胆道闭锁Kasai术后自体肝生存良好患儿的营养状况调查

目的回顾性调查胆道闭锁行肝门空肠吻合术(Kasai术)后自体肝生存良好患儿的营养状况,为制定个体化营养方案提供依据。方法收集46例胆道闭锁Kasai手术后1年且自体肝生存良好患儿的临床资料,包括年龄、身高/身长、体重、血清脂溶性维生素(A、D、E、K)水平。以WHO生长曲线软件分别计算患儿年龄别身高Z评分(height-for-age,HAZ)、年龄别体重Z评分(weight-for-age,WAZ)、身高别体重Z评分(weight-for-height,WHZ);以正常参考值为标准,计算营养不良和维生素缺乏的比例。结果46例患儿中男童26例,女童20例,平均年龄(14.5±0.8)个月。患儿HAZ评分为(-0.14±0.86),WAZ评分为(0.21±0.81),WHZ评分为(0.62±1.80),其中生长迟缓2例(4.3%),无低体重及消瘦患儿。25例行脂溶性维生素检查的患儿,其临床和实验室指标与46例自体肝生存良好的患儿均无明显差异(P>0.05)。25例患儿维生素A、D、E、K的水平分别为(290.61±80.26)ng/mL、(30.88±16.15)ng/mL、(7.69±2.77)μg/mL和(1.34±0.98)ng/mL。其中维生素A缺乏4例(16%),维生素D缺乏5例(20%),维生素E缺乏1例(4%),无一例维生素K缺乏者;至少有一种维生素缺乏者有7例(28%)。结论胆道闭锁行Kasai术后1年,自体肝生存良好的患儿营养状况良好;脂溶性维生素A、D缺乏较为常见,应在术后注意监测并补充。     

早期胆管炎对Kasai's术远期疗效的影响

目的 探讨Kasai's术后胆管炎对胆道闭锁(BA)长期牛存的影响.方法 通过对92例BA行Kasai's术时的手术年龄、术式和术后胆管炎发生等临床资料进行收集和分析,特别是重点分析早期胆管炎对患儿的影响.结果 对1989年3月至1997年3月共92例BA行Kasai's术,手术年龄30～137 d.其中男55例,女37例.失访3例,死亡66例,存活23例巾男14例,女9例,存活患儿年龄最大者现已满19岁.92例中,在出生后60 d内手术25例,现存活5例;61～90 d手术53例.现存活15例.91 d以上手术14例,现存活3例.本组发生早期胆管炎58例,现仍存活7例.19例因肝门部胆管梗阻再次手术,现存活4例.结论 ①胆管炎的处理是BA治疗过程中最困难的一环.胆管炎是BA术后最常见又是最难处理的并发症;②防止早期胆管炎的发生是手术成功的关键,早期胆管炎的危害大.在适宜的年龄进行Kasai's术时,有无胆管炎发生与生存率关系更密切;③对因胆管炎引起的肝门部胆管梗阻应积极治疗;④早期胆管炎不但影响手术后的牛存率,还对远期生活质量有影响.     

胆道闭锁Kasai手术后自体肝生存时间小于2年的危险因素分析

目的探讨胆道闭锁(biliary atresia,BA)Kasai手术后自体肝生存(native liver survival,NLS)时间小于2年的危险因素。方法回顾性分析山西省儿童医院2009年1月至2017年6月行Kasai手术的BA患者临床资料及随访资料。根据术后NLS时间是否小于2年分为死亡组(n=78)和生存组(n=46)。将BA分型、性别、巨细胞病毒(cytomegalovirus,CMV)感染、手术年龄、术后使用抗生素方案、术后使用激素方案、是否合并早期胆管炎及术后黄疸是否消退作为自变量,采用Kaplan-Meier法绘制生存曲线并进行Log-rank检验,采用Cox比例风险模型(逐步前进法)筛选BA患者Kasai手术后NLS时间小于2年的危险因素。结果共纳入124例BA患者,其中生存组46例,死亡组78例,2年NLS率为37.1%。单因素分析结果显示合并早期胆管炎及术后黄疸消退是影响BA患者术后2年NLS率的因素(P<0.05)。Cox比例风险模型分析结果显示术后3个月内黄疸未消退为BA患者Kasai手术后NLS时间小于2年的独立危险因素,术后3个月内黄疸未消退组患者NLS时间小于2年的风险是黄疸消退患者的5.65(95%CI:2.45~13.04)倍。结论BA患者Kasai手术后3个月内黄疸未消退是NLS时间小于2年的危险因素。     

胆道闭锁Kasai术后肝脏纤维化及生化指标变化趋势的横断面研究

目的 研究胆道闭锁患儿Kasai术后肝脏纤维化及生化指标的变化趋势.方法 采用横断面研究方法,对2013年1月至2013年12月于首都医科大学附属北京儿童医院普外科随访的胆道闭锁Kasai术后患儿进行复查资料收集,术后随访时间6个月以上,资料完整的121例纳入研究.按照Kasai术后胆红素降至正常的时间,以术后3个月、6个月为界分为优、良、差三组,获取患儿术时年龄、术前和术后Fibroscan肝脏硬度测量值及生化结果,绘制趋势图并进行统计学分析研究各组患儿Kasai术后肝脏纤维化及生化指标的变化趋势.结果 纳入本研究胆道闭锁患儿共121例,男69例(57.0％),女52例(43.0％);其中优组63例(52.1％),良组34例(28.1％),差组24例(19.8％).三组患儿术时年龄差异无统计学意义.三组患儿Fibroscan肝脏硬度测量值在术后1年内波动进展,1年后趋于稳定;单因素方差分析及秩和检验结果显示优良组差异无统计学意义,优良组与差组患儿Fibroscan肝脏硬度测量值在术后1年内差异均有统计学意义.优良组患儿总胆红素在术后前3个月下降较快,随后缓慢下降,至术后6个月稳定于正常值,而差组患儿总胆红素术后前2个月下降较快,但随后出现较大波动.三组患儿ALT趋势图均在术后1个月出现波峰,优良组术后1～6个月有所下降,但之后持续波动不能稳定,差组持续波动;三组患儿AST术后6个月内有所下降,但之后波动较大不能稳定.三组患儿CGT术后1个月达到最高峰,至术后6个月下降较快,随后逐渐趋于稳定小幅波动.结论 ①胆道闭锁患儿Kasai术后1年内肝脏纤维化波动性进展,自肝存活超过1年者肝纤维化情况进展缓慢趋于稳定,优组患儿在2年后更加稳定;②Kasai术后1个月内胆红素下降最快,3～6个月胆红素可降至正常的患儿,其胆红素水平可维持长期正常;③肝脏炎症、胆管反应、功能损害在术后仍继续进展,术后1个月开始减轻,术后6个月趋于稳定.     

The value of cholinesterase activity after Kasai operation

Cholinesterase (ChE) is an enzyme synthesized in the liver. The aim of this study was to determine the value of ChE as an index of liver function. We measured the ChE activity as well as the values of bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, aminotransferases and albumin before and 7 days after Kasai operation in 25 infants with biliary atresia. The increased activity of ChE in plasma after Kasai operation was accompanied by a decrease of other measured values (P<0.0001), except for albumin. We can conclude that the increase of ChE activity together with the decrease of bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase show early improvement of liver function after Kasai operation. ChE activity can be used to assess liver function in terms of synthesis.     

先天性巨结肠Swenson改良术后排便功能与生活质量研究

目的：评估先天性巨结肠Swenson改良术后排便功能和生活质量。方法：随访常见型先天性巨结肠Swenson行改良术后患儿45例（男37例，女8例），手术年龄2．5个月－6岁，平均1．6岁。术后随访8－16年，平均10．9年，评估其排便功能和生活质量。结果：术后并发症有：污染和小肠结肠炎17例（37．8％），便秘3例（6．7％），大便失禁3例（6．7％），小便失禁4例（8．9％）；吻合口狭窄2例（4．4％）和粘连性梗阻1例（2．2％）。23例（51％）表现不同程度的排便障碍，但肛门功能优良率仍达到84．4％（李正评分）和93．4％（Rintala评分），生活质量评分显示，优者18例（40％），良者21例（46．7％），差者6例（13．3％），结论：先天性巨结肠Swenson改良术后，多数患儿远期肛门功能和生活质量优良，排便功能障碍是影响生活质量的主要因素。     

胆道闭锁Kasai术后相关预后因素分析和对策

目的 探讨影响胆道闭锁(biliary atresia,BA) Kasai术后预后的相关因素,了解我省BA的治疗现状.方法 回顾性分析2009年1月至2015年12月间,在山西省儿童医院行腹腔镜探查、胆道造影确诊胆道闭锁后行Kasai术且随访资料完整的91例患儿.采用Kaplan-Meier法计算各亚组患儿自体肝存活率.各亚组之间自体肝存活率的比较应用Log-rank检验,多因素分析采用COX回归模型.结果 全组患儿6个月、1年、2年的自体肝存活率分别为76.9％(70/91)、48.3％(44/91)、36.3％(33/91).按手术日龄将患儿分为:＜60 d(34例)、60～90(含60)d(47例)、90～120(含90)d(8例)和≥120 d(2例)组,各组2年累计自体肝存活率分别为55.8％(19/34)、44.7％(21/47)、12.5％(1/8)和0(P=0.047).男、女童2年累计自体肝存活率分别为36.4％(16/44)和46.8％(22/47),差异无统计学意义(P=0.313).有胆管炎发作组(67例)与无胆管炎发作组(24例)的2年累计自体肝存活率分别为31.3％(21/67)和62.5％(15/24)(P=0.011);黄疸消退明显组(61例)和黄疸消退不明显组(30例)的2年累计自体肝存活率分别为50.8％(31/61)和23.3％ (7/30) (P=0.012);肝功能恢复良好组(53例)和肝功能恢复较差组(38例)2年累计自体肝存活率分别为56.6％(30/53)和21.1％(8/38)(P=0.01);Ⅰ型、Ⅱ型、Ⅲ型闭锁的2年累计自体肝存活率分别为77.8％(7/9)、66.7％(4/6)和31.6％(24/76)(P=0.023),差异均有统计学意义.结论 手术日龄、有无胆管炎发作、黄疸消退情况、肝功能恢复情况及胆道闭锁分型为影响Kasai手术预后的影响因素,其中手术日龄、黄疸消退和肝功能恢复情况是影响生存的独立预后因素.提高民众对胆道闭锁的认知水平,加强术后随访评估,对提高胆道闭锁生存率有重要意义.     

Prognostic factors indicating survival with native liver after Kasai procedure for biliary atresia

Background

The number of the bile ducts in the portal canal/measured surface area of the portal canal (BDP ratio) indicates prognosis in biliary atresia (BA), as does an elevated cytokeratin 7 positivity percentage (PCK7). We compared these two markers.

Methods

We reviewed 32 BA cases undergoing Kasai operation from 1976 to 2016 with >5 portal canals in biopsy samples. Group I required liver transplantation or died within a year of operation (n = 8). Group II survived with their native liver (n = 24). We determined the BDP ratio (10²/mm²) and PCK7 (%), subdividing patients into three groups by their age at operation: Group A ≤60 days (n = 6, 1 Group I), 60< Group B ≤90days (n = 16, 5 Group I), Group C >90 days (n = 10, 2 Group I).

Results

PCK7 (%) was 2.71 ± 1.87 in Group I and 4.25 ± 2.56 in Group II (p = 0.13). BDP ratio (10²/mm²) was 1.19 ± 0.424 in Group I and 1.64 ± 0.534 in Group II (p = 0.04). Both markers were higher in Group C than in Group A or B (p < 0.01).

Conclusion

The BDP ratio is a better prognostic indicator than PCK7 in BA.

     

Impaired T-lymphocyte proliferation function in biliary atresia patients with chronic cholestatic jaundice after a Kasai operation

To investigate the association between chronic cholestatic jaundice, systemic immunity, and various infectious complications in patients with biliary atresia (BA), we performed a survey of the systemic immune function in 30 children with BA. Patients were divided into a jaundice group (total serum bilirubin > or = 2 mg/dL for >6 mo) and control group (total serum bilirubin <2 mg/dL for >6 mo) with comparable age. Patients were tested for serum immunoglobulin and complement levels, mitogen response, interleukin (IL)-4, IL-5, and interferon-gamma production after phytohemagglutinin (PHA) stimulation, blood cell and lymphocyte subpopulation counts, phagocytic function, and leukocyte adhesion complex. They were then followed prospectively for 6 mo, and severe infectious complications requiring hospitalization were recorded. Compared with jaundice-free patients, T-lymphocyte proliferation function, determined by PHA mitogen test was significantly lower (p = 0.02) in BA patients with chronic cholestatic jaundice after a Kasai operation. During the study period, patients with chronic cholestatic jaundice had a higher risk of severe infectious complications than their jaundice-free counterparts (risk ratio = 5.87; p = 0.001). In conclusion, BA patients with chronic cholestatic jaundice are associated with impairment of T-lymphocyte proliferation and increased incidence of severe infectious complications.     

Different polyunsaturated fatty acid profiles in patients with biliary atresia after successful Kasai operation and liver transplantation

Background  Although Kasai operation eliminates jaundice in patients with biliary atresia, inflammation at Glisson’s area persists and fibrosis advances slowly to liver cirrhosis. Profiles of polyunsaturated fatty acids, on which metabolic products have an immunoregulative effect, were investigated in this study. Methods  Blood samples were obtained from patients including 21 jaundice-free patients with biliary atresia after Kasai operation (native liver group) and 18 patients in whom Kasai operation failed and liver transplantation was performed (transplantation group). All of these patients are without any complications for more than 6 months. Blood samples from 18 patients with inguinal hernia were assigned as normal controls (control group). Profiles of fatty acids in whole serum lipids were measured using gas chromatography. The n-3/n-6 ratio of polyunsaturated fatty acids was compared among the three groups. Results  The n-3/n-6 ratio was 0.114 in the native liver group, which was significantly lower than 0.145 in the transplantation group (P = 0.009) and 0.158 in the control group (P = 0.004). There was no significant difference between the transplantation and control groups (P = 0.83). Results  The n-3/n-6 ratio was abnormal after Kasai operation despite normal liver function. This seems to be one factor of persisting inflammation in Glisson’s area.     

Kasai术后近期胆管炎相关危险因素分析

目的 探讨Kasai术后近期胆管炎发生的可能相关因素.方法 回顾2002年9月～2005年11月于我院行Kasai术的胆道闭锁患儿资料.肝炎病毒筛查阴性,生存1年以上者123例.平均随访时间(20.54±8.57)个月(13～41个月).分析术后胆管炎与患儿手术年龄、是否合并巨细胞病毒感染、术中胆汁引流量、黄疸消退时间等因素的相关性.结果 平均手术年龄(70.48±11.23)d(32～126 d),术后1年内胆管炎发生率52.85%(65/123).手术年龄是胆管炎发作的危险因素(Odds Radio=1.921,P＜0.01),胆管炎首次发作时间与手术年龄负相关(Spearman's rho=-0.3646,P=0.037＜0.05).约三分之一患儿1年内发作≥3次(23/65),但次数多少与手术年龄及首次发作时间不相关(P＞0.05).巨细胞病毒活动性感染与否(P=0.1523＞0.15)和术中胆流量多少(P=0.399＞0.15)不是影响胆管炎发作的危险因素.术后6个月总黄疸消退率58.62%,黄疸消退受术后胆管炎发作次数影响(Odds Radio=3.7668,P＜0.01),并与术中胆流量情况相关(Odds Radio=0.3280,P=0.011＜0.05).20例胆管炎病例常规血培养,仅1例1次大肠埃希菌阳性.结论 Kasai术年龄与胆管炎发作相关.巨细胞病毒活动性感染并不是胆管炎发生的危险因素.手术近期胆管炎发作的次数影响术后黄疸的消退,并可能影响整个疾病的预后.     

Incidentally detected cholangiocarcinoma in an explanted liver with biliary atresia after Kasai operation

This report presents the case of a 30‐yr‐old woman with BA who developed incidental cholangiocarcinoma following the Kasai operation. She showed progressive liver dysfunction and cirrhosis at the age of 30 yr and underwent LDLT. A 4‐cm‐diameter liver tumor in the anastomotic site of portoenterostomy was incidentally found as a result of a pathological examination of the explanted native liver. The tumor was pathologically diagnosed to be intrahepatic cholangiocarcinoma. Although cholangiocarcinoma in patients with BA has been previously reported in only three cases, it should be nevertheless always considered in the differential diagnosis of hepatic tumors during a long follow‐up course in patients with BA.     

Outcomes of Alagille syndrome following the Kasai operation: a systematic review and meta-analysis

Purpose

Infants with Alagille syndrome (AGS) frequently develop neonatal cholestasis, and some AGS infants who suspected of biliary atresia subsequently undergo the Kasai operation with the diagnosis of biliary atresia. The aim of this study was to investigate the effect of the Kasai operation on liver and patient outcomes among AGS patients, using a meta-analysis.

Methods

A systematic review and meta-analysis of studies describing the outcomes of AGS patients with/without the Kasai operation were conducted. The analyzed outcomes were liver transplantation, not living with the native liver, and mortality for any reason.

Results

We identified 6 studies (394 AGS patients). All studies were retrospective cohort or case-control studies. The incidences of liver transplantation, not living with the native liver, and mortality were significantly higher in AGS patients who underwent the Kasai operation than in those who did not undergo the Kasai operation (odds ratio: 6.46, 95% CI 3.23–12.89, p?<?0.00001; odds ratio: 25.88, 95% CI 2.83–236.84, p?<?0.004; odds ratio: 15.05, 95% CI 2.70–83.93, p?=?0.002, respectively).

Conclusion

The Kasai operation was associated with poor outcomes in AGS patients. It remains unclear if the Kasai operation directly deteriorates liver and patient outcomes in AGS patients.

     

胆道闭锁术后高胆红素血症并胆管扩张二次手术的探讨

目的 探讨胆道闭锁(BA)术后高胆红素血症者二次手术的条件及必要性、可行性和效果.方法 2001年3月至2007年12月,共对10例BA术后患儿实施了二次手术,男4例,女6例;年龄5个月～6.5岁.距第一次Kasai's手术时间2个月～6年.其中Ⅲ型BA Kasai's手术后9例,Ⅱ型BA囊肿空肠吻合术后1例;所有患儿第一次术后3个月总胆红素(TBIL)直接胆红索(DBIL)曾降至正常,谷草转氨酶(AST)、谷丙转氨酶(ALT)等酶水平下降,后再次出现高胆红素血症、酶水平升高、陶土样便等情况.二次术前经影像学检查证实所有患儿肝门、肝内胆管扩张,1例并发肝门胆管结石;6例伴有肝门部囊肿形成.结果 8例患儿行开腹肝门空肠再吻合术,2例患儿实施囊肿空肠吻合术,手术全部成功,无术中并发症发生.手术时间为2.6～3.2h(平均3.0h),术中出血15～30ml.术后进食中位数时间32h(24～52h);术后2～4d(平均3d)排黄色大便;腹腔引流放置中位时间58 h(38～96 h),黄疸减退至轻度或消退中位时间为术后12 d(7～24 d),6例患儿术后4周 TBIL、DBIL,降至正常水平,4例患儿6周后降至正常水平,转氨酶术后均下降.术后中位住院时间15 d(12～29 d).术后随访4～36个月,3例患儿于术后4周内发牛胆管炎,2例患儿于术后6个月内发作胆管炎2次,均治愈.术后3个月所有患儿 TBIL、DBIL、总蛋白(TP)正常;3例患儿术后3个月AST、ALT、ALP恢复正常,3例术后5～8个月恢复正常.生长发育正常.无吻合口狭窄、粘连肠梗阻等术后并发症.结论 对BA术后高胆红素血症患儿恰当的实施二次肝门肠吻合术能够建立有效的胆汁引流,改善患儿症状,提高生活质量,并长期带自体肝脏生存,避免肝移植或为等待肝源提供时间保障.     

Long-term follow-up study of patients with cholangitis after successful Kasai operation in biliary atresia: selection of recipients for liver transplantation

Since the introduction of cyclosporine A, liver transplantation has become accepted as the therapy for end-stage liver disease. However, there are no definite criteria for liver replacement in biliary atresia. We investigated (a) the survival rate after hepatic portoenterostomy (n = 131), (b) liver function tests in fatal cases after an initially successful hepatic portoenterostomy (n = 9), and (c) liver function tests in the patients with episodes of cholangitis after a successful surgical treatment (n = 8). Patients with persisting jaundice after the surgery cannot be expected to survive long, and therefore they definitely should undergo liver transplantation. When total bilirubin concentration was above 10 mg/dl in patients with cholangitis after a successful operation, conservative therapy had almost no effect. Therefore, patients with total bilirubin levels above 10 mg/dl should be considered for liver transplantation. Of the liver function tests, only total bilirubin was reliable as a marker for hepatic failure in the end stage of biliary atresia. Prolongation of thrombo test and episodes of gastrointestinal bleeding also were used in selection of patients for liver replacement.     

Evaluation of a standardized protocol in the use of steroids after Kasai operation

Although the Kasai operation is still the treatment of choice for infants with biliary atresia, the long-term success rate, as defined by survival without transplantation, is only about 25-40%. It has been proposed that post-operative inflammatory changes affect the bile flow and eventually lead to cholangitis and liver failure. Recent case reports have suggested that the administration of steroids post-operatively can improve outcomes. Since 2004, our unit has adopted a strict protocol for the use of post-operative steroids for patients who undergo Kasai operation. The aim of this study is to access the early outcomes of these patients. A retrospective analysis was carried out for all patients who received Kasai operation between 1996 and 2006. For the treatment group, patients all received prednisolone at 4 mg/kg 1 week after operation as guided by protocol. The demographics and outcomes, including post operative bilirubin level, episodes of cholangitic attack, the need for early liver transplantation (transplant within 1 year of Kasai), and transplantation-free survival, were noted. Statistical analysis was done using Fisher's exact test and unpaired t-test when appropriate. A value of P < 0.05 was considered to be statistically significant. Kasai operation was performed in 30 patients (11 boys and 19 girls) during the study period. Thirteen patients received post-operative prednisolone according to protocol. The average age at operation and the mean preoperative bilirubin levels for the steroid and non-steroid group were not significantly different. A normal post-operative bilirubin (defined as bilirubin level less than 20 mumol/L) was achieved at 6 months in 7 (53.9%) patients who received steroid and 8 (47.0%) patients who did not (P = 0.71). A statistically significant reduction in the post-operative bilirubin level was also seen at 3 and 6 months in the steroid group. Early liver transplantation was required in 5 (38.5%) patients with steroid and 5 (29.4%) patients without it (P = 0.60). No significant difference in terms of cholangitic attack was observed. There was also no steroid-associated complication reported. We conclude that lower post-operative bilirubin level can be achieved with the routine use of prednisolone. However, there is no statistical improvement in terms of early liver transplantation and cholangitis. This may be attributed to the small sample size of our study population. Based on this pilot study, a multi-centre randomized trial is needed.     

胆道闭锁Kasai手术效果影响因素的研究进展

胆道闭锁(biliary atresia,BA)是肝内外胆管进行性纤维化引起肝内外胆管硬化和闭锁的一种常见疾病,Kasai手术(肝门空肠吻合术)改善了患儿预后.手术时肝脏的病理状态,包括肝脏纤维化程度、胆管板畸形、肝门部纤维斑块、胆道闭锁类型都对Kasai术后的效果有影响.单纯用年龄评价手术预后有欠妥当.建立胆道闭锁治疗中心以提高外科医师实施Kasai手术的经验有助于改善手术预后,而胆道闭锁脾脏畸形综合征、早产儿、CMV感染对预后有不利影响.激素、熊去氧胆酸及抗生素的预防性使用其有效性目前尚有争议.