脐血干细胞移植治疗失代偿期肝硬化的临床疗效

目的:探讨人脐血干细胞(umbilical cord blood stem cell,UCBSC)外周静脉移植治疗失代偿期肝硬化的临床疗效及可行性.方法:20例失代偿期肝硬化患者采用人UCBSC外周静脉移植治疗,治疗后定期观察患者血清转氨酶(ALT、AST)、总胆红素(TBIL)、白蛋白(ALB)、凝血酶原时间(PT)和纤维蛋白原(FIB)水平变化,并观察患者临床症状及体征的改善情况及不良反应.结果:UCBSC移植治疗后2周,各项肝功能指标较治疗前无显著性差异(P＞0.05);治疗后4周,除ALT和AST有所改善外(P＜0.05),其余指标无明显改善;治疗后8周各项肝功能指标均有改善(P＜0.05),12周有显著性改善(P＜0.01).治疗后4周大多数患者的临床症状有明显改善,腹水减少和双下肢浮肿减轻15例(75.0%)、乏力好转16例(80%)、食欲改善13例(65%).UCBSC移植后12周患者总体生存率为90%,其中2例患者分别在UCBSC静脉移植后4周和8周因为肝性昏迷和自发性细菌性腹膜炎而死亡.所有患者均未发现与细胞移植相关的副作用.结论:UCBSC外周静脉移植是治疗失代偿期肝硬化一种安全有效的方法,短期内可以改善失代偿期肝硬化患者肝功能及临床症状,是一种值得推荐的治疗方法.     

脐血干细胞静脉输注治疗失代偿期肝硬化1例并文献复习

目的:探讨脐血干细胞静脉输注对失代偿期肝硬化的临床治疗效果.方法:患者为慢性重症肝炎、肝硬化失代偿期,采用脐血干细胞静脉输注治疗共2次,治疗后半年观察血清转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、r-谷氨酰转肽酶(GGT)、白蛋白(ALB)、总胆红素(TBIL)、结合胆红素(DBIL)、非结合胆红素(IBIL)、凝血酶原时间(PT)水平变化,同时观察临床症状、体征改善情况.结果:各项实验室指标逐渐正常,腹水消退,临床症状明显改善.结论:脐血干细胞静脉输注治疗失代偿期肝硬化安全、简便、有效.     

脐血干细胞治疗失代偿期肝硬化的疗效及对门静脉血流动力学的影响

目的:观察脐血干细胞治疗失代偿期肝硬化的疗效及对门静脉血流动力学的影响。方法:选取30例失代偿期肝硬化患者,用负收集法分离提取脐带血干细胞,经股动脉穿刺插管,从肝固有动脉缓慢注入。同时选择20例失代偿期肝硬化患者,分别于治疗前,治疗后1周、1个月、3个月、6个月观察肝功能、凝血指标、AFP、CT肝脏容积、门静脉血流动力学等指标。结果:干细胞治疗组与对照组同期比较:白蛋白治疗后4、12、24周明显改善,PT治疗后12、24周降低;AFP治疗后4、12、24周升高;两组患者治疗前后门静脉血流动力学参数变化差异无统计学意义;肝脏体积治疗组与对照组同期比较,肝脏体积有增大趋势但差异无统计学意义;治疗组1例第10周确诊为原发性肝细胞癌,与对照组比较差异无统计学意义。结论:脐血干细胞治疗失代偿期肝硬化可以改善肝脏的合成功能,促进肝组织再生,有新生血管重建情况发生,未发现门静脉血流动力参数的改变。     

经肝固有动脉自体骨髓干细胞移植治疗失代偿期肝硬化患者18例

目的 观察分析经肝固有动脉行自体骨髓干细胞移植治疗失代偿期肝硬化的疗效及其安全性。方法 将2010年4月至2010年12月我院感染科收治的36例失代偿期患者随机分为治疗组和对照组各18例。对照组予以基础治疗(护肝、降黄、对症和支持治疗),治疗组在基础治疗上行经肝固有动脉注入自体骨髓干细胞治疗。结果 治疗8周后,治疗组腹水消退10例(55.55﹪),腹胀减轻16例(88.99﹪),下肢浮肿减轻6例(33.33﹪),对照组分别为2例(11.11﹪)和6例(33.33﹪),1例(5.55﹪),差异具有统计学意义(P值分别为0.005,0.001,P均<0.05);治疗组治疗后的白蛋白(ALB)、凝血酶原活动度(PTA)、纤维蛋白原(FIB)、丙氨酸转氨酶(ALT)指标较治疗前均有明显改善;且与对照组治疗后各项指标比较也有改善。其中治疗组与对照组治疗后的ALB(P=0.002)、PTA(P=0.020)、ALT(P=0.010)水平差异具有统计学意义(P<0.05);治疗组内治疗前后的ALB(P=0.001)、PTA(P=0.093)、ALT(P=0.000)指标的改善差异具有统计学意义(P<0.05)。全部患者在移植术中移植术后近期未发生严重并发症。结论 经肝固有动脉行自体骨髓干细胞移植治疗失代偿期肝硬化疗效明显、可使失代偿期肝硬化患者肝功能明显改善,治疗安全有效且副作用小,可作为中晚期肝硬化患者可选择的临床治疗方案。     

脐血间充质干细胞移植治疗遗传性痉挛性截瘫1例及文献复习

目的:观察脐血间充质干细胞移植治疗遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)的疗效和安全性.方法:将细胞总数为(2～6)× 107个脐血间充质干细胞通过静脉输注和腰穿鞘内注射途径移植到自愿接受干细胞移植的1例HSP患者体内.术后随访1年余定期观察患者临床症状及各项指标的变化并进行综合分析.结果:脐血间充质干细胞移植后患者临床症状明显好转:双下肢肌张力明显降低,不需借助拐杖或他人帮助可独立行走,并且步态平稳,移植后各项生化指标正常,未出现严重的并发症和明显的不良反应.随访1年余该患者的症状持续缓解无复发.结论:脐血间充质干细胞移植治疗HSP近期疗效明显,可以改善患者的临床症状,延缓病情的进展,是一种值得借鉴的治疗方法.     

丙型肝炎肝硬化失代偿期患者行自体外周血干细胞移植术后进行抗病毒治疗一例报道

干扰素联合利巴韦林仍是目前治疗丙型肝炎病毒的标准治疗方案,而肝硬化失代偿期是干扰素治疗的禁忌证。由于病毒不能有效清除,病情不断进展,逐渐进展为终末期肝病或肝癌。有学者提出对丙型肝炎肝硬化失代偿期患者经过积极对症治疗后,在病情平稳、严密监测的前提下可以尝试给予个体化抗病毒治疗[1]。随着对干细胞研究的深入,干细胞移植为治疗肝硬化失代偿期患者的治疗提供了一条新的途径。     

粒细胞集落刺激因子对失代偿期肝硬化患者骨髓干细胞的动员效果及安全性观察

目的观察失代偿期肝硬化患者行自体骨髓干细胞移植前粒细胞集落刺激因子（G-CSF）对骨髓干细胞的动员效果及安全性。方法在51例失代偿期肝硬化患者行自体骨髓干细胞经肝动脉移植术前,连续2 d给予G-CSF 4μg/（kg·d）动员骨髓干细胞。抽取骨髓的当日化验血常规、肝肾功等指标;从患者髂后上棘抽取骨髓150-200 ml,分离收集骨髓单个核细胞并计数,应用流式细胞仪检测CD34＋细胞并计数,观察应用G-CSF期间不良反应的类型和发生率。患者治疗前后比较采用配对t检验进行统计学分析。结果G-CSF皮下注射后,外周血白细胞由术前（3.31±0.96）×10^9/L升至（11.35±1.92）×10^9/L（P〈0.01）,骨髓单个核细胞数（1.91±0.83）×10^9/kg,CD34＋细胞为（2.02±1.29）×10^7/kg;患者皮下注射后,发热率17.6﹪,体温最高38℃,停药后降至正常;腹部胀痛3例,四肢皮肤散发皮疹2例,均未给予特殊处理,2-3 d后恢复正常。结论给予G-CSF皮下注射后提取骨髓干细胞移植治疗失代偿期肝硬化的是一种临床确切有效的、安全的干细胞动员方法。     

自体干细胞移植治疗失代偿期肝硬化的疗效及对肝脏储备功能、血清LPS、HGF水平的影响

目的:探讨自体干细胞移植治疗失代偿期肝硬化的疗效及对肝脏储备功能、血清内毒素(LPS)、肝细胞生长因子(HGF)水平的影响。方法:选择2015年9月至2017年9月我院接诊的86例失代偿期肝硬化患者作为本研究对象,通过随机数表法将其分为观察组和对照组,每组43例。对照组给予失代偿期肝硬化常规综合治疗,观察组在对照组基础上进行自体干细胞移植治疗。比较两组治疗前、治疗12周后实验室指标、终末期肝病模型系统评分(MELD)、血清LPS、HGF水平的变化以及不良反应的发生情况。结果:治疗后,两组丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBil)水平均明显低于治疗前,白蛋白(ALB)较治疗前显著升高(P0.05),观察组ALT、AST、TBil均明显低于对照组,ALB水平明显高于对照组[(45.60±4.12)U/L vs.(56.84±6.20)U/L,(57.45±5.01)U/L vs.(68.99±6.84)U/L,(36.53±3.45)g/L vs.(30.42±2.89)g/L,(50.23±4.83)μmol/L vs.(62.30±6.76)μmol/L](P0.05);治疗后,两组MELD评分较治疗前显著降低(P0.05),观察组MELD评分明显低于对照组[(21.89±2.74)分vs(27.84±3.51)分](P0.05);治疗后,两组血清LPS较治疗前显著降低,HGF较治疗前显著升高(P0.05),观察组血清LPS明显低于对照组,HGF明显比对照组高[(0.43±0.05)ng/mLvs(0.60±0.09)ng/mL,(389.56±27.40)pg/mL vs(301.23±22.30)pg/mL](P0.05)。对照组和观察组治疗期间不良反应总发生率分别为8.89%(4/43)、13.95%(6/43),差异无统计学意义(P0.05)。结论:自体干细胞移植治疗失代偿期患者可明显改善肝功能、肝脏储备功能及血清LPS、HGF的表达,且安全性高。     

复合乳酸杆菌治疗肝硬化失代偿期患者效果分析

目的:探讨分析复合乳酸杆菌在治疗肝硬化失代偿期患者中的效果。方法:选择2011年1月~2014年12月间在我院住院治疗的54例肝硬化失代偿期患者为研究对象,随机分为观察组和对照组各27例,选取同时期健康体检者27例为健康对照组。观察组患者接受复合乳酸杆菌联合肝硬化常规治疗,对照组仅接受肝硬化常规治疗。治疗8周后,比较对照组和观察组治疗前后及健康对照组患者血浆ALT、AST、内毒素、IL-1β、TNF-α、血氨及消化道症状积分的差异。结果:观察组和对照组患者治疗前血浆ALT、AST、内毒素、IL-1β、TNF-α、血氨水平及消化道症状积分差异无统计学意义(P0.05),均明显高于健康对照组(P0.05);治疗后两组患者上述指标均明显降低(P0.05),但观察组较对照组下降更为明显(P0.05)。结论:复合乳酸杆菌联合常规疗法在肝硬化失代偿期患者的治疗方面发挥了重要作用,值得临床推广。     

自体骨髓干细胞移植治疗失代偿期肝硬化的临床效果分析

目的:观察自体骨髓间充质干细胞(BMSC)移植治疗合并不同并发症的失代偿期肝硬化的临床效果。方法:回顾性分析我院自2008年12月至2013年12月收治的148例经自体BMSC移植治疗的肝硬化合并肝性脑病、肝肾综合征、肝源性糖尿病以及消化道出血患者治疗前后的肝、肾功能、血清蛋白、血常规等指标的变化情况。结果:治疗后,肝硬化合并肝性脑病患者的ALT、血氨水平改善明显,TBIL反复;合并肝肾综合征的患者HB、Crea水平改善明显,ALT、AST、DBIL反复;合并肝源性糖尿病患者的ALT、TBIL、DBIL、TB、ALB、血糖水平改善明显;合并消化道出血患者的ALT、TP、ALB改善明显,AST、TBIL、PLT反复。结论:自体BMSC移植治疗肝硬化合并肝源性糖尿病的效果较好,对合并肝性脑病、肝肾综合征以及消化道出血患者的效果欠佳。     

Use of a transjugular intrahepatic portosystemic shunt combined with autologous bone marrow cell infusion in patients with decompensated liver cirrhosis: an exploratory study

Background aimsCurrently, there is no treatment for decompensated liver cirrhosis except for liver transplantation. The safety and effect on liver function of a transjugular intrahepatic portosystemic shunt (TIPS) with and without autologous bone marrow cell (BMC) infusion in patients with decompensated liver cirrhosis were determined.MethodsTen patients who were diagnosed with decompensated liver cirrhosis during the period from September 2011 to July 2012 were enrolled in this study. The patients underwent TIPS (TIPS group) or combined treatment with TIPS and BMC infusion through the hepatic artery (TIPS+BMC group). All patients were monitored for adverse events, liver function and complications caused by portal hypertension during a period of 52 weeks.ResultsThe number of infused BMCs was 2.65 ± 1.20 ×10⁹. Significant improvements in the serum levels of albumin and total bilirubin and decreased Child-Pugh scores were observed in patients treated with both TIPS and BMCs (P < 0.05), whereas no such changes were observed in the TIPS group. Endoscopic findings showed that varices in the esophagus and the gastric fundus were alleviated after either treatment. All 10 patients showed a complete or partial resolution of ascites at 4 weeks. No major adverse effects were noted during the follow-up period for patients in either group.ConclusionsTIPS combined with BMC infusion is clinically safe; the treatment improved liver function and alleviated complications caused by portal hypertension; therefore, this combination has potential for treatment of patients with decompensated liver cirrhosis.     

Extreme elevation of serum alpha fetoprotein in decompensated cirrhosis without HCC: an ominous sign

Three cases of extreme elevation of serum alpha fetoprotein (>10,000 ng/mL) with decompensated cirrhosis without demonstrable hepatocellular carcinoma are reported. While 2 patients died of liver failure, 1 survived after liver transplantation. Extreme elevation of alpha fetoprotein not associated with hepatocellular carcinoma in liver cirrhosis heralds an ominous prognosis necessitating urgent liver transplantation.     

Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating interleukin-17

Background

Accumulating evidences have identified the immunoregulatory features of stem cells. In this study, the immunoregulation of bone marrow-derived stem cells (BMSCs) transplanted into patients with HBV-related decompensated cirrhosis and mouse model of liver injury induced by carbon tetrachloride (CCl₄) administration was observed.

Results

Compared with healthy controls, patients with HBV-related decompensated cirrhosis showed significantly higher levels of TNF-alpha, IL-12, TGF-beta1, IL-17, and IL-8. However, only IL-17 was markedly decreased after autologous BMSCs transplantation during their follow-up. The same results were found in the CCl₄-treated mice. Furthermore, we found that exogenous IL-17 partly abolished the therapeutic effect of BMSCs whereas IL-17-specific antibody promoted improvement of liver injury in CCl₄-treated mice, resembling the therapeutic effect of BMSCs transplantation.

Conclusions

These data suggested that BMSCs transplantation induces a decrease of IL-17 level, which at least in part delineates the mechanisms of stem cells-mediated therapeutic benefit on liver disease.

     

Recurrent primary biliary cirrhosis after liver transplantation--the disease and its management

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the destruction of interlobular and septal bile ducts that can lead to fibrosis and cirrhosis. Orthotopic liver transplantation (OLT) remains the definitive treatment for decompensated liver disease secondary to PBC. An estimated 10% to 40% of patients develop clinical, biochemical, and histologic changes consistent with recurrent PBC after OLT. However, the presence of recurrent PBC does not appear to affect either graft or patient survival rates. There is conflicting evidence regarding the effect of specific immunosuppressant medications (eg, tacrolimus vs cyclosporine) on the risk of recurrent PBC. Most experts favor the use of ursodeoxycholic acid (UDCA) for recurrent PBC given its beneficial effect in patients with pretransplant PBC and its improvement of biochemical markers in the posttransplant setting. However, despite its potential benefit, there is no evidence that UDCA improves graft or patient survival in recurrent PBC.     

肝硬化患者术后感染的危险因素及干预措施

目的:感染是肝硬化患者肝移植术后常见的并发症之一,影响患者的治疗效果和生存质量。本文针对肝硬化患者术后感染的危险因素进行分析,探讨有效的干预措施以提高临床疗效,为肝硬化术后并发症的预防提供可借鉴的方法。方法:对2008年10月-2013年9月在我院接受手术治疗的120例肝硬化患者的临床资料进行回顾性分析。根据术后并发症的发生情况选择其中60例发生感染的患者作为感染组,另外60例未发生感染的患者作为对照组。观察两组患者的年龄、肝硬化分期及用药情况等,对比不同的干预措施产生的临床效果。结果:感染组患者的平均年龄、肝功能障碍、抗生素使用量及术前合并感染的比率均显著高于正常对照组,差异具有统计学意义(P0.05)。两组患者进行针对性的护理干预均获得良好的治疗效果,未发生死亡病例。结论:患者的年龄、肝功能分级、用药及合并症等均为肝硬化术后感染的危险因素,临床中应实施针对性的干预措施以提高疗效。     

Serum apoproteins A and B and the lecithin: cholesterol acyl transferase activities in liver cirrhosis and hepatic coma patients

Serum apoproteins A and B and LCAT activities were estimated in 80 patients, 46 with posthepatic cirrhosis and 34 with alcoholic cirrhosis. The cirrhosis patients were also divided into compensated, decompensated, and hepatic coma subgroups. Apo-A and LCAT activities were significantly decreased in both cirrhotic groups without any significant difference between posthepatitic and alcoholic cirrhotic groups, while Apo-B was decreased in hepatic coma patients only. The decompensated cirrhosis patients showed lower Apo-A levels than the compensated cirrhosis patients and hepatic coma patients showed still lower levels compared to decompensated subgroup, while no significant decrease was observed in LCAT activities between compensated and decompensated cirrhosis patients. Apo-A level was correlated more significantly with serum albumin level than the LCAT activity. The study confirms that Apo-A level is highly related to the degree of liver injury and also suggests that this decrease may be mainly due to impaired liver synthesis and that the serum levels of Apo-A and Apo-B can be utilized in the differential diagnosis of chronic liver diseases.     

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study

AIM To evaluate the long-term efficacy and safety of autologous stem cell transplantation(SCT) for decompensated liver cirrhosis.METHODS Consecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation(non-SCT) group according to whether they received SCT treatment. Patients werefollowed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma(HCC) were compared between groups.     

Differences between the metabolic profiles of decompensated and compensated cirrhosis patients with Hepatitis B virus infections under high-performance liquid chromatography-mass spectrometry

To improve the grading and staging of liver cirrhosis among patients with HBV infection noninvasively, a high-performance liquid chromatography with mass spectrometry metabolomics method was used to investigate the potential metabolic biomarkers in the serum of patients with different degrees of hepatic cirrhosis. The results demonstrate that lysophosphatidyl choline (LPC) from positive electrospray ionization (ESI) mode, and fatty acids and bile acids from negative ESI mode play important roles in distinguishing decompensated from compensated cirrhosis. A total of 21 differential metabolites were found from the two groups of patients. LPCs, fatty acids, and taurocholic acid (TCA) 3-sulfate decreased in patients with decompensated cirrhosis, whereas other bile acids increased significantly. The levels of TCA 3-sulfate, LPC 16:0, and LPC 18:0 were significantly correlated with the stages of the decompensated cirrhosis, and they may serve as potential biomarkers for the stage assessment of liver cirrhosis in patients with HBV infections.