血液净化在儿童急性肝功能衰竭中的应用

儿童急性肝功能衰竭(ALF)是儿科危重症,病死率高。体外肝脏支持系统包括生物型人工肝、非生物型人工肝和混合型人工肝,它可以为肝功能恢复创造机会或为肝移植治疗等待供肝赢得时间。非生物型人工肝的本质是血液净化,其已被证明可以改善患者的临床生化指标,但对于最终预后的影响不确定。与成人相比,儿科关于ALF的治疗数据较少,但近年来一些新的血液净化模式及组合式血液净化模式在ALF的治疗中显示了潜能,该文旨在介绍血液净化治疗儿童ALF的现状,为其治疗提供参考。     

人工肝支持系统在肝功能衰竭中的应用

肝功能衰竭是多种因素引起的严重肝脏损害,在儿科病因更为复杂且病情凶险,传统的内科综合治疗效果欠佳,病死率高.人工肝支持系统也常称为人工肝,是一种能够替代或模拟正常肝脏的部分或全部功能的体外装置,可以使因肝功能衰竭所产生的各种有害物质得以清除,并替代肝脏的部分代谢功能,以维持患者生命.人工肝应用至今已逾50年,其血液净化方式包括血液透析、血浆置换、血液灌流、吸附、全血或血浆滤过以及应用肝组织或细胞研制的有生物效应的治疗方法等.由于肝脏有强大的再生能力,人工肝可为病变肝脏自身再生恢复或接受肝移植尽可能争取时间.随着人工肝支持系统相关技术的不断完善,非生物型人工肝治疗已在临床广泛应用,并取得很好的疗效,成为各种重症肝功能衰竭的重要治疗手段之一.人工肝在儿科临床也有应用报道,但资料有限,仍需要进一步研究和实践.     

血浆置换联合持续性血液透析滤过治疗小儿急性肝功能衰竭的临床应用

急性肝功能衰竭病因复杂,病情进展迅速,单纯保肝治疗病死率高,是儿科临床危重症。人工肝支持治疗系统是目前治疗急性肝功能衰竭的重要手段,它主要借助一种体外的机械、理化或生物的装置,清除患者体内蓄积的各种有毒物质,暂时替代肝脏的部分代谢、解毒或合成功能,为肝细胞再生及进一步的临床治疗赢得宝贵时间。由于不同血液净化模式的局限性,人工肝支持治疗系统多采用组合式血液净化模式。该文主要对血浆置换联合持续性血液透析滤过治疗小儿急性肝功能衰竭的效果作一综述。     

非生物型人工肝在肝衰竭患儿中的应用

目的 探讨非生物型人工肝支持治疗在肝衰竭患儿中的应用效果.方法 2003年8月-2009年4月在首都医科大学附属北京儿童医院确诊为肝衰竭患儿11例,采用非生物型人工肝支持治疗,包括应用血浆置换、血液灌流、持续血液滤过、血液透析等治疗方法.结果 非生物型人工肝支持治疗过程中并发症少.11例患儿顺利进行了23次血浆置换治疗,7次血液灌流治疗,5次血液透析治疗,3次持续血液滤过治疗(2例治疗顺利,1例在治疗中出现病情恶化、心跳骤停而终止治疗).10例患儿血液净化治疗后临床症状均有不同程度好转,监测血生化各项指标与治疗前比较亦有明显好转.11例获随访,其中2例毒蕈中毒肝衰竭患儿临床治愈出院,其中包括1例多脏器衰竭患儿,随访1 a,肝功能正常;3例病情好转出院;3例病情进展恶化,放弃治疗死亡;3例自动出院.结论 应用以血浆置换治疗为主的非生物型人工肝治疗急慢性肝衰竭患儿,可使患儿临床症状及各项检测指标有不同程度好转,提高患儿存活率.人工肝治疗技术应用于肝衰竭患儿治疗中应注意充分考虑儿童病理生理特点,制定合理的治疗方案,同时采取有效的预防措施和密切的病情监测,以保障治疗的顺利进行.     

人工肝支持系统在肝功能衰竭中的应用

肝功能衰竭是多种因素引起的严重肝脏损害,在儿科病因更为复杂且病情凶险,传统的内科综合治疗效果欠佳,病死率高.人工肝支持系统也常称为人工肝,是一种能够替代或模拟正常肝脏的部分或全部功能的体外装置,可以使因肝功能衰竭所产生的各种有害物质得以清除,并替代肝脏的部分代谢功能,以维持患者生命.人工肝应用至今已逾50年,其血液净化方式包括血液透析、血浆置换、血液灌流、吸附、全血或血浆滤过以及应用肝组织或细胞研制的有生物效应的治疗方法等.由于肝脏有强大的再生能力,人工肝可为病变肝脏自身再生恢复或接受肝移植尽可能争取时间.随着人工肝支持系统相关技术的不断完善,非生物型人工肝治疗已在临床广泛应用,并取得很好的疗效,成为各种重症肝功能衰竭的重要治疗手段之一.人工肝在儿科临床也有应用报道,但资料有限,仍需要进一步研究和实践.

Abstract：

Despite a combination of all available treatment, the mortality of liver failure is very high,especially in children patients. Artificial liver support methods have been tested for over 50 years. Standard techniques of blood purification like hemodialysis, adsorption, hemo or plasma filtration as well as bioreactorbased approaches using liver cells or tissues have been used. It' s believed that the damaged liver has the ability to return to normal. Artificial liver support systems are expected to be useful for temporary support of liver function. If the liver does not regenerate to normal functions, an artificial liver support system may be useful as a bridge to liver transplantation. In conclusion, artificial liver support method appears to be a reliable therapy for advanced liver diseases and has significantly decreased the mortality of liver failure. Artificial liver support system has been used in children patients as well, but it still needs more researches.     

血液净化救治毒蕈中毒患儿的疗效观察

目的 探讨致命毒蕈白毒伞中毒患儿早期血液净化救治的临床效果.方法 对2例急性白毒伞中毒致急性中毒性肝损害的患儿进行内科综合治疗、血浆置换、血浆置换联合血液滤过的相关治疗.监测肝功能、血氨、凝血四项等指标的恢复情况.结果 2例患儿经早期4次全量的血浆置换、血液滤过,可基本清除体内的白毒伞毒素,患儿的肝功能逐渐好转恢复.结论 在综合治疗的基础上,相对轻症病例单用血浆置换,重症病例血浆置换联合血液滤过可降低转氨酶、血氨,取得满意疗效,提高救治成功率.     

血液净化救治毒蕈中毒患儿的疗效观察

目的 探讨致命毒蕈白毒伞中毒患儿早期血液净化救治的临床效果.方法 对2例急性白毒伞中毒致急性中毒性肝损害的患儿进行内科综合治疗、血浆置换、血浆置换联合血液滤过的相关治疗.监测肝功能、血氨、凝血四项等指标的恢复情况.结果 2例患儿经早期4次全量的血浆置换、血液滤过,可基本清除体内的白毒伞毒素,患儿的肝功能逐渐好转恢复.结论 在综合治疗的基础上,相对轻症病例单用血浆置换,重症病例血浆置换联合血液滤过可降低转氨酶、血氨,取得满意疗效,提高救治成功率.     

联合血液净化治疗儿童毒蕈中毒

目的 总结儿童毒蕈中毒的临床特点,评价联合血液净化治疗儿童毒蕈中毒的疗效.方法 对2011年至2013年应用联合血液净化救治的7例重症毒蕈中毒患儿的临床资料进行回顾性研究.结果 5例患儿采用血液灌流＋连续性静静脉血液透析滤过（continuous veno-venous hemodia-lysisfiltration,CVVHDF）方式治疗,经1～2次血液灌流及20～ 54h CVVHDF治疗,各项指标恢复至正常,尿量在停止净化后72 h均恢复正常;2例肝功能衰竭患儿行血浆置换联合CVVHDF方式治疗,经2～3次血浆置换及73～79 h CVVHDF治疗后,生化指标及尿量恢复正常,7例患儿均治愈,住院时间7～22d.结论 联合应用血液净化,充分发挥各自的优点,克服各自的缺点,使大、中、小分子毒素均能得以清除,能极大地提高救治成功率及缩短病程.     

儿童血液净化治疗现况

急性肾功能衰竭(ARF)是儿童中最重要的需要进行血液净化治疗的临床疾病,尽管ARF在儿童并不十分常见,但是其发病率却在逐渐增加.当保守治疗失败时,每种不同的透析治疗方式在ARF的治疗中各有利弊.另外,血液净化治疗也适用于一些其他临床疾病,如透析和血液灌流可用于中毒的治疗,血浆置换、免疫吸附是治疗一些免疫性、代谢性和中毒性急症有效的血液净化技术.     

不阻断肝门肝切除在小儿肝脏肿瘤切除术中的应用

小儿肝脏肿瘤主要以肝母细胞瘤、肝血管瘤、肝错构瘤多见。肝叶切除目前仍是肝脏原发和继发性肿瘤治疗的最佳治疗手段。常规阻断肝门会造成肝脏缺血、回心血量下降，影响肝脏功能恢复和引起血液动力学改变。我们自2001年1月至2007年5月采用不阻断肝门规则性肝切除技术治疗小儿肝脏肿瘤37例，手术肿瘤完整切除率100％，手术期间的死亡率为零，术后无肝功能衰竭，现总结探讨不阻断肝门肝切除的应用。     

Liver retransplantation in children: The Atlanta experience

Heffron TG, Pillen T, Smallwood G, Henry S, Sekar S, Solis D, Casper K, Fasola C, Romero R. Liver retransplantation in children: The Atlanta experience.
Pediatr Transplantation 2010: 14:417–425. © 2010 John Wiley & Sons A/S. Abstract: Liver retransplantation is routinely offered at our institution. Previous reports document that patient and graft survival is significantly less after pediatric rLT compared to primary LT. This has engendered intense debate regarding optimal allocation of organs. Here, we examine our program’s approach to pediatric hepatic retransplantation related to patient factors affecting outcomes. Between 1997 and 2009, 272 LTs were performed in 234 patients (mean survival 1994 ± 1367 days) at our center. Thirty‐four patients required rLT including 10 who received their primary transplant elsewhere and four who required two retransplantations. Patient survival did not differ significantly between rLT and LT at one and three yr (p = 0.56). Graft survival between rLT and LT was also similar (p = 0.606) at one and three yr. No significant difference in graft or patient survival was noted between: Patients retransplanted <30 days after LT vs. those >30 days (p = 0.152); patients transplanted with technical variants vs. whole grafts (p = 0.966); technical variants utilized for LT vs. rLT (p = 0.713); rLT recipient age (< or >5 yr; p = 0.298); or ABOI for rLT and LT (p = 0.650). Retransplantation should be offered to optimize pediatric recipient survival after LT and offers similar survival as primary transplant.     

Pediatric liver transplantation for acute liver failure at a single center: A 10‐yr experience

Heffron TG, Pillen T, Smallwood G, Rodriguez J, Sekar S, Henry S, Vos M, Casper K, Gupta NA, Fasola CG, Romero R. Pediatric liver transplantation for acute liver failure at a single center: A 10‐yr experience.
Pediatr Transplantation 2010:14:228–232. © 2009 John Wiley & Sons A/S. Abstract: Children transplanted for ALF urgently require an optimal graft and have lower post‐transplant survival compared with children transplanted for chronic liver disease. Over 10 yr, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type ABOI, XL (GRWR > 5%), DDSLT, LDLT and WLT were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. Twelve of 33 received ABOI, five XL grafts, 18 DDSLT, and three LDLT. Waiting time pretransplant was 2.1 days. One‐ and three‐yr patient survival in the ALF group was 93.4% and 88.9%, and graft survivals were 86.4% and 77.7%. Median follow‐up was 1452 days. ABOI one‐ and three yr patient and graft survival in the ALF was 91.6% and 78.6%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group or the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, XL grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival comparable to patients with non‐acute disease.     

Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: The UNOS experience

Guiteau JJ, Cotton RT, Karpen SJ, O’Mahony CA, Goss JA. Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: The UNOS experience.
Pediatr Transplantation 2010: 14: 326–331. © 2009 John Wiley & Sons A/S. Abstract: Treatment for HEH does not follow a standardized algorithm. From clinical experience, it is assumed that pediatric patients with HEH will fare as well as other common pediatric liver tumors post‐OLT. The UNOS dataset was examined for patients with pediatric OLT between 1987 and 2007. Patients were grouped into non‐tumors, HB, HCC, HEH, and rare liver tumors. COD analysis was calculated using Fisher’s exact test. Patient, allograft, and recurrence‐free survival were compared using Kaplan–Meier curves and log‐rank tests. A total of 366 patients with pediatric OLT were identified with primary liver tumors (HB – 237, HCC – 58, HEH – 35, other – 36). HEH patient survival (five yr: 60.6%) was poorer than non‐tumor OLTpatient survival (five yr: 84.4%). Survival was worse when compared to HB (five yr: 72%) and rare liver tumors (five yr: 78.9%), but better than HCC (five yr: 53.5%). Allograft survival in HEH (five yr: 50.1%) lies between HB (five yr: 63.6%) and HCC (five yr: 42.8%). COD analysis demonstrates recurrence as a major cause in HB and HCC, but not for HEH or other liver tumors. The data suggest that patient survival may not be as high as previously believed and further investigation is warranted.     

Heterozygote to homozygote related living donor liver transplantation in maple syrup urine disease: A case report

Liver transplantation is an accepted treatment modality in the management of MSUD. To our knowledge, ours is only the second successful case to date of a patient with MSUD receiving an allograft from an RLD who is a heterozygous carrier for the disease. In view of the worldwide shortage of available organs for transplantation, heterozygote to homozygote transplantation in the setting of MSUD may provide a viable alternative for those awaiting transplantation. We report on the case of a two‐yr‐old infant with MSUD, who received a left lateral segment (segments II and III) liver transplant from his mother, a heterozygote carrier of one of the three abnormal genes implicated in MSUD. Post‐operative BCAA levels normalized in our patient and remained so on an unrestricted protein diet and during times of physiological stress. To date, this is only the second case of a successful RLD liver transplant in a child with MSUD. Preliminary results indicate that RLD liver transplants are at least equivalent to deceased donor liver transplants in the treatment of MSUD, although longer term follow‐up is required. Heterozygote to homozygote RLD transplant in patients with MSUD presents a new pool of potential liver donors.     

Application of MARS artificial liver support as bridging therapy before split liver retransplantation in a 15-month-old child

Molecular Adsorbent Recirculating System (MARS) is a blood-filtering system designed to provide biological artificial liver support. We describe its use in a small child to illustrate its effectiveness and practicality in this age group. A 15-month-old male underwent split liver transplantation for acute liver failure following bone marrow transplantation. After development of graft dysfunction we instituted MARS-dialysis. MARS therapy led to a dramatic fall in serum bilirubin and transaminases. Liver synthetic function was not affected. This was accompanied by a stabilization of the patients clinical condition until repeat split liver transplantation was performed 2 weeks after the first graft. MARS-dialysis is practical in the small child. In this case, it did not provide definitive treatment but was an excellent bridging therapy before retransplantation.     

Hemodynamic failure as an indication to urgent liver transplantation in infants with giant hepatic hemangiomas or vascular malformations--report of four cases

Abstract:  The aim of this study was to present acute hemodynamic failure as a rare indication for liver transplantation in neonates and infants with liver hemangiomatosis. We report four patients aged one to six months with giant liver hemangiomas, with huge arterio-venous shunting within these malformations. In three, many skin hemangiomas were found. All children developed right ventricular failure. In two, a trial of pharmacological reduction was attempted with corticosteroids and cyclophosphamide. In one patient, the arterio-venous fistulas were embolized without any improvement in hemodynamic status. Two children underwent rescue hepatic artery surgical ligation, which did not prevent heart and then multiorgan failure including liver failure. After unsuccessful conventional therapy, all infants were considered for urgent liver transplantation; in three cases, it was performed with a living-related donor, and in one case with a deceased donor. All patients are alive and well with the follow-up between nine and 37 months after transplantation. Liver transplantation should be considered as a rescue treatment in children with hepatic vascular malformations leading to hemodynamic insufficiency when conventional therapy is unsuccessful and multiorgan failure develops.     

Liver involvement in celiac disease

Celiac disease may present as a cryptogenic liver disorder being found in 5–10% of patients with a persistent and cryptogenetic elevation of serum aminotransferase activity. In fact, a wide spectrum of liver injuries in children and adults may be related to CD and in particular: (1) a mild parenchymal damage characterised by absence of any clinical sign or symptom suggesting a chronic liver disease and by non-specific histological changes reversible on a gluten-free diet; (2) a chronic inflammatory liver injury of autoimmune mechanism, including autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis, that may lead to fibrosis and cirrhosis, generally unaffected by gluten withdrawal and necessitating an immunosuppressive treatment; (3) a severe liver failure potentially treatable by a gluten-free diet. Such different types of liver injuries may represent a spectrum of a same disorder where individual factors, such as genetic predisposition, precocity and duration of exposure to gluten may influence the reversibility of liver damage. A rigorous cross-checking for a asymptomatic liver damage in CD individuals and conversely, for CD in any cryptogenic liver disorder including end-stage liver failure is recommended.     

Liver transplantation for a patient with homocystinuria

Lin N‐C, Niu D‐M, Loong C‐C, Hsia C‐Y, Tsai H‐L, Yeh Y‐C, Tsou M‐Y, Liu C‐S. Liver transplantation for a patient with homocystinuria.
Pediatr Transplantation 2012. © 2012 John Wiley & Sons A/S. Abstract: A 24‐yr‐old man was diagnosed with HCU during neonatal screening and remained on a pyridoxine, vitamin B12, folic acid, and betaine regimen with dietary methionine restriction for more than 10 yr. He had normal mental development, marfanoid appearance, myopia because of lens dislocation, and recurrent ankle subluxation during adolescence. Thereafter, he was a poor adherent to the conventional diet‐restrictive therapy, and LT was considered when he developed hypertension and multiple infarctions over the right cerebellum early in the second decade of his life despite taking aspirin as a prophylaxis from 17 yr of age. In November 2009, he received a deceased whole LT from a blood group compatible donor. Along with the success of the transplantation, he was completely disease free without dietary or nutritional control. To the best of our knowledge, this is the first case of LT intended to cure HCU, and with promising results. This case provides an insight into the role of LT for this congenital metabolic disease, for which the decision should be made by judging between the severity of the disease and the risk of the operation, as well as the life quality of the patient.     

Utility of liver biopsy culture in pediatric liver transplant recipients

Abstract: The purpose of our study was to determine the utility of the practice of culturing percutaneous liver biopsy specimens obtained from pediatric LT recipients for evaluation of fever and/or elevated serum aminotransferases. Accordingly, a retrospective analysis was done of the 101 liver biopsies obtained during an eight-year period which had been submitted for bacterial, fungal and/or viral culture (out of a total of 174 biopsies in 38 patients). The purpose of the analysis was to ask three questions. (1) What organisms were cultured? (2) Were there clinical profiles that were characteristic of the type of organism? (3) Was the practice cost-effective? The analysis indicated that 34/86 biopsy cultures were positive for bacteria, 4/75 for fungus and 2/81 for virus. Clinical and laboratory data for children with cultures positive for enteric flora (n = 9) were compared to those with cultures positive for Gram-positive organisms (n = 17), laboratory contaminants (n = 8), and those with negative cultures (n = 52). Children with biopsies positive for enteric flora had a ‘cholestatic profile’: mean direct bilirubin 7 mg/dl, ALT 78 IU/l, direct bilirubin/ALT 0.09, in comparison to children with biopsies positive for Gram-positive flora. These children had a ‘hepatocellular profile’: mean direct bilirubin 4 mg/dl, ALT 332 IU/l, direct bilirubin/ALT 0.01 (p = 0.04 versus the enteric flora values) and a high percentage of polymorphonuclear leukocytes (mean 69% versus 38% for those with negative cultures, p = 0.001.) The charge for performing each bacterial culture was $28 (total $28 × 86 = $2408: $268 per enteric flora-positive biopsy; $93 per biopsy positive for either enteric flora or Gram-positive flora). The charge for each fungal culture was also $28 (total $28 × 75 = $2100: $525 per positive culture), while the cost for each viral culture was $140 (total $140 × 81 = $11 340: $5670 per positive culture). Thus, discounting the eight cultures positive for laboratory contaminants, a total of $15 848 was spent for 32 positive cultures. Given the high cost of liver transplantation, this information suggests that discretion should be used in submission of liver biopsy samples for culture in pediatric transplant patients. We recommend that when liver biopsies are performed for evaluation of elevated serum aminotransferases and/or fever, culture of biopsy specimens for bacteria should be considered in children with a ‘cholestatic profile’: direct bilirubin ≥ 7 mg/dl and direct bilirubin/ALT > 0.08, or a ‘hepatocellular profile’: direct bilirubin ≤ 4 mg/dl and direct bilirubin/ALT < 0.05, together with polymorphonuclear leukocytes > 70%. Following these guidelines might provide valuable information pertinent to patient management (especially since Gram-negative organisms can sometimes be cultured from the liver and not from blood) while reducing costs. Fungal cultures should be restricted to critically ill children. However, our data suggest that the practice of obtaining fungal and viral cultures of the liver in most pediatric transplant patients has an unacceptably high cost/benefit ratio, particularly since recovery of the organism from the peripheral blood is likely.