免疫性和酒精性肝纤维化大鼠肝脏细胞质膜的蛋白质组学研究

目的 研究肝纤维化的发生机制,寻找新的与肝纤维化相关的生物学标志物. 方法将48只大鼠分为乙醇组、免疫组和对照组,分别进行乙醇灌胃、猪血清注射与等渗盐水注射处理.采用James's网状染色法染色并检测处理后第2、4、6、8周大鼠肝脏的病理学变化.将处理后第2、4、6、8周的各组大鼠分别处死4只后取肝,并将肝脏组织作匀浆处理,通过2次蔗糖密度梯度离心获得细胞质膜组分,用Western blot法检测细胞质膜的纯度.提取肝脏细胞质膜蛋白质,通过双向凝胶电泳分析各个时期的大鼠肝脏细胞质膜蛋白质,差异蛋白质点在酶解后经戴安纳升级液相色谱Ultimate 3000串联布鲁克高容量离子阱质谱HCT进行鉴定.并对被鉴定的差异蛋白质进行功能和定位的分类分析. 结果大鼠肝脏细胞质膜得到了有效富集.双向凝胶电泳分析第2周和第8周的大鼠肝细胞质膜蛋白质,共找到87个差异蛋白质点,这些蛋白质点经过质谱鉴定后对应于30个非冗余蛋白质,包括膜联蛋白A2,细胞支架角蛋白8和18. 结论膜联蛋白A2、细胞支架角蛋白8和18等蛋白质可成为肝纤维化诊断的新标志物.     

沉默结缔组织生长因子对大鼠肝纤维化的影响

目的 研究结缔组织生长因子(CTGF)小干扰RNA(siRNA)在CCl4诱导的大鼠肝纤维化模型中的抗肝纤维化作用及其对肝星状细胞(HSC)激活的影响.方法 雄性SD大鼠24只,随机分成4组.模型组:皮下注射CCl4及经门静脉注射等渗盐水,每3 d 1次,连续6周(给药频率与时间,下同);CTGF siRNA干预组:皮下注射CCl4及经门静脉注射CTGF siRNA ;对照siRNA干预组:皮下注射CCl4及经门静脉注射对照siRNA;正常对照组:经门静脉注射等渗盐水.用HE染色和Sirius red染色评估大鼠肝组织学变化,Western blot检测肝组织CTGF及α平滑肌肌动蛋白(α-SMA)的表达,免疫组织化学染色评估肝组织α-SMA阳性细胞数量.对实验数据用单因素方差分析或Kruskal-Wallis检验分析.结果 模型组及对照siRNA组大鼠肝组织CTGF及α-SMA蛋白表达显著上调,α-SMA染色阳性细胞数量明显增加.与模型组相比,CTGF siRNA组CTGF及α-SMA蛋白表达分别下调95%±2%和86%±11%(F值分别为21.234和12.473,P值均＜0.01);肝组织α-SMA染色阳性细胞数减少76%±9%(F=9.179,P＜0.01);组织学检查显示肝纤维化程度明显减轻.结论 siRNA沉默CTGF基因能显著减轻大鼠实验性肝纤维化,减少活化HSC数量可能是其改善肝纤维化的主要机制之一.     

醛固酮拮抗剂对肝纤维化大鼠NOX4蛋白表达的抑制作用

目的 探讨醛固酮拮抗剂对肝纤维化大鼠NOX4蛋白表达的抑制作用. 方法 体内实验:雄性Wistar大鼠24只,随机分为3组,每组8只.模型组:用四氯化碳(CCl4)油2.5 ml/kg皮下注射,3次/周;安体舒通组:CCl4油注射的同时予以安体舒通20 mg/kg灌胃,1次/d;对照组:用橄榄油皮下注射,于4周后处死实验动物取材.用HE染色观察肝组织形态结构;Masson染色进行METAVIR肝纤维化评分;免疫组织化学法检测NOX4蛋白的表达.体外实验:将大鼠HSC-T6细胞株与不同剂量的醛固酮(10-9、10-7、10-5 mol/L,观察剂量效应)作用不同时间(6、12、24h)以观察时间效应.给予醛固酮(Ald)1μmol/L、依普利酮1μmol/L预处理60min,再给予Ald刺激大鼠HSC-T6细胞,设立阴性对照组.Western blot方法检测NOX4蛋白的表达.采用Oneway ANOVA方差分析法,首先用Levene方法进行方差齐性检验,确定方差齐且整体比较组间差异有统计学意义后进一步做多重比较,多重比较采用LSD法. 结果 CCl4组纤维化程度较对照组明显增高(相对表达量为16.060±0.300比2.471±0.160),两组比较,差异有统计学意义.CCl4+Sp组纤维化程度较CCl4组低(相对表达量为5.761±0.152比16.060±0.300),两组比较,差异有统计学意义.免疫组织化学结果显示,与对照组相比,CCl4组NOX4蛋白表达明显增高(相对表达量为7.231±0.211比1.350±0.252),两组比较,差异有统计学意义.与CCl4组相比,CCl4+Sp组NOX4蛋白表达下降(相对表达量为4.270±0.242比7.231±0.211),两组比较,差异有统计学意义.Ald刺激HSC-T6细胞后NOX4蛋白表达增强,并呈时间、浓度依赖性,在10-5 mol/L浓度刺激24h达到峰值;与对照组相比,Ald组NOX4表达明显增加(相对表达量为0.710±0.011比0.316±0.015),两组比较,差异有统计学意义.与Ald组相比,Ald+依普利酮组NOX4的表达减少(相对表达量为0.615±0.014比0.710土0.011),两组比较,差异有统计学意义.结论 醛固酮拮抗剂通过抑制Ald诱导的氧化应激效应抑制肝纤维化大鼠NOX4蛋白的表达.     

大鼠肝纤维化肝组织中抗衰老标志蛋白和抗增殖蛋白的表达研究

目的 研究猪血清所致肝纤维化大鼠肝组织中抗衰老标志蛋白(RGN)、抗增殖蛋白(PHB)表达及谷胱甘肽复方注射液(CGII)对其的干预. 方法 健康雄性Wistar大鼠40只,随机分为正常组、造模组.正常组予等渗盐水腹腔注射0.5 ml/只,造模组予腹腔注射无菌猪血清0.5ml/只,每周两次,连续8周,随机处死造模大鼠4只行病理学检查,验证造模成功后,停止注射猪血清,剩余造模组大鼠随机分为纤维化组和CGII干预组.CGII干预组大鼠给予浓度60 mg/mlCGII肌肉注射;正常组和纤维化组均予等单位体质量容积的等渗盐水肌肉注射,每日一次,连续6周.取大鼠肝组织行HE及Masson染色.RT-PCR和免疫组织化学检测肝组织中RGN、PHB mRNA及蛋白质表达. 计量资料采用单因素方差分析,两两比较采用LDS检验,病理学半定量结果采用秩和检验分析. 结果 纤维化组大鼠肝组织RGN、PHB mRNA相对表达量分别为75.99±12.8、64.54±12.35较正常组的182.09±17.84、192.20±17.12明显减低,F值分别为105.646、347.232,P值均＜0.001,差异均有统计学意义;RGN、PHB相对蛋白表达量分别为10.85±2.81、14.5±2.75较正常组的61.08±7.10、55.86±4.23表达均明显降低,F值分别为226.343、525.889,P值均＜ 0.001,差异均有统计学意义.CGII干预后大鼠肝纤维化程度较纤维化组明显减轻(P值均＜ 0.001),肝组织RGN、PHB的mRNA和蛋白表达均较纤维化组明显增高,差异有统计学意义(P值均＜ 0.001).结论 RGN及PHB在猪血清所致大鼠肝纤维化肝组织表达降低.     

骨形成蛋白7干预肝纤维化小鼠肝组织E3泛素连接酶Arkadia表达的实验研究

目的 探索E3泛素连接酶Arkadia在CCl4所致肝纤维化小鼠肝组织中的动态表达,以及骨形成蛋白7 (BMP-7)对其的阻断作用. 方法 30只健康雄性ICR小鼠,随机分为正常对照组(6只)、模型组(18只)和BMP-7干预组(6只);模型组再按不同的时间点分为4周、8周和12周3个亚组.在小鼠双后肢皮下交替注射60％ CCl4/花生油溶液(5ml/kg),每周2次,共持续12周,制备肝纤维化模型;BMP-7干预组在皮下注射CCl4的同时,从第9周开始腹腔注射BMP-7 (300Pg/g)溶液,隔天1次,共4周.苏木素-伊红(HE)和Masson染色观察肝组织病理变化;RT-PCR、免疫组织化学和Western blot法检测肝组织中Arkadia的mRNA和蛋白质表达量.样本均数比较用单因素方差分析和(或)配对t检验,方差齐时采用LSD -t检验;相关性分析用Pearson直线相关分析法. 结果 成功建立了肝纤维化小鼠模型.模型组Arkadia、Smad7和TGFβ 1的mRNA表达量在纤维化过程中逐渐升高,12周时达高峰(相对表达量分别为1.3434±0.0149、1.2200±0.0093和1.1258±0.0065),BMP-7干预组表达量降低(相对表达量分别为0.9867±0.0169、0.9517±0.0120和0.9029±0.0085),与对照组(相对表达量分别为0.5398±0.0025、0.7467±0.0072和0.6318±0.0041)相比,差异有统计学意义(F值分别为812.801、451.462和998.957,P值均＜0.01);BMP-7干预组Arkadia、Smad7和TGF β1的mRNA表达明显低于12周模型组(t值分别为12.108、18.737和16.364,P值均＜0.01).正常肝组织中Arkadia、Smad7、TGF β1蛋白仅在汇管区少量表达(相对表达量分别为2.1702±0.0518、2.0798±0.0547和2.4515±0.0487),模型组中其表达量逐渐增加(12周的相对表达量分别为3.4198±0.0279、5.4480±0.0565和5.2619±0.0530),主要在汇管区和肝细胞胞质内表达,BMP-7干预后表达量降低(分别为3.1457±0.0424、3.5616±0.0491和3.5282±0.0195),与对照组相比,差异有统计学意义(F值分别为8.399、609.690和900.561,P值均＜0.01);与12周模型组相比,BMP-7干预组Arkadia、Smad7、TGF β1的蛋白质表达量明显降低(t值分别为23.438、11.667和42.889,P值均＜0.01).结论 Arkadia在肝纤维化进展过程中呈上升趋势,BMP-7具有抗肝纤维化作用并可以抑制纤维化过程中Arkadia的表达.     

肝纤维化小鼠肝组织血管新生特点及其形成机制

目的 探讨肝纤维化小鼠肝组织血管新生特点及其形成机制.方法 C57BL/6小鼠随机分为正常对照组与模型18 h、4周、8周组,共4组.采用CCl4诱导小鼠肝纤维化模型.天狼猩红染色观察肝组织胶原沉积;免疫荧光检测肝组织vWF蛋白表达,分析微血管密度;扫描电镜及透射电镜观察肝窦内皮结构;Western blot法检测肝组...     

肝内转移和多中心发生的多结节肝癌蛋白质表达谱的差异分析

目的 比较分析多结节肝癌的肝内转移癌灶和多中心发生癌灶的蛋白质表达谱,为更加准确的分子分型方法提供实验依据. 方法对5例肝内转移(IM)和6例多中心发生(MO)的多结节肝癌按照结节大小分为IM1、IM2、MO1、MO2四组,联合双向凝胶电泳与质谱技术分析多结节肝癌的蛋白质表达谱;并用Westem blot验证质谱结果.结果 双向凝胶电泳联合质谱技术鉴定IM1、IM2、MO1、MO2四组共30个差异蛋白质点,确认为25种差异表达的蛋白质;Gene Ontology 分类显示其与细胞运动、信号转导、氧化还原、脂类代谢、氨基酸代谢等有关. 结论多结节肝癌肝内转移和多中心发生的蛋白质表达不同;双向凝胶电泳联合质谱技术可作为二者分子分型的方法,有利于临床医师对肝癌患者实施治疗和判断预后.     

蓝莓对肝纤维化大鼠血红素加氧酶-1表达的影响

目的 观察蓝莓对大鼠肝纤维化的预防作用及对血红素加氧酶-1(HO-1)表达的影响.方法 45只SD大鼠随机分为生理盐水对照组(A组)、模型组(B组)、蓝莓汁预防组(C组)、丹芍化纤胶囊预防组(D组)及蓝莓汁加丹芍化纤胶囊预防组(E组),每组9只.CCl4复合因素制备大鼠肝纤维化模型,各预防组给予蓝莓汁或(和)丹芍化纤胶囊灌胃,共饲养8周.测定各组大鼠血清ALT水平及肝组织匀浆中超氧化物歧化酶(SOD)和丙二醛(MDA)的表达,并进行肝组织病理学检查.采用实时荧光定量聚合酶链反应、免疫组织化学法和Western blot分析大鼠肝组织HO 1的mRNA及蛋白质表达.多组间数据比较用单因素方差分析,等级资料用秩和检验.结果 B组大鼠血清ALT水平高于A组[(203.25±31.62)U/L比(57.25±6.88)U/L,F=92.498,P＜0.05)],各预防组较B组明显减少[C、D和E组分别为(149.44±16.51)U/L、(136.88±10.07)U/L和(127.38±11.03)U/L,F=92.498,P＜0.05)].C、D、E组大鼠肝组织匀浆SOD水平分别为(1.36±0.09)U/mg、(1.42±0.13)U/mg、(1.50±0.15)U/mg,高于B组的(1.08±0.19)U/mg(F=13.671,P＜0.05);MDA水平分别为(0.294±0.026)nmol/mg、(0.285±0.025)nmol/mg、(0.284±0.028)nmol/mg,低于B组的(0.335±0.056)nmol/mg(F=20.809,P＜0.05).各预防组肝纤维化程度较B组也有所减轻(x2-24.956,P＜0.05).B组大鼠肝组织HO-1的mRNA和蛋白质表达高于A组(F值分别为4.549和22.926,P值均＜0.05),各预防组大鼠肝组织HO-1的mRNA和蛋白质表达均高于B组,但差异无统计学意义(P＞0.05).结论 蓝莓对CCl4所致大鼠肝纤维化有一定的预防作用;在慢性肝损伤时,蓝莓对HO-1的表达无明显影响.     

沉默结缔组织生长因子对大鼠肝纤维化及细胞外基质积聚的影响

目的 研究结缔组织生长因子(CTGF)小干扰RNA(siRNA)在CCl4诱导的大鼠肝纤维化模型中的抗肝纤维化作用及其对细胞外基质积聚的影响.方法 雄性SD大鼠30只,随机分成5组.模型组:皮下注射CCl4及经门静脉注射等渗盐水,3 d 1次,连续6周;预防组:皮下注射CCl4及经门静脉注射CTGF siRNA,连续6周;治疗组:皮下注射CCl4 2周,随后给予CTGF siRNA及CCl4 4周;对照siRNA干预组:皮下注射CCl4及经门静脉注射对照siRNA,连续6周;空白对照组:经门静脉注射等渗盐水6周.用HE和Sirius red染色评估大鼠肝组织学变化,RTPCR或(和)Western blot检测肝组织CTGF、Ⅰ与Ⅲ型胶原及层黏连蛋白的表达,放射免疫法检测外周血Ⅲ型前胶原及透明质酸含量.结果 模型组及对照siRNA组大鼠肝组织CTGF、Ⅰ与Ⅲ型胶原及层黏连蛋白基因表达显著上调;与模型组相比,预防组及治疗组由CCl4诱导的CTGF mRNA和蛋白表达及Ⅰ与Ⅲ型胶原、层黏连蛋白mRNA表达分别下调76%±8%、95%±2%、74%±8%、78%±8%、31%±7%和80%±3%、93%±3%、57%±6%、59%±10%、43%±9%(F值分别为68.630,21.234,24.219,16.315和9.716,P值均＜0.01),肝纤维化程度明显减轻,大鼠外周血Ⅲ型前胶原和透明质酸含量也显著降低.结论 经门静脉注射CTGF siRNA能显著抑制实验大鼠肝CTGF基因表达,由此通过阻止细胞外基质积聚而缓解肝纤维化.     

瘦素特异性小干扰RNA对实验性肝纤维化的影响

目的 研究针对大鼠瘦素基因的小干扰(si)RNA对肝纤维化的治疗效果.方法 将40只雄性SD大鼠平均分为4组,正常对照组皮下注射橄榄油溶液3 ml/kg,2次/周,共6周;肝纤维化模型组皮下注射60% CCl4 3 ml/kg,2次/周,共6周;siRNA治疗组和阴性对照组均于皮下注射60% CCl4 3 ml/kg,2周后尾静脉分别注射siRNA或阴性对照质粒0.2 mg/kg.每周测体质量1次,根据体质量调整药物用量.设计针对瘦素mRNA的siRNA,并构建其表达载体;用脂质体方法通过尾静脉注射转染入CCl4诱导的肝纤维化大鼠体内,然后分别采用逆转录-聚合酶链反应、免疫组织化学方法检测瘦素与Ⅰ、Ⅲ型胶原在肝脏组织中的表达.免疫组织化学资料采用等级资料秩和检验.PCR结果采用单因素方差分析进行统计学处理,P＜0.05时用SNK法进行多重比较.结果 瘦素mRNA在正常对照组组、肝纤维化模型组、siRNA治疗组和阴性对照组的相对表达量分别为0.75±0.03、2.34±0.14、0.90±0.06、2.31±0.13,各组比较,F=797.64,P=0.000,差异有统计学意义;Ⅰ型胶原mRNA在各组的相对表达量分别为1.10±0.11、2.75±0.13、1.27±0.08、2.77±0.12,各组比较,F=695.71,P=0.000,差异有统计学意义;Ⅲ型胶原mRNA在各组的相对表达量分别为0.62±0.07、1.52±0.09、0.85±0.08、1.51±0.07,各组比较,F=371.57,P=0.000,差异有统计学意义.结论 针对瘦素基因的siRNA对肝纤维化有明显的治疗作用.     

Ultrasound liver elastography beyond liver fibrosis assessment

Several guidelines have indicated that liver stiffness(LS) assessed by means of shear wave elastography(SWE) can safely replace liver biopsy in several clinical scenarios, particularly in patients with chronic viral hepatitis. However, an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation, acute hepatitis, obstructive cholestasis, liver congestion, infiltrative liver diseases. This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure, congenital heart diseases or valvular diseases. In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events. The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS) and in the Budd-Chiari syndrome. In the hepatic SOS, an increase of LS is observed some days before the clinical manifestations;therefore, it could allow an early diagnosis to timely start an effective treatment.Moreover, it has been reported that patients that were successfully treated showed a LS decrease, that reached pre-transplantation value within two to four weeks. It has been reported that, in patients with Budd-Chiari syndrome, LS values can be used to monitor short and long-term outcome after angioplasty.     

Recurrent nonviral liver disease following liver transplantation

Recurrent disease after liver transplantation is well recognized and remains a potential cause of premature graft loss. The rates of recurrence are difficult to establish because of the lack of consistency in diagnostic criteria and approaches to diagnosis. Owing to the fact that recurrent parenchymal disease may occur in the presence of normal liver tests, those centers that use protocol biopsies will report greater rates of recurrence. It is important to recognize that rates of recurrence vary according to indication and show little correlation with rates of graft loss from recurrent disease. Recurrance rates are greatest for primary sclerosing cholangitis and autoimmune hepatitis, and low reccurrance rates are reported for alcoholic liver disease and recurrent primary biliary cirrhosis. The impact of recurrent nonalcoholic fatty liver disease is not yet clear. Patients and clinicians need to be aware of the possibility of recurrent disease in the differential diagnosis of abnormal liver tests, and management stategies may require alteration to reduce the impact of disease recurrence on outcome. Finally, an understanding of which diseases do recur after transplantation and identification of the risk factors may lead to a better understanding of the pathogenetic mechanisms of these conditions.     

脂肪性肝病与原发性肝癌

脂肪性肝病是隐原性肝硬化的主要原因之一,其经过肝硬化进展至原发性肝癌的过程已被认可,但是近年来越来越多的研究证实脂肪性肝病本身存在有促肿瘤形成的机制,它可以不经过肝硬化而直接进展成原发性肝癌,两者之间的具体机制还未明确.此文就脂肪性肝病向原发性肝癌进展的可能机制作一综述.     

Auxiliary liver transplantation for acute liver failure

BACKGROUND: In patients with acute liver failure (ALF) who fulfil criteria, liver transplantation is the only effective treatment which can substitute metabolic and excretory function of the liver. Auxiliary liver transplantation was developed because a significant minority of patients with ALF who fulfil transplant criteria can have a complete morphological and functional recovery of their liver. The favourable outcome reported in European series using auxiliary partial orthotopic liver transplantation (APOLT), the greater experience as well as the lessons from split liver and from living related donors have revived interest in this approach. In selected patients aged <40 years without haemodynamic instability, the use of ABO-compatible, non-steatotic grafts harvested from young donors with normal liver function can restore liver function and prevent the occurrence of irreversible brain damage. In the majority of cases the auxiliary graft is a right graft which is placed orthotopically after a right hepatectomy in the recipient. After standard immunosuppression, the recovery of the native liver is assessed by biopsies, hepatobiliary scintigraphy and computed tomography. When, on the basis of histological, scintigraphical and morphological data, there is evidence of sufficient regeneration of the native liver, immunosuppression can be discontinued progressively. Complete regeneration of the native liver can be observed in >50% of patients, who can be withdrawn from immunosuppression. Therefore the advantages of auxiliary transplantation seem to balance favourably with the potential inconvenience of this technique in selected patients.     

非酒精性脂肪性肝病与肝硬化

非酒精性脂肪性肝病（Nonalcoholic fatty liver disease, NAFLD）发病与胰岛素抵抗（Insulin resistance, IR） 和遗传易感性密切相关,病理学改变与酒精性肝病（Alcoholic liver disease, ALD）相似,但无过量饮酒史^[1]。在此要强调NAFL与NASH的不同,NAFL是指病理活检显示肝脏脂肪变性,但是不具有肝纤维化或气球样变性的肝细胞损伤。NASH指在肝脏脂肪变基础上出现气球样肝细胞损伤伴或不伴肝纤维化^[2],NASH发生肝纤维化、肝硬化、肝细胞癌风险明显增高,而NAFL则很低^[2],NASH是NAFL发生肝硬化的必经阶段^[3]。     

中国肝癌肝移植的现状与展望

肝癌行肝移植治疗的指征、效果和相关问题一直存在争论,国际上已经有数个通用的肝癌肝移植标准,如Milan标准、Pittsburgh标准、UCSF标准等等,中国的移植学家们也在纷纷探讨适合中国的肝癌肝移植标准.本文收集并分析近年来国内外的文献,结合本移植中心460例肝移植的病例,对肝癌的分期标准、晚期肝癌行肝移植的指征进行了探讨,笔者认为影响我国肝癌肝移植的主要因素有:供肝的来源、术后乙肝及肿瘤的复发及相关社会因素等.     

Chronic liver diseases as liver tumor precursors

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence increased over the past 4 decades in some Western countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most common cause of cancer mortality (behind only lung and colorectal cancer) with approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC almost entirely develops in the context of inflammation and organ injury and is related to cirrhosis in about 85% of the cases. Among underlying etiologies of liver cirrhosis, most frequent are viral infection and toxic substances, mostly alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus infection. Hepatitis C virus infection is the main risk factor in Western countries. Hereditary hemochromatosis is not a very frequent cause of liver cirrhosis, but these patients are at higher risk for HCC compared with other etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of plant mold, can play a role in some countries in Asia and Africa, and can have a synergistic effect with hepatitis B infection.     

Fatty liver in liver transplantation and surgery

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (> 60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (< 30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.