Managing liver failure

Liver disease is rare in childhood, but important new developments have altered the natural history and outcome. It is important that clinicians are aware of these diseases and their management. Acute liver failure is most often due to viral hepatitis, paracetamol overdose, or inherited metabolic liver disease. The clinical presentation includes jaundice, coagulopathy, and encephalopathy. Early diagnosis is necessary to prevent complications such as cerebral oedema, gastrointestinal bleeding, and renal failure. Early supportive management, in particular intravenous N-acetylcysteine, may be effective but liver transplantation is usually the definitive treatment and thus early referral to a specialist unit for liver transplantation is mandatory. Chronic liver failure may be due to unresolved neonatal liver disease, either inherited biliary hypoplasia or extrahepatic biliary atresia, while in older children, autoimmune liver disease or cystic fibrosis are the commonest causes. Treatment includes specific medication, nutritional support, and liver transplantation, which now has a 90% survival with good quality life.     

重型肝炎多器官功能衰竭52例临床研究

目的研究重型肝炎多器官功能衰竭的发生和转归。方法随机选取收治的重型肝炎患者共52例,研究其各器官衰竭的发生比例及与预后的关系。结果在重型肝炎时,器官功能衰竭的发生率由高到低依次为肝脏、血液系统、脑、胃肠系统和肾脏等;患者受累器官的数目多少与恶化病死率呈正相关。结论重型肝炎应采取综合治疗,在治疗肝炎的同时,注意保护其他器官系统的功能。     

When the heart kills the liver: acute liver failure in congestive heart failure

Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases.Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach.As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST), bilirubin, and international normalized ratio (INR) did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI) was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m² vs. 1.6 L/min/m², p = 0.04). Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock.In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.     

地西泮和莫达非尼对小鼠试验性急性肝衰竭的影响

目的：研究地西泮、莫达非尼对小鼠试验性急性肝衰竭的影响。方法：雄性昆明小鼠240只,给予D-半乳糖胺(D-GalN)和脂多糖（LPS）同时腹腔注射,制备小鼠急性肝衰竭模型;并于造模前2h,治疗组分别给予相应药物灌胃,对照组给予蒸馏水灌胃。比较各组小鼠的24h存活率,血清转氨酶水平,肝脏组织病理学改变,血清TNF-α,IL-1的水平,肝脏组织中SOD,MDA ,GR,１GSH,NO,NOS的水平。结果：地西泮可以提高小鼠存活率,减轻肝脏病变程度,降低血清转氨酶活性及TNF-α,IL-1的浓度,增加肝脏组织中SOD,GR的活性,降低NOS的活性及MDA,NO的浓度。莫达非尼可加重肝脏病变程度,升高血清转氨酶的活性及 TNF-α,IL-1的浓度,降低肝脏组织中SOD,GR的活性及升高MDA的浓度。结论 ：地西泮可减轻D-GalN/LPS所致的急性肝衰竭,提高小鼠的存活率,莫达非尼可加重小鼠的肝损伤。     

Acute liver failure

Acute liver failure is a complex multisystemic illness that evolves quickly after a catastrophic insult to the liver leading to the development of encephalopathy. The underlying aetiology and the pace of progression strongly influence the clinical course. The commonest causes are paracetamol, idiosyncratic drug reactions, hepatitis B, and seronegative hepatitis. The optimal care is multidisciplinary and up to half of the cases receive liver transplants, with survival rates around 75%-90%. Artificial liver support devices remain unproven in efficacy in acute liver failure.     

Accidental paracetamol overdosing and fulminant hepatic failure in children

OBJECTIVE: To delineate clinical characteristics useful for identifying children with liver failure due to accidental paracetamol overdose. DESIGN: Retrospective review of medical records of all patients admitted from 1985 to 1998 with fulminant hepatic failure. SETTING: Royal Alexandra Hospital for Children, a tertiary referral centre for paediatric liver transplantation. MAIN OUTCOME MEASURES: Contribution of paracetamol to liver failure; other risk factors for liver failure; comparison of clinical features of paracetamol group and others. RESULTS: 18 patients were identified. Eight were considered to have accidental paracetamol hepatotoxicity. In a further three, other risk factors were present but paracetamol was considered a major contributor to liver failure. The seven remaining patients had other risk factors for liver failure. Patients with paracetamol-induced liver failure usually had an acute prodromal illness with prolonged fasting and, at presentation, had encephalopathy, coagulopathy, very high transaminase levels, but disproportionately low total bilirubin levels. Five patients had hypoglycaemia. End-stage liver failure occurred in 4/11 of the paracetamol group compared with 7/7 of the others. CONCLUSION: Accidental paracetamol overdose is associated with fulminant hepatic failure in infants and children. Patients present with high transaminase levels and liver synthetic failure out of proportion to the level of serum bilirubin. Prompt identification of such patients is important as many recover with supportive therapy.     

IL-18和caspase-1在大鼠急性肝衰竭模型中表达及其意义

目的 了解IL-18与caspase1在大鼠急性肝功能衰竭的可能作用和机制.方法 模型组(n=50)D-氨基半乳糖(D-GalN)/脂多糖(LPS)诱导大鼠急性肝衰竭模型.对照组(n=10)以生理盐水代替药物.于不同时间点对大鼠血清和肝脏组织进行HE和TUNEL染色观察,并对血清ALT、AST和TBIL,IL-18 ...     

肝衰竭的诊断和治疗

肝衰竭是临床医生最具挑战性的疾病之一。迄今国际上尚无统一的命名、分类和诊断标准。肝衰竭至今尚无特效的治疗方法，目前仍强调内科综合治疗。肝移植巳成为治疗肝衰竭切实有效的手段，其它方法包括人工肝支持系统和肝细胞移植。     

不同剂量精氨酸对急性肝衰竭大鼠肝功能的影响

目的：探讨精氨酸对急性肝衰竭大鼠肝功能影响的剂量效应关系。方法：60只健康雄性Wistar大鼠按体重随机分为6组：A正常对照组,B肝衰竭对照组,C精氨酸强化Ⅰ组[0．4g/（kg·d）],D精氨酸强化Ⅱ组[0．8g/（kg·d）],E精氨酸强化Ⅲ组[1．6g／（kg·d）],F精氨酸强化Ⅳ组（3．2g／（kg·d）],观察给药14d后不同剂量精氨酸对肝衰竭大鼠肝功能的影响。结果：肝衰竭大鼠肝功能明显下降,转氨酶升高、血浆蛋白合成下降、凝血酶原时间延长。精氨酸强化后,各组肝功能指标均优于肝衰竭对照组,其中以0．8g／（kg·d）和1．6g／（kg·d）较好。结论：精氨酸剂量为1．6g／（kg·d）时对肝衰竭大鼠安全有效。     

An Experimental Study on the Disorders of Hepatic Hemodynamics and Changes of Plasma Histamine in Dogs with Fulminant Hepatic Failure

Alotofresearchprojectshavebeenconductedabouttherelationshipbetweenthehepatichemodynamicsandplasmavascularactivitysubstancesincirrhosiswithportalhypertension["ZJ.Buttherearefewarticlesaboutthechangesofhepatichemodynamicsandplasmahistamineinacutefulminanthepaticfailure.Themodeloffulminanthepaticfailureinducedbyacetaminophenwasestablishedindogstoobservethechangesofhepatichemodynamicsandplasmahistaminelevelsinportalvein,hepaticvein,abdominalaortaandinferiorvenacava.1MATERIALSANDMETHODS1'1E…     

慢加亚急性肝衰竭患者低磷血症的发生情况

目的探讨慢加亚急性肝衰竭患者低磷血症发生的情况及其与肝功能的关系。方法97例乙肝患者分为慢性肝炎组（30例）、肝硬化组（28例）、慢加亚急性肝衰竭组（39例）,检测电解质、肝功能．分析3组患者的电解质异常情况,低磷血症发生情况。结果慢性肝炎组低磷血症发生率为6．7％．肝硬化组为28．6％．慢加亚急性肝衰竭组为87．2％。3组血磷浓度分别为（1．11±O．18）mmo]／L、（0．88±0．24）mmol／L、（0．46±0．28）mmol/L,差异有统计学意义（P=0．000）。在肝衰竭组,轻中度和重度低磷血症患者的肝肾功能、凝血酶原活动度比较,差异无统计学意义。结论低磷血症是慢加亚急性肝衰竭患者常见的电解质紊乱．需要密切监测血磷情况。     

降钙素原、白细胞介素 6、sCD14、CD64 检测 在肝功能衰竭患者诊治中的临床研究

目的??研究降钙素原 （PCT） 、 白细胞介素 6 （IL-6） 、 sCD14、 CD64 检测对肝功能衰竭诊治的临床价值。 方法??选取承德医学院附属医院收治的 40 例肝功能衰竭合并细菌感染患者（感染组） 、40 例肝功能衰竭不合并 细菌感染患者（非感染组）及同期 40 例体检健康人员（对照组） 。分别通过双抗夹心酶联免疫吸附试验检测、 流式细胞仪检测研究对象血清 PCT、IL-6、sCD14、CD64。根据患者转归结果分为治愈好转组与病死组,比较 两组入院时血清 PCT、IL-6、sCD14、CD64 水平。通过受试者操作特征（ROC）曲线分析血清相关指标对肝 功能衰竭合并细菌感染的诊断效能。结果??与对照组比较,非感染组入院时血清 PCT、IL-6、sCD14、CD64 水 平均升高（ P <0.05） ; 与非感染组比较, 感染组患者入院时血清 PCT、 IL-6、 sCD14、 CD64 水平均升高（ P <0.05） ;感染组和非感染组患者治疗后血清 PCT、IL-6、sCD14、CD64 水平比治疗前均下降（ P <0.05） ; 感染组治愈好转率为 55.00%,低于非感染组的 77.50%,差异有统计学意义（ P <0.05） ; 与治愈好转组比较,病死组患者入院时血清 PCT、IL-6、sCD14、CD64 水平均升高（ P <0.05） ; 血清 PCT、IL-6、sCD14、CD64 诊断肝功能衰竭合并细菌感染曲线下面积（AUC）分别为 0.596、0.700、0.642 和 0.618,敏感性分别为 40.00%、69.16%、68.35%和 53.50%, 特异性分别为 84.00%、78.27%、67.80% 和 77.35%。结论??肝功能衰竭患者血清 PCT、IL-6、sCD14、CD64 水平均升高, 其对肝功能衰竭合并细菌感染诊断有一定的价值, 可作为患者预后转归评估有效指标。     

肝衰竭分期对HBV感染慢加急性肝衰竭预后判断的意义

目的 探讨肝衰竭分期对乙型慢加急性肝衰竭（HBV-acute-on-chronic liver failure,HBV-ACLF）预后判断的临床意义.方法 将我院2009年6月-2011年4月收治的422例HBV-ACLF患者作为研究对象,根据入组时病情及住院期间最差状态将患者分为早、中、晚期,分析其24周生存状况.结果 按入组时凝血酶原活动度（prothrombin activity,PA）、并发症情况判断的早、中、晚期患者分别有183例、133例、106例,4周时死亡率分别为18.58％、24.81％、79.25％,24周时死亡率分别为33.33％、45.11％、84.91％.按患者住院期间最差状态分期,199例患者属于晚期,24周死亡率为88.44％.根据入组后1个月内最高晚期肝病模型（model for end-stage liver disease,Meld）分值将422例患者分为5组,组间24周死亡率差异有统计学意义,但死亡率并未与Meld评分完全呈正比.结论 肝衰竭分期可更好地预测HBV-ACLF患者的24周死亡风险.     

51例药物性肝衰竭临床特征及生存分析

目的 分析51例药物性肝衰竭的病因、临床特点及预后相关因素,以加深对药物性肝衰竭的认识.方法 采用回顾性研究对51例药物性肝衰竭住院患者的用药史、临床表现、实验窜检查、并发症及预后相关因素进行综合分析.结果 51例患者中,引起肝衰竭的药物主要是中药(28例次,54.9%)和抗结核药(13例,25.5%),肝衰竭类型以急性(13.7%)、亚急性(78.4%)为主;并发症以肝性脑病、电解质紊乱和腹水为主;总治愈好转率为29.4%,无效组肝性脑病、电解质紊乱的发病率均高于好转组,差异有显著统计学意义(P＜0.01),通过对实验室指标分析表明,凝血酶原活动度在好转组与无效组之间差异有统计学意义(P＜0.01),而总胆红素、胆碱酯酶和总胆固醇在两组间差异无统计学意义.结论 药物性肝衰竭的致病药物主要是中药(包括成药及汤剂)和抗结核药,其治愈好转率低下,预后不良,用药过程中应予以严密监测.     

肝衰竭并发感染患者的临床特征分析

目的探讨肝功能衰竭合并感染患者的临床特点,指导临床治疗。方法对278例肝衰竭患者的继发感染发生率、常见感染部位和常见菌株及其构成,感染对预后影响等进行回顾性分析。结果 278例肝功能衰竭患者并发感染212例,感染率76.3%;其中医院感染47例(22.2%)。感染部位依次为腹腔(43.2%)、胆道系统(29.3%),呼吸系统(14.3%)和肠道(6.0%)。主要致病菌为白色念珠菌(39.3%)、大肠埃希氏菌(14.3%)、肺炎克雷伯菌(14.3%)、铜氯假单胞菌(10.7%)。278例肝衰竭总病死率33.8%,感染组病死率(41.0%),非感染组病死率(10.6%),两组差异有统计学意义(P0.01)。结论肝衰竭患者继发感染发生率高,感染是导致死亡的重要因素,有效控制继发感染,是提高肝衰竭患者存活率的重要手段。     

Intensive care management of acute liver failure

Acute liver failure represents one of the most challenging conditions in intensive care treatment. In most cases there is no causal medical therapy available for survive making the intensive care treatment as the most important management tool, as bridge to transplant or still the recovery of the liver! These patients frequently develop multi-organ failure, placing them at risk of hemodynamic disorder, cerebral edema, coagulopathy and various renal and metabolic complications.     

Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

The role of the high mobility group box 1 （HMGB-1） in acute hepatic failure and the effect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） levels were detected by the enzyme linked immunosorbent assay （ELISA）, the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system （P〈0.05）. It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.     

糖尿病对慢性重型肝炎病情的影响分析

目的分析慢性重型病毒性肝炎合并糖尿病,临床转归上的特点。方法回顾性分析慢性重型病毒性肝炎合并糖尿病患者肝功能各项指标、各种并发症以及转归。结果在相同住院时间段慢性重型病毒性肝炎合并糖尿病组患者胆红素值较无合并糖尿病组高（P〈0．05）,且合并糖尿病组患者起病后总胆红素增至峰值的时间延长（51．4±36．7Vs40．9±34．6d,P=0．039）,住院期间总胆红素恢复的速率更缓慢（P〈0．001）。合并糖尿病组患者更容易并发感染、肝肾综合症、肝性脑病（P〈0．05）。合并糖尿病组患者病情未愈或死亡的比例更高（54／87Vs46／121,P=0.001）。结论慢性重型病毒性肝炎合并糖尿病导致病情不易恢复,预后差。易并发感染、肝肾综合症、肝性脑病等,总胆红素增至峰值所需的时间延长,恢复缓慢。     

Fulminant hepatic failure in non-Hodgkin's lymphoma

Two patients with fulminant hepatic failure presenting during the course of non-Hodgkin''s lymphoma are described. One patient had no previous history of lymphoma whereas in the other a small bowel lymphoma had recently been diagnosed. Both patients had histological evidence of lymphomatous infiltrate in the liver and no other cause for the fulminant hepatic failure could be found. Neither patient responded to treatment with corticosteroids: the cautious use of combined chemotherapy may be justified.     

肝功能障碍患者并发感染的临床研究

目的了解肝功能障碍患者并发感染的特点,探讨引起感染的危险因素,为并发感染的防治提供参考和依据。方法回顾性分析2003年1月~2013年1月住院的521例肝功能障碍患者的资料,对病例的一般资料、感染部位、病原体种类等,采用SPSS13.0进行统计学分析,对非连续变量采用logistic回归分析。结果肝功能障碍患者并发感染率为35.7%(186例),最常见感染部位依次为呼吸道、消化道、泌尿道和腹腔,G-杆菌感染101例,G+球菌感染37例,混合感染35例,真菌感染13例。logistic回归分析结果显示血清白蛋白低等5个与感染相关的危险因素。结论肝功能障碍患者并发感染率高,不合理使用抗生素、介入性操作等多种因素可能在并发感染的发生中起作用。