儿童肝移植

Pediatric liver transplantation has long been developed in the western world.Currently,favorable outcomes after liver transplantation have been achieved in pediatric recipients and the postoperative 5-...     

Pediatric liver transplantation for primary hepatocellular carcinoma associated with hepatitis virus infection

We report two cases of early primary hepatocellular carcinoma (PHC) in children, after probable maternal transmission of hepatitis B, that were treated with orthotopic liver transplantation (OLT). Both children were 8.5 years old and had elevated levels of serum alpha-fetoprotein. The diagnosis of PHC was made at 8 years and confirmed histologically. Serum hepatitis B surface antigen (HBs Ag) was detected in the mothers and suggested vertical transmission. An attempt at complete liver tumor resection failed, leading to OLT. In order to prevent recurrence of the hepatitis B virus (HBV) infection, hepatitis B immunoprophylaxis was used. Two years after OLT, one child presented with recurrent HBV infection. No tumor recurrence was observed at follow-up in either of the patients. From these two cases we conclude that (1) HBV infection may play an important causal role in PHC in children, with an even shorter incubation period than that in adults; (2) close follow-up is needed for children who are HBs Ag-positive carriers; and (3) liver transplantation should be proposed early after the diagnosis of PHC, when tumor resection is not feasible.     

Arterial steal: an unusual cause for hepatic hypoperfusion after liver transplantation

Case reports of two patients with an unusual cause for a rapid increase in transaminases following liver transplantation are described. In the postoperative course, angiography revealed an arterial, hypoperfusion of the liver due to a steal phenomenon with blood shunting from the hepatic to the splenic artery. In one case, the underlying pathophysiology was a pre-existing filiform stenosis of the celiac trunk with insufficient recruitment of arterial blood from the superior mesenteric artery via the pancreatic arcade. Adequate liver perfusion was restored by simple ligation of the common hepatic artery. In the other case, angiography showed an arteriovenous fistula formation of the splenic vessels and minimal blood flow through the hepatic vessels. This was successfully corrected by angiographic embolization of the splenic artery with metal coils. After therapeutic intervention, both patients rapidly recovered with excellent liver function.     

Combined liver and kidney transplantation

Patients with end-stage renal and hepatic failure may be treated with combined liver and kidney transplantation (CLKTx). We reviewed the indications and outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and 1994. The majority of the recipients (87.5%) were young patients affected by congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen were treated with cyclosporin-based immunosuppression and had an excellent outcome: with an average of 6 years of follow-up, patient survival was 85.7%, liver graft survival 85.7%, and kidney graft survival 72%. The incidence of rejection episodes was similar to the rate of rejection in our solitary kidney and liver transplants. In conclusion, our experience supports the value of CLKTx in treating patients with simultaneous failure of both organs or with congenital enzymatic hepatic deficits leading to renal failure.     

Conversion from cyclosporin to FK 506 after liver transplantation

Thirty-seven liver-grafted patients with steroid-resistant acute or chronic graft rejection or with cyclosporin-related complications were converted from CyA to FK 506. The clinical outcome of the patients primarily depended on the degree of liver dysfunction present at initiation of FK 506 treatment. In patients switched to FK 506 for treatment of acute or early chronic graft rejection, CyA nephrotoxicity, or CyA malabsorption, the FK 506 therapy was associated with a clear improvement in the clinical course. In contrast, in patients with advanced chronic graft rejection, a lower response rate to the conversion in immunosuppression was observed. The lower response rate was associated with a higher patient mortality. These studies demonstrate that FK 506 represents a valuable alternative immunosuppressant for liver-grafted patients. The conversion from CyA to FK 506 should take place before serious — and potentially irreversible — disturbances in liver function are observed.     

大鼠心脏停搏供体肝移植的实验研究

目的 探讨大鼠原位肝移植过程中,供肝可能耐受心脏停搏热缺血损伤的时间极限,方法 雄性SD大鼠,以供肝获取前供体大鼠经历心脏停搏时间0、15、30、45、60min分为5组（HB组、N-15组、N-30组、N-45组和N-60组）,而后行大鼠原位肝移植,比较各组的术后肝功能、肝脏病理和存活率。结果 HB、N-15、N-30、N-45和N-60的大鼠肝移植术后1周存活率分别为：100%（8/8）、75%（6/8）、62.5%(5/8)、25%（2/8）和0%（0/8）。其中HB、N-15、N-30组和N-45组的大鼠肝移植最长存活时间超过30d。结论 大鼠供肝对于热缺血损伤的时间应越短越好,但耐受30min心脏停搏热缺血损伤时,仍可使1周存活率达62.5%,极限时间为45min。     

Reduced size liver transplantation,split liver transplantation,and living related liver transplantation in relation to the donor organ shortage

Because of the shortage of cadaveric donors, three techniques of partial liver grarting have been developed. These techniques are placed in perspective in relation to the organ shortage. Reduced size liver transplantation (RSLTx) is widely used and has results comparable to those from whole liver grafting. However, this technique, while benefitting pediatric patients, reduces the adult donor liver pool. It also makes inefficient use of an available adult donor liver. In split liver transplantation (SPLTx), the whole liver is used after bipartition for two recipients. The results are comparable to those of RSLTx. The problem with SPLTx is that it is a very demanding technique applied only in centers with extensive experience with liver resection and reduction. Living related liver transplantation (LRLTx) yields excellent results; however, it places an otherwise healthy person at risk. It is argued that instead of performing risky operations on healthy persons, the health authorities should take specific measures to alleviate the organ shortage. In the meantime, SPLTx should be developed further because of its optimal use of donor tissue. As for LRLTx, its excellent results and the present shortage of size-matched pediatric liver donors justify its use, at least for now.     

Loss of speech after orthotopic liver transplantation

Alteration of speech is a rare but distressing complication of orthotopic liver transplantation (OLT). We describe a characteristic speech disorder identified in a large series of consecutive patients undergoing OLT. Between 1988 and 1993, 525 adults underwent OLT. For all recipients with neurologic complications, we reviewed clinical findings, imaging and electrophysiologic test results, and perioperative laboratory data. Five patients (ages 23–52; UNOS status 3–4) exhibited a characteristic pattern of stuttering dysarthria, leading to complete loss of speech production, occasionally with elements of aphasia. In four of the five patients, right-sided focal seizures were subsequently noted. All cases presented within the first 10 postoperative days and improved within 1 month of cessation of cyclosporin (CyA), although halting, monotonous speech was evident to some degree in all five for up to 1 year. There was no correlation between onset of symptoms and CyA levels. None of the patients had clinical or radiologic findings suggestive of central pontine myelinolysis or akinetic mutism. EEGs and Spect scan results were consistent with dysfunction in the left frontotemporoparietal regions of the brain. A characteristic speech disorder, which may be described as cortical dysarthria or speech apraxia, occurs in approximately 1% of adults undergoing OLT. Prompt recognition of this syndrome and temporary cessation of CyA therapy may favorably affect the course.     

Transjugular intrahepatic portosystemic shunt and liver transplantation

Transjugular intrahepatic portosystemic stent shunting (TIPSS) appears to be an attractive, nonsurgical procedure to overcome complications of end-stage liver disease. During the period August 1992 to February 1995, 23 adults who had previously undergone TIPSS received liver transplants. These patients were compared to 36 cirrhotic patients, grafted during the same time period, in relation to the implantation technique, the intraoperative use of blood products, and the length of their hospital stay. These groups were comparable for previous right upper quadrant surgery, splanchnic vein modifications, and Child-Pugh classification. Liver transplantation was performed electively in all TIPSS patients. Ten patients (43.4%) presented with a significant shunt stenosis at a median follow-up time of 4.5 months (range 2.5 to 30 months). At transplantation 8 of the 23 TIPSS patients (34.8%) had specific TIPSS-related modifications i.e., extrahepatic portal vein aneurysm formation (n=2), dislocation of the distal end of the stent into the inferior vena cava (n=4) or into the main portal vein trunk (n=1), bilioportal fistula (n=1), and pronounced phlebitis of the inferior vena cava and hepatic veins due to redilation of shunt stenosis (n=4). The intraoperative blood product requirement at transplantation was similar in the 23 TIPSS-patients and in the 36 cirrhotic patients who received transplants without the TIPSS procedure during the same time period [median 800 ml (range 0–20300 ml) vs median 620 ml (range 0–7600 ml), respectively]. There was also no difference between the two groups in length of hospital stay [median 18 days (range 0–34 days) vs median 19 days (range 0–66 days), respectively]. We conclude that TIPSS plays an important role in the management of life-threatening complications of end-stage liver disease arising in potential liver transplant candidates. TIPSS should be considered as a temporary, effective bridge to elective transplantation and not as a means to lower the blood product requirement at transplantation. Specific TIPSS-related modifications should be recognized early by the transplant surgeon in order to adapt the technique of graft implantation.     

Conversion to tacrolimus after liver transplantation

We have reviewed our experience with conversion to tacrolimus after 435 liver transplantations. Tacrolimus was administered as a rescue agent in 33 patients until October 1993. Indications for rescue therapy were: cholestatic forms of severe, steroid-resistant cellular rejection (n=8), OKT3-resistant cellular rejections (n=6), cellular rejections in patients suffering from cyclosporin malabsorption (n=4), late onset cellular rejections (n=4), early chronic rejections (n=3), and chronic vascular or ductopenic rejections (n=8). Response was evident in 29 of the 33 patients (88%), whereas 4 patients (12%) were nonresponsive. Patient and graft survival were 76% and 70%, respecitively. Graft loss with or without patient death occurred in three of eight patients suffering from severe, steroid-resistant cellular rejection, in two of six patients with OKT3-resistant cellular rejections, and in five of eight patients undergoing chronic rejection. In severe steroid-resistant cellular rejection, successful tacrolimus rescue therapy corresponded to a significantly lower total serum bilirubin than unsuccessful therapy (12.0±5.6 mg% vs 29.7±5.9 mg%, P(0.05). We conclude that tacrolimus rescue therapy is a safe and efficient alternative for high-risk cases that do not respond to conservative treatment. In severe, steroid-resistant cellular rejection and in chronic ductopenic rejection, conversion to tacrolimus is beneficial only in a limited number of cases. A predictive parameter, which total serum bilirubin may prove to be in severe, steroid-resistant cellular rejection, is needed to select those cases that might benefit more from retransplantation than from conversion to tacrolimus.     

A comparative study on changes in hemostasis in orthotopic and auxiliary liver transplantation in pigs

We compared blood loss and hemostasis in pigs which had undergone either orthotopic liver transplantation (OLT) (group A, n=12) or auxiliary heterotopic partial liver transplantation (APLT) (group B, n=11). Blood samples were taken at regular intervals during and after the operations. In both groups, nine animals survived longer than 24 h and data from these animals were used for analysis. Median (range) intraoperative blood loss was 825 ml (250–1500 ml) in OLT and 425 ml (300–750) in APLT (P<0.01). Routine clotting times, as the activated partial thromboplastin time, prothrombin time and thrombin time, showed no major intraoperative changes in either group. Fibrinogen levels decreased in both groups, but no significant difference was found between the two groups. The only significant difference between group A and B was a more sustained increase in fibrinolytic activity after graft recirculation in group A. Post-operatively, restoration of fibrinogen, antithrombin-III and ₂-antiplasmin levels was slightly faster in group B, resulting in significantly higher levels during the first day. We conclude that, in this animal model, APLT is associated with significantly lower blood loss and less severe fibrinolytic activity, than OLT. This difference might result from the lack of an anhepatic period and the reduced surgical trauma in auxiliary heterotopic liver transplantation.     

Orthotopic liver transplantation for hepatic-based metabolic disorders

Between January 1989 and June 1993, a total of 470 liver transplantations were performed at King's College Hospital. Thirty-seven transplantations were performed in 34 patients with liver-based metabolic disease. There were 16 females and 18 males with a median age of 19 years (range 1 month to 62 years). There were 14 patients under 16 years of age. The indications for liver transplantation were Wilson's disease (n=16), alpha 1-antitrypsin deficiency (n=10), tyrosinaemia (n=2), primary hyperoxaluria type 1 (PH1; n=2), congenital haemochromatosis (n=1), familial amyloidotic polyneuropathy (FAP; n=1, familial hypercholesterolaemia) (n=1) and Crigler-Najjar syndrome type I (CNS1; n=1). These included two patients who received combined heart-liver grafts for familial hypercholesterolaemia and FAP, respectively. Two patients received combined liver-kidney transplants for PH1. There were four deaths: from sepsis (n=2), acute hepatic vein obstruction in a left lateral segment graft (n=1) and portal vein thrombosis with liver necrosis (n=1). Three patients were retransplanted, one for chronic rejection and two for hepatic artery thrombosis, giving an overall graft survival of 81% and patient survival of 88% (30/34), at a mean follow-up of 34 months (range 10–64 months).This paper was presented as a poster at the 6th ESOT Congress in Rhodes, Greece in October 1993     

Relevance of a positive crossmatch in liver transplantation

We studied 27 liver transplants in 24 patients performed between November 1984 and January 1988. We investigated retrospectively the importance of donor reactive HLA class I and class II and of non-HLA antibodies for graft survival in these patients. In order to determine the specificity and class of the antibodies, we used monoclonal antibodies to HLA-A,-B,-C and DR and DQ antigens to block cytotoxicity of sera and the reagent dithiothreitol to characterize the immunoglobulin class. We found that humoral immunity to HLA antigens in liver-grafted patients, demonstrable as the presence of cytotoxic antibodies reactive with donor splenic T and/or B cells in the pretransplantation period, is associated with significantly lower graft survival as compared with patients without demonstrable preformed HLA antibodies (P=0.01). In addition we found that a substantial proportion of patients had donor-reactive cytotoxic antibodies which were not HLA specific. Thus, our study shows that HLA immunity can influence liver allograft survival, and that it is useful to have patient cytotoxic antibodies characterized with regard to HLA reactivity prior to transplantation.     

劈离式肝移植

劈离式肝移植术是一种理想的扩大供肝利用和缓解供肝短缺矛盾的方法,可以缩短受者等待时间,降低等待期间患者病死率.劈离式肝移植与全肝移植比较,在供肝及受者选择、移植物血管分配、供肝劈分技术要点及移植物保护等方面的要求更严格,是影响劈离式肝移植效果的关键因素.随着对部分肝移植认识的加深,器官保存技术、外科技术的不断发展,并发症预防手段的进步,劈离式肝移植必将拥有更广泛的发展空间.     

Pediatric liver transplantation in Hong Kong—a domain with scarce deceased donors

Aim

The study aimed to assess the outcome of live-donor liver transplantation for pediatric patients in a region with limited access to deceased donors.

Patients and Methods

From September 1993 to September 2008, 78 pediatric patients aged between 73 days and 17 years (mean, 40 months) received 83 liver transplants. Sixty-two were living-related liver transplantations (LRLTs), and 21 were deceased-donor liver transplantations (DDLTs). The mean follow-up period was 6.5 years. The prospectively collected data of these patients were analyzed retrospectively.

Results

The 1-, 2-, and 5-year survival rates of patients and grafts were 91%, 90%, 88% and 87%, 86%, 83%, respectively. The survival rates of LRLT patients and DDLT patients were 89%, 89%, 87%, and 90%, 86%, 86%, respectively (P = .58). The survival rates of patients aged 12 months or younger and patients older than 12 months were 95%, 92%, 90% and 90%, 90%, 87%, respectively (P = .65). One live donor developed temporary peroneal palsy, and another developed lung collapse (3%, 2/62). All live donors resumed their normal activities with no difficulty.

Conclusion

With meticulous surgical techniques and postoperative care, it is justifiable to accept donated livers from voluntary live donors for transplantation to save pediatric patients in a place with scarce deceased donors.     

Biliary complications in orthotopic liver transplantation: experience with a modified technique of duct-to-duct reconstruction

Biliary complications are described as frequent causes of morbidity during the postoperative course of orthotopic liver transplantation (OLTx), even in recent papers. The authors report here on their experience with duct-to-duct anastomosis as their method of choice for biliary reconstruction in a consecutive series of 100 OLTx in adult patients. The original technique, as described by Starzl, was modified by the authors by performing a wide, longitudinal plasty of both the donor and recipient bile ducts, joined together with two polidioxanone running sutures, producing the effect of a side-to-side anastomosis. This technique was used in all procedures, even when a significant discrepancy was evident between the ducts (n=10). Follow-up was completed in 100% of the patients for a period of 2–40 months (mean 13.1 months). Four major complications (4%) occurred including hepatic abscesses due to ascending cholangitis, T-tube dislocation, partial occlusion by a branch of the T-tube at the anastomotic site, and disruption of the bile duct after T-tube removal. In four other patients, transient abdominal pain followed removal of the stent. Neither strictures nor fistulas were observed. Choledochocholedochostomy on a T-tube stent represents, in our experience, the technique of choice for biliary reconstruction in OLTx. The procedure, as described in the present study, proved to be safe in preventing strictures and leakages and appears to be feasible in nearly 100% of all adult patients undergoing OLTx.     

The intra-operative use of trasylol (aprotinin) in liver transplantation

Aprotinin has been reported to reduce blood loss in difficult cases requiring cardiopulmonary bypass surgery and more recently in liver transplantation. Over a 9-month period were compared the effects of an intra-operative infusion of aprotinin on transfusion requirements and coagulation profiles in 12 patients undergoing liver transplantation for end-stage cirrhosis with an equal number of consecutive transplants in patients with similar pathology who did not receive aprotinin. Transfusion of blood and blood products was reduced to one-third in the aprotinin-treated group. Operative time was also significantly reduced, as was ICU stay post-operatively. Aprotinin profoundly inhibits fibrinolysis and this is likely to be the major effect by which blood loss is reduced. Thromboelastography revealed severe fibrinolytic changes in the anhepatic stage in 4 of 6 controlled patients; this accelerated in 3 following reperfusion of the new graft. By contrast, only 1 patient of 12 in the aprotinin-treated group showed fibrinolytic activity in the anhepatic period, and none showed evidence of fibrinolysis following reperfusion of the new graft.     

Changes in blood ketone body ratio with reference to graft viability after liver transplantation in rats

Arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR), which reflects hepatic mitochondrial redox potential, was measured during a 2-week period after orthotopic liver transplantation in three groups of rats: group 1, the isogenic combination of LEW (RT1¹) graft to LEW recipient as control; group 2, the allogenic combination of ACI (RT1^a) graft to LEW recipient without immunosuppressive treatment; and group 3, the allogenic combination of ACI to LEW with immunosuppressive treatment using cyclosporin (CyA). Isogenic recipients survived indefinitely. Allogenic recipients in group 2 had severe rejection with a mean survival of 10.3±0.54 days, while 77.8% of the allogenic recipients in group 3 survived more than 30 days. KBR of rats surviving more than 2 weeks in groups 1 and 3 gradually increased post-transplantation and was maintained at a high level. By contrast, though KBR in group 2 was restored at 3 days, it gradually fell and remained at a significantly low level (P<0.001). It is suggested that KBR provides an accurate indicator for evaluating metabolic viability of the critically deteriorating liver graft accompanied by severe rejection.     

Analysis of growth in children after orthotopic liver transplantation

Growth after pediatric liver transplantation is an important factor in determining the quality of life. We collected data on height, skeletal age, and liver function of 45 consecutive pediatric transplant recipients and assessed the influence of primary diagnosis, liver function, and immunosuppressive regimen on their growth. Height and skeletal age were plotted as median standard deviation scores versus years post-transplantation. Growth, in terms of both height and skeletal age, were continuous without catch-up growth. Primary diagnosis was found to have no influence on height and poor liver function had a negative effect on both height and skeletal growth. A higher alternate day prednisolone maintenance dose also had a negative effect on skeletal growth. Thus, it can be concluded that a pretransplant lack of growth will not be restored and is an indication for early transplantation in endstage liver disease, especially in younger children.     

Orthotopic liver transplantation in hemophilia B: a case report

Liver transplantation is a treatment modality that is being used with increasing frequency in cases of liver-based metabolic defects. This is a case report of a patient with hemophilia B who was treated since childhood with factor IX replacement for recurrent hemarthroses. Subsequent hepatitis B (HBV) and C (HCV) infection had resulted in the development of chronic active hepatitis, ultimately leading to cirrhosis. Orthotopic liver transplantation performed for endstage liver disease resulted in a rise in factor IX levels from 2% to 83% of normal values within 24 h post-operatively, and levels remained above 90% of normal values after postoperative day 3 without factor IX replacement. To our knowledge, only two cases of hemophilia B treated by orthotopic liver transplantation have been reported. This procedure has, however, only been implemented in cases of terminal liver insufficiency in hemophiliacs.