自体骨髓干细胞移植治疗失代偿期肝硬化

目的 探讨自体骨髓干细胞移植对失代偿期肝硬化患者的疗效.方法 回顾性分析2009年7月至2010年3月解放军第一○五医院收治的28例失代偿期肝硬化患者的临床资料.抽取患者骨髓后,体外分离、纯化骨髓间充质干细胞(BMSCs),经股动脉置管至肝固有动脉,再将BMSCs植入肝脏.自体移植后观察患者临床症状、体征,术前、术后第2、4、8、12周检测肝功能生化指标.组间比较采用单因素方差分析,当方差齐时,组间多重比较采用LSD法分析,若方差不齐则采用Dunnett's法.结果 本组中,26例患者术后1周食欲增加,乏力明显改善;23例术后第4周腹腔积液明显减少或消失.至第12周,患者ALT由(99±36)U/L降至(48±26)U/L,AST由(86±36)U/L降至(46±22)U/L,TBil由(38±16)μmol/L降至(18±13)μmol/L,Alb由(29±4)g/L升至(35±5)g/L,PT由(19±4)s降至(13±4)s.治疗前、后患者各实验室指标比较,差异有统计学意义(F=267.35,143.52,218.74,125.57,331.25,P<0.05).本组患者未见发热、皮疹、过敏反应等并发症,其中1例髂后上棘穿刺点出现血肿,1周后自行消退;1例在施行BMSCs移植过程中出现肝区不适,移植完毕拔管后症状消失;1例于术后3个月因上消化道大出血死亡.结论 BMSCs移植治疗失代偿期肝硬化近期安全有效,远期效果有待进一步观察.     

自体骨髓干细胞移植治疗失代偿期肝硬化

Objective To investigate the therapeutic effects of bone marrow stem cells for the treatment of decompensated liver cirrhosis. Methods The clinical data of 28 patients with decompensated liver cirrhosis who were admitted to the No. 105 Hospital of PLA from July 2009 to March 2010 were retrospectively analyzed. Bone mesenchymal stem cells (BMSCs) were separated and purified from the bone marrow cells of the patients in vitro,and then they were transplanted into the liver of the patients through proper hepatic artery. The clinical symptoms and physical signs of the patients were monitored, and the biochemical indexes of the liver were measured at the 2nd, 4th, 8th and 12th weeks after operation. All data were analyzed using the analysis of variance, LSD test or Dunnett's test. Results The appetite and physical strength of 26 patients were apparently improved one week after operation. The ascites of 23 patients were reduced at the end of the 4th week. At the end of the 12th week,the level of alanine aminotransferase was decreased from (99 ± 36)U/L to (48 ± 26 )U/L, aspartate aminotransferase was decreased from (86 ±36)U/L to (46 ±22)U/L, total bilirubin was decreased from (38 ± 16)μmol/L to (18 ± 13)μmol/L, albumin was increased from (29 ± 4)g/L to (35 ± 5 )g/L, and the prothrombin time was decreased from ( 19 ±4)s to ( 13±4) s. There were significant differences in the biochemical indexes of the liver after operation when compared to those before operation ( F =267. 35, 143. 52, 218. 74, 125. 57, 331.25, P <0.05). No fever, rash or allergic reaction was detected. Hematoma was detected in the incision site of the posterior superior iliac spine in one patient, and it disappeared one week later; one patient had discomfort in the liver area during the process of the BMSCs transplantation, and the discomfort disappeared at the end of the process; one patient died of hemorrhage of the upper gastrointestinal tract at the end of the 3rd month after operation. Conclusion The short term outcome of the autologous BMSCs transplantation for the treatment of decompensated liver cirrhosis is satisfactory, while its long term effect needs to be further investigated.     

自体骨髓干细胞移植治疗晚期肝硬化综述

干细胞是一类具有自我更新、增殖和多向分化能力的细胞,具有不对称分裂和无限增殖的特点,按来源可分为胚胎干细胞和成体干细胞.骨髓干细胞肝脏移植是将患者自体骨髓干细胞移植到其肝脏内,分化为有功能的实质细胞,以替代因退变、损伤、基因缺陷或自身免疫而受损的肝细胞,重构组织器官的结构和功能具体方法是从患者体内抽出少量骨髓,用先进的细胞分离技术分出移植所需的干细胞,通过介入把提取的干细胞注入病肝.目前,骨髓干细胞移植已具有较为完备的理论及实验基础,而自体骨髓移植、肝动脉插管介人治疗等均为临床上已经成熟的技术,因此在理论与技术方面均为干细胞肝脏移植提供了保障.我国是肝病尤其是病毒性肝炎的高发区,各种原因导致的肝硬化患者众多,在药物及原位肝移植治疗之外,自体骨髓源性干细胞移植治疗失代偿期肝硬化是一种全新而有效的新方法,其虽不能给肝病患者带来治愈性的效果,但可在很大程度上控制肝硬化的进展速度,提高肝硬化患者的生存质量.     

一氧化氮与肝硬化门脉高压症

一氧化氮(NO)与肝硬化门脉高压症(PHT)时全身及内脏高动力循环状态有关,阐明其中的关系和机理将为PHT的治疗提供一种新的思想     

胆汁性肝硬化门脉高压症的治疗

目的 探讨肝胆管结石、胆管狭窄所致胆汁性肝硬化门脉高压症的外科治疗。方法 总结了我院14例中、晚期胆汁性肝硬化门脉高压症的临床特征、手术方式及效果。结果 脾切除、胃冠状静脉栓塞改良术式8例；脾切除、贲门周围血管离断改良术式5例；脾动脉结扎、胃周血管离断l例。随访0．5—5年，2例死亡(14．3％)。患者肝功能好转率71．4％(10／14)。食道静脉曲张好转率64．3％(9／14)。消化道出血3例，再出血率21．4％。结论 治疗过程中应充分认识中、晚期胆汁性肝硬化门脉高压症的临床特征。创伤较小，简单而较彻底的断流术也是一种有效的治疗措施。     

门肝分流术治疗猪肝硬化门脉高压症

目的 观察肝侧门静脉-肝总动脉侧端分流术和侧侧分流术(统称门肝分流术)对猪肝硬化门脉高压症动物模型的治疗效果.方法 对照组和实验组(即肝硬化门脉高压模型组)实验猪各15头分别行门肝分流术,观察门静脉血入肝及降压的过程.结果 对照组和实验组门肝分流术前门静脉压力分别为(20.51±0.74) cm H2O(1 cm H2O=0.098 kPa)和(30.82±2.53)cm H2O(P＜0.05);术后30 d分别为(19.75±0.84) cm H2O和(20.84±1.36) cm H2O(P＞0.05).对照组和实验组门静脉与肝总动脉的压力差术前分别为(7.20±0.34) cm H2O和(17.34±0.62) cm H2O(P＜0.05);术后30 d分别为(6.40±0.21) cm H2O和(7.84±1.32) cm H2O(P＞0.05).分流后术中脾静脉注射亚甲蓝肝脏染色良好.术后观察30 d无肝坏死及肝性脑病发生,脾肿大恢复正常.门肝分流术对肝功能的影响较大,对其他血生化代谢指标影响较小.结论 门肝分流术后虽然门静脉血入肝通道发生变更,但门脉血流动力学并未受到显著影响,反而建立了新的平衡机制来维持门脉血流动力学的稳定,达到门脉降压效果.门肝分流术后肝功能恢复所需时间较长,且需进一步治疗.     

肝硬化门脉高压症合并胆囊结石的治疗

目的总结肝硬化门脉高压症合并胆囊结石的外科治疗经验。方法回顾性分析17例肝硬化门脉高压症合并单纯胆囊结石的临床诊治资料。结果10例行断流术并结合治疗胆囊结石组(3例同期手术),5例分期手术,2例并中西利胆排石)与7例单纯断流术组近期肝功能改善率及食道胃底静脉曲张消除率比较无明显差异(P>0.05),远期肝功能改善率明显优于单纯断流术组,分别为71.4%和14.3%(P<0.05),再出血率小于单纯断流术组(P<0.05)。结论肝硬化门脉高压症合并胆囊结石行断流术结合治疗胆囊结石的预后较单纯断流术好,并且只要加强围手术期的处理,同期手术是安全可行的。     

肝硬化门脉高压症研究治疗的现状

随着21世纪的到来，外科领域正在发生巨大的变化，门脉高压症外科也不可避免地面临巨大的挑战，经历巨大的变化。     

肝硬化门脉高压动物模型的研究进展

建立合适的肝硬化门脉高压动物模型对于评价临床上治疗肝硬化门脉高压伴出血效果具有不可忽视的作用.目前门脉高压动物模型的制备方法较多,可通过药物、手术及手术与药物联合的方法制备.现就门脉高压动物模型的研究进展作一综述,分析不同门脉高压动物模型制备方法的优点与不足,以期对门脉高压动物模型的研究有所帮助.     

经肝动脉骨髓干细胞移植治疗肝硬化的初步临床应用

目的探讨经肝动脉自体骨髓干细胞肝内移植治疗失代偿期肝硬化的临床应用可能性及效果。方法20例失代偿期肝硬化患者，乙型肝炎后肝硬化19例，酒精性肝硬化1例。Child—Pugh分级：A级2例，B级6例，C级12例。所有患者术前均行影像学及肝脏功能等检查。移植术当日抽取患者自体骨髓30～50ml，分离出骨髓干细胞，经肝固有动脉注入。对于造影发现肝内有单发小肝癌者，先行肝段超选择TACE治疗，再选择性插管至正常肝动脉供血区，注入骨髓干细胞。术后1周、2周、1月观察患者临床症状、体征，复查肝功能等实验室指标。结果2例造影发现合并单发小肝癌。20例患者中，14例有效，6例无效。所有病例术后均未出现发热、过敏反应及其他不适。结论经肝动脉行自体骨髓干细胞移植安全可行；部分肝硬化患者用此方法治疗近期有效；治疗中通过肝动脉造影可能发现其他影像学检查未能显现的早期肝癌。     

超声引导下经门静脉穿刺干细胞移植治疗肝纤维化

Liver cirrhosis;Mesenchymal stem cell transplantation     

肝硬变大鼠门静脉转流下耐受入肝血流阻断的安全时限

目的　探讨在门静脉转流条件下肝硬变大鼠耐受入肝血流阻断的安全时限。方法　观测门静脉转流与非门静脉转流条件下阻断入肝血流不同时程后动物存活率及肝脏能量代谢的变化 ,包括肝细胞线粒体呼吸控制率 (RCR)、肝组织三磷酸腺苷 (ATP)含量、动脉血酮体比值 (AKBR)。结果术后两周存活率 :肝硬变大鼠PBB 30min组和PBB 4 5min组为 10 0 % ,PTC 30min组、PBB 6 0min组、PBB 75min组及PBB 90min组分别为 73.3%、75 %、4 6 .7%及 2 6 .7%。正常大鼠PTC 30min组为4 0 %。肝脏能量代谢 :缺血后肝组织ATP、RCR及AKBR均明显下降 (P <0 .0 5 )。再灌注后上述指标逐惭恢复 ,但随缺血时间延长 ,升高幅度明显降低 ,甚至难以恢复。结论　肝硬变大鼠常温下耐受入肝血流阻断的安全时限是 4 5min。     

远端脾静脉-肝动脉分流术治疗猪肝硬化门脉高压症

目的 观察小型猪肝硬化门脉高压症动物模型建立远端脾静脉-肝总动脉分流术(下称脾肝分流术)后降低胃脾区静脉压力的效果.方法 对照组和实验组猪各15头分别建立脾肝分流术,对照组猪术后处死不饲养,实验组猪术后饲养30d处死.结果 脾肝分流术后胃脾区静脉血入肝亚甲蓝肝脏染色良好.维持静脉血入肝的脾静脉压力对照组为(20.51±0.74) cm H2O(1cm H2O=0.098 kPa),实验组为(23.09±1.36) cm H2O(P＜0.05) 脾肝分流术建立后静脉和动脉两端形成压力差,对照组为(7.17±1.02) cm H2O,实验组为(9.55±1.32) cm H2O(P＜0.05).术后实验猪无肝坏死及肝性脑病发生,脾肿大消失,肝功能等生化代谢指标术后7d波动最大,14 d逐渐恢复,30 d恢复到成模时状态.　结论 压力差是维持静脉血入肝降低胃脾区静脉压力的原始动力.术后肝功能等生化代谢指标紊乱需要进一步治疗.     

骨髓单个核细胞经门静脉移植对大鼠肝纤维化的减轻作用

目的 对比研究骨髓单个核细胞经门静脉移植治疗大鼠肝硬化的疗效,为临床应用提供依据.方法 采用四氯化碳(CCl4)综合法制作Wisrar大鼠肝硬化模型,8周后经病理检查证实成模者共20只进入实验.随机分为治疗组和对照组,每组10只,两组大鼠分别经门静脉注入骨髓单个核细胞和等体积的肝素生理盐水.各组大鼠继续皮下注射CCl4(CCl4使用方法与前述造模方法相同),在原环境下继续饲养4周后处死.切取肝组织分别作HE及Masson染色.疗效评价指标包括:①一般情况;②肝脏羟脯氨酸和胶原纤维含量;③肝纤维化病理学分级.结果 (1)治疗组大鼠一般情况改善;对照组无明显改变.(2)治疗组与对照组中肝脏羟脯氨酸含量分别为(0.50±0.12)g、(0.59±0.34)g;胶原纤维含量百分数分别为(3.75±0.98)%、(5.02±0.44)%.两组之间各指标均有统计学差异(P<0.05).(3)治疗组肝纤维化病理分级也有下降,治疗前后差异明显(P<0.05),而对照组无明显变化.表明治疗组行骨髓单个核细胞移植后大鼠肝纤维化程度减轻.结论 骨髓单个核细胞肝内移植能改善大鼠肝纤维化程度,为临床肝硬化的治疗带来了新的手段.     

Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure

Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age‐ and gender‐matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty‐one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other.     

门静脉血栓对终末期肝硬化病人行肝移植手术的影响

目的探讨合并门静脉血栓(portal vein thrombosis,PVT)的终末期肝硬化病人行肝移植手术的处理方法及其疗效。方法回顾性分析2010年1月至2015年12月在中山大学附属第一医院器官移植中心接受肝移植手术的152例终末期肝硬化病人的临床资料。32例合并PVT的病人作为PVT组,其中Ⅰ级10例、Ⅱ级13例、Ⅲ级8例、Ⅳ级1例。其余120例无PVT的病人作为对照组。结果PV/T组术前脾切除史的比例明显高于对照组(46.8%比18.3%,P0.05),差异有统计学意义。PVT组较对照组明显延长无肝期时间[(72.5±25.3)min比(57.6±18.4)min,P0.05]和总手术时间[(622.4±183.5)min比(503.2±123.6)min],差异均有统计学意义。2组病人在术中出血量、ICU住院时间、术后并发症发生率、围手术期病死率、1年及3年生存率的比较上差异均无统计学意义(P0.05)。PVT组术后再栓塞率高于对照组(9.4%比1.7%,P0.05)。结论门静脉血栓一定程度上增加了终末期肝硬化病人肝移植手术的难度,Ⅰ~Ⅲ级PVT不影响病人的预后,仍可通过肝移植手术取得良好的疗效。Ⅳ级PVT肝移植手术的难度和风险会明显增加,应谨慎对待。     

Altered metabolism of tacrolimus in hepatic veno-occlusive disease

Tacrolimus is widely used for the prophylaxis and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT) and graft rejection in solid organ transplantation. The metabolism of tacrolimus has been reported to be impaired in association with liver dysfunction, mostly as documented in liver transplant recipients. Hepatic veno-occlusive disease (VOD) is one of the serious complications after allogeneic HSCT. It is characterized by jaundice, fluid retention, and painful hepatomegaly, caused by endothelial cell injury resulting from the toxicity of the conditioning regimen. The impaired metabolism of tacrolimus in hepatic VOD has not previously been reported in the literature. Here, we report the notable alteration in the metabolism of tacrolimus in two patients with hepatic VOD, in whom the half-lives of tacrolimus were markedly prolonged (288 and 146 h).     

Liver transplantation for small HCC in cirrhosis

Segmental liver resection is generally considered the treatment of choice for small HCC in cirrhotic livers. Although in selected patients with small encapsulated nodules and low alpha-fetoprotein levels long-term survival can be expected after resection [4], Western experience is still limited, and follow-up studies too short so that the data presently available cannot be considered satisfactory [3]. The true value of alcoholization as a possible alternative therapy in these patients is still to be ascertained. When using these treatment modalities, the major problem is the high tumour recurrence within the liver [1, 6]. Three main reasons could explain these clinical observations:

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肝静脉压力梯度的影响

目的 观察肝静脉交通支对肝硬化门静脉高压(PHT)患者肝静脉压力梯度(HVPG)的影响。方法 回顾性分析接受TIPS治疗的513例肝硬化PHT患者,TIPS术中均测量肝静脉压力并行球囊阻断加压肝静脉造影;根据肝静脉交通支显影情况将患者分为早期交通支显影组(早显组)、中晚期交通支显影组(中晚显组)、门静脉显影组及无交通支组,对比组间HVPG、门静脉压力梯度(PPG)、肝静脉楔压(WHVP)和门静脉压(PVP),分别以Pearson相关分析、组内相关系数(ICC)及Bland-Altman分析评估各组内WHVP与PVP、HVPG与PPG的相关性及其一致性。结果 球囊阻断加压肝静脉造影中,163例肝静脉交通支早期显影,140例中晚期显影,166例门静脉显影,44例无交通支显影;4组间HVPG、PPG、WHVP及PVP总体差异均有统计学意义(P均＜0.01),HVPG、WHVP呈逐渐增加,PPG、PVP呈逐渐降低趋势。各组内HVPG与PPG、WHVP与PVP差异均有统计学意义(P均＜0.05);HVPG与PPG、WHVP与PVP均呈正相关(P均＜0.001),且相关性及一致性在门静脉显影组均优于其他3组、而在早显组均不及其他3组。结论 肝静脉交通支对肝硬化PHT患者HVPG存在一定影响。