采用不含肝中静脉的活体右半肝移植成为安全可靠的手术方式。     

How transplant surgeons can overcome the inevitable insufficiency of allograft size during adult living-donor liver transplantation: strategy for donor safety with a smaller-size graft and excellent recipient results

Small-for-size grafts are an issue in liver transplantation. Portal venous pressure (PVP) was monitored and intentionally controlled during living-donor liver transplantation (LDLT) in 155 adult recipients. The indocyanine green elimination rate (kICG) was simultaneously measured in 16 recipients and divided by the graft weight (g) to reflect portal venous flow (PVF). The target PVP was <20 mmHg. Patients were divided by the final PVP (mmHg): Group A, PVP < 12; Group B, 12 ≤ PVP < 15; Group C, 15 ≤ PVP < 20; and Group D, PVP ≥ 20. With intentional PVP control, we performed splenectomy and collateral ligation in 80 cases, splenectomy in 39 cases, and splenectomy, collateral ligation, and additional creation in five cases. Thirty-one cases received no modulation. Groups A and B showed good LDLT results, while Groups C and D did not. Final PVP was the most important factor for the LDLT results, and the PVP cutoffs for good outcomes and clinical courses were both 15.5 mmHg. The respective kICG/graft weight cutoffs were 3.5580 × 10(-4) /g and 4.0015 × 10(-4) /g. Intentional PVP modulation at <15 mmHg is a sure surgical strategy for small-for-size grafts, to establish greater donor safety with good LDLT results. The kICG/graft weight value may have potential as a parameter for optimal PVF and a predictor for LDLT results.     

改进成人间活体供肝移植的手术技术

目的研究并改进成人间活体供肝移植的手术技术。方法自2002年1月至2005年8月,施行了16例成人间活体右半供肝移植。手术中改进了技术,包括右肝静脉重建、肝中静脉分支搭桥、肝动脉搭桥及胆道吻合等。结果所有供者均无严重并发症及死亡。移植肝与受者重量比（GRWR）为0．72％～1．24％,其中9例〈1．0％,2例〈0．8％。手术除了采用移植肝的右肝静脉与受者下腔静脉（IVC）直接吻合外,5例加行右肝下静脉重建、5例取自体大隐静脉行肝中静脉分支与IVC间搭桥,保证了右肝流出道通畅。最早手术的2例受者中,1例发生肝静脉吻合口狭窄,另1例发生小肝综合征,最终导致死亡。后阶段手术的14例受者均未发生小肝综合征;发生并发症5例,分别为急性排斥反应、肝动脉栓塞、胆漏、左膈下脓肿及肺部感染;1例再次肝移植后因肺部感染,多器官功能衰竭（MOF）死亡。结论活体供肝移植中采用改进的手术技术,特别是肝静脉流出道重建的方法,可有效避免发生小肝综合征。