慢加急性乙型肝衰竭患者骨髓源性干细胞自发动员的影响因素

目的探讨慢加急性乙型肝衰竭患者骨髓源性干细胞自发动员的影响因素。方法入组慢加急性乙型肝衰竭患者66例,收集患者临床资料、血液生化、乙肝病毒学指标及外周血CD34+细胞计数,先后采用双变量回归、多元线性回归分析法对CD34+细胞计数峰值的影响因素进行分析。结果ALT(B=-0.244,P<0.001)、ALT/AST(B=-0.364,P<0.001)、AFP(B=-0.248,P=0.006)、淀粉酶(AMY)(B=0.681,P<0.001)、TG(B=0.578,P<0.001)、胆碱酯酶(CHE)(B=0.16,P=0.04)、国际标准化比值(INR)(B=-0.173,P=0.002)、WBC(B=0.373,P<0.001)对慢加急性乙型肝炎肝衰竭患者骨髓源性干细胞动员的影响具有统计学意义,R2=0.843。结论 ALT、ALT/AST、AFP、INR值与骨髓源性干细胞自发动员呈负相关,AMY、TG、CHE、WBC与骨髓源性干细胞自发动员呈正相关。

拉米夫定治疗病毒性肝炎乙型慢加亚急性肝衰竭临床观察

目的了解病毒性肝炎乙型慢加亚急性肝衰竭患者使用拉米夫定抗病毒治疗疗效、对预后的影响及不良反应。方法对65例病毒性肝炎乙型慢加亚急性肝衰竭患者,随机分为治疗组(31例)和对照组(34例),治疗组在综合治疗基础上加用拉米夫定抗病毒治疗。结果治疗组HBVDNA转阴率78.7%,对照组12.5%,治疗组好转率89.4%,对照组76.7%,死亡率治疗组10.5%,对照组23.26%。治疗组对照组治疗后比较,差异有显著性(P<0.05)。结论综合治疗基础上加用拉米夫定抗病毒,能有效抑制病毒复制,提高好转率,降低死亡率,且近期无明显不良反应。

NBAS基因突变致婴儿肝衰综合征2型1例并文献复习

目的分析NBAS基因突变所致婴儿肝衰竭综合征2型(ILFS2)的临床表现、诊断、治疗及预后情况,提高儿科医师对本病的认识,减少漏诊、误诊。方法对近3年在江西省儿童医院诊治的1例ILFS2患儿的临床资料进行回顾分析,并结合国内外文献,总结NBAS基因突变所致ILFS2的临床表现、诊断、治疗及预后的特点。结果(1)患儿每次发病时均有转氨酶的急剧升高,伴或不伴有胆汁淤积、高氨血症、凝血功能障碍、低血糖、乳酸堆积等代谢紊乱表现,且自然杀伤细胞计数及百分数均低于正常;(2)目前该病无特异性治疗,主要通过经验性感染、护肝、血浆置换及积极改善代谢紊乱等对症支持治疗,以改善内质网应激,恢复内质网及线粒体稳态;(3)远期预后仍有待大样本长期随访观察。结论儿童发热相关的复发性肝衰竭,应警惕NBAS基因突变所致ILS2,且ILS2多伴有免疫功能异常,尽早恢复内质网及线粒体稳态尤为重要。我们首次提出线粒体应激与ILS2发病可能相关,有待深入研究验证。

miRNA-17-5p在慢加急性肝衰竭合并乙型病毒性肝炎患者中的表达及与自噬相关蛋白表达的关系

目的:探讨微小RNA-17-5p(miRNA-17-5p)在慢加急性肝衰竭合并乙型肝炎(HBV-ACLF)患者中的表达水平及其与自噬相关蛋白Beclin1、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)表达的相关性。方法:选取2019年2月至2020年5月HBV-ACLF住院患者82例为HBV-ACLF组,选取同期住院治疗的慢性乙型肝炎(CHB)患者79例作为CHB组,选取同期健康体检者86例作为对照组。采用实时荧光定量PCR(qRT-PCR)法检测血清miRNA-17-5p水平;酶联免疫吸附(ELISA)法检测血清Beclin1、LC3-Ⅱ、总胆红素、白蛋白水平;PCR结合荧光探针的体外扩增技术测定血清HBV DNA载量;Pearson法分析HBV-ACLF患者血清miRNA-17-5p与Beclin1、LC3-Ⅱ、总胆红素、白蛋白、HBV DNA载量的相关性;受试者工作特征曲线(ROC)分析血清miRNA-17-5p、Beclin1、LC3-Ⅱ水平对HBV-ACLF的诊断价值;多因素Logistic回归分析影响HBV-ACLF发生的因素。结果:HBV-ACLF组患者血清Beclin1、LC3-Ⅱ、总胆红素水平高于CHB组和对照组,miRNA-17-5p、白蛋白低于CHB组和对照组(P<0.05);CHB组患者血清Beclin1、LC3-Ⅱ、总胆红素水平高于对照组,miRNA-17-5p、白蛋白低于对照组(P<0.05);HBV-ACLF组患者血清HBV DNA载量高于CHB组(P<0.05)。HBV-ACLF组患者血清miRNA-17-5p水平与Beclin1、LC3-Ⅱ呈负相关(r=-0.580、-0.511;均P<0.05);Beclin1、LC3-Ⅱ与总胆红素、HBV DNA载量均呈正相关,与白蛋白呈负相关(P<0.05);miRNA-17-5p与总胆红素、HBV DNA载量均呈负相关,与白蛋白呈正相关(P<0.05)。血清miRNA-17-5p、Beclin1、LC3-Ⅱ水平诊断HBV-ACLF的曲线下面积(AUC)分别为0.862、0.784、0.886,特异性分别为88.4%、80.2%、81.4%,敏感度分别为74.4%、63.4%、81.7%;三者联合诊断的AUC为0.915,特异性为88.4%,敏感度为82.9%。Beclin1、HBV DNA载量是影响HBV-ACLF发生的独立危险因素(P<0.05),miRNA-17-5p是影响HBV-ACLF发生的保护因素(P<0.05)。结论:HBV ACLF患者血清miRNA-17-5p表达水平降低,与Beclin1、LC3-Ⅱ呈明显负相关,且三者均对HBV-ACLF有一定的诊断价值。

恩替卡韦治疗慢性乙型病毒性肝炎慢加急性肝衰竭的价值

目的:分析恩替卡韦治疗慢性乙型病毒性肝炎慢加急性肝衰竭的价值。方法:选取本院2016年1月—2017年12月收治的72例慢性乙型病毒性肝炎慢加急性肝衰竭患者作为研究对象,按照随机数表法分为参照组和观察组,各36例。所有患者实行常规方式进行治疗。参照组使用阿德福韦酯片进行治疗,对观察组使用恩替卡韦分散片进行治疗,比较两组治疗效果以及治疗前后两组AST、ALB、ALT和胆红素等肝功能指标。结果:观察组的治疗效果优于参照组并且差异显著(P<0.05);治疗后观察组AST、ALB、ALT和胆红素等肝功能指标明显优于参照组,差异具有统计学意义(P<0.05)。结论:在对慢性乙型病毒性肝炎慢加急性肝衰竭治疗过程中,恩替卡韦分散片临床治疗成效非常显著,可以在一定程度上优化肝功能。

亚急性、慢性重症肝炎临床分型的必要性

经病理确诊的亚急性和慢性重症肝炎122例,依临床表现被分成重度黄疸腹水(SJ-A)型(93例,76.2％)和亚暴发肝衰竭(SFHF)型(29例,23.8％),二者之比为3.2:1。SFHF的突出特点是首发肝性脑病,腹水出现较晚或不出现,临床极易误诊为暴发性肝炎。与SJ-A型相比,本型平均血清胆红质较低,凝血酶原活动度下降更显著,提示肝坏死、肝衰竭进展迅速而严重。SFHF型病死率型显著高于SJ-A型,前者主要死于脑水肿或脑疝,后者主要死于出血、感染和肝肾综合征,故推测两型的发病机理可能不同。这种分型能更精确地反映肝衰竭的不同发展过程和特点,便于临床正确诊断。

护理风险预警机制在慢性乙型病毒性肝炎肝衰竭患者中的应用研究

目的探究护理风险预警机制在慢性乙型病毒性肝炎肝衰竭患者中的应用价值。方法方便选取2021年1月—2022年12月期间福建医科大学孟超肝胆医院诊治的96例慢性乙型病毒性肝炎肝衰竭患者为研究对象,以本院护理风险预警机制开展时间(2022年1月)为界将其分为A组、B组,各48例。A组实施常规护理干预,B组实施护理风险预警机制干预,比较两组患者护理前后肝功能[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)]水平、营养指标[前清蛋白(PAB)、白蛋白(ALB)、转铁蛋白(TRF)]、情绪状态[抑郁自评量表(SDS)、焦虑自评量表(SAS)]、并发症发生率及护理满意度。结果护理前,B组ALT、AST、TBIL水平与A组比较,差异无统计学意义(P>0.05)。护理后1个月,B组ALT、AST、TBIL水平低于A组,差异有统计学意义(P<0.05)。护理前,B组PAB、ALB、TRF水平与A组比较,差异无统计学意义(P>0.05);护理后1个月,B组PAB、ALB、TRF水平高于A组,差异有统计学意义(P<0.05)。护理前,B组SDS、SAS评分与A组比较,差异无统计学意义(P>0.05)。护理后1个月,B组SDS、SAS评分低于A组,差异有统计学意义(P<0.05)。B组并发症发生率较A组低(6.25%vs 25.00%),差异有统计学意义(χ^(2)=6.400,P<0.05)。B组护理满意度较A组高(97.92%vs 85.42%),差异有统计学意义(P<0.05)。结论在慢性乙型病毒性肝炎肝衰竭患者护理干预中实施护理风险预警机制护理,可改善肝功能及营养指标,改善不良情绪,降低并发症发生率,提升护理满意度。

甲亢合并严重肝损的治疗策略分析

目的比较甲亢合并严重肝损时针对甲亢的不同治疗方法,探讨有效的治疗方案。方法回顾性分析2003年6月～2017年6月来我院住院及随访的甲亢合并严重肝损的患者共47例(慢乙肝重度20例及肝衰竭27例)的临床资料,分析临床特点、针对甲亢的治疗分为未抗甲状腺治疗组、抗甲状腺药物治疗组、碘131组,比较不同治疗后结果。结果 20例慢乙肝重度患者未抗甲状腺治疗组4例好转,2例无效,抗甲状腺药物治疗组12例全部好转,碘131治疗组2例全部好转。抗甲状腺药物治疗组随访三个月,未出现肝损加重及白细胞减少等抗甲状腺药物副作用。肝衰竭患者中未抗甲状腺治疗组10例死亡7例、2例无效,1例好转。抗甲状腺药物治疗组9例好转,2例死亡。碘131组共6例,5例均好转,1例无效。抗甲状腺药物治疗组及碘131组有效率高于未抗甲状腺药物治疗组,差异比较有统计学意义(P <0.05);慢乙肝重度及肝衰竭患者中抗甲状腺药物治疗组及碘131治疗组FT3、ALT、TB较未抗甲状腺治疗组降低,差异比较有统计学意义(P <0.05),TSH较未抗甲状腺治疗组升高,差异比较有统计学意义(P <0.05)。结论甲亢合并严重肝损的治疗主要是针对不同的病因采用不同治疗方法,严重肝损的患者在排除甲状腺药物导致的肝损的基础上使用抗甲状腺药物是安全有效的,碘131治疗前后联合血浆置换是治疗肝衰竭的有效办法,建议在肝功能好转后再开始使用碘131。

新神经母细胞瘤扩增序列基因突变致婴儿肝衰竭综合征2型一例并文献复习

目的通过临床病例及文献复习,了解神经母细胞瘤扩增序列(NBAS)基因突变相关的儿童急性肝衰竭临床特征,探讨该病的治疗措施和预后情况。方法对1例NBAS基因突变致儿童复发性肝衰竭的临床病例进行整理报道;以“急性肝衰竭”“NBAS”“婴儿肝衰竭综合征2型”为关键词,对中国期刊全文数据库、万方数据知识服务平台进行检索,以“acute liver failure”“NBAS”为关键词,对Web of Science数据库、PubMed进行检索,对数据库建库至2023年1月收录的文献进行复习,总结该病发病机制、临床特征、治疗及预后。结果患儿,男,8月龄至1岁4月龄间发生急性肝衰竭3次,病初有呼吸道感染病史,后出现发热、呕吐、精神萎靡,入院辅助检查提示谷丙转氨酶、谷草转氨酶异常升高,凝血功能障碍。高通量测序发现患儿存在NBAS基因c.1857G>T(p.G619G)/c.3596G>A(p.C1199Y)复合杂合变异。入院后予低脂低蛋白饮食、保肝降酶、白蛋白补充、人纤维蛋白原及凝血酶原复合物补充、维生素K1补充、抗感染等治疗,好转出院。现患儿生长发育如同龄儿,定期随访中。通过文献复习,共收集符合条件的中国儿童病例31例。婴幼儿期起病占83.9%(26/31),起病急,进展快;主要为上呼吸道感染、发热后起病,严重者早期可出现肝性脑病,可合并有低血糖症、低蛋白血症、凝血障碍、T细胞免疫紊乱;最终通过全外显子二代测序确诊;治疗方案以对症治疗为主;疾病早期积极退热、护肝降酶,一般预后良好。结论NBAS双等位基因突变有明确致病性,急性肝衰竭为重要临床特征。对于反复出现发热后肝衰竭的婴儿,应考虑进行遗传检测。

婴儿肝衰竭综合征1型一家系临床及遗传学特征

目的分析婴儿肝衰竭综合征1型(ILFS1)一家系的临床特点和致病基因突变,总结本病的临床表型与基因型及相互关系。方法对2016年10月河北医科大学第二医院收治的ILFS1先证者的临床资料、体格检查、相关实验室检查(包括肝功能、凝血常规、肝纤维四项、肝炎筛查、TORCH10项及肝胆动态显像等)进行回顾性分析。提取先证者及其父母外周血基因组DNA,采用代谢性肝病相关基因外显子组捕获二代高通量测序技术对临床诊断ILFS1患儿进行检测,同时采用Sanger测序技术对患者胞质亮氨酰-tRNA合成酶基因(LARS)突变进行验证。结果先证者为4月龄女婴,低出生体质量(1950g),早期生长迟缓,肝损伤,重度淤胆。天门冬氨酸氨基转移酶(AST):115.5U/L(13~35U/L),γ-谷氨酰转肽酶257U/L(7~45U/L),总胆汁酸176.9μmol/L(0~10μmol/L)。总胆红素134.27μmol/L(3.4~17.1μmol/L),结合胆红素115.44μmol/L(0~6.8μmol/L),肝肋下4cm,剑下3cm。并中度小细胞低色素性贫血,顽固性低蛋白血症,迁延下呼吸道感染后导致急性肝衰竭。父母及姐姐临床表型均正常。该家系先证者为LARS基因c.2422delA(Thr808fs)/c.478A>G(p.Ile160Val)复合杂合突变,父亲为c.2422delA(Thr808fs)携带者,母亲及姐姐为c.478A>G(p.Ile160Val)携带者,此2个基因突变为首次发现。本先证者为世界第12例ILFS1患者。结论低出生体质量、早期生长迟缓、小细胞性贫血、低蛋白血症、复发肝功能障碍和婴儿期急性肝衰竭为ILFS1的典型临床特点,ILFS1患者存在因各种感染触发的脑病和肝衰竭致命的风险,建议早期入院,积极干预,尽可能降低病死率。

一例小儿肝衰竭综合征2型患儿的临床特征及基因变异分析

目的分析1例小儿肝衰竭综合征2型患儿的临床特征及基因变异特点, 探讨其分子遗传学发病机制。方法对1例小儿肝衰竭综合征2型患儿进行临床特点总结、二代测序及基因致病性分析。结果发现患儿NBAS基因存在复合杂合变异, 包括一个位于第24外显子的新杂合无义变异c.2746A>T(p.R916X, 1456)与一个已知的第31外显子c.3596G>A(p.C1199Y)错义变异, 患儿父亲携带c.2746A>T杂合变异, 母亲携带c.3596G>A杂合变异, 患儿的变异分别源自其父亲和母亲。经检索发现c.2746A>T变异为未报道过的新变异, c.3596G>A变异为已报道与小儿肝衰竭综合征2型相关的变异。结论 NBAS基因c.3596G>A和c.2746A>T变异是该小儿肝衰竭综合征2型患儿的致病原因。

新生儿期起病的婴儿肝衰竭综合征1型1例

本文报告1例婴儿肝衰竭综合征1型早产儿,生后早期出现直接胆红素和总胆汁酸进行性升高、纤维蛋白原降低、顽固性低蛋白血症、肝功能损伤及凝血功能异常,予保肝利胆、纠正低蛋白血症、贫血及凝血功能等治疗效果欠佳。全外显子基因检测结果提示LARS1基因c.497T>C(p.L166P)和c.2806T>C(p.C936R)复合杂合变异,转院治疗后5月龄死亡。

TypeⅠinositol 1, 4, 5-triphosphate receptors increase in kidney of mice with fulminant hepatic failure

AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.

An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

AIM:To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acuteon-chronic liver failure(HBV-ACLF).METHODS:Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed.Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS:A total of 190 patients were included in this study.The overall 1-year survival rate was 57.6%.Patients not treated with antiviral drugs had a significantly higher mortality[relative risk(RR)=0.609,P=0.014].The highest risk of death in patients with ACLF was associated with hepatorenal syndrome(HRS)(RR=2.084,P=0.026),while other significant factors were electrolyte disturbances(RR=2.062,P=0.010),and hepatic encephalopathy(HE)(RR=1.879,P<0.001).CONCLUSION:Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate.HRS,electrolyte disturbances,and HE also affect patient survival.

A Macaca mulatta model of fulminant hepatic failure

AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin.Clinical features,biochemical indexes,histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS:Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration.Coagulation activity was significantly decreased.Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h.The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h,respectively.The autopsy showed typical yellow atrophy of the liver.Hepatic encephalopathy of the models was also confirmed by hepatic coma,MRI and pathological changes of cerebral edema.The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices,imaging and histopathology.CONCLUSION:We have established an appropriate large primate model of FHF,which is closely similar to clinic cases,and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.

Tumor necrosis factor alpha increases intestinal permeability in mice with fulminant hepatic failure

AIM:To determine the effect of tumor necrosis factor alpha(TNF-α) on intestinal permeability(IP) in mice with fulminant hepatic failure(FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate as an index of IP,induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-α,assessed the results using an enzymatic-spectrophotometric method,transmission electron microscopy,immunohistochemistry,Western blotting and real-time quantitative polymerase chain reaction.The effect of the administration of antiTNF-α immunoglobulin G(IgG) antibody,before the administration of D-galactosamine/lipopolysaccharide,on TNF-α was also assessed.RESULTS:IP was significantly increased in the mouse model of FHF 6 h after injection(13.57 ± 1.70 mg/L,13.02 ± 1.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.001).Electron microscopic analysis revealed tight junction(TJ) disruptions,epithelial cell swelling,and atrophy of intestinal villi.Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models(occludin:0.57 ± 0.159 fold vs baseline,P = 0.000;claudin-1:0.3067 ± 0.1291 fold vs baseline,P = 0.003),as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein(occludin:0.61 ± 0.0473 fold vs baseline,P = 0.000;claudin-1:0.6633 ± 0.0328 fold vs baseline,P = 0.000).Prophylactic treatment with antiTNF-α IgG antibody prevented changes in IP(4.50 ± 0.97 mg/L vs 3.76 ± 0.67 mg/L,P = 0.791),intestinal tissue ultrastructure,and the mRNA levels of occludin and claudin-1 expression(occludin:0.8865 ± 0.0274 fold vs baseline,P = 0.505;claudin-1:0.85 ± 0.1437 fold vs baseline,P = 0.1),and in the protein levels(occludin:0.9467 ± 0.0285 fold vs baseline,P > 0.05;claudin-1:0.9533 ± 0.0186 fold vs baseline,P = 0.148).CONCLUSION:Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1,and destruction of the TJ in the colon,which were induced by TNF-α in FHF mice.

Predictors of the outcomes of acute-on-chronic hepatitis B liver failure

AIM： To identify the risk factors in predicting the out- come of acute-on-chronic hepatitis B liver failure pa- tients. METHODS： We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus （ACLF-HBV） and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy. Their demographic, clinical, and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test, Fisher＇s exact test, and a multiple logistic regres- sion analysis. RESULTS： The study included 113 patients （87 men and 26 women） with a mean age of 49.84 years. Fifty- two patients survived, and 61 patients died. Liver failure （85.2%）, sepsis （34.4%）, and multiple organ failure （39.3%） were the main causes of death. Mul- tivariate analyses showed that Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱ scores ≥ 12 [odds ratio （OR） = 7.160, 95% CI： 2.834-18.092, P 〈 0.001] and positive blood culture （OR = 13.520, 95% CI： 2.740-66.721, P = 0.001） on the day of diagnosis and model for end-stage liver disease （MELD） scores 28 （OR = 8.182, 95% CI： 1.884-35.527, P = 0.005） after the first week of treatment were independent predictors of mortality. CONCLUSION： APACHE II scores on the day of diag- nosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF- HBV patients.

Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure

AIM:To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure(ALF).METHODS:Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h.Plasma samples were withdrawn every five hours from a central vein.Three animals were used as controls and were maintained under anaesthesia only.Using 1 H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma samples.RESULTS:No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia only.If we look at the ALF animals,we observed a statistically significant rise of lactate(P<0.003)and pyruvate(P<0.018) at the end of the experiments.We also observed statistically significant rises in the concentrations of alanine(P<0.002),glycine(P<0.005),threonine(P< 0.048),tyrosine(P<0.000),phenylalanine(P<0.000) and isoleucine(P<0.01).Valine levels decreased significantly(P<0.05).CONCLUSION:Our pig model of ALF is characterized by an altered gluconeogenetic capacity,an impaired tricarboxylic acid(TCA)cycle and a glycolytic state.