Current use of transjugular intrahepatic portosystemic shunts

The principal indication for transjugular intrahepatic portosystemic shunts (TIPS) continues to be rescue therapy for variceal hemorrhage that cannot be controlled by endoscopic or medical therapy. TIPS provide no survival advantage in prevention of rebleeding or refractory ascites. The indications for TIPS continue to expand, however, especially for Budd-Chiari syndrome and hydrothorax. Other more novel indications include bleeding portal hypertensive gastropathy or ectopic varices, Budd-Chiari syndrome, veno-occlusive disease, hepatorenal syndrome, hepatopulmonary syndrome, hepatocellular carcinoma, and polycystic liver disease. Great strides have been made recently in models to predict mortality and complications following TIPS placement. Graft stents hold promise based on early studies. Finally, complications are common and may be life threatening.     

Portal hypertension, varices, and transjugular intrahepatic portosystemic shunts

Transjugular intrahepatic protosystemic shunts (TIPS) is the newest and the least invasive method of eradicating varices. This article defines portal hypertension succinctly, describes how it gives rise to varices and their consequences, and briefly reviews the development, short experience with, and current status of TIPS.     

Influence of transjugular intrahepatic portosystemic shunts (TIPS) on tissue oxygenation in patients with cirrhosis

ABSTRACT— Aims/Backgrounds: The aim of this prospective study was to evaluate the influence of transjugular portosystemic intrahepatic shunts (TIPS) on tissue oxygenation in patients with cirrhosis and refractory ascites. Methods: Five shunted patients were included in the study. The blood and tissue oxygenation values were analyzed 12 days and 4 months after TIPS procedure. The results were compared with those observed in patients treated by paracentesis. Results: Unlike patients treated by paracentesis, PaO₂ values remained unchanged throughout follow-up in shunted patients. After the TIPS procedure, there was a transient increase in systemic O₂ transport and O₂ uptake and a transient decrease in O₂ saturation of hepatic oxyhemoglobin. After 4 months, TIPS resulted in an increase in PCO₂ values and bicarbonate concentrations. Conclusions: The TIPS procedure seems to prevent the decrease in PaO₂ observed in patients treated by paracentesis and may improve the respiratory alkalosis of cirrhosis.     

经颈静脉肝内门体分流术治疗食道静脉曲张破裂出血

采用经颈静脉肝内门体分流术(TIPSS)治疗5例肝硬化门静脉高压症(CPH)食管静脉反复破裂出血病人,平均门静脉压力由术前3.6±0.7kPa,降至术后1.73±0.35kPa,术后24小时全部病例出血均停止,门静脉血流阻力系数降低,曲张静脉消失或减轻。TIPSS 治疗门脉高压食管静脉反复性出血具有损伤小、合并症少,近期疗效确切等特点,是治疗门脉高压食道静脉破裂出血的首选方法。     

A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts

Transjugular intrahepatic portosystemic shunts (TIPS) may worsen liver function and decrease survival in some patients. The Child-Pugh classification has several drawbacks when used to determine survival in such patients. The survival of 231 patients at 4 medical centers within the United States who underwent elective TIPS was studied to develop statistical models to (1) predict patient survival and (2) identify those patients whose liver-related mortality post-TIPS would be 3 months or less. Among these elective TIPS patients, 173 had the procedure for prevention of variceal rebleeding and 58 for treatment of refractory ascites. Death related to liver disease occurred in 110 patients, 70 within 3 months. Cox proportional-hazards regression identified serum concentrations of bilirubin and creatinine, international normalized ratio for prothrombin time (INR), and the cause of the underlying liver disease as predictors of survival in patients undergoing elective TIPS, either for prevention of variceal rebleeding or for treatment of refractory ascites. These variables can be used to calculate a risk score (R) for patients undergoing elective TIPS. Patients with R > 1.8 had a median survival of 3 months or less. This model was superior to both the Child-Pugh classification, as well as the Child-Pugh score, in predicting survival. Using logistic regression and the same variables, we also developed a nomogram that indicates which patients survive less than 3 months. Finally, the model was validated among an independent set of 71 patients from the Netherlands. This Mayo TIPS model may predict early death following elective TIPS for either prevention of variceal rebleeding or for treatment of refractory ascites.     

Long-term renal sodium handling in patients with cirrhosis treated with transjugular intrahepatic portosystemic shunts for refractory ascites

PURPOSE: The long-term effects of transjugular intrahepatic portosystemic shunts on renal sodium excretion are not known. We sought to determine these long-term effects, as well as to measure the effects of a sodium load in patients who are free of ascites. SUBJECTS AND METHODS: Ten patients with cirrhosis who had been successfully treated with transjugular intrahepatic portosystemic stent shunt for refractory ascites were studied before the shunt and again at 6 and 14 months after the shunt while on a 22 mmol sodium/day diet. At 14 months they were also studied on a 200 mmol sodium/day diet for 7 days without diuretics. Renal sodium handling, central blood volume, neurohumoral factors, and hepatic function were measured. RESULTS: Sodium balance was negative at 6 months (urinary sodium excretion [mean +/- SD] 51 +/- 11 mmol/day versus 7 +/- 2 mmol/day pre-shunt; P < 0.05), was maintained at 14 months (22 +/- 4 mmol/day; P < 0.05 versus pre-shunt), and was associated with normalization of renin activity and aldosterone levels, but not norepinephrine levels, as well as significantly improved renal hemodynamic measurements. Sodium loading with 200 mmol/day resulted in weight gain associated with increased central blood volume and appropriate renal sodium handling in most but not all patients (urinary sodium excretion 188 +/- 14 mmol/day), despite persistent nonsuppressibility of sympathetic hyperactivity. CONCLUSIONS: In cirrhotic patients with refractory ascites treated with a transjugular intrahepatic portosystemic stent shunt, long-term renal sodium handling is improved. Adequate intravascular filling in ascites-free cirrhotic patients with normal portal pressure permits an improved but not normalized renal response to a sodium load, possibly due to persistently elevated sympathetic activity. Therefore, these patients should increase their sodium intake cautiously.     

Hepatic and splanchnic perfusion and oxygenation after transjugular intrahepatic portosystemic shunt.

OBJECTIVE: in patients with cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) decreases the pressure in the portal vein by rerouting nearly all the portal blood flow to the systemic circulation. This may lead to hypoperfusion of the liver and worsening function. Our aim was to investigate whether TIPS actually reduced hepatic and splanchnic perfusion. METHODS: we studied 25 patients who required placement of a TIPS (20 for variceal bleeding and 5 for refractory ascites). We evaluated the clinical condition, laboratory results, blood velocity in the portal vein and hepatic artery by echo-Doppler ultrasonography, systemic hemodynamic-oxygenation status and hemodynamic-oxygenation status in the portal and suprahepatic veins before TIPS, 15 min after the procedure, and 30 days later. Hepatic and splanchnic perfusion were evaluated as the arteriovenous difference in O2 content and as the O2 extraction rates in the hepatic and splanchnic territories. RESULTS: TIPS induced an immediate decrease in portal pressure, a significant increase in systemic hyperdynamic state, and an increase in blood flow velocity in the portal vein and hepatic artery. Thirty days after the procedure these changes persisted, although they were somewhat attenuated. Although splanchnic and liver perfusion were not changed 15 min or 30 days after TIPS, there was a slight tendency toward a decrease in liver perfusion during follow-up. CONCLUSIONS: TIPS increased the hyperdynamic state in the systemic side. However, portal blood shunting did not change liver or splanchnic perfusion.     

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。     

Fasting hyperglucagonemia in patients with transjugular intrahepatic portosystemic shunts (TIPS).

BACKGROUND: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). METHODS: Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). RESULTS: Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. CONCLUSION: In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.     

Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation.

OBJECTIVE: To determine the safety and efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in controlling bleeding from esophageal varices in patients awaiting liver transplantation. DESIGN: Prospective, uncontrolled trial. SETTING: University medical center with an active liver transplant program. PATIENTS: Thirteen patients referred for liver transplantation with either active variceal hemorrhage or recurrent variceal hemorrhage despite sclerotherapy; four patients had been previously treated with surgical portosystemic shunts. INTERVENTION: An intrahepatic portosystemic shunt created via a transjugular approach to the hepatic veins using expandable, flexible metallic stents. MEASUREMENTS: Portal pressures before and after the creation of the shunt, the direction of portal blood flow at differing diameters of the shunts, procedure-related complications, and outcome in terms of survival, liver transplantation, and recurrent variceal bleeding. MAIN RESULTS: The transjugular intrahepatic portosystemic shunt was placed successfully in 13 patients, and bleeding was controlled acutely in all 13. After the procedure, the mean portal pressure decreased from 34 +/- 8.9 cm H2O to 22.4 +/- 5.4 cm H2O (P less than 0.001). No complications were associated with the procedure; however, two patients died of causes unrelated to the procedure. Seven patients subsequently underwent liver transplantation and are doing well, and three patients are being managed conservatively. Bleeding recurred in one patient 102 days after the procedure secondary to shunt occlusion caused by neointimal proliferation. CONCLUSION: Placement of a transjugular intrahepatic portosystemic shunt is apparently safe and effective therapy for variceal hemorrhage in patients referred for liver transplantation.     

Safety and efficacy of transarterial chemoembolization in patients with transjugular intrahepatic portosystemic shunts

BackgroundTransarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) is an important option as the majority of patients present with advanced disease. Data regarding treatment outcomes in patients who have undergone transjugular intrahepatic portosystemic shunts (TIPS) are limited. The present study seeks to evaluate the safety and efficacy of TACE in HCC patients with a TIPS.MethodsA retrospective review identifying patients with HCC and concomitant TIPS who were treated with TACE was performed.ResultsFrom 1999 to 2014, 16 patients with HCC underwent a total of 27 TACE procedures; eight patients required multiple treatments. The median patient age at the time of the initial TACE was 60.5 years [interquartile range (IQR) : 52.5–67.5] with the majority being male (n = 12, 75%) and Childs–Pugh Class B (n = 12, 75%). At 6 weeks after TACE, 56.3% of patients achieved an objective response rate (complete and partial response) by mRECIST criteria. Clavien Grade 3 or higher complications occurred in 11.1% of TACE procedures. There were no peri-procedural deaths. The median progression-free (PFS) and overall survival (OS) were 9 and 22 months, respectively, when censored for liver transplantation (median follow-up: 11.5 months).ConclusionTACE is an effective treatment strategy for HCC in TIPS patients; albeit may be associated with higher complication rates.     

Effect of technical parameters on transjugular intrahepatic portosystemic shunts utilizing stent grafts

AIM: To assess the effect of technical parameters on outcomes of transjugular intrahepatic portosystemic shunt(TIPS) created using a stent graft.METHODS: The medical records of 68 patients who underwent TIPS placement with a stent graft from 2008 to 2014 were reviewed by two radiologists blinded to the patient outcomes.Digital Subtraction Angiographic images with a measuring catheter in two orthogonal planes was used to determine the TIPS stent-to-inferior vena cava distance(SIVCD),hepatic vein to parenchymal tract angle(HVTA),portal vein to parenchymal tract angle(PVTA),and the accessed portal vein.The length and diameter of the TIPS stent and the use of concurrent variceal embolization were recorded by review of the patient's procedure note.Data on re-intervention within 30 d of TIPS placement,recurrence of symptoms,and survival were collected through the patient's chart.Cox proportional regression analysis was performed to assess the effect of these technical parameters on primary patency of TIPS,time to recurrence of symptoms,and all-cause mortality.RESULTS: There was no significant associationbetween the SIVCD and primary patency(P = 0.23),time to recurrence of symptoms(P = 0.83),or allcause mortality(P = 0.18).The 3,6,and 12-mo primary patency rates for a SIVCD ≥ 1.5 cm were 82.4%,64.7%,and 50.3% compared to 89.3%,83.8%,and 60.6% for a SIVCD of 1.5 cm(P = 0.29).The median time to stenosis for a SIVCD of ≥ 1.5 cm was 19.1 mo vs 15.1 mo for a SIVCD of 1.5 cm(P = 0.48).There was no significant association between the following factors and primary patency: HVTA(P = 0.99),PVTA(P = 0.65),accessed portal vein(P = 0.35),TIPS stent diameter(P = 0.93),TIPS stent length(P = 0.48),concurrent variceal embolization(P = 0.13) and reinterventions within 30 d(P = 0.24).Furthermore,there was no correlation between these technical parameters and time to recurrence of symptoms or all-cause mortality.Recurrence of symptoms was associated with stent graft stenosis(P = 0.03).CONCLUSION: TIPS stent-to-caval distance and other parameters have no significant effect on primary patency,time to recurrence of symptoms,or all-cause mortality following TIPS with a stent-graft.     

Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt

BACKGROUND: A portosystemic stent shunt may impair cardiac function and haemodynamics. AIMS: To investigate the effects of a transjugular intrahepatic portosystemic shunt (TIPS) on cardiac function and pulmonary and systemic circulation in patients with alcoholic cirrhosis. PATIENTS/METHODS: 17 patients with alcoholic cirrhosis and recent variceal bleeding were evaluated by echocardiography and catheterisation of the splanchnic and pulmonary circulation before and after TIPS. The period of catheter measurement was extended to nine hours in nine of the patients. The portal vein was investigated by Doppler ultrasound before and nine hours after TIPS. RESULTS: Baseline echocardiography showed the left atrial diameter to be slightly increased and the left ventricular volume to be in the upper normal range. Nine hours after TIPS, the left atrial diameter and left ventricular end diastolic volume were increased (by 6% (p<0.01) and 7% (p<0.01) respectively); end systolic volume had not changed significantly. Invasive measurements showed a sharp increase in right atrial pressure (by 101%; p<0.01), mean pulmonary artery pressure (by 92%; p<0.01), pulmonary capillary wedge pressure (by 111%; p<0.01), and cardiac output (8.1 (1.6) to 11.9 (2.4) l/min; p<0.01). Systemic vascular resistance decreased (824 (242) to 600 (265) dyn.s.cm-5 p<0.01), and total pulmonary resistance increased (140 (58.5) to 188 (69.5) dyn.s.cm-5; p<0.05). Total pulmonary resistance (12%; NS), cardiac output (1.4 l/min; p<0. 05), and portal vein blood flow (1.4 l/min; p<0.05) remained elevated for nine hours after TIPS in the subgroup. Portoatrial pressure gradient (43%; p<0.05), portohepatic vascular resistance (72%; p<0.05), and systemic vascular resistance (27%; p<0.01) were consistently reduced. CONCLUSIONS: The increase in the left atrial diameter, the pulmonary capillary wedge pressure, and total pulmonary resistance observed after the TIPS procedure reflected diastolic dysfunction of the hyperdynamic left ventricle in patients with alcoholic cirrhosis. The haemodynamic effects of the portosystemic stent shunt itself on the splanchnic circulation seem to be mainly responsible for the further decrease in systemic vascular resistance. TIPS may unmask a coexisting preclinical cardiomyopathy in patients with alcoholic cirrhosis and portal hypertension.     

Refractory chylothorax in hepatic cirrhosis: successful treatment by transjugular intrahepatic portosystemic shunt

Patients with cirrhosis and portal hypertension have increased thoracic duct lymph flow. Correction of portal hypertension is associated with decreases in thoracic duct flow. The authors present a case of rapid resolution of refractory chylothorax caused by thoracic duct injury proven by lymphangiography and helical CT scan in a patient with cirrhosis of the liver by using a transjugular intrahepatic portosystemic shunt to decrease portal pressure and thereby reduce thoracic duct lymph flow.