Transjugular intrahepatic portosystemic shunt (TIPS): current indications and strategies to improve the outcomes.

Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of complications of portal hypertension. Established indications to TIPS in cirrhotic patients include portal hypertensive bleeding and refractory ascites. Over the years additional indications have been proposed, such as the treatment of vascular disease of the liver, hepatic hydrothorax, hepatorenal syndrome and bleeding from ectopic varices. Indications under evaluation include treatment of portal hypertension prior to major abdominal surgery and treatment of portal vein thrombosis. In spite of these advances, there are still uncertainties regarding the appropriate workup for patients to be scheduled for TIPS. Moreover, prevention and management of post-TIPS complications including hepatic encephalopathy and heart failure are still suboptimal. These issues are particularly relevant considering aging in TIPS candidates in Western countries. Correct selection of patients is mandatory to prevent complications which may eventually frustrate the good hemodynamic results and worsen the patient's quality of life or even life expectancy. The possible role of small diameter TIPS to prevent post-procedural complications is discussed.

TIPSS for variceal bleeding in patients with idiopathic non-cirrhotic portal hypertension: comparison with patients who have cirrhosis.

BACKGROUND: In patients with idiopathic non-cirrhotic portal hypertension (INCPH), the usual recommended strategy for management of variceal bleeding is the same as that in cirrhosis. However, this policy has been challenged by the different natural history between INCPH and cirrhosis. AIM: To compare outcomes after transjugular intrahepatic portosystemic shunt (TIPSS) between INCPH and cirrhotic patients admitted for variceal bleeding. METHODS: Between March 2001 and September 2015, 76 consecutive patients with biopsy-proven INCPH undergoing TIPSS for variceal bleeding in a tertiary-care centre were included. 76 patients with cirrhotic portal hypertension receiving TIPSS for variceal bleeding, and matched for age, sex, Child-Pugh class, stent type and index year of TIPSS creation served as controls. RESULTS: Patients with INCPH, compared to those with cirrhosis, had significantly lower mortality (11% vs 36% at 5 years, adjusted HR, 0.37; 95% CI 0.15-0.87, P = 0.022), overt hepatic encephalopathy (16% vs 33% at 5 years, adjusted HR, 0.35; 95% CI 0.16-0.75, P = 0.007) and hepatic impairment, despite similar rates of further bleeding (33% vs 32% at 5 years, adjusted HR, 0.72; 95% CI 0.36-1.44, P = 0.358), and shunt dysfunction (35% vs 36% at 5 years, adjusted HR, 0.84; 95% CI 0.41-1.72, P = 0.627). These findings were consistent across different relevant subgroups. CONCLUSIONS: Patients with INCPH treated with TIPSS for variceal bleeding had similar progression of portal hypertension (further bleeding and shunt dysfunction) but fewer complications of liver disease (overt hepatic encephalopathy and hepatic insufficiency) and lower mortality rate compared with cirrhotic patients with comparable liver function.

Review article: a multidisciplinary approach to the diagnosis and management of Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is a rare but fatal disease caused by obstruction in the hepatic venous outflow tract. AIM: To provide an update of the pathophysiology, aetiology, diagnosis, management and follow-up of BCS. METHODS: Analysis of recent literature by using Medline, PubMed and EMBASE databases. RESULTS: Primary BCS is usually caused by thrombosis and is further classified into "classical BCS" type where obstruction occurs within the hepatic vein and "hepatic vena cava BCS" which involves thrombosis of the intra/suprahepatic portion of the inferior vena cava (IVC). BCS patients often have a combination of prothrombotic risk factors. Aetiology and presentation differ between Western and certain Asian countries. Myeloproliferative neoplasms are present in 35%-50% of European patients and are usually associated with the JAK2-V617F mutation. Clinical presentation is diverse and BCS should be excluded in any patient with acute or chronic liver disease. Non-invasive imaging (Doppler ultrasound, computed tomography, or magnetic resonance imaging) usually provides the diagnosis. Liver biopsy should be obtained if small vessel BCS is suspected. Stepwise management strategy includes anticoagulation, treatment of identified prothrombotic risk factors, percutaneous revascularisation and transjugular intrahepatic portosystemic stent shunt to re-establish hepatic venous drainage, and liver transplantation in unresponsive patients. This strategy provides a 5-year survival rate of nearly 90%. Long-term outcome is influenced by any underlying haematological condition and development of hepatocellular carcinoma. CONCLUSIONS: With the advent of newer treatment strategies and improved understanding of BCS, outcomes in this rare disease have improved over the last three decades. An underlying haematological disorder can be the major determinant of outcome.

Diastolic dysfunction on echocardiography does not predict survival after transjugular intrahepatic portosystemic stent-shunt in patients with cirrhosis.

BACKGROUND: Cardiac dysfunction is frequently observed in patients with cirrhosis. There remains a paucity of data from routine clinical practice regarding the role of echocardiography in the pre-assessment of transjugular intrahepatic portosystemic stent-shunt. AIM: Our study aimed to investigate if echocardiography parameters predict outcomes after transjugular intrahepatic portosystemic stent-shunt insertion in cirrhosis. METHODS: Patients who underwent echocardiography and transjugular intrahepatic portosystemic stent-shunt insertion at the liver unit (Birmingham, UK) between 1999 and 2016 were included. All echocardiography measures (including left ventricle ejection fraction; early maximal ventricular filling/late filling velocity ratio, diastolic dysfunction as per British Society of Echocardiography guidelines) were independently reviewed by a cardiologist. Predictors of 30-day and overall transplant free-survival were assessed. RESULTS: One Hundred and Seventeen patients with cirrhosis (median age 56 years; 54% alcohol; Child-Pugh B/C 71/14.5%; Model For End-Stage Liver Disease 12) underwent transjugular intrahepatic portosystemic stent-shunt for ascites (n = 78) and variceal haemorrhage (n = 39). Thirty-day and overall transplant-free survival was 90% (n = 105) and 31% (n = 36), respectively, over a median 663 (IQR 385-2368) days follow-up. Model for End-Stage Liver Disease (P < 0.001) and Child-Pugh Score (P = 0.002) significantly predicted 30-day and overall transplant-free survival. Model for End-Stage Liver Disease ≥15 implied three-fold risk of death. Six per cent (n = 7) of patients pre-transjugular intrahepatic portosystemic stent-shunt had a history of ischaemic heart disease and 34% (n = 40) had 1 or more cardiovascular disease risk factors. Fifty per cent (n = 59) had an abnormal echocardiogram and 33% (n = 39) had grade 1-3 diastolic dysfunction. On univariate analysis none of the echocardiography measures pre-intervention were related to 30-day or overall transplant-free survival post-transjugular intrahepatic portosystemic stent-shunt. CONCLUSIONS: Ventricular, in particular diastolic dysfunction in patients with cirrhosis does not predict survival after transjugular intrahepatic portosystemic stent-shunt insertion. Model for End-Stage Liver Disease and Child-Pugh scores remain the best predictors of survival. Further prospective study is required to clarify the role of routine echocardiography prior to transjugular intrahepatic portosystemic stent-shunt insertion.

Predictors of Re-bleeding and Mortality Among Patients with Refractory Variceal Bleeding Undergoing Salvage Transjugular Intrahepatic Portosystemic Shunt (TIPS).

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has proven clinical efficacy as rescue therapy for cirrhotic patients with acute portal hypertensive bleeding who fail endoscopic treatment. AIMS: To investigate predictive factors of 6-week and 1-year mortality in patients undergoing salvage TIPS for refractory portal hypertensive bleeding. METHODS: A total of 144 consecutive patients were retrospectively evaluated. Three logistic regression multivariate models were estimated to individualize prognostic factors for 6-week and 12-month mortality. Log-rank test was used to evaluate survival according to Child-Pugh classes and Bureau's criteria. RESULTS: Mean age 51 ± 10 years, 66% male, mean MELD 18.5 ± 8.3, Child-Pugh A/B/C 8%/38%/54%. TIPS failure occurred in 23(16%) patients and was associated with pre-TIPS portal pressure gradient and pre-TIPS intensive care unit stay. Six-week and 12-month mortality was 36% and 42%, respectively. Pre-TIPS intensive care unit stay, MELD, and Child-Pugh score were independently associated with mortality at 6 weeks. Independent predictors of mortality at 12 months were pre-TIPS intensive care unit stay and Child-Pugh score. CONCLUSIONS: In this large cohort of patients undergoing salvage TIPS, MELD and Child-Pugh scores were predictive of short- and long-term mortality, respectively. Pre-TIPS intensive care unit stay was independently associated with TIPS failure and mortality at 6 weeks and 12 months. Salvage TIPS is futile in patients with Child-Pugh score of 14-15.

Combined diffusion tensor imaging and magnetic resonance spectroscopy to predict neurological outcome before transjugular intrahepatic portosystemic shunt.

BACKGROUND: Hepatic encephalopathy (HE) may occur after transjugular intrahepatic portosystemic shunt (TIPSS) placement. Multimodal magnetic resonance imaging (MRI), combining anatomical sequences, diffusion tensor imaging (DTI) and 1 H magnetic resonance spectroscopy, is modified in cirrhotic patients. AIMS: To describe multimodal MRI images before TIPSS, to assess if TIPSS induces changes in multimodal MRI, and to find predictors of HE after TIPSS in patients with cirrhosis. METHODS: Consecutive cirrhotic patients with an indication for TIPSS were prospectively screened. Diagnosis of minimal HE was performed using psychometric HE test score. Multimodal MRI was performed before and 3 months after TIPSS placement. RESULTS: Twenty-five consecutive patients were analysed (median age = 59, male gender 76%, median Child-Pugh score = 8 [5-8], MELD score = 12 [9-17], indication for TIPSS placement: ascites/secondary prophylaxis of variceal bleeding/other 20/3/2), no HE/minimal HE/overt HE: 21/4/0. 8/25 patients developed HE after TIPSS. Before TIPSS placement, metabolite concentrations were different in patients with or without minimal HE (lower myo-inositol, mI, higher glutamate/glutamine), but there were no differences in DTI data. TIPSS placement induced changes in metabolite concentrations even in asymptomatic patients, but not in DTI metrics. Baseline fractional anisotropy was significantly lower in patients who developed HE after TIPSS in five regions of interest. CONCLUSIONS: TIPSS placement induced significant changes in cerebral metabolites, even in asymptomatic patients. Patients who developed HE after TIPSS displayed lower fractional anisotropy before TIPSS. Brain MRI with DTI acquisition may help selecting patients at risk of HE.

Variable efficacy of TIPSS in the management of ectopic variceal bleeding: a multicentre retrospective study.

BACKGROUND: Evidence for the efficacy of TIPSS in ectopic variceal bleeding (EctVB) is largely based on relatively small series. AIM: To define the efficacy of TIPSS in EctVB. METHODS: Retrospective analysis of consecutive patients with chronic liver disease who presented with EctVB and received TIPSS in three tertiary centres in 1992-2016. RESULTS: The study included 53 patients (70% male, median age 61 years, median model for end-stage liver disease (MELD) score 11). The ectopic varices were located around the insertion of stomas (40%), duodenum (23%), rectum (17%) and at other sites (20%). Three-quarters of the patients had previously received unsuccessful medical, endoscopic or surgical therapy. The median follow-up was 14.0 months. Following TIPSS, bleeding recurred in 12 patients: 6 of 12 (50%) with duodenal varices, 2 of 9 (22%) with rectal varices and one each with stomal (1/21), intraperitoneal (1/3), hepaticojejunostomy (1/2) and ascending colon varices (1/2). The risk factors for re-bleeding were MELD score at TIPSS placement (HR: 1.081 per point; 95% confidence interval (CI): 1.012-1.153; P = 0.034), varices located at site other than an enterostomy (HR: 9.770; 95%CI: 1.241-76.917; P = 0.030) and previous local therapy (HR: 5.710; 95%CI: 1.211-26.922; P = 0.028). The estimated cumulative re-bleeding rate was 23% at 1 year, 26% at 3 years and 32% at 5 years. Post-TIPSS hepatic encephalopathy manifested or worsened in 16 of 53 patients (30%). CONCLUSION: TIPSS provides long-term control of bleeding in most cirrhotic patients with EctVB. TIPSS is particularly effective in stomal EctVB, the most frequent cause of EctVB, but might not be as effective in duodenal EctVB.

National Trends and Outcomes of Transjugular Intrahepatic Portosystemic Shunt Creation Using the Nationwide Inpatient Sample.

PURPOSE: To elucidate trends in transjugular intrahepatic portosystemic shunt (TIPS) use and outcomes over the course of a decade, including predictors of inpatient mortality and extended length of hospital stay. MATERIALS AND METHODS: The Nationwide Inpatient Sample was interrogated for the most recent 10 years available: 2003-2012. TIPS procedures and associated diagnoses were identified via International Classification of Diseases (version 9) codes, with the latter categorized into primary diagnoses in a hierarchy of disease severity. Linear regression analysis was used to determine trends of TIPS use and outcomes over time. Independent predictors of mortality and extended length of stay were determined by logistic regression. RESULTS: A total of 55,145 TIPS procedures were captured during the study period. Annual procedural volume did not change significantly (5,979 in 2003, 5,880 in 2012). The majority of TIPSs were created for ascites and/or varices (84%). Inpatient mortality (12.5% in 2003, 10.6% in 2012; P < .05) decreased but varied considerably by diagnosis (from 3.7% to 59.3%), with a disparity between bleeding and nonbleeding varices (18.7% vs 3.8%; P < .01). Multivariate predictors of mortality (P < .001 for all) included primary diagnoses (bleeding varices, hepatorenal and abdominal compartment syndromes), patient characteristics (age > 80 y, black race), and sequelae of advanced cirrhosis (comorbid hepatocellular carcinoma, spontaneous bacterial peritonitis, encephalopathy, and coagulopathy). CONCLUSIONS: National TIPS inpatient mortality has decreased since 2003 while procedural volume has not changed. Postprocedural outcome is a function of patient demographic and socioeconomic factors and associated diagnoses. Independent predictors of poor outcome identified in this large national population study may aid clinicians in better assessing preprocedural risk.

Management of gastric varices: a French national survey.

BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices. METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire. RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: ß-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; P<0.001) and TIPS (78.5 vs. 3.5%; P<0.001). Early TIPS was proposed by 53.6% (72.1 vs. 39.2%; P<0.001). Glue obliteration was performed under general anesthesia (86.1%) using Glubran (43.1%) or Histoacryl (52.9%), and lipiodol (78.8%) with varying degrees of dilution (1 : 10 to 3 : 4). The injected volume per varix varied widely (1-20 ml). Glue obliteration, band ligation, or both were used by, respectively, 64.2, 18.2, and 17.5% of practitioners. Almost all hepatogastroenterologists (98%) performed secondary prophylaxis: ß-blockers 74.7% (75.0 vs. 74.4%, university vs. general hospitals; P=0.93), glue obliteration 66.0% (76.9 vs. 57.6%; P=0.013), and TIPS 30.0% (39.1 vs. 23.3%; P=0.037). CONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies.

No effect of albumin infusion on the prevention of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

Hepatic encephalopathy (HE) is a major problem in patients submitted to TIPS. Previous studies identified low albumin as a factor associated to post-TIPS HE. In cirrhotics with diuretic-induced HE and hypovolemia, albumin infusion reduced plasma ammonia and improved HE. Our aim was to evaluate if the incidence of overt HE (grade II or more according to WH) and the modifications of venous blood ammonia and psychometric tests during the first month after TIPS can be prevented by albumin infusion. Twenty-three patients consecutively submitted to TIPS were enrolled and treated with 1 g/Kg BW of albumin for the first 2 days after TIPS followed by 0,5 g/Kg BW at day 4th and 7th and then once a week for 3 weeks. Forty-five patients included in a previous RCT (Riggio et al. 2010) followed with the same protocol and submitted to no pharmacological treatment for the prevention of HE, were used as historical controls. No differences in the incidence of overt HE were observed between the group of patients treated with albumin and historical controls during the first month (34 vs 31 %) or during the follow-up (39 vs 48 %). Two patients in the albumin group and three in historical controls needed the reduction of the stent diameter for persistent HE. Venous blood ammonia levels and psychometric tests were also similarly modified in the two groups. Survival was also similar. Albumin infusion has not a role in the prevention of post-TIPS HE.

Portosystemic Shunts: Stable Utilization and Improved Outcomes, Two Decades After the Transjugular Intrahepatic Portosystemic Shunt.

PURPOSE: The aim of this study was to assess national trends in utilization, demographics, hospital characteristics, and outcomes of patients undergoing surgical or percutaneous portal decompression since the introduction of transjugular intrahepatic portosystemic shunts (TIPS). METHODS: A retrospective analysis of patients undergoing surgical portal decompression and TIPS procedures was conducted using Medicare Physician/Supplier Procedure Summary Master Files from January 2003 through December 2013 and National (Nationwide) Inpatient Sample data from 1993, 2003, and 2012. Utilization rates normalized to the annual number of Medicare enrollees, estimated means, and 95% confidence intervals were calculated. RESULTS: The Medicare total annual utilization rate per million for all portosystemic decompression procedures decreased by 6.5% during the study period, from 15.3 in 2003 to 14.3 in 2013. TIPS utilization increased by 19.4% (from 10.3 to 12.3 per million), whereas open surgical shunt utilization decreased by 60.0% (from 5.0 to 2.0 per million). TIPS procedures represented 86% of all procedures in 2013. From 1993 to 2012, mean age increased slightly (from 53.0 to 55.5 years, P < .05). The percentage of procedures performed at teaching hospitals increased, whereas in-hospital mortality and length of stay decreased by 42% (P < .05) and 20% (P < .05), respectively. Of factors evaluated, the performance of procedures on an elective basis was the most influential on in-hospital mortality (P < .01, all years studied) and length of stay (P < .0001, all years studied). CONCLUSIONS: Approximately two decades after the introduction of TIPS, the utilization of all portal decompression procedures has remained relatively stable. The TIPS procedure represents the dominant portal decompression technique. In-hospital mortality and mean length of stay after decompression have decreased, partially because of the performance of procedures during elective admissions.

Surgical portosystemic shunts in the era of TIPS and liver transplantation are still relevant.

BACKGROUND: The surgical portosystemic shunts (PSS) are a time-proven modality for treating portal hypertension. Recently, in the era of liver transplantation and the transjugular intrahepatic portosystemic shunts (TIPS), use of the PSS has declined. OBJECTIVES: This study was conducted to evaluate changes in practice, referral patterns, and short- and longterm outcomes of the use of the surgical PSS before and after the introduction of the Model for End-stage Liver Disease (MELD). METHODS: A retrospective analysis of 47 patients undergoing PSS between 1996 and 2011 in a single university hospital was conducted. RESULTS: Subgroups of patients with cirrhosis (53%), Budd-Chiari syndrome (13%), portal vein thrombosis (PVT) (26%), and other pathologies (9%) differed significantly with respect to shunt type, Child-Pugh class, MELD score and perioperative mortality. Perioperative mortality at 60 days was 15%. Five-year survival was 68% (median: 70 months); 5-year shunt patency was 97%. Survival was best in patients with PVT and worst in those with Budd-Chiari syndrome compared to other subgroups. Patency was better in the subgroups of patients with cirrhosis and other pathologies compared with the PVT subgroup. Substantial changes in referral patterns coincided with the adoption of the MELD in 2002, with decreases in the incidence of cirrhosis and variceal bleeding, and increases in non-cirrhotics and hypercoagulopathy. CONCLUSIONS: Although the spectrum of diseases benefiting from surgical PSS has changed, surgical shunts continue to constitute an important addition to the surgical armamentarium. Selected subgroups with variceal bleeding in well-compensated cirrhosis and PVT benefit from the excellent longterm patency offered by the surgical PSS.

Transjugular intrahepatic portosystemic stent-shunt: technical factors and new developments.

The introduction of expandable metal stents in the mid 1980s led to the development of transjugular intrahepatic portosystemic stent-shunt (TIPSS) as we know it today. Short-lived detrimental effects on the hyperdynamic circulation in cirrhosis accompany the acute reduction in portal pressure following TIPSS creation. Caution is needed in patients with cardiac dysfunction or pulmonary hypertension. With increasing expertise and careful patient selection, fatal procedural complications are rare and TIPSS can even be safely used as a bridge to liver transplantation. Shunt insufficiency and hepatic encephalopathy are more common following TIPSS. Currently, however, novel approaches to tackling both these limitations exist. These include the combination of uncovered TIPSS with variceal band ligation, and the introduction of polytetrafluoroethylene covered stents. Despite the lack of controlled studies, covered stents are now widely used and have the potential to drastically reduce shunt insufficiency, the need for long-term shunt surveillance and even hepatic encephalopathy.

Transjugular intrahepatic portosystemic shunts: an update.

Transjugular intrahepatic portosystemic shunts (TIPS) have been used in the treatment of complications of portal hypertension. TIPS is used for the control of acute variceal bleeding and for the prevention of vericeal rebleeding when pharmacologic therapy and endoscopic therapy have failed. Patients with refractory ascites with adequate hepatic reserve and renal function who fail to respond to large volume paracentesis may be reasonable candidates for TIPS. Promising indications for TIPS are Budd-Chiari syndrome uncontrolled by medical therapy, severe portal hypertensive gastropathy, refractory hepatic hydrothorax, and hepatorenal syndrome. TIPS cannot be recommended for preoperative portal decompression solely to facilitate liver transplantation. Special care should be taken to insure proper placement of the stent to avoid increasing the technical difficulty of the transplantation procedure. The major limiting factors for TIPS success are shunt dysfunction and hepatic encephalopathy. Because shunt stenosis is the most important cause of recurrent complications of portal hypertension, a surveillance program to monitor shunt patency is mandatory. The MELD score may be useful in predicting post-TIPS survival, and also in counseling patients and their families.

Transjugular intrahepatic portosystemic shunt (TIPS): current status and future possibilities.

Since the insertion of the first TIPS in 1989 much has been learned about this therapeutic procedure. It has an established role for the treatment of some complications of portal hypertension: prevention of recurrent variceal bleeding and rescue of patients with acute uncontrollable variceal bleeding. In addition TIPS is useful for Budd-Chiari syndrome, refractory ascites and hepatorenal syndrome, although its specific role in these indications remains to be definitively established. However, the decrease in sinusoidal blood flow induced by TIPS can lead to the patient developing hepatic encephalopathy and liver failure in some cases. Therefore, TIPS should be used with caution in patients with very poor liver function. From a technical point of view, successful placement of TIPS is achieved in more than 98% of cases by experienced groups. At present, evaluation of TIPS dysfunction based on morphology probably leads to an overdiagnosis of this complication since most of these cases are not associated with clinical manifestations (recurrent bleeding or refractory ascites). The major disadvantage of TIPS remains its poor long-term patency requiring a mandatory surveillance program. The indicator for shunt function/malfunction should be the portosystemic pressure gradient, which is best assessed by intravascular measurements. Shunt obstructions may be prevented or reduced by the use of stent-grafts in the future.