经颈静脉肝内门体分流术治疗肝硬化顽固性腹水的现状

顽固性腹水是肝硬化失代偿期门静脉高压的并发症之一,其治疗难度大,病死率高。目前经颈静脉肝内门体分流术(TIPS)作为顽固性腹水的二线治疗,能通过降低门静脉压力来改善腹水症状。国内外大量研究已经提出,使用覆膜TIPS支架,谨慎选择适用人群可以改善顽固性腹水患者的预后,因此有学者提出TIPS可作为顽固性腹水的一线治疗手段。本文将全面介绍国内外TIPS治疗肝硬化顽固性腹水的现状,并对相关研究进展进行阐述,旨在推动我国TIPS治疗顽固性腹水相关研究的发展。     

经颈静脉肝内门体分流术后分流道失功再通肝硬化患者预后影响因素分析

目的 探讨影响经颈静脉肝内门体分流术(TIPS)后分流道失功行再通的肝硬化患者的预后及危险因素分析。方法 回顾性分析2013年1月-2019年2月南京大学医学院附属鼓楼医院收治的因肝硬化食管胃底静脉曲张破裂出血行TIPS术,且术后因分流道失功行再通的69例患者的临床资料,包括患者初次TIPS和再通术中、术前及术后资料;支架参数、门静脉压力梯度、门静脉穿刺部位、实验室指标等。Kaplan-Meier曲线评估再通后患者的累积分流道失功率和生存率,2组间累积通畅率比较采用log-rank检验。Cox回归模型分析影响再通患者术后发生分流道再失功和生存的影响因素。结果 69例患者再通术后28例(40.6%)发生再失功,15例(21.7%)死亡。再失功中位时间11.3个月。患者1、2、3、5年再失功的累积发生率分别为29.8%、41.6%、48.0%、52.7%,累积生存率分别为96.9%、94.8%、83.0%和62.6%。单纯行支架内球囊扩张术患者与行支架置入术患者累积通畅率比较差异有统计学意义(χ^2=9.494,P=0.009)。初次TIPS前肝功能CTP分级、初次手术支架直径、再通前INR和PT水平与再失功相关(P值均<0.05),再通前INR升高是分流道再失功的独立危险因素[风险比(HR)=4.398, 95%可信区间(95%CI):1.848~10.467, P=0.001];再通术中置入支架是分流道再失功的独立保护性因素 (HR=0.370, 95%CI: 0.194~0.704, P=0.002)。初次TIPS术前CTP分级和MELD评分与再通后患者生存相关(P值均<0.05),MELD评分升高是再通后患者死亡唯一的独立危险因素 (HR=1.293, 95%CI: 1.054~1.627, P=0.026)。结论 对于TIPS术后分流道失功行再通术的患者,再通术中置入支架是更合理的选择,而MELD评分升高提示着患者预后较差。     

肝硬化患者TIPS术后再出血原因分析

经颈静脉肝内门体分流术（TIPS）是缺乏外科手术指征且内镜治疗失败的肝硬化食管胃静脉曲张破裂出血（EGVB）患者的重要治疗选择.目的：分析TIPS术后再出血患者的出血原因.方法：2006年10月-2010年10月于昆明医学院第二附属医院接受TIPS治疗的124例肝硬化EGVB患者纳入研究,对术后随访中再次发生消化道出血者的再出血原因和相应处理方法进行回顾性分析.结果：TIPS手术成功率和术后即刻止血率为98.4%（122例）.21例（17.2%）患者于术后10h至22个月再次发生消化道出血,再出血原因分别为分流道狭窄、闭塞引起的曲张静脉破裂（66.7%）、食管责门黏膜撕裂综合征（9.5%）、急性胃黏膜病变（14.3%）和抗凝过度（9.5%）.经再次、三次介入治疗或对症治疗后,大部分患者成功止血.结论：分流道狭窄、闭塞是肝硬化患者TIPS术后再出血的主要原因,同时亦应重视其他因素引起的再出血,从而提高,TIPS的远期疗效.     

肝功能评价对肝硬化患者TIPSS的指导意义

目的探讨肝硬化患者术前的肝储备功能及肝脏容积的评价对TIPSS术后疗效的影响。方法回顾性分析肝硬化行TIPSS术治疗患者的病历资料,对肝功能进行Child-Pugh分级,同时测量肝脏容积,探讨二者与肝性脑病发病的相关性。结果TIPSS术对肝储备功能及肝脏容积不同的肝硬化患者产生不同程度的肝性脑病及病死率（P〈0.01）。结论术前正确评价肝储备功能和肝脏容积,恰当选择适应证将会减少病死率,对于TIPSS手术有积极的意义。     

TIPS治疗肝硬化门脉高压急性静脉曲张出血：救命治疗还是一线治疗？

美国肝脏病学会门静脉高压防治指南和TIPS治疗门脉高压指南均推荐TIPS应作为药物及内镜控制急性静脉曲张出血失败后的＂救命＂治疗。然而,虽然出血控制率较好,但病死率仍较高。最近,对肝功能不好的肝硬化急性静脉曲张出血患者的多中心随机对照研究显示,用覆膜支架早期TIPS与药物联合内镜比较,前者能显著减低出血控制失败率和延长生存率。当急性静脉出血发生在Child-Pugh B级或C级（≤13分）患者时,应将覆膜支架TIPS做为一线治疗,而非＂救命＂治疗。     

经颈静脉肝内门体静脉分流术治疗肝硬化静脉曲张出血预后因素分析

目的 分析经颈静脉肝内门体静脉分流(TIPS)术治疗肝硬化静脉曲张出血患者的预后因素.方法 收集2003年1月至2008年12月162例行TIPS术的肝硬化静脉曲张出血患者基本资料、术前7 d内相关生化指标,定期随访观察术后情况和生存期资料.Cox回归模型评估影响预后生存的指标.结果 TIPS术成功率99%(161/162).中位随访时间21个月.Child-Pugh评分和血小板计数与生存密切相关(P值分别=0.003和0.024).Child-Pughr评分<9分者的累积生存率[75%(102/136)]高于评分≥9分者[50%(13/26),χ2=9.12,P=0.003].血小板计数>47×109/L者的累积生存率[74%(82/112)]高于≤47×109/L者[66%(33/50),χ2=4.528,P=0.033].肝功能Child-Pugh A、B、C级术后1年累积生存率分别为92%、85%、55%.结论 Child-Pugh评分和血小板计数是预测TIPS术治疗肝硬化静脉曲张出血者生存情况的独立因素,当ChildPugh评分≥9分和(或)血小板计数≤47×109/L时术后危险性增加.

Abstract：

Objective To analyze the prognostic factors in treating variceal hemorrhage patients of liver cirrhosis and portal hypertension with transjugular intrahepatic portosystemic shunt (TIPS).Methods From January 2003 to December 2008, the data of 162 variceal hemorrhage patients with liver cirrhosis and portal hypertension treated with TIPS was collected, which included basic information, biochemical examination results within 7 days before the operation, regular follow-up observation after the surgery and survival data. The survival prognostic indexes were assessed with Cox regression model. Results The successful rate of TIPS was 99% (161/162). The median follow up duration was 21 months. Child-Pugh score and blood platelet count (PLT) were closely correlated with survival (P = 0. 003 and 0. 024). The total cumulative survival rate in patients with Child-Pugh score below nine (75%, 102/136) was higher than over nine (50%, 13/26) (χ2 = 9. 12,P=0. 003).The total cumulative survival rate of patients with PLT count over 47 ×109/L (74%, 82/112) was higher than below 47 × 109/L(66 %, 33/50, χ2 =4. 528, P = 0. 033). The one year after operation cumulative survival rate of liver function Child-Pugh class A, B, and C was 92%, 85%, 55% respectively. Conclusion Child-Pugh score and platelet count are independent predictable factors for the survival of variceal hemorrhage patients with liver cirrhosis and portal hypertension treated by TIPS. The risk increase after operation when Child-Pugh score over 9 and/or PLT count less 47×109 /L.     

不同评分模型对肝硬化患者经颈静脉肝内门体分流术后生存的预测价值

目的 探讨Child-Pugh评分、终末期肝病模型(MELD)评分、联合血清钠离子的终末期肝病模型(MELD-Na)评分、慢性肝衰竭联盟-急性失代偿(CLIF-C AD)评分和经颈静脉肝内门体分流术(TIPS)术后生存Freiburg指数(FIPS)评分对肝硬化患者生存的预测价值。方法 回顾性分析2014年1月—2021年2月我国西南地区多家医院行TIPS治疗的447例肝硬化患者的临床资料,其中生存组306例,死亡组62例。计算五种评分模型分值,并基于五种评分模型分别对患者进行生存分析。正态分布的计量资料组间比较采用独立样本的t检验;不符合正态分布的计量资料组间比较采用非参数Mann-Whitney U检验;计数资料组间比较采用Pearson χ²检验;采用Cox回归分析各评分模型对TIPS患者预后的影响;Kaplan-Meier法分析不同评分水平的患者死亡风险的差异,并采用Log-rank检验。各模型预测能力采用受试者工作特征曲线下面积(AUC)、不同时间点C指数及决策曲线进行评估。结果 生存组患者年龄(Z=2.884)低于死亡组,Alb(t=3.577)、Na...     

经颈静脉肝内门体静脉分流治疗肝硬化的内科体会

我们自1994年4月开展经颈静脉肝内门体静脉分流(TIPSS)治疗肝硬化5例,病例由内科选择推荐.经颈静脉放置导管引导支撑管(Palmaz 管),经肝静脉与门静脉之间架桥的全过程由介入放射学科医师进行.术中超声探查支撑管,并监测其合适位置由B超室协助.术中及术后由消化内科协助观察病人,并具体执行术前后的内科治疗,及追踪病人.本文仅就内科参予过程,总结初步体会.     

经颈静脉肝内门体分流术治疗原发性胆汁性肝硬化门静脉高压的效果及安全性

目的探讨经颈静脉肝内门体分流术(TIPS)应用于失代偿期原发性胆汁性肝硬化(PBC)患者的短期疗效及安全性。方法对2009年1月-2015年5月于南京大学医学院附属鼓楼医院行TIPS治疗的26例失代偿期PBC患者的临床数据进行回顾性分析。对比术前术后门静脉压力、肝功能、生存率等指标及术后1年的随访情况。用Friedman检验进行多个相关样本的秩和检验,Wilcoxon检验进行配对秩和检验,对整个随访期内患者生存率作Kaplan-Meier分析曲线。结果 26例患者术后平均门静脉压力为19.11(16.35~22.05)mm Hg,较术前27.93(25.26~30.87)mm Hg显著下降,差异具有统计学意义(Z=-4.199,P0.001)。术后3个月内TBil、终末期肝病模型评分、胆汁酸等较术前明显上升(χ2值分别为26.000、18.429、16.353,P值均0.001)。术后最常见并发症为发热,发生率为80.77%(21/26),其次为肝性脑病,发生率为19.23%(7/26),术后6、12个月生存率均为92.3%(24/26)。结论 TIPS治疗失代偿期PBC患者短中期疗效及安全性较好,长期疗效尚需进一步观察。     

经颈静脉肝内门体分流术对酒精性肝硬化导致门静脉高压的治疗效果与安全性分析

目的分析经颈静脉肝内门体分流术(TIPS)治疗酒精性肝硬化导致门静脉高压的有效性及安全性。方法回顾性总结2006年6月至2011年6月本院30例接受TIPS治疗的酒精性肝硬化导致门静脉高压的患者资料,记录术前及术后门静脉压力、腹水、脾功能亢进、肝功能等指标。随访终点为术后2 a,观察术后并发症包括消化道再出血、支架堵塞、腹水及肝性脑病发生情况,并分析肝性脑病发生与患者临床参数的关系。穿刺前、后门静脉压力差别采用配对t检验分析;Kaplan-Meier方法用于术后临床参数与肝性脑病发生相关性分析。结果 TIPS手术成功率为100%(30/30),门静脉压力术前(37.27±2.52)cm H2O降为术后(24.6±2.58)cm H2O,差异具有统计学意义(P0.05)。术后2 a内,消化道再出血率为3.3%(1/30);腹水治疗有效率达88.9%(16/18);支架狭窄发生率为6.7%(2/30);肝性脑病发生率为40%(12/30)。Kaplan-Meier分析发现患者术前Child-Pugh分级与术后肝性脑病发生密切相关(P=0.04)。结论 TIPS是治疗酒精性肝硬化门静脉高压相关并发症安全有效的微创方法,术前ChildPugh分级是影响患者肝性脑病发生的重要因素。     

Management of refractory ascites and hepatorenal syndrome

Refractory ascites and hepatorenal syndrome (HRS) are the late complications of the terminal stages of cirrhosis. The definitions of refractory ascites and HRS proposed by the International Ascites Club in 1996 are now widely accepted, and are useful in diagnosis, treatment and research in this field. In both conditions, the only treatment of proven value for improved survival is liver transplantation. However, because of better understanding about the pathophysiology of HRS, including the roles of portal hypertension, ascites formation and hemodynamic derangements, treatments such as transjugular intrahepatic portasystemic shunt (TIPS) and new pharmacological agents may be considered to alleviate the problem prior to transplantation. Symptomatic treatment of refractory ascites includes TIPS and repeated large volume paracentesis. Transjugular intrahepatic portasystemic shunt can improve survival while waiting for liver transplantation. Practical management guidelines for TIPS and large volume paracentesis, including the prevention and management of further complications, are considered in this review.     

Transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of refractory ascites

Background: The Transjugular Intrahepatic Portosystemic Shunt (TIPS) corrects portal hypertension and has proven to be effective in controlling variceal bleeding in patients with cirrhosis. Several reports have now appeared suggesting a possible role in patients with refractory ascites.
Aims: To examine the outcome of TIPS for the treatment of refractory ascites in patients with cirrhosis.
Methods: Fifteen patients underwent TIPS for ascites between April 1992 and December 1996. The clinical findings, response to treatment, complications, shunt patency and survival of these patients were analysed.
Results: TIPS was successfully placed in all patients. The mean period of follow-up was 375 days (range: 14–1165 days). In eight patients (53%) there was a reduction in the degree of ascites after shunt insertion, with six patients (40%) having complete resolution. Age, Child-Pugh class or portal pressure gradient, before or after the procedure, were not predictive of response. Of five patients with renal insufficiency (serum creatinine >130 umol/L), only one had improvement in ascites control. Six patients (40%) required shunt revision during follow-up, either for acute thrombotic occlusion (two) or stent stenosis (four). New or worsening encephalopathy developed in ten patients (67%). Two patients (13%) died of liver failure within 30 days. Cumulative survival was 46% at one year and 18% at two years. Treatment response was associated with increased survival (ρ=0.02), with median survival of 658 days as compared with 71 days for treatment failure.
Conclusions: TIPS can be effective in the treatment of refractory ascites in patients with cirrhosis. Our experience suggests the benefit may be less for patients with advanced liver disease and renal impairment. Controlled trials are needed to compare TIPS with other treatment modalities such as large volume paracentesis or peritoneovenous shunting.     

肝硬化患者经颈静脉肝内门体分流术前后肠道菌群特征分析

目的 对比分析肝硬化患者经颈静脉肝内门体分流术(TIPS)前后肠道菌群的特征。方法 选取2018年7月-2019年7月西南医科大学附属医院消化内科住院行TIPS的肝硬化患者18例,术前采集粪便18例,术后1个月采集粪便6例,术后3个月采集粪便9例,同时收集患者术前及术后肝功能和凝血检验结果。对粪便样本采用16S rRNA高通量测序方法,生物信息分析流程使用QIIME2推荐的DADA2方法,以生成的扩增特征序列(OTU)为单位研究肠道菌群,采用多重假设检验LEfSe、SPSS(Alpha分析)、PERMANOVA(Beta分析)、Pheatmap方法分析肠道菌群。符合正态分布的计量资料不同采集时间点的指标组间比较采用重复测量资料方差分析;不符合正态分布的计量资料各时间点的组间比较采用广义估计方程,进一步两两比较采用Bonferroni法。结果 TIPS术前与术后3个时期肝功能指标对比中,TBil和总胆汁酸组间差异均有统计学意义(F值分别为8.201、39.482,P值分别为0.001、<0.001)。术后1个月粪便样本较术前相比存在Beta多样性变化(F=2.603, P=0.02),但3个时期粪便Alpha多样性差异无统计学意义(P值均>0.05)。TIPS术前门静脉压力在属水平上与双歧杆菌属﹑柯林斯菌属﹑瘤胃球菌属具有负相关性(r值分别为-0.35、-0.38、-0.34,P值分别为0.04、0.02、0.04),与牛肝菌属具有正相关性(r=0.41,P=0.015),其他检验指标也与不同的肠道菌群存在相关性(P值均<0.05)。结论 TIPS术前临床指标与肠道菌群具有相关性,TIPS术后肠道菌群组成发生变化,在属水平上差异显著。     

TIPS for management of refractory ascites: response and survival are both unpredictable

Refractory ascites is a serious complication of advanced cirrhosis with a 1-year transplant-free survival of 20–50%. The aim of our study was to investigate the short- and long-term effects of transjugular intrahepatic portosystemic shunt (TIPS) in the management of refractory ascites. In all 65 patients (39 M, 26 F; Child B 55%, Child C 45%, mean MELD score 14.8 ± 6.6) with liver disease (alcoholic 40%, cryptogenic 20%, HCV 14%, others 26%) and refractory ascites were included in this study. Forty-eight (74%) patients had no signs of hepatic encephalopathy (HE), 16 (24%) had mild and 1 (2%) had moderate HE before TIPS; 28 (43%) had mild (>1.2 and <2.4 mg/dl) and 6 patients (9%) had moderate (>2.4 mg/dl) renal dysfunction. Mean follow-up was 55.5 ± 70.2 weeks. Treatment success, defined as complete response, partial response, and no response, and survival was determined at 3 weeks, and 3, 6, 12, 24, and 36 months after TIPS. TIPS was successful in all patients. Mean portal venous pressure gradient improved significantly after TIPS (24 ± 8 to 10 ± 4). During follow-up, 40 (58%) patients died and 17 (27%) patients had liver transplantation (OLT); 20 (31%) patients had 38 shunt revisions due to lack of initial response or recurrence of ascites. The response was assessed in patients who were alive, without OLT, at each time point. Complete response was seen in 10%, 23%, 17%, 11%, 22% and 33%; partial response was seen in 46%, 46%, 40%, 44%, 28%, and 8%; and no response was seen in 44%, 31%, 43%, 41%, 39%, and 50% at 3 weeks, and 3, 6, 12, 24, and 36 months respectively. There were no pre-TIPS variables that could predict the response at 3 weeks, 3 months, or 6 months. Mild HE was seen in 8 (12%) patients and severe HE was seen in 16 (25%) immediately after TIPS. The mortality at 3 weeks, and 3, 6, 12, 24, and 36 months was 26%, 38%, 46%, 51%, 57%, and 58%, respectively. Three-week (P = 0.01) and 3-month (P = 0.04) mortality was higher in Child C patients compared to Child B. However, there were no independent predictors of survival on multivariate analysis at 3 or 6 months. Child-Pugh score 3 weeks after TIPS was a strong predictor of mortality. In conclusion, in patients with refractory ascites, TIPS was associated with a high mortality and morbidity. The response and the mortality were both unpredictable on the basis of pretransplant variables.     

Differences in long-term survival after transjugular intrahepatic portosystemic shunt for refractory ascites and variceal bleed

OBJECTIVE: To compare the survival after transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites and variceal bleed, and to identify the factors predictive of survival. METHODS: Single tertiary center, retrospective-prospective study. Chart review was performed on all patients who underwent TIPS between 1993 and 2000 and prospective follow-up to determine survival. Pre- and post-TIPS clinical parameters were compared and Kaplan-Meier analysis was applied to compare the survival of both groups. Cox regression was used to identify predictors of survival after TIPS. RESULTS: A total of 163 patients were included, 62 with refractory ascites and 101 with variceal bleed. Both groups had similar age (48.2 vs 48.9 year; P = 0.65) and consisted of predominantly Caucasians (51%) and Mexican-Americans (39%). More than 75% had chronic hepatitis C, alcoholic liver disease or both. Overall, the median survival was significantly better for variceal bleed (2 years) compared with refractory ascites (6 months) (P < 0.001). This survival advantage persisted in patients with Mayo risk score greater than 1.17. Transjugular intrahepatic portosystemic shunt improved severe ascites in 45% of patients (P = 0.03). Mayo risk score was highly predictive of survival after TIPS with a hazard ratio of 2.3, followed by Child-Pugh score, creatinine, albumin and ethnicity, with better survival among Mexican-Americans. Shunt dysfunction (31%) and hepatic encephalopathy (27%) were the most common complications of TIPS. CONCLUSIONS: Patients who received TIPS for variceal bleed had significantly longer survival compared with those for refractory ascites. Mexican-Americans had an improved long-term survival compared with Caucasians. The reason for this ethnic difference in survival is unclear and warrants further prospective evaluation.