Pre‐operative trans‐catheter arterial chemo‐embolization increases hepatic artery thrombosis after liver transplantation – a retrospective study

Little is known about nonsurgical risk factors for hepatic artery thrombosis (HAT ) after liver transplantation (LT ). We determined risk factors for HAT occurring within 90 days post‐LT and analysed the effect of HAT on graft and patient survival. Donor and recipient demographics, surgery‐related data and outcome in transplants complicated by thrombosis (HAT +) and their matched controls (HAT ?) were compared. Risk factors were assessed by univariate logistic regression. Median (IQR ) is given. A total of 25 HAT occurred among 1035 adult LT (1/1997–12/2014) and 50 controls were manually matched. Donor and recipient demographics were similar. Pre‐LT trans‐catheter arterial chemo‐embolization (TACE ) was more frequent in HAT + (HAT + 20% vs. HAT ? 4%, P = 0.037). HAT + had longer implantation [HAT + 88 min (76–108) vs. HAT ? 77 min (66–93), P = 0.028] and surgery times [HAT + 6.25 h (5.18–7.47) vs. HAT ? 5.25 h (4.33–6.5), P = 0.001]. Early graft dysfunction and sepsis were more frequent in HAT + and hospitalization longer. TACE had the greatest odds ratio in unadjusted analysis (OR : 6, 95% CI : 1.07–33.53, P = 0.03). All but seven grafts were lost after HAT (HAT + 72% vs. HAT ? 36%, P = 0.003); however, patient survival was unaffected (HAT + 79.8% vs. HAT ? 76%, P = 0.75). LT candidates undergoing TACE are at risk of developing HAT early after transplant.     

Prognostic value of enzymatic liver function for the estimation of short‐term survival of liver transplant candidates: a prospective study with the LiMAx test

LiMAx has been recently proposed as a new quantitative liver function test. Thus, we aimed to evaluate the diagnostic ability of LiMAx to assess short‐term survival in liver transplant candidates and compare its performance to the model for end‐stage liver disease (MELD) and indocyanine green plasma disappearance rate (ICG‐PDR). Liver function of 167 chronic liver failure patients without hepatocellular carcinoma was prospectively investigated when they were evaluated for liver transplantation. Primary study endpoints were liver‐related death within 6 months of follow‐up. Within 6 months of follow‐up, 18 patients died and 36 underwent liver transplantation. Median LiMAx results on evaluation day were significantly lower in patients who died (99 μg/kg/h vs. 55 μg/kg/h; P = 0.024), while median ICG‐PDR results did not differ within both groups (4.4%/min vs. 3.5%/min; P = 0.159). LiMAx showed a higher negative predictive value (NPV: 0.93) as compared with ICG‐PDR (NPV: 0.90) and the MELD (NPV: 0.91) in predicting risk of death within 6 months. In conclusion, LiMAx provides good prognostic information of liver transplant candidates. In particular, patients who are not at risk of death can be identified reliably by measuring actual enzymatic liver function capacity.     

Hepatic artery thrombosis and intraoperative hepatic artery flow rates in adult orthotopic liver transplantation

Introduction: Thrombosis of the hepatic artery following orthotopic liver transplantation (OLT) can be a devastating com­plication impacting on recipient outcome. The utility of routine intraoperative flow measurements of the hepatic artery in predicting subsequent hepatic artery thrombosis (HAT) is presented in this study. Methods: Data on all adult OLT recipients between July 1995 and May 2000 were analysed. This included the routine intra­operative flow measurements of both the hepatic artery and portal vein using a Doppler flow meter. Results: Thirteen out of 198 (6.6%) instances of OLT were complicated by HAT. The mean and median flow rates of the hepatic artery in the OLT with HAT were 262 mL/min and 220 mL/min, respectively. These were significantly lower than the respective values of 436 mL/min and 400 mL/min in the OLT without HAT (P = 0.0036). This was independent of recipient age, sex, weight and intraoperative portal flow rates. However there was extensive overlap for the intraoperative hepatic artery flow rates obtained between the HAT and non‐HAT groups. The risk of HAT was increased by a factor of 6 if the intraoperative hepatic artery flow rate was less than 200 mL/min. The average allograft survival was significantly lower in the HAT group at 373 days vs the non‐HAT group at 763 days (P = 0.026). Conclusion: The routine use of intraoperative flow measurements of the hepatic artery may be a useful adjunct in identifying the hepatic artery reconstruction, which is at risk of subsequent HAT.     

The impact of meticulous management for hepatic artery thrombosis on long‐term outcome after pediatric living donor liver transplantation*

Abstract: To analyze the risk factors in the development of hepatic artery thrombosis (HAT) and assess the impact of our perioperative management for HAT on the long‐term outcome after pediatric living donor liver transplantation (LDLT), we reviewed 382 patients under 12 yr of age who underwent 403 LDLT from January 1996 to December 2005. One‐ and 10‐yr patient survival rates were 78% and 78% in the patients with HAT (27 patients; 6.7%), and 84% and 76% in the patients without HAT, respectively (p = n.s.). Univariate analysis showed gender (female), body weight (lower), and graft‐to‐recipient weight ratio (higher) were significant risk factors in the patients with HAT (p < 0.05). Patients with Doppler ultrasound signal loss of the hepatic artery (HA) accompanied by an increase of liver enzymes underwent thrombectomy and reanastomosis (S‐group, n = 13), and patients with a weak HA signal underwent anticoagulant therapy (M‐group, n = 13). One patient underwent re‐LDLT. One‐ and five‐yr patient survival rates were 83% and 83% in the S‐group, and 77% and 77% in the M‐group (p = n.s.). The incidence of biliary complications in the S‐group (58%) was significantly higher than that of the M‐group (15%). For a successful long‐term outcome, the early detection of HAT and prompt medical and surgical intervention are crucial to minimize the insult of HAT.     

Hepatic effects of an open lung strategy and cardiac output restoration in an experimental lung injury

Background: Ventilation with high positive end‐expiratory pressure (PEEP) can lead to liver dysfunction. We hypothesized that an open lung concept (OLC) using high PEEP impairs liver function and integrity dependent on the stabilization of cardiac output. Methods: Juvenile female Pietrain pigs instrumented with flow probes around the common hepatic artery and portal vein, pulmonary and hepatic vein catheters underwent a lavage‐induced lung injury. Ventilation was continued with a conventional approach (CON) using pre‐defined combinations of PEEP and inspiratory oxygen fraction or with an OLC using PEEP set above the lower inflection point of the lung. Volume replacement with colloids was guided to maintain cardiac output in the CON(V+) and OLC(V+) groups or acceptable blood pressure and heart rate in the OLC(V?) group. Indocyanine green plasma disappearance rate (ICG‐PDR), blood gases, liver‐specific serum enzymes, bilirubin, hyaluronic acid and lactate were tested. Finally, liver tissue was examined for neutrophil accumulation, TUNEL staining, caspase‐3 activity and heat shock protein 70 mRNA expression. Results: Hepatic venous oxygen saturation was reduced to 18 ± 16% in the OLC(V?) group, while portal venous blood flow decreased by 45%. ICG‐PDR was not reduced and serum enzymes, bilirubin and lactate were not elevated. Liver cell apoptosis was negligible. Liver sinusoids in the OLC(V+) and OLC(V?) groups showed about two‐ and fourfold more granulocytes than the CON(V+) group. Heat shock protein 70 tended to be higher in the OLC(V?) group. Conclusions: Open lung ventilation elicited neutrophil infiltration, but no liver dysfunction even without the stabilization of cardiac output.     

Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End‐Stage Liver Disease Exception Scores

Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End‐Stage Liver Disease exception scheme for retransplantation. Early relisting (E‐RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L‐RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E‐RL group, 372 [9.5%] in the L‐RL group). The E‐RL and L‐RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L‐RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3‐ to 12‐mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L‐RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS.     

成人肝移植术后早期肝动脉血栓形成的诊断与治疗

目的 探讨成人肝移植术后肝动脉血栓形成(hepatic artery thrombosis,HAT)的诊断与治疗,及其对患者预后的影响.方法 2007年6月至2010年10月我中心共实施成人尸体肝脏移植387例.术后采用床边彩色多普勒超声监测移植肝血流.疑有肝动脉血栓形成时,采用超声造影或肝动脉造影明确诊断,根据病情采用介入溶栓治疗、手术再血管化治疗及再次肝移植等治疗.结果 387例中术后共有10例患者发生HAT,发生率2.6％.发生HAT的中位时间为肝移植术后7(范围2～18)d.2例采用介入溶栓治疗,其中1例伴肝动脉狭窄放置支架,均痊愈;3例再次手术行肝动脉重建联合肝动脉局部溶栓治疗,其中1例术后再次出现HAT,死亡;2例行再次肝移植,痊愈;3例出现肝内脓肿,严重感染,肝功能恶化死亡.死亡率为40％(4/10).结论 肝移植术后常规彩色多普勒超声监测肝动脉血流是早期发现HAT的关键,超声造影及肝动脉造影可明确诊断;及时采用介入溶栓、手术再血管化及再次肝移植等治疗虽然可减少患者死亡,但预防HAT发生更为重要.     

肝移植术后肝动脉血栓的处理及预后

目的了解肝移植术后肝动脉血栓（HAT）的处理方法及预后。方法收集2004年至2010年在北京佑安医院肝移植中心施行的427例肝移植病例的临床资料,分析HAT的临床处理方法及预后情况。结果 427例肝移植患者中,共发生HAT5例（1.2%）,发生时间为4～91d（中位时间28d）。经尿激酶介入溶栓、血栓取出、肝动脉重建、再次肝移植及高压氧等治疗后,5例患者中死亡3例。移植物存活时间为8～690d（中位时间298d）,患者存活时间为13～1005d（中位时间298d）。结论肝移植术后HAT发生率较低,但预后极差。一旦确诊及时采用尿激酶介入溶栓、血栓取出、肝动脉重建、再次肝移植及高压氧等治疗,以降低病死率。     

Analysis of risk factors following pediatric liver transplantation

Abstract Several recipient, donor and operation factors as well as postoperative complications related to patient survival after liver transplantation (LT) in children were studied by univariate and multivariate analyses. In a 13‐year period, 103 patients under 15 years of age underwent 120 LT; the mean age was 63 months and 36% were under 2 years of age. Indications for LT were cholestatic disease in 68 (56%), metabolic diseases in 18 (14%), fulminant hepatic failure in 8 (7.5%), cirrhosis in 7 (5.8%), and retransplants in 17 (14%). Whole liver was transplanted in 79% of cases and partial liver in 21 %. Actuarial survival at 1, 5, and 10 years was 70 %, 61 %, and 57 %, respectively. United Network of Organ Sharing (UNOS) I recipients (RR = 2.7), primary non‐function (PNF) (RR = 13.9), and hepatic artery thombosis (HAT) (RR = 3.8) were independent factors for lower patient survival in multivariate analysis. Thus, in our experience, postoperative mortality as a consequence of the patient's condition before transplantation, or complications such as PNF or HAT, are the major causes of decreased survival in pediatric LT.     

活体亲属供肝部分肝移植术后肝动脉的彩色多普勒超声监测

目的探讨应用彩色多普勒超声(CDFI)对亲属活体供肝部分肝移植术后早期监测肝动脉的价值。方法对33例活体供肝部分肝移植术后2周内每日行彩色多普勒超声检查,根据彩色血流及频谱情况判断有无肝动脉血栓形成;6例行动脉造影;所有存活者均进行随访观察。结果经彩色多普勒超声监测发现2例肝动脉血栓(HAT)形成。1例行急诊取栓和肝动脉重建术无效,再次行肝移植后存活(供肝为脑死亡者);另1例发生HAT后,经急诊取栓肝动脉重建术后恢复。结论肝移植术后行彩色多普勒超声监测对早期诊断HAT形成具有重要的价值。     

活体肝移植术后早期肝动脉血栓形成的诊断与治疗

目的探讨活体肝移植术后早期肝动脉血栓形成的诊断与治疗。方法2006年9月至2009年8月天津市第一中心医院单一外科组共实施110例活体肝移植,移植术后7d内每日用彩色多普勒超声(彩超)监测肝动脉血流,怀疑肝动脉血栓形成行肝动脉造影或腹部CT检查,确诊者予介入治疗或手术治疗。结果该组3例术后5～6d发生肝动脉血栓,肝动脉血栓发生率2.7%(3/110)。其中1例再次手术行肝动脉取栓,术后血流正常;2例行介入治疗,放置支架,术后1例再次血栓形成,1例血流流速偏低,2例均发生胆道并发症,但肝功能正常。3例均存活。结论术后早期用彩超监测对肝动脉血栓的诊断至关重要,及时手术取栓或介入放置支架效果良好。     

Experimental study of liver dysfunction evaluated by direct indocyanine green clearance using near infrared spectroscopy.

BACKGROUND: Blood clearance of indocyanine green (ICG) is an objective test of liver function. Hepatic ICG clearance can now be measured directly using near infrared spectroscopy (NIRS). The aim of this study was to evaluate measurement of hepatic ICG clearance by NIRS in an animal model of acute hepatic dysfunction. METHODS: New Zealand white rabbits (n = 36) underwent laparotomy for liver exposure. Hepatic blood flow and microcirculation were measured along with hepatic ICG concentration by NIRS. Hepatic ICG clearance was measured in groups of six animals after reduction of the hepatic blood flow by hepatic artery occlusion and portal vein partial occlusion, lobar ischaemia and reperfusion (I/R), colchicine administration and bile duct ligation. Hepatic ICG uptake and excretion rates were calculated by a non-linear least square curve fitting method from the ICG concentration-time curve. RESULTS: There was a significant positive correlation between hepatic ICG rate of uptake and both hepatic blood flow and microcirculation (r = 0.79, P = 0.0001; r = 0.59, P = 0.005 respectively). I/R resulted in a significant reduction of both the rates of ICG uptake (mean(s.d.) 0. 85(0.59) min-1; P = 0.0002 versus control) and ICG excretion (0. 020(0.006) min-1; P = 0.02 versus control). Colchicine decreased the rate of hepatic ICG excretion (0.030(0.010) min-1; P = 0.02 versus control) as did bile duct ligation (0.002(0.001) min-1; P = 0.01 versus control). CONCLUSION: Measurement of hepatic ICG clearance by NIRS is a promising technique for assessing hepatic parenchymal dysfunction and may have application in liver surgery and transplantation.     

Indocyanine green elimination but not bilirubin indicates improvement of graft function during MARS therapy

Measurement of indocyanine green plasma disappearance rate (PDR(ICG)) has been suggested as a meaningful liver function parameter. However, there are only very limited data concerning its value in the monitoring of graft dysfunction (GDF) and primary non-function (PNF) especially during molecular absorbent recirculating system (MARS) therapy. This study was therefore performed to evaluate the diagnostic accuracy to detect and monitor GDF with the measurement of the PDR(ICG) in direct comparison with conventional markers like bilirubin and prothrombin time (PT). Of the 19 liver recipients, four patients with GDF and two patients with PNF were treated with 38 MARS cycles. Only PDR(ICG) did reliably indicate liver function between patients with GDF/PNF and patients with sufficient graft function who served as controls. Moreover, receiver operating characteristic analysis showed the highest areas under the curve (AUC) for PDR(ICG) (AUC(PDRICG max): 0.840, AUC(PDRICG max): 0.822), followed by bilirubin (AUC(bilirubin): 0.528) and PT (AUC(PT): 0.546). In contrast to the decrease of the serum bilirubin concentration due to MARS, a noticeable improvement of PDR(ICG) was evident only in patients with GDF. Patients with acute fulminant failure and PNF had significantly lower PDR(ICG) values, which did not improve even during continuous MARS treatments. Conclusively, monitoring of PDR(ICG) is superior to bilirubin and PT measurements to determine the graft function especially in patients with PNF and GDF undergoing MARS therapy.     

Intraoperative assessment of reconstructed vessels in living-donor liver transplantation, using a novel fluorescence imaging technique

Background/Purpose In living-donor liver transplantation (LDLT), hepatic arterial thrombosis and portal venous thrombosis are critical problems that can result in graft loss. Only intraoperative Doppler ultrasound (IDUS) is able to evaluate blood flow in the reconstructed vessels. The aim of this study was to evaluate the utility of a newly developed fluorescence imaging technique using indocyanine green (ICG) for visualizing reconstructed vessels. Methods In three patients who had undergone LDLT, IDUS was performed after reconstruction of the portal vein and hepatic artery. Fluorescence images were then recorded, using a SPY system (Novadeq Technologies), which employs ICG as a fluorescent imaging medium activated by light. The ICG (3.75 mg) was injected intravenously, then, 10 s later, the images were recorded for 30 s (first photographic recording). Two minutes later, the same procedure was repeated (second photographic recording), and 40 min later, images were obtained without injection of ICG (third photographic recording). Results After portal venous reconstruction, IDUS demonstrated a nonphasic and continuous waveform, with a mean velocity of 52.1 cm/s and a mean portal blood flow volume of 69.5 ml/s per kg. After hepatic arterial reconstruction, a pulsatile waveform with a mean peak systolic velocity of 52.4 cm/s and a mean resistance index of 0.76 was obtained. The first photographic recording clearly visualized the blood flow in the reconstructed hepatic artery, without kinking or stenosis, in all three patients. The second photographic recording visualized the flow in the portal vein without stenosis, kinking, or stagnation. The third photographic recording demonstrated the excretion of ICG into bile, thus confirming bile production by the grafts. Conclusions Fluorescence imaging can clearly visualize the reconstructed hepatic artery and portal vein and demonstrate the production of bile by a transplanted liver graft. A combination of IDUS and the new system can guarantee the patency of the reconstructed vessels.     

Sevoflurane reduced but isoflurane maintained hepatic blood flow during anesthesia in man

The indocyanine green (ICG) clearance rate (K) and estimated total hepatic blood flow (THBF) were studied by the single injection technique. The THBF was estimated from the calculated circulating blood volume and the fixed extraction rate. The blood concentration of ICG was determined by the finger piece technique. Twenty-seven patients were randomly divided into three groups of nine and received 67% nitrous oxide, 33% oxygen, and the following volatile anesthetics: 0.8% halothane, 1.2% isoflurane, or 1.7% sevoflurane. ICG (0.5 mg·kg⁻¹) was administered intravenously and K was determined three times following the injection. The K value in the halothane and sevoflurane groups decreased significantly 1 h after induction of anesthesia: from 0.188±0.048 to 0.142±0.029 in the halothane group and from 0.178±0.027 to 0.155±0.021 in the sevoflurane group. There was no significant change in the K value in the isoflurane group throughout the study.     

Risk of Hepatic Artery Complications After Liver Transplantation in Patients Who Received Pretransplant Transarterial Chemoembolization Therapy: A Single-Center Experience

BackgroundPretransplant transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hepatic artery thrombosis (HAT) after liver transplantation (LT). Innovative surgical LT and interventional vascular radiology TACE techniques may mitigate the risk of HAT. We sought to investigate the incidence of HAT after LT in patients who received pre-transplant TACE at our center.MethodsWe performed a single-center retrospective review of all LT patients, >18 years of age, from October 1, 2012, to May 31, 2018. Outcomes were compared between patients who received pre-LT TACE and those who did not. Median follow-up was 26 months.ResultsAmong the 162 LT recipients, 110 (67%) patients did not receive pre-LT TACE (Group I), while 52 (32%) received pre-LT TACE (Group II). The <30-day incidence rates of post-LT HAT were as follows: Group I = 1.8% and Group II = 1.9% (P = .9). Most hepatic arterial complications occurred >30 days after LT. Based on competing risks regression analysis, TACE was not associated with an increased risk of HAT. Patient or graft survivals were comparable between the 2 groups (P = .1 and .2, respectively).ConclusionsOur study shows a similar incidence of hepatic artery complications post-LT in patients who received TACE before LT compared with those who did not. In addition, we suggest that the surgical technique of early vascular control of the common hepatic artery during LT, in combination with a super-selective vascular intervention radiology approach, has clinical utility in reducing the risk of HAT in patients requiring pre-transplant TACE.     

33例小儿活体肝移植术肝动脉并发症分析

目的研究小儿活体肝移植手术后肝动脉并发症,分析肝动脉血栓形成(HAT)相关原因及其诊治经验。方法回顾分析上海交通大学医学院附属仁济医院器官移植科自2006年10月至2009年9月所行33例小儿活体肝移植手术相关资料。结果 33例移植患儿均接受亲属左外叶供肝,随访1年。共出现肝动脉栓塞3例(9.1%),2例经DSA溶栓后痊愈。结论小儿活体肝移植术术后发生肝动脉血栓几率较高,使用显微外科技术吻合肝动脉可以降低肝动脉血栓发生率,对可疑患者行肝动脉造影可有效诊断和治疗肝动脉血栓。     

Long‐term,maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case–control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well‐matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.     

The effect of prone positioning with surgical bolsters on liver blood flow in healthy volunteers

This study sought to identify changes in hepatic flood flow and cardiac output during prone positioning on surgical bolsters in awake volunteers, and was prompted by a local incident of significant hepatic dysfunction following surgery in the prone position. Cardiac output was determined using the non‐invasive Peñáz technique, and plasma disappearance rate of indocyanine green (ICG‐PDR) was measured as a surrogate maker for hepatic blood flow along with serum hepatic enzyme assays. Measurements were made after one hour in supine, prone and returned supine positions. Ten volunteers completed the study. There were significant changes in the disappearance rate of indocyanine green, which decreased this from mean (SD) 31.1 (9.70) supine to 19.6 (4.37)%.min prone, respectively (p = 0.02), increasing on return to the supine position to 24.6 (5.54)%.min (p = 0.019). Cardiac output was also significantly reduced when changing from the supine to the prone position, from mean (SD) 4.7 (1.0 to 3.5 (1.1) (l.min^?1), respectively (p = 0.002). We demonstrated an acute and reversible change in both hepatocellular function and cardiac output associated with the prone position.