慢性乙型肝炎患者血清肝纤维化指标与病理的关系

目的探讨慢性乙型肝炎患者血清肝纤维化指标透明质酸（HA）、Ⅳ型胶原（IV—C）、层粘连蛋白（LN）及Ⅲ型前胶原（PCⅢ）与肝脏病理的关系。方法慢性乙肝患者40例,行肝穿刺,制片,HE染色及浸银染色后作病理学检查;取血,分离血清,应用放射免疫法检测HA、IV—C、LN及PCⅢ水平,对肝组织进行炎症活动度分级（G）及纤维化分期（s）。结果40例慢性乙肝患者血清HA、Ⅳ-C、LN及PCⅢ水平随肝脏炎症活动度升高而升高,随肝组织纤维化程度的加重而升高。结论血清HA、Ⅳ-C、LN及PCⅢ水平与肝组织纤维化程度呈正相关。检测上述指标有助于判断肝炎疾病的严重程度,并能反映肝组织纤维化程度。     

双环醇对慢性乙型肝炎患者肝星状细胞活化和胶原合成的影响

目的:观察双环醇对慢性乙型肝炎(乙肝)患者肝组织炎症、纤维化程度、肝星状细胞活化和胶原合成的影响,探讨其抗纤维化作用机制。方法:20例慢性乙肝患者以双环醇150mg/d治疗24周,治疗前、后分别行肝穿刺活体组织病理学检查,评估治疗前、后肝组织炎症及纤维化程度;并应用免疫组织化学技术和彩色病理图文分析系统观察治疗前、后肝组织内α平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)表达状况和Ⅰ、Ⅲ型胶原含量的变化。结果:慢性乙肝患者经双环醇治疗后,其血清丙氨酸氨基转移酶(ALT)和γ谷氨酰转移酶(γ-GT)水平可显著降低,复常率分别达95%和70%,不仅肝组织炎症和纤维化程度明显改善,且肝组织内α-SMA和TGF-β1的表达强度明显减弱,同时Ⅰ、Ⅲ型胶原的含量也较治疗前明显降低。结论:双环醇治疗可减轻慢性乙肝患者肝脏炎症反应和纤维化程度,同时明显降低肝组织内TGF-β1、α-SMA的表达,阻止肝星状细胞活化和Ⅰ、Ⅲ型胶原的合成,从而发挥抗纤维化作用。     

慢性乙型肝炎患者ALT、HBV DNA及血清肝纤维化标志物与肝纤维化程度的关系

目的探讨ALT、HBV DNA以及血清纤维化标志物透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原(CⅣ)与慢性乙型肝炎肝纤维化程度的关系。方法检测281例慢性乙型肝炎患者血清中ALT、HBV DNA和纤维化标志物(HA、LN、PⅢP及CⅣ)的水平,并行肝活检检测肝组织病理纤维化分期。结果 HBeAg阴性慢性乙型肝炎患者HBV DNA水平较低、纤维化程度较高。HBeAg阳性患者纤维化程度与HBV DNA呈负相关(r=-0.251,P<0.001),S≥3组水平最低。慢性乙型肝炎患者纤维化程度与PⅢP水平呈正相关,其水平随着纤维化程度的加重而明显升高。结论 PⅢP水平可能作为评估慢性乙型肝炎患者肝纤维化程度的血清学指标,血清HBV DNA与肝脏纤维化严重程度的关系仍需进一步深入探讨。     

肝爽颗粒联合阿德福韦酯治疗肝纤维化的疗效分析

目的观察肝爽颗粒抗肝纤维化的疗效。方法选取本院2010年7月-2013年1月收治的68例慢性乙型肝炎肝硬化患者,分为试验组和对照组,每组34例。2组患者均治疗12个月,在单独使用阿德福韦酯治疗6个月后,试验组同时使用肝爽颗粒6个月,而对照组不用肝爽颗料。观察比较2组患者治疗前后肝纤维化血清指标:透明质酸(HA),层粘连蛋白(LN),Ⅳ型胶原(CⅣ),Ⅲ前胶原(PCⅢ)水平及肝脏硬度指标的变化。治疗前后比较采用配对t检验。结果试验组治疗前后血清HA、LN、CⅣ和PCⅢ值分别下降37.5%、34.2%、35.4%和39.9%,肝硬度值下降40.6%,治疗前后差异有统计学意义(t=2.238、2.151、2.148、2.189、2.189,P均0.05),而对照组治疗前后上述指标差异无统计学意义。结论肝爽颗粒可改善乙型肝炎肝硬化患者血清肝纤维化标志物水平及降低肝硬度值,表明其有抗肝纤维化疗效。     

透明质酸、层粘连蛋白、Ⅲ型前胶原和Ⅳ型胶原血清学指标对肝硬化诊断的价值

目的:评价血清纤维化指标对于诊断肝硬化的应用价值。方法:52例经肝穿刺确诊为慢性乙型肝炎及肝硬化患者,应用放射免疫法检测血清HA(透明质酸)、LN(层粘连蛋白)、PCⅢ(Ⅲ型前胶原)、CⅣ(Ⅳ型胶原)水平。结果:肝脏病理炎症及纤维化分级与血清HA、LN、PCⅢ、CⅣ水平有显著相关性,组间对比部分有统计学意义,炎症分级组较为明显。结论:检测血清HA、LN、PCⅢ、CⅣ水平对于判断肝脏炎症及纤维化程度有一定价值和意义。     

依那普利联合鸦胆子油对肝硬化模型大鼠肝纤维化的影响

目的通过研究依那普利联合鸦胆子油对肝硬化模型大鼠肝脏纤维化的影响,探讨其作用机制。方法将SD大鼠随机分为空白组、模型组、鸦胆子油组、依那普利组、两药联合组,采用0.5%二甲基亚硝胺(DEN)生理盐水溶液腹腔注射制备大鼠肝硬化模型。各组给药治疗后,取大鼠血清检测反映肝功能的总胆红素(T-Bil)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)、白蛋白(Alb)、总蛋白(TP)以及肝纤维化相关指标Ⅲ型前胶原(PⅢ)、透明质酸(HA)、层黏蛋白(LN)和Ⅳ型胶原(CⅣ)的含量。另外,利用ELISA法测定血清α-肌动蛋白(SMA)、基质金属蛋白酶组织抑制因子(TIMP)-1、细胞间黏附分子(ICAM)-1和基质金属蛋白酶(MMP)-1的表达情况,取部分肝脏进行HE染色观察肝脏病理形态变化。结果与空白组相比,模型组血清中T-Bil、ALT、AST、GGT、PⅢ、HA、LN、CⅣ、α-SMA、TIMP-1、ICAM-1和MMP-1含量均显著升高,而Alb和TP含量明显降低(P<0.05,P<0.01)。HE染色显示模型组大鼠肝脏出现炎性细胞活动及纤维组织增生等病理改变。与模型组比较,单一用药组血清中T-Bil、ALT、AST、GGT、PⅢ、HA、LN、CⅣ含量有所降低,而Alb和TP含量有所升高,其中鸦胆子油组的差异有统计学意义(P<0.05);联合用药组血清中T-Bil、ALT、AST、GGT、PⅢ、HA、LN、CⅣ含量降低更明显,而Alb和TP含量显著升高(P<0.01)。大鼠肝组织病理状态也有所改善,其中联合用药组比单一用药组的肝脏组织状态、炎性细胞浸润及纤维组织增生情况明显改善,受损肝小叶结构极少,没有间隔出现。结论依那普利联合鸦胆子油可协同治疗肝硬化,同时也减轻肝脏功能的损害,使肝纤维化症状得到改善,且效果比单一用药好。因此,依那普利与鸦胆子油联合用药对提高肝硬化的治疗效果有着重要的临床意义。     

IFNα-2b对CHB患者血清肝纤维化和肝功能指标的影响

目的 观察IFNα-2b对慢性乙型肝炎（CHB）患者肝纤维化水平和肝功能的影响.方法 对63例CHB患者予IFNα-2b 500 U肌注,隔日1次,连续治疗3个月.治疗前后检测血清肝纤维化指标Ⅲ型前胶原氨基末端肽（PⅢP）、Ⅳ型胶原（CⅣ）、层粘连蛋白（LN）、透明质酸（HA）和肝功能指标ALT、AST、总胆红素（TB）、白蛋白（A）和球蛋白（G）.结果 治疗后CHB患者血清PⅢP、CⅣ、LN、HA及ALT、AST、TB、A水平均显著低于治疗前（P均＜0.01）,血清G水平显著高于治疗前（P＜0.01）.结论 IFNα-2b可改善CHB患者的肝纤维化水平和肝功能.     

蝎仙口服液治疗慢性肝病肝纤维化的临床研究

目的：观察自制中药蝎仙口服液对慢性肝病肝纤维化的临床疗效。方法：60例慢性肝病肝纤维化患者随机分为两组：治疗组30例给予蝎仙口服液口服，对照组30例则予安慰剂生理盐水口服，两组均常规使用肝太乐、肌苷、VitC、VitBco片口服；治疗前后检测患者血清透明质酸（HA）、层粘蛋白（LN）、Ⅳ型胶原（Ⅳ-C）水平，观察主要症状和体征，肝功能指标及肝脏B超声像图情况。结果：治疗组治疗前后HA、LN和Ⅳ-C的水平比较差异有显著性意义（P〈0．01）。两组间在脾脏回缩、ALT、Alb、GGT及HA、LN和Ⅳ-C方面比较差异有显著性意义（P〈0．01）。结论：蝎仙口服液对慢性肝病肝纤维化患者有较好的抗肝纤维化作用。     

肝纤维化分期和血清生化学关系的研究

目的：探讨肝纤维化程度与血清纤维化标志物的关系。方法：67例肝炎患者均作肝脏活组织检查,标本行苏木精伊红染色（HE）和免疫组化染色,用光镜确定肝组织纤维化分期。采用放 射免疫法测定血清透明质酸（HA）,Ⅲ型前胶原（PCⅢ）,层粘连蛋白（LN）、Ⅳ型胶原（ⅣC）含量。结果：随着肝组织纤维化程度增加（S1→S4）,血清HA、PCⅢ、LN、ⅣC水平呈同步升高,在纤维化分期为S4时,含量最高。血清HA、PCⅢ、LN、ⅣC含量与慢性肝炎疾病进展呈一致性,随疾病加重而升高,在肝硬化阶段处于最高水平。结论：肝组织纤维化分期与血清HA、PCⅢ、LN、ⅣC有较好的相关性,血清纤维化指标可作为反映肝纤维化程度的指标之一。     

前列腺素E1治疗慢性乙型肝炎108例疗效观察

目的：探讨治疗乙型肝炎（乙肝）及抗肝纤维化的有效方法。方法：采用前列腺素E1（PGE1）静脉滴注治疗慢性乙肝患者108例（治疗组），并与行综合治疗90例（对照组）疗效比较，观察两组治疗前后，后血清Ⅲ型前胶原（PCⅢ），层粘蛋白（LN）、透明质酸（HA）、Ⅳ型胶原（Ⅳ－C）、肝功能等指标变化。结果：治疗组血清肝纤维化指标（PCⅢ、LN、HA、Ⅳ－C），丙氨酸转氨酶，天冬氨酸转氨酶，总清总胆红素均明显降低，与治疗前及对照组比较差异均有非常显著性意义（均P＜0．01），结论：PGE1具有较好的保肝和抗肝组织纤维化作用。     

Current management of liver diseases and the role of multidisciplinary approach

Liver is an organ having extremely diversified functions, ranging from metabolic and synthetic to detoxification of harmful chemicals. The multifunctionality of the liver in principle requires the multidisciplinary and pluralistic interventions for its management. Several studies have investigated liver function, dysfunction and clinic. This editorial work discusses new ideas, challenges and perspectives of current research regarding multidisciplinary and pluralistic management of liver diseases. In one hand the discussions have carried out on the involvement of extracellular vesicles, Na⁺/H⁺ exchangers, severe acute respiratory syndrome coronavirus 2 and Epstein–Barr virus infections, Drug-induced liver injury, sepsis, pregnancy, and food supplements in hepatic disorders. In the other hand this study has discussed hepatocellular carcinoma algorithms and new biochemical and imaging experiments pertaining to liver diseases. Relevant articles with an impact index value "> 0" from reference citation analysis, which is an open multidisciplinary citation analysis database based on artificial intelligence technology, have served for the study’s argumentation. This work may be a useful tool for the clinical practice and research in managing and investigating liver disorders.     

Liver regeneration after liver resection: Clinical aspects and correlation with infective complications

AIM:To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications.METHODS:A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010.Regeneration was evaluated by multidetector computed tomographyat a mean follow-up of 43.85 d.The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation,and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data.Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration.RESULTS:Ten of the 27 patients(37%)underwent chemotherapy prior to surgery,with a statistically significant prevalence of patients with metastasis(P=0.007).Eight patients(30%)underwent embolization,3 with primary tumors,and 5 with secondary tumors.Twenty patients(74%)experienced complications,with 12(60%)experiencing Clavien-Dindo Grade 3a to 5 complications.Regeneration≥100%occurred in 10(37%)patients.The predictors were smaller future remnant liver volume(-0.002;P<0.001),and a greater spleen volume/future remnant liver volume ratio(0.499;P=0.01).Patients with a resection of≥5 Couinaud segments experienced greater early regeneration(P=0.04).Nine patients experienced surgical site infections,and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected(P=0.016).There were no significant differences between patients with primary or secondary tumors,and either onset or infections or severity of surgical complications.CONCLUSION:Regardless of the onset of infective complications,future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.     

活体肝移植的进展与展望

活体肝移植（LDLT）可扩大供肝来源,有效缓解供体紧缺局面,尤其是对儿童、急性肝功能衰竭患者和无,法长期等待的肝癌患者有着十分重要的意义。为尽可能减少LDLT潜在的手术风险,尤其是供者的风险,应由肝病内外科医师共同进行严格的供受体术前评估和准备,选择恰当的手术方案。中闰应稳步开展LDLT,并积极拓展尸体和脑死亡供体肝移植,进一步发展儿童LDLT和劈离式肝移植（SIX）以提高器官利用率。在第六届上海国际胃肠病学会议期间,国内外肝病专家就LDLT的现状作了相关报道,本文就此次会议的有关内容和最新进展作一简要介绍。     

人工肝在肝移植围手术期的应用

目的 探讨人工肝支持系统在肝移植围手术期的应用效果。方法采用非生物人工肝治疗9例等待供肝患者，3例肝移植术后患者(包括1例等待供肝成功过渡到肝移植患者)。9例等待供肝患者中4例成功过渡到肝移植。结果 人工肝支持后患者肝性脑病有所好转，血清胆红素明显下降。4例成功过渡到肝移植的启者中2例痊愈出院，已存活12和14个月。结论 术前使用人工肝支持系统能改善患者一般情况；原位肝移植加人工肝支持系统是治疗慢性肝衰竭的有效方法。     

慢性乙型肝炎患者肝组织病理研究

目的:探讨慢性乙型肝炎(CHB)患者临床表现和病理诊断的相关性.方法:收集30例CHB患者的临床资料,分析临床表现与病理诊断的相关性.结果:肝组织的炎症和纤维化程度的相关性显著(r=0.659,P＜0.01),白蛋白/球蛋白比值(A/G)与肝脏炎症和纤维化分级显著负相关(r=-0.368,P＜0.05;r=-0.401,P＜0.05).年龄、性别及其他化验指标如ALT、AST、TP、ALB、GLO、TBil、PLT、PT、PTA、门静脉宽度、脾脏厚度等与肝组织炎症和纤维化分级无显著相关性(P＞0.05).结论:慢性乙型肝炎肝脏炎症和纤维化的严重程度密切相关,仅根据肝功能判断轻中度的CHB患者的肝脏炎症及纤维化程度有相当的局限性.     

Introducing an Optimal Liver Allocation System for Liver Cirrhosis Patients

Background

Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients.

Objectives

This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease.

Patients and Methods

Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R softwares.

Results

During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables (total bilirubin and albumin) and the patients'' age (year) by applying the Cox model:NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln (albumin) + 0.025 × age + 1.776)

Conclusions

The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested.     

肝窦内皮细胞在肝损伤中的功能研究进展

肝窦内皮细胞（liver sinusoidal endothelial cells, LSECs）位于肝血窦表面，是肝脏与血液接触的第一道防线，也是肝脏中含量最多的非实质细胞。在生理情况下，LSECs通过参与物质运输、代谢废物清除而诱导肝脏免疫耐受，从而维持肝脏稳态；在病理情况下，LSECs通过抗原递呈促进肝脏炎症反应。LSECs在维持肝再生和肝纤维化平衡中发挥了重要的调节作用。本文对LSECs功能、LSECs在肝损伤中的变化、调节LSECs功能相关的信号通路以及LSECs与肝内其他细胞的相互作用等四方面研究进展进行综述，从而进一步明确LSECs的功能及在肝损伤中的作用。     

Right hepatic lobe living donation: A 12 years single Italian center experience

Mini invasive techniques are taking over conventional open liver resections in the setting of left lateral segmentectomy for living liver donation,and hydride procedure are being implemented for the living related right hepatectomy.Our center routinely performs laparoscopic left lateral segmentectomy for pediatric recipient and has been the first in the Europe performing an entirely robotic right hepatectomy.Great emphasis is posed on living donor safety which is the first priority during the entire operation,then the most majority of our procedures are still conventional open right hepatectomy(RHLD),defined as removal of a portion of liver corresponding to Couinaud segments 5-8,in order to obtain a graft for adult to adult living related liver transplant.During this 10 years period some changes,herein highlighted,have occurred to our surgical techniques.This study reports the largest Italian experience with RHLD,focused on surgical technique evolution over a 10 years period.Donor safety must be the first priority in right-lobe living-related donation:the categorization of complications of living donors,specially,after this"highly sensitive"procedure,reflects the need for prompt and detailed reports.     

Isolated Tuberculosis of Transplanted Liver,A Case Report and Review of the Literature

Introduction

Recipients of liver transplantation are prone to different types of infections such as tuberculosis (TB).

Case Presentation

Herein we report a 59-year-old man with liver transplantation due to HBV cirrhosis who developed isolated hepatic TB, 18 months after OLT (orthotropic liver transplantation). He has been successfully treated with anti-TB regimen and now after 12 months he is completely symptom-free.

Conclusions

Organ transplantation and treatment of transplanted patients with immunosuppressive drugs would prone them to various unusual infections. One of these is unusual primary involvement of liver by tuberculosis which has been extremely rare in the previous reports.     

肝脏特异性基因miR-122与肝脏疾病研究进展

作为肝脏特异性基因miRNA之一的miR-122,其与肝脏生理及病理过程有密切联系。它不仅可促进肝细胞分化,还可调控脂类代谢。对肝脏疾病,miR-122可通过慢性丙型肝炎病毒（HCV）基因5＇-UTR结合序列相互作用来促进HCV病毒复制,反之,亦可通过miR-122-cylin G1/p53-HBV调控路径抑制慢性乙型肝炎病毒（HBV）表达及复制过程。另外,miR-122可抑制肝细胞增殖过程及其恶性转化。值得注意的是,用于HCV慢性感染治疗的首个miR-122靶向药物已研究中。随着miR-122调控慢性肝炎、肝癌作用机制及影响肝功能发挥的研究逐渐被人们所认知,在慢性感染性疾病及肿瘤治疗中,其已成为一个重要且有效治疗途径。