A case report of pediatric fulminant hepatitis treated with plasma diafiltration

Plasma diafiltration (PDF) is blood purification therapy in which simple plasma exchange is performed with a membrane plasma separator while dialysate flows outside the hollow fibers. A 14-year-old boy with fulminant hepatitis underwent two sessions of PDF and one session of hemodiafiltration. We infused filtered replacement fluid for artificial kidneys at a dialysate flow rate of 600 mL/h and a replacement flow rate of 450 mL/h. We infused fresh frozen plasma (1200 mL) and 25% albumin solution (50 mL) intravenously over 8 h. Each PDF session lasted 8 h. The patient's total bilirubin, interleukin-18, and cystatin C levels decreased with treatment, and he recovered from hepatic failure. PDF may be an extremely useful blood purification therapy for pediatric fulminant hepatitis in terms of both medical economics and cytokine removal.     

肝肾综合征与血氨水平的关系

目的 分析肝硬化患者肝肾综合征(HRS)的患病率,研究HRS患者血氨水平与肾功能的关系,探讨HRS在肝性脑病发生和发展中的作用.方法 收集我院2007年1月-2009年3月465例肝硬化患者以及2009年3月80例单纯肾功能障碍患者、80例健康体检者的血清和血浆,检测其肝功能(ALT、AST、γ-谷氨酰转肽酶、总胆红素、血清总蛋白、白蛋白)、肾功能(尿素氮、肌酐)指标和血氨.分别以尿素氮和肌酐为诊断标准,比较两种诊断标准的HRS患病率;分析HRS组与非HRS组及单纯肾功能障碍组之间血氨水平的差异;并对40例HRS患者肾功能指标与血氨水平的相关性进行追踪分析.结果 以尿素氮为诊断标准的HRS患病率为39.6%,明显高于以肌酐为标准的17.4%(χ~2=97.33,P<0.01);以尿素氮和肌酐为标准的HRS组血氨水平分别为(57.39±48.83)μmol/L和(64.80±47.25)μmol/L,明显高于非HRS组的(47.58±36.28)μmol/L和(46.13±29.99))μmol/L(t值分别为-3.07和-3.67,P值均<0.01);单纯肾功能障碍组血氨水平为(26.59±14.34)μmol/L,明显低于肝硬化HRS组和非HRS组(P值均<0.01),但与健康对照者组的(22.36±8.72)μmol/L比较,差异没有统计学意义(t=1.52,P>0.05).HRS组追踪分析发现,血氨水平与尿素氮和肌酐呈正相关关系,相关系数分别为0.874和0.834(P值均<0.05).结论 肝性脑病实质是肝-肾-肠-脑综合征.肝肾综合征影响血氨水平,从而促进了肝性脑病的发生和发展.     

血浆置换联合持续血液滤过治疗重型肝炎肝肾综合征疗效观察

目的观察血浆置换联合持续血液滤过治疗重型肝炎合并肝。肾综合征的疗效。方法应用血浆置换加持续血液滤过治疗13例重型肝炎合并肝。肾综合征患者并与单纯药物治疗进行比较。结果血浆置换联合持续血液滤过治疗组肝。肾功能及电解质恢复明显好于单纯药物治疗组，且生存率较单纯药物治疗组明显升高。结论血浆置换联合持续血液滤过是治疗重型肝炎并发肝。肾综合征的有效方法。     

肝肾综合征的诊断

肝肾综合征(hepatorenal syndrome,HRS)又称功能性肾衰竭,是慢性肝病和晚期肝功能衰竭患者的严重并发症,更是造成患者死亡的主要原因.近年来,随着对HRS发病机制研究的深入,HRS的诊断也取得了一定的进展.现对HRS诊断方面的研究进展内容综述如下. 一、HRS的分型 临床上根据HRS的病情进展、严重程度及预后等,将其分为两个型.即Ⅰ型(急进型)和Ⅱ型(缓慢型).     

白蛋白透析联合去甲肾上腺素治疗重型肝炎Ⅰ型肝肾综合征临床研究

目的观察白蛋白透析联合去甲肾上腺素治疗重型肝炎Ⅰ型肝肾综合征的疗效。方法应用白蛋白透析联合去甲肾上腺素治疗15例重型肝炎Ⅰ型肝肾综合征患者,并与传统的多巴胺药物治疗进行比较。结果白蛋白透析联合去甲肾上腺素治疗组肝肾功能、血流动力学及电解质恢复明显好于多巴胺药物治疗组,且生存率较单纯多巴胺药物治疗组明显提高。结论白蛋白透析联合去甲肾上腺素是治疗重型肝炎并发Ⅰ型肝肾综合征的有效方法。     

A case of drug-induced hypersensitivity syndrome with multiple organ involvement treated with plasma exchange

A 53-year-old male patient began treatment for systemic exanthema with diaphenylsulfone (DHS) on 21 November 2002. On 18 December 2002, the patient developed a fever and additional systemic erythematous exanthema. Systemic lymphadenopathy, hepatosplenomegaly, leukocytosis (in particular, an increase in the number of atypical lymphocytes) and liver dysfunction followed. After cessation of the DHS treatment on 25 December 2002, acute renal failure occurred and the patient was transferred to Shinshu University Hospital on 4 January 2003. The patient was diagnosed with drug-induced hypersensitivity syndrome (DIHS). Steroid pulse therapy (methylprednisolone 1000 mg/day for 3 days) was given, followed by 60 mg/day of prednisolone. The patient's renal functions recovered and he was taken off hemodialysis therapy. However, the patient relapsed twice despite two sessions of steroid pulse therapy and an increase in the dose of prednisolone to 100 mg/day. Plasma exchange (PE) was carried out to reduce the activity of the disease. With a total of four plasma exchanges, we were able to reduce the dose of prednisolone from 100 mg/day to 60 mg/day without relapse. There were no adverse effects from the plasma exchanges. Plasma exchange should be considered in the treatment with corticosteroid-resistant DIHS with multiple organ lesions.     

肝肾综合征的发病机制

近年来,大量研究较详细的描述了肝肾综合征(hepatorenal syndrome,HRS)的病理生理学情况,认为其特点是内脏血管床血管扩张的同时体循环血管阻力下降、动脉血压降低和心输出量下降,促使肾脏血管强烈收缩导致肾小球滤过率下降[1].这些特点主要与肝功能损害、门静脉高压、血液循环功能障碍、心脏病变和肾脏神经、体液调节异常等因素相关.     

肝肾综合征治疗新动向

肝肾综合征(hepatorenal syndrome,HRS)是发生于晚期肝硬化腹水或肝衰竭患者的潜在可逆性的功能性肾衰竭,也可发生于急性肝衰竭和洒精性肝炎患者.其特征是内脏动脉血管扩张,外周血管阻力降低和全身动脉血压降低,肾素-血管紧张素-醛固酮系统和交感神经系统过度激活,肾血管强烈收缩,肾血流量和肾小球滤过率显著降低,肾功能严重受损.其具体发病机制非常复杂,至今没有完全阐明.近年来,比较认可的机制有动脉扩张学说、肝硬化性心肌病学说等,这些机制的深入研究为临床诊断、治疗和预防等提供了理论基础.近年来对HRS诊治领域的研究有了新的进展,现报道如下.     

特利加压素治疗肝肾综合征有效性及安全性的Meta分析

目的 评价特利加压素治疗肝肾综合征(HRS)的有效性及安全性.方法 采用Cochrane系统评价方法,计算机检索MEDLINE,PubMed,Embase,Medline,Cochrane Library及Google(TM)Scholar databases,检索时间截止至2012年4月公开发表的随机对照临床试验.根据纳入与排除标准筛选文献、评价文献质量、提取资料,采用RevMan 5.1软件进行Meta分析.结果 在47篇文献中纳入4篇文献,包括了234例HRS患者.文献的Cochrane质量评价均为B级,均属于较高质量文献.Meta分析结果显示,特利加压素治疗HRS的有效率为47％,明显高于对照组的11.9％(P＜0.00001).结论 特利加压素可显著提高HRS患者肾小球滤过率,降低肌酐水平,改善肾脏功能.     

关注肝肾综合征研究新进展

肝肾综合征（hepatorenal syndrome,HRS）是由严重肝脏疾病引起的一种以肾功能衰竭为特征的并发症。HRS的发病机制是有效血容量不足和内脏血管活性物质失衡导致肾内血管收缩。HRS的预后非常差,其出现往往预示肝病进入终末期。近年来,血管收缩剂、经颈静脉肝内门体分流和肝移植等治疗方法已应用于HRS。本文将就HRS的发病率、发病机制、诊断和治疗方面的新进展作一评价。     

特利加压素联合大剂量白蛋白治疗肝硬化肝肾综合征的疗效观察

目的观察特利加压素及其联合大剂量白蛋白治疗肝肾综合征的疗效。方法53例患者分为三组，在综合治疗的基础上，A组使用多巴胺，B组使用特利加压素，C组使用特利加压素联合大剂量白蛋白。治疗期间观察患者临床症状、尿量、血肌酐、腹水消长情况。终止治疗事件及治疗后的转归。结果B、C组尿量、肌酐清除率显著增加。血肌酐降低，且C组变化比B组明显，A组仅轻度改善，三组间比较有显著差异。结论特利加压素对肝肾综合征的治疗有确切的疗效．大剂量白蛋白扩容可提高特利加压素对肾功能的作用。     

Longitudinal assessment of prognostic factors for patients with hepatorenal syndrome in a tertiary center

Introduction  

Hepatorenal syndrome (HRS) is one of the serious complications in patients with advanced cirrhosis and ascites. In tertiary centers, most patients were classified as having type 1 HRS for their rapid progressive diseases. However, no significant predictors have been assessed previously for patients with type 1 HRS. In addition to the initial model of end-stage liver disease (MELD) scores and biochemistry parameters, we want to further investigate the prognostic importance of changes in MELD scores and biochemistry parameters over time for patients with type 1 HRS.     

全身炎症反应与肝肾综合征关系的研究

目的分析肝衰竭患者并发肝肾综合征(HRS)与全身炎症反应(SIRS)的关系。方法在137例肝衰竭患者中,合并HRS68例,单纯肝衰竭69例。收集两组患者Child-Pugh分级、终末期肝病模型(MELD)和SIRS评分。结果 HRS患者SIRS评分为0.70±0.86分,高于对照组0.36±0.54分(P<0.05),白细胞计数为8.96±4.45×109/L,显著高于对照组(5.79±2.40×109/L,P<0.05);HRS患者总胆红素和凝血酶原时间分别为404.5μmol/L和21.7±8.8s,高于对照组(259.0μmol/L和17.6±9.6s,P<0.05),而钠和氯分别为132.6±6.0mmol/L和92.2±9.1mmol/L,显著低于对照组(137.2±3.8mmol/L和99.5±9.3mmol/L,P<0.05)。结论 SIRS与肝衰竭患者并发HRS关系密切。     

Multicenter study of plasma diafiltration in patients with acute liver failure

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.     

特利加压素与去甲肾上腺素在肝肾综合征治疗中的比较

目的 比较去甲肾上腺素与特利加压索在肝肾综合征(HRS)治疗中的效果.方法 59例Ⅰ型HRS患者中,20例接受去甲肾上腺素治疗,6～16 mg/d,治疗至肾功能逆转,最多15 d;16例接受特利加压素治疗,0.5～2 mg/4h,治疗至肾功能逆转,最多15 d;23例为安慰剂治疗(对照组).所有患者均用白蛋白10 g/d治疗.观察患者治疗前后肝功能、肾功能、电解质、存活时间.统计学处理采用t检验和X2检验.结果 治疗15d后,20例接受去甲肾上腺素治疗的HRS患者,12例肾功能逆转(60％);16例接受特利加压素治疗患者,14例肾功能逆转(87.5％);对照组23例病情较治疗前恶化;特利加压素组与其他两组比较,差异有统计学意义(P＜0.05).去甲肾上腺素组、特利加压素组和对照组的综合应答率分别为80％、100％和17.4％,差异有统计学意义(P＜0.05).结论 特利加压素、去甲肾上腺素是治疗HRS的有效药物,特利加压素疗效更佳,两者远期疗效尚不确定.     

特利加压素对1型肝肾综合征的治疗疗效:一项系统评价及meta分析

目的评价特利加压素治疗1型肝肾综合征的安全性和有效性。方法检索PubMed、Embase等数据库特利加压素治疗1型肝肾综合征有关的随机对照试验;2名研究者独立地对文献进行筛选、质量评价和数据提取,并用RevMan 5.3软件进行安全性和有效性分析。结果研究共纳入13项随机对照试验,共746例患者,试验组均为特利加压素治疗组;对照组包括5项安慰剂、6项去甲肾上腺素、1项多巴胺和1项奥曲肽治疗。总的肝肾综合征缓解为33.7%,死亡率60.1%,meta分析显示特利加压素治疗比对照组更能提高肝肾综合征缓解率(RR=2.13,95%CI:1.26~3.61,P=0.005,I2=51%);但同时伴有更多的不良反应(RR=2.05,95%CI:1.36~3.09,P=0.0006,I2=0%)。亚组分析显示特利加压素比安慰剂对治疗肝肾综合征具有优势;但其疗效和安全性与去甲肾上腺素比较差异无统计学意义。结论特利加压素是治疗1型肝肾综合征患者有效的药物之一。     

Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis

BackgroundPrediction of hepatorenal syndrome (HRS) remains difficult in advanced cirrhotic patients.AimsTo evaluate use of serum and urine biomarkers to predict HRS.MethodsWe prospectively recruited Child’s B or C cirrhotic patients with normal serum creatinine, and followed them for 12 weeks for the development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl-β-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine liver-type fatty acid binding protein (LFABP) were measured at recruitment (baseline), and their relationship with subsequent HRS investigated.Results43 patients were included. 12 (27.9%) developed HRS at 7.3 ± 5.1 weeks from baseline. Logistic regression analysis showed that baseline urinary NGAL and urinary KIM-1 were significantly associated with the development of HRS (RR 1.007, 95% CI 1.001–1.012, p = 0.014; RR 1.973, 95% CI 1.002–3.886, p = 0.049). The cut-off values for NGAL and KIM-1 to predict HRS were 18.72 ng/mL and 1.499 ng/mL respectively (AUCs 0.84, p = 0.005; and 0.78, p = 0.008).ConclusionUrinary NGAL and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic patients.     

Cox回归分析对肝肾综合征预后因素的评估

目的 探讨影响肝肾综合征(HRS)预后的参数及最佳预后指标。方法 对71例肝硬化合并HRS患者进行研究，以确诊HRS时间为基线，选择35个可能对肝肾综合征预后产生影响的临床及生物化学指标，通过Cox比例风险模型对患者预后进行多因素分析。结果Child-Pugh评分是HRS的独立危险因素，相对危险度=1．333，95％可信区间为(1．026，1．731)。结论 Child—Pugh评分是临床上判断HRS患者预后的最重要指标。     

Efficacy and safety of plasma diafiltration: Review of case reports and case series

Plasma diafiltration (PDF), a blood purification procedure that combines dialysis with plasma filtration by a selective membrane, has been used to treat acute liver failure, sepsis, and other acute conditions. We reviewed 14 eligible case reports and case series that examined PDF in 357 patients to assess its efficacy and safety. Fourteen diseases may be indications for PDF. The primary indication in the included studies was acute liver failure without obvious inducement or cause not mentioned. Eighty-three patients reached the primary endpoint (31 deaths, 52 recoveries) and the efficacy was 62.7%. There were large changes in 16 toxins or clinical markers after PDF, including total bilirubin, IL-18, IL-6. In conclusion, PDF appears to be an effective treatment for clearance of bilirubin and other inflammatory mediators in patients with acute liver injury or a disease characterized by a systemic inflammatory state. Randomized controlled trials are needed to compare PDF with other blood purification methods, such as plasma exchange and the Molecular Adsorbent Recirculating System™.     

血浆置换联合血液透析滤过治疗重型肝炎肝肾综合征

目的观察血浆置换(plasma exchange,PE)联合血液透析滤过(hemodiafiltration,HDF)治疗重型肝炎肝肾综合征(hepatorenal syndrome,HRS)的临床疗效。方法临床纳入重型肝炎HRS患者70例,根据临床治疗方案不同分为观察组和对照组。对照组给予PE治疗,观察组给予PE联合HDF治疗。观察两组患者治疗前后肝肾功能及电解质的变化、近期疗效及治疗前后细胞因子的变化。结果观察组近期治疗有效率(82.86%)高于对照组(51.43%),差异有统计学意义(P0.05);治疗前,两组患者血尿素氮(BUN)、血清肌酐(Scr)、血清总胆红素(TBIL)、NH3、白蛋白(ALB)、胆碱酯酶(CHE)、Na+、K+等水平相比,差异均无统计学意义(P0.05);治疗后,研究组BUN、Scr、TBIL、NH3、ALB、CHE、Na+、K+等水平均明显优于对照组,差异有统计学意义(P0.05);治疗前,两组患者IL-8、IL-10、TNF-α等水平相比,差异均无统计学意义(P0.05);治疗后,观察组IL-8、IL-10、TNF-α等水平均明显低于对照组,差异有统计学意义(P0.05)。结论 PE联合HDF治疗重型肝炎HRS,与单独PE治疗相比,具有较高的近期治疗有效率。此外,还能够改善肝肾功能及电解质平衡,减少促炎因子,提高抗炎因子,值得临床推广。