siRNA在实验性急性肝衰竭中的治疗作用研究进展

RNA干扰(RNA interference,RNAi)是指导入特异性针对目标基因的同源双链RNA,引起目标基因的不表达或减效表达.小干扰RNA(small interfering RNA或shortinterfering RNA,siRNA)是RNAi发挥作用的重要中间效应分子[1].siRNA具有潜在的临床治疗应用前景,目前至少有5种siRNA药物已进入临床试验[2].     

急性肝衰竭的研究概况

肝衰竭(ALF)是临床具有较高病死率的严重疾病之一,也是临床医生面临的最具挑战性的问题.ALF是肝细胞死亡的发生和程度与肝细胞的再生不平衡所产生.肝细胞死亡有两种形式,凋亡和坏死,其中急性肝衰竭引起的细胞死亡是与线粒体损伤程度密切相关.后者足以使三磷酸腺苷的贮存耗尽而引起多器官衰竭.     

急性肝衰竭的治疗进展

急性肝衰竭(acute liver failure,ALF)是指原来无肝脏疾病(主要指肝硬化)的患者,由于肝细胞大量坏死或功能丧失发生急性严重肝功能不全,导致以肝性脑病(hepatic encephalopathy,HE)和凝血功能障碍为主要特征的临床综合征。此综合征病情严重、临床症状复杂、病死率高。患者的生存率与病因、脑病程度及多器官衰竭密切有关,主要的死因是感染和进行性脑水肿。随着肝移植的开展,短期生存率超过境5%。尽管如此,急性肝衰竭的治疗仍面临一些挑战。1重症监护与一般治疗对于确诊的ALF的患者,尽早转入重症监护病房(ICU)中密切观察生命体征,严格消…     

慢加急性肝衰竭并发急性肾损伤的诊治进展

慢加急性肝衰竭(ACLF)是国内最常见的肝衰竭类型,临床表现复杂,病死率高。ACLF并发急性肾损伤(AKI)时患者住院时间延长,多器官衰竭风险更高,常提示预后不良。简述了近年来ACLF并发AKI的定义、诱因、预后判断、诊断标志物、治疗等方面取得的进展,认为早期识别诊断AKI,并予以干预,有助于逆转肾损伤,避免发生重症AKI。     

新生儿急性肝衰竭的病因、诊断及治疗

新生儿急性肝衰竭是发生在新生儿期的急性肝功能完全或大部分丧失、危及生命的一种少见疾病,出生后即可有肝硬化表现,病死率高。主要病因包括妊娠期自身免疫性肝病、病毒感染、血液病、代谢性疾病和缺血性损伤及其他罕见原因等。治疗手段主要为对因治疗,病因不明或既定治疗无反应患者,肝移植仍然是其一项重要的治疗选择。目前新生儿急性肝衰竭相关研究较少,因此需要对影响治疗和预后的因素进行前瞻性研究。     

美国肝病学会急性肝衰竭处置指南要点

1要点 1．1急性肝衰竭（acuteliverfailure,ALF）是发生于无肝病史患者的一种罕见临床症候群,患者因肝功能急剧恶化,表现为意识障碍和凝血功能紊乱。据估计,美国每年大约发生2000例ALF。     

儿童急性肝衰竭的病因及诊治

1 儿童肝衰竭的定义 肝衰竭是指多种因素引起的严重肝脏损害,导致其合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,出现以凝血机制障碍、黄疸、肝性脑病、腹水等为主要表现的一组临床症候群. 在国内,儿童肝衰竭又有儿童重症肝炎、小儿暴发性肝炎之称.儿童急性肝衰竭(pediatric acute liver failure,PALF)定义为原先无肝脏损害,8周内突发严重肝功能障碍,注射维生素K1无法纠正的凝血障碍,凝血酶原时间(PT)＞20 s或国际标准化比值(INR)＞2.0,可无肝性脑病;或肝性脑病合并凝血障碍,PT＞15 s或INR＞1.5.这一概念对儿童有不足之处,有些儿童代谢性疾病累及肝脏,平时无症状,可突然表现为急性肝衰竭(ALF),可有脑病症状,但和ALF无关.     

肝衰竭的治疗现状

肝衰竭是多种因素引起的严重肝损伤。对目前治疗肝衰竭采用的方法进行了总结归纳,公认的治疗方法有重症监护与支持治疗、针对病因治疗、调节免疫治疗、防治各种并发症、人工肝支持治疗以及肝移植等。认为肝衰竭的治疗更应强调内科-人工肝-肝移植的综合治疗模式,临床工作中坚持早诊断、早治疗,针对不同病因采取相应的综合治疗措施,积极防治各种并发症,同时还应建立多学科团队,制订个性化的诊疗方案,从而降低病死率,改善患者的临床结局。     

重庆地区急性肝衰竭病因和结局分析

目的了解重庆地区急性肝衰竭（acute liver failure,ALF）的病因和结局,评价英国皇家学院（King’s College Hospital,KCH）标准和终末期肝病模型（modelforend-stage liver disease,MELD）评分对其结局的判断价值。方法回顾性分析第三军医大学西南医院1999年12月-2008年4月国际标准化比值≥1．5,且伴有肝性脑病的ALF住院患者的病因与结局,用KCH标准和MELD评分预测患者的结局。结果共323例符合标准,纳入研究。270例（83．6％）病因为HBV感染,22例（6．8％）病因不明,16例（5．0％）为药物引起,15例（4．6％）由其他原因引起。24例（7．4％）失访。获随访的299例中,240例（80．3％）死亡,59例（19．7％）自然康复。KCH标准预测ALF患者死亡或存活的灵敏度、特异度、阳性预测值、阴性预测值和正确率分别为74．2％、64．4％、89．4％、38．0％和72．2％;MELD评分预测AIJF患者死亡或存活的上述指标分别为82．1％、61．0％、89．5％、45．6％和77．9％。结论重庆地区AIF的主要病因为HBV感染,KCH标准和MELD评分预测患者结局的阳性预测值较高,MELD评分的预测正确率高于KCH标准。     

肝衰竭的诊治进展

肝功能衰竭是危及生命的严重疾病,并发症多,预后较差。肝功能衰竭的治疗包括药物治疗、人工肝支持治疗、肝移植及干细胞移植等。近年来,在肝功能衰竭治疗方面有了较大进展,但现阶段多环节的内科综合治疗仍然非常重要。     

TECA hybrid artificial liver support system in treatment of acute liver failure

AIM:To assess the efficacy and safety of TECA type hybridartificial liver support system(TECA-HALSS)in providingliver function of detoxification,metabolism and physiologyby treating the patients with acute liver failure(ALF).METHODS:The porcine liver cells(1-2)×10~(10) wereseparated from the Chinese small swine and cultured in thebloreoctor of TECA-BALSS at 37.0℃ and circulated throughthe outer space of the hollow fiber tubes in BALSS.The sixliver failure patients with vadous degree of hepatic comawere treated by TECA-HALSS and with conventionalmedicines.The venous plasma of the patients wasseparated by a plasma separator and treated by charcoaladsorbent or plasma exchange.The plasma circulatedthrough the inner space of the hollow fiber tubes of BALSSand mixed with the patients' blood cells and flew back totheir blood circulation.Some small molecular weightsubstances were exchanged between the plasma andporcine liver cells.Each treatment lasted 6.0-7.0h.Physiological and biochemical parameters were measuredbefore,during and after the treatment.RESULTS:The average of porcine liver cells was(1.0-3.0)×10~(10) obtained from each swine liver using our modifiedenzymatic digestion method.The survival rate of the cellswas 85%-93% by trypan blue stain and AO/PI fluorescentstain.After cultured in TECA-BALSS bioreactor for 6 h,thesurvival rate of cells still remained 70%-85%.At the end ofTECA-HALSS treatment,the levels of plasma NH_3,ALT,TBand DB were significantly decreased.The patients who werein the state of drowsiness or coma before the treatmentimproved their appetite significantly and regainedconsciousness,some petients resumed light physical workon a short period after the trestment.One to two days afterthe treatment,the ratio of PTA increased warkedly.Duringthe treatment,the heart rates,blood pressure,respirationcondition and serum electrolytes(K~ ,Na~ and cr)werestable without thrombosis and bleeding in all the sixpatients.CONCLUSION:TECA-HALSS treatment could be a rapid,safe and efficacious method to provide temporary liversupport for patients with ALF.     

Aetiology and outcome of acute liver failure

Background:

Acute liver failure (ALF) is a clinical syndrome characterized by the sudden onset of coagulopathy and encephalopathy. The outcome is unpredictable and is associated with high morbidity and mortality. We reviewed our experience to identify the aetiology and study the outcome of acute liver failure.

Methods:

A total of 1237 patients who presented with acute liver failure between January 1992 and May 2008 were included in this retrospective study. Liver transplantation was undertaken based on the King''s College Hospital criteria. Data were obtained from the units prospectively collected database. The following parameters were analysed: patient demographics, aetiology, operative intervention, overall outcome, 30-day mortality and regrafts.

Results:

There were 558 men and 679 women with a mean age of 37 years (range: 8–78 years). The most common aetiology was drug-induced liver failure (68.1%), of which 90% was as a result of a paracetamol overdose. Other causes include seronegative hepatitis (15%), hepatitis B (2.6%), hepatitis A (1.1%), acute Budd–Chiari syndrome (1.5%), acute Wilson''s disease (0.6%), subacute necrosis(3.2%) and miscellaneous (7.8%). Three hundred and twenty-seven patients (26.4%) were listed for liver transplantation, of which 263 patients successfully had the procedure (80.4%). The current overall survival after transplantation was 70% with a median follow-up of 57 months. After transplantation for ALF, the 1-year, 5-year and 10-year survival were 76.7%, 66% and 47.6%, respectively. The 30-day mortality was 13.7%. Out of the 974 patients who were not transplanted, 693 patients are currently alive. Among the 281 patients who died without transplantation, 260 died within 30 days of admission (26.7%). Regrafting was performed in 31 patients (11.8%), the most common indication being hepatic artery thrombosis (11 patients).

Conclusion:

Paracetamol overdose was the most common cause of acute liver failure. Liver transplantation, when performed for acute liver failure, has good long-term survival.     

从慢加急性肝衰竭共识讨论到肝衰竭定义和分型诊断

2008年3月23-26日,第18届亚太肝脏研究学会(APASL)年会在韩国首尔召开.此次大会的主题为"肝脏病学新视野".     

Advances in the management of acute liver failure

Acute liver failure(ALF)is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver.The causes of ALF encompass a wide variety of toxic,viral,metabolic,vascular and autoimmune insults to the liver,and identifying the correct cause can be difficult or even impossible.Many patients with ALF develop a cascade of serious complications involving almost every organ system,and death is mostly due to multi-organ failure,hemorrhage,infection,and intracranial hypertension.Fortunately,the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology,and the advanced intensive care management.For most severely affected patients who fail to recover after treatment,rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop.This review focuses on the recent advances in the understanding of various contributing etiologies,the administration of etiology-specific treatment to alleviate the liver injury,and the management of complications(e.g.,encephalopathy,coagulopathy,cardiovascular instability,respiratory failure,renal failure,sepsis and metabolic disturbance)in patients with ALF.Assessment of the need for liver transplantation is also presented.     

非酒精性脂肪性肝病的治疗进展

非酒精性脂肪性肝病(NAFLD)在我国的发病率逐年攀升,已是严重影响我国居民健康的常见慢性疾病。介绍了生活方式的干预在NAFLD治疗中的地位,简述了药物在NAFLD治疗中的种类与价值,总结了改善肠道菌群在NAFLD治疗中的方法与途径,分析了外科手术干预在NAFLD治疗中的临床获益与经济效价。指出加强对NAFLD患者的有效管理可能是未来对该疾病治疗的一个新研究方向。     

Hyperlactatemia in patients with non-acetaminophen-related acute liver failure

AIM:To characterize hyperlactatemia in patients withnon-acetaminophen acute liver failure(ALF)in anattempt to clarify the mechanisms implicated and therole as a prognosis factor.METHODS:In the setting of liver transplantation,63consecutive patients with non-acetaminophen acute liverfailure were studied in relation to tissue oxygenation,hemodynamic and metabolic parameters.Before andafter transplantation,the number of infected patientsand outcome were registered.RESULTS:Acute ALF showed higher levels of lactatethan subacute ALF(5.4±1 mmol/L versus 2.2±0.6mmol/L,P=0.01).Oxygenation parameters were withinthe normal range.Lactate levels showed good correlationwith respiratory quotient(r=0.759,P<0.005),meanglucose administration(r=0.664,P=0.01)andencephalopathy(r=0.698,P=0.02),but not withsplanchnic arteriovenous difference in PCO2,pH and thepresence of infection(P=0.1).Portal vein lactate washigher(P<0.05)than arterial and mixed venous lactate,suggesting its production of hyperlactatemia in theintestine and spleen.The presence of infection was anindependent predictor of survival.CONCLUSION:Hyperlactatemia is not a prognosisfactor due to byproduct of the overall acceleration inglycolysis.