小儿肝移植的探讨

目的本研究探讨肝移植治疗小儿终末期肝病的方法和疗效。方法我院分别于2001年11月至2002年12月对7例患儿(先天性胆道闭锁5例，先天性肝纤维化1例和肝脏血管内皮肉瘤1例)进行肝移植术，患儿年龄6个月至12岁。其中亲体部分肝移植术两例，供体分别为患儿的母亲和父亲。手术分别切取供体的右半肝和左外侧叶。受体行保留下腔静脉的全肝切除术，然后将供肝进行原位移植。减体积肝移植3例，取左半肝和左外侧叶为移植物。割离式肝移植2例，分别取左外后叶和右后叶为移植物。结果7例患儿分别移植肝重260～565g，亲体肝移植的两例供体随访14～15个月，均无并发症健康生活。接受移植的7例患儿中6例术后已经分别健康存活15～1个月，1例于术后第5天死于心功能衰竭。结论肝移植是治疗小儿终末期肝病的有效方法，术前准确的血管影像学检查，严格的围手术期管理特别是精确的手术技术是小儿肝移植成功的关键。     

Liver transplantation in children.

Although liver transplantation is now accepted as the ideal therapy for end-stage liver disease, relatively few centers have gained a large experience in children, and good results have been elusive. Technical difficulty and a high incidence of graft failure are among the obstacles to success. At the University of California at Los Angeles, 39% of our liver transplants are in the patients who are younger than 18 years. We have analyzed our experience with 103 patients to emphasize factors important to a favorable outcome with the procedure. One hundred twenty-three transplants were performed in 103 children (mean age, 5.2 years; 48% younger than 3 years). No reduced-size grafts were used. Scrupulous attention to technical details of the vascular reconstruction, including frequent use of the supraceliac aorta of the recipient and interrupted suture techniques, ensured construction of sound hepatic artery and portal vein anastomoses at the first operation. Preoperative exchange transfusions were used if the prothrombin time was prolonged beyond 7 seconds, resulting in an average blood loss of only 3.3 volumes. Cyclosporine dosage was maintained in the high therapeutic range for the first 4 weeks, and anti-T-cell antibody (OKT3) was used for rejection (38%). Amphotericin prophylaxis was used for biliary atresia patients with multiple previous operations. Eighty-two of one hundred three patients (80%) are alive. There were no intraoperative deaths. Actuarial survival rates at 6 months, 1 year, and 5 years are 80%, 79%, and 77%, respectively. Survival of patients who underwent transplantation at age less than 1 year is 65% versus 85% at age more than 1 year (p = 0.08). Retransplantation was performed in 19 patients (18%), with a survival rate of 58%. Hepatic artery thrombosis, the most frequent technical complication, occurred in only 16 patients (13%). Survival rates of ABO identical-match versus nonidentical-match grafts were 96% and 60%, respectively (p = 0.02). Graft survival was only 47% if more than one steroid cycle was needed, compared to 75% survival with OKT3 treatment. Despite impairment of renal function (glomerular filtration rate [GFR] less than 80 cc/kg/min) in 54% of patients and hypertension requiring therapy in 27%, 90% of the children demonstrated enhancement of growth, development, and functional status. The following conclusions were made. (1) Pediatric liver transplantation is the treatment of choice for all types of end-stage liver disease and should be considered early. (2) Factors that enhance survival include technical precision, aggressive retransplantation, antifungal chemoprophylaxis and therapy, and judicious immunosuppression with use of OKT3 for rejection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Postoperative morphine consumption in children with sickle-cell disease

BACKGROUND: Effective pain control is a primary goal in the perioperative management of patients with sickle-cell disease. To understand analgesic requirements better, the authors compared postoperative morphine consumption and pain scores in sickle and non-sickle children who had undergone laparoscopic cholecystectomy. METHODS: We reviewed the medical records of all sickle and non-sickle children referred to the Acute Pain Service of a tertiary care teaching hospital for patient-controlled analgesia (PCA) following laparoscopic cholecystectomy from 1996 to 2003. Data collected included postoperative morphine consumption, visual analogue pain scores, and perioperative outcome. RESULTS: Total postoperative morphine consumption in sickle children (n = 12) (1.58 +/- 0.78 mg.kg(-1)) was more than double when compared with non-sickle children (n = 10) (0.65 +/- 0.32 mg.kg(-1)) (P < 0.005). Duration of PCA use among sickle children (51 +/- 25 h) was more than double when compared with non-sickle children (21 +/- 11 h) (P < 0.005). Sickle patients had greater pain scores in the initial 24 h after surgery (P < 0.05) and used more adjuvant analgesics (P < 0.05). Duration of postoperative hospital stay was 3.4 +/- 1.6 days and 1.5 +/- 0.5 days for sickle and non-sickle children, respectively (P < 0.005). CONCLUSIONS: Sickle children self-administered more than double the amount of morphine, reported more intense pain, and remained hospitalized for more than twice as long as nonsickle children undergoing the same surgical procedure. These findings probably have a multifactorial origin, and might be attributable in part to alterations in pain perception, opioid pharmacokinetics, opioid tolerance, and psychosocial variables.     

Liver cell transplantation in children

Abstract:  With increasing shortage of donor organs and changes in organ allocation systems, there is a considerable need for alternative or supportive techniques in the field of liver transplantation. Liver cell transplantation (LCT) is such an innovative technique that is especially promising for use in children, because it is less invasive than orthotopic liver transplantation (OLT). Two main indications exist: acute liver failure (ALF) and hepatic-based inborn errors of metabolism. Ten children with ALF underwent LCT so far. One patient recovered without OLT, five were successfully bridged to OLT, and four died. Clinical improvement like reduced hyperammonemia, improved coagulation, and regression of hepatic encephalopathy occurred in the majority of patients. For the treatment of inborn errors of metabolism, experience exists with Crigler–Najjar syndrome type 1 (CNS 1, n = 5) and urea cycle disorders (UCD, n = 6). All but two patients experienced metabolic stabilization for a mean period of 9.7 months, before the majority of children underwent OLT. Whereas transplant success in CNS 1 patients can be easily monitored by plasma bilirubin levels, it is much more difficult in UCDs, where many factors can contribute to clinical deterioration. Nevertheless, these individual therapeutic attempts of LCT yielded encouraging results, and prospective studies should be initiated.     

Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults

Arnon R, Annunziato R, Schilsky M, Miloh T, Willis A, Sturdevant M, Sakworawich A, Suchy F, Kerkar N. Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults.
Clin Transplant 2011: 25: E52–E60. © 2010 John Wiley & Sons A/S. Abstract: Liver transplantation (LT) is lifesaving for patients with Wilson disease (WD) presenting with fulminant hepatic failure (FHF) or chronic liver disease (CLD) unresponsive to treatment. Aim: To determine the outcome of LT in pediatric and adult patients with WD. Methods: United Network for Organ Sharing data on LT from 1987 to 2008 were analyzed. Outcomes were compared for patients requiring LT for FHF and CLD after 2002. Multivariate logistic regression was used to determine risk factors for death and graft loss. Results: Of 90 867 patients transplanted between 1987 and 2008, 170 children and 400 adults had WD. The one‐ and five‐yr patient survival of children was 90.1% and 89% compared to 88.3% and 86% for adults, p = 0.53, 0.34. After 2002, 103 (41 children) were transplanted for FHF and 67 (10 children) for CLD. One‐ and five‐yr patient survival was higher in children transplanted for CLD compared to FHF; 100%, 100% vs. 90%, 87.5% respectively, p = 0.30, 0.32. One‐ and five‐yr patient survival was higher in adults transplanted for CLD compared to FHF; 94.7%, 90.1% vs. 90.3%, 89.7%, respectively, p = 0.36, 0.88. Encephalopathy, partial graft, and ventilator use were risk factors for death by logistic regression. Conclusion: LT is an excellent treatment option for patients with WD. Patients transplanted for CLD had higher patient survival rates than patients with FHF.     

Liver transplantation for alcoholic liver disease.

BACKGROUND. Alcoholism is the leading cause of end-stage liver failure in the United States, but the application of liver transplantation to the treatment of alcoholic liver disease remains controversial because of medical and ethical concerns. Information about the outcome of patients who undergo transplantation for alcoholic cirrhosis would help to resolve these concerns. METHODS. The results of 41 patients (Group 1) with alcoholic liver disease were compared with those of patients who underwent liver transplantation for other medical problems (group 2) at this center. Thirty of the 32 survivors from group 1 and 30 matched subjects from group 2 were interviewed to assess substance dependence, recidivism, and activity level. RESULTS. Compared with control subjects, patients with alcoholic liver disease had equivalent patient and graft survival rates and achieved an equal level of postoperative health. These results were achieved even though patients with alcoholic liver disease had significantly worse liver failure and more morbidity before surgery, and one third of the patients in this group were not abstinent before transplantation. CONCLUSIONS. We conclude that patients with alcoholic liver disease merit equal consideration for liver transplantation compared with other causes of liver failure. Treatment of the addictive disorder should be included before and after surgery.     

Liver transplantation in infants and children

Orthotopic liver transplantation has become an accepted form of therapy for advanced liver disease. Over a 44-month period, we performed 27 liver transplants in 25 pediatric recipients, including 14 infants (mean age, 7.2 months; mean weight, 5.9 kg) and 11 children (mean age, 9.0 years; mean weight, 34.8 kg). Indications for transplantation were biliary atresia (16), tyrosinemia (3), chronic hepatitis with cirrhosis (2), fulminant hepatic failure (2), and one patient each with Wilson's disease and primary hepatoma. Eighteen patients (72%) had undergone a previous laparotomy, including 19 Kasai procedures in 13 patients with biliary atresia. The average time on the waiting list was 26.8 days (range, 1 to 60), and no patients died while awaiting transplantation. Mean preservation time was 6.9 hours (range, 2 to 13.5), employing cold storage with Collin's solution (16), or more recently, UW solution (11). Urgent liver transplantation was performed in seven cases (25.9%), although at present, we perform liver transplantation as a scheduled semielective procedure with extended preservation times in stable patients. The recipient hepatectomy and orthotopic liver transplantation were performed by standard techniques, with venous bypass used in three cases. Biliary reconstruction was performed with a Roux limb in 16 and via choledochocholedochostomy in ten cases, while arterial reconstruction was end-to-end hepatic artery in 21, and aorto-aortic anastomosis in the remaining six. Two hepatic artery thromboses (7.4%) and two biliary complications (7.4%) occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Liver transplantation for severe hepatic graft-versus-host disease in two children after hematopoietic stem cell transplantation

Chronic graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). After the skin, the liver is the second, most frequent target of GVHD, which presenting with hyperbilirubinemia, elevated liver enzymes, and coagulopathy. Progressive destruction of small intrahepatic bile ducts causes vanishing bile duct syndrome and leads to end-stage liver disease. We report 2 successful cases of orthotopic liver transplantation performed in children with severe GVHD after hematopoietic stem cell transplantation from a matched unrelated donor (HSCT-MUD).     

Liver transplantation in children with progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is caused by mutations of the bile salt export pump or the multidrug resistance P-glycoprotein, resulting in chronic hepatic failure. Partial external diversion of bile or ileal bypass is effective in some cases and, in others, liver transplantation (OLT) is necessary. Forty-two children were included in this study. Twenty-six children suffered from PFIC type 2 and 16 from PFIC type 3. Symptoms included pruritus, cholestasis, liver cirrhosis, and growth retardation. Seventeen patients received external biliary diversion. Ten had to undergo OLT in the following course. As of this report, three of the remaining patients were on the wait list for OLT. Twenty-three children received a liver graft primarily with excellent outcome. Our data show that OLT is the option of choice in symptomatic PFIC and whenever liver cirrhosis is present. We suggest a very restrictive recommendation of external biliary diversion. However, gene therapy may be a future option for children with PFIC.     

Liver transplantation with monosegments.

BACKGROUND: Shortage of size-matched pediatric donors led to the development of surgical techniques to reduce or split livers and thus increase the potential pool of donors. Despite this, neonatal transplantation remains a problem because of the small size of the recipients. Further reduction of the left lateral segment is possible to provide a single segment graft (segment III). We report our experience of transplanting 6 babies using this technique. METHODS: Of 310 children transplanted in our center between October 1989 and March 1998, 6 patients, 2 male and 4 female, median age 37.5 days (range 5 to 92 days), median weight 3.45 kg (range 2.45 to 5.46 kg) were transplanted with a monosegment. The cause of liver failure was neonatal hemochromatosis in 4, retransplantation for hepatic artery thrombosis in 1, and hepatitis B in one. The donor liver was reduced or split to a left lateral segment. Segment II was then resected and discarded before transplantation. RESULTS: Overall, graft and patient survival is 83.3%. Five patients are alive with good graft function at a mean follow-up of 30.4 months (range 8 to 82 months). One child who was transplanted for hepatic artery thrombosis died from sepsis and multiorgan failure 48 hrs after transplant. None of the survivors had vascular or biliary complications. CONCLUSIONS: Monosegment liver transplantation with segment III appears to be a satisfactory option for treating small babies with liver failure.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Liver transplantation in children. Blood transfusion and metabolic disorders

Metabolic disorders during hepatic transplantation can be partly induced by blood transfusion. A retrospective survey of perioperative biological data recorded in patients under 18 years of age having liver transplantation was performed. Blood transfusion was also studied. For this evaluation, patients were divided in a paediatric group I (n = 20; mean age: 3.7 years) and an adolescent group II (n = 11; mean age: 14.3 years). Blood transfusion was significantly (p less than 0.05) more important in group I (302 +/- 286 ml X kg-1) than in group II (148.5 +/- 156 ml X kg-1). Autotransfusion of washed red cells was performed in six patients, allowing a mean 17 +/- 7% saving in blood transfusion. Severe hypernatraemia over 152 mmol X l-1 due to blood transfusion was observed only in five patients in group I. Hyperglycaemia increasing till the revascularization of the new liver was constant in both groups, but significantly more pronounced in group II. Cardiac arrest occurred twice in group I at initial revascularization. In group I, children with biliary atresia were not significantly different from the others for the duration of operation and the volume of blood transfusion; however the latter was more abundant. Conversely, in group II, the duration of operation was longer (p less than 0.05) in patients with previous abdominal surgery than in others. Finally the paediatric group differs from the adolescent group by obvious differences in anaesthesia and intensive care and specifically in hepatic transplantation by larger volume of blood transfusion leading to severe hypernatraemia. In further studies, adolescents should be distinct from the paediatric group and included in the adult group.     

Successful liver transplantation in a patient with sickle-cell anaemia

Liver transplantation in the setting of sickle-cell anaemia poses several new challenges to the transplant team. Hypoxaemia, acidosis and a decrease in body temperature are common occurrences that can cause sickling in the peri-operative period, putting the patient at risk of sickle-cell crises or graft dysfunction. We describe a patient with sickle-cell anaemia who successfully underwent transplantation, and we discuss the rationale of various precautions that had to be taken.