What are ascites TIPS?

TIPS is a procedure that lowers pressure in the portal vein. That’s the vein that moves blood to your liver. The medical name for it is transjugular intrahepatic portosystemic shunt. Most people just call it TIPS.

When pressure in the portal vein gets too high (called portal hypertension), it can back up and make the veins around your stomach and esophagus, or food pipe, swell. These swollen veins are called varices. If they swell too much, they break open and bleed. This is called variceal bleeding. High pressure can also cause fluid to leak out and build up in your belly (ascites) or around your lungs (pleural effusion).

Doctors might use a TIPS procedure to treat variceal bleeding, ascites, or pleural effusion, when other treatments aren’t working.

The Procedure

Before the procedure, you’ll get a general anesthetic that puts you to sleep. The doctor will insert a thin, flexible tube, called a catheter, into a blood vessel in your neck. They’ll use an imaging test, usually an x-ray with contrast dye, to guide the catheter until it gets to your liver. Then the doctor will create a channel from the hepatic vein (the vein that takes blood out of the liver), to the portal vein. This channel allows blood to bypass your liver.

The TIPS stent, which is a wire mesh tube, will be placed to keep the channel open. Then, the doctor can measure the blood flow in your veins to make sure the pressure drops. If it’s still too high, they might use a balloon on the catheter to open the stent wider. The procedure usually takes 2 to 4 hours.

After the Procedure

After the procedure, you’ll stay in the hospital, but most people can go home after a day or 2. It can take weeks or months for the TIPS to work. So if you have fluid build-up in (ascites or pleural effusion), it may take time for the fluid to go away.

After you go home, rest and drink lots of water. For at least 10 days, don’t do heavy exercise (like running), and don’t lift more than 10lbs (4.5 kg). You can still do gentle activity, like walking, each day.

It’s really important to watch for symptoms like memory trouble, feeling sleepy, and balance problems. Also watch for yellow skin and swollen legs. Call your doctor or nurse right away if you have any of these symptoms.

You’ll need to have follow-up tests to help your healthcare team check your progress. The TIPS stent can get narrower over time. If this happens, you may need another procedure to make it wider.

Risks and Side Effects

A TIPS procedure can help you feel better and lower your chances of complications from varices, ascites and pleural effusion. But just like any procedure, there are risks and side effects you should know about. You’ll do tests before the procedure to check your risk of side effects.

Because it’s the liver’s job to filter toxins out of your blood, sending some blood through the TIPS means less of it goes through the liver to get filtered. This can cause toxins to build up in your body. Toxin buildup is called hepatic encephalopathy. It can cause you to feel confused, have balance problems, and feel sleepy. About 3 out of 10 people will get hepatic encephalopathy after a TIPS. It can usually be treated with medicine.

Some people might have more liver problems because less blood goes to the liver. Or they might have heart problems because more blood flows into the heart through the TIPS. If you get major problems that can’t be managed with medicine, your doctor may block off the TIPS stent.

Other side effects are rare. This procedure could cause bleeding, infection, or damage to your kidneys or lungs

The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites should be considered in patients with moderate decompensation and not as a last resort, as lower paracentesis frequency and creatinine levels pre-TIPS are associated with superior ascites control. In turn, failure to control ascites seems to be the only predictor of liver transplantation and death.

TIPS-placement in patients with lower paracentesis frequency and creatinine levels is associated with superior ascites control. Thus, TIPS implantation should be considered in moderate decompensation and not as a last resort. Persistent ascites post-TIPS seems to be the only predictor of liver transplantation and death.

A detailed retrospective analysis of 128 patients receiving expanded polytetrafluoroethylene-covered stents for the treatment of refractory ascites was performed. Persistent ascites post-TIPS was defined as the prolonged need for paracentesis >3 months after TIPS. The influence of demographics, laboratory results, pre-TIPS heart and liver ultrasound results, and invasive hemodynamic parameters on persistent ascites was evaluated by univariable and multivariable logistic regression. Predictors of the composite endpoint liver transplantation/death were analyzed using a multivariable Cox regression.

Liver cirrhosis is a major global health problem associated with high morbidity and mortality. [1] , [2] During its natural history, the formation of ascites is a key event in disease progression, which is related to a drastically decreased survival. [3] , [4] Ascites that cannot be mobilized successfully by diuretics or recurs early after paracentesis despite sufficient medical therapy is called refractory ascites, 5 and its management remains a serious clinical problem and matter of debate. Currently, large-volume paracentesis (LVP) with albumin substitution or the implantation of a transjugular intrahepatic portosystemic shunt (TIPS) are used for the treatment of refractory ascites. Several randomized controlled trials [6] , [7] , [8] , [9] , [10] , [11] and meta-analyses [12] , [13] have compared these approaches with regard to their effect on survival, showing an overall survival benefit in patients receiving a TIPS. 12 However, patient selection is crucial, as bilirubin levels > 3 mg/dl and platelet count < 75,000/μl, 14 older age, pre-TIPS hepatic encephalopathy (HE) 15 and cardiac impairment defined as an E/A ratio < 1 16 are associated with a poor outcome after TIPS. Regarding the efficacy of TIPS-placement on ascites control, a recent meta-analysis reported a complete response in 51% of patients and a partial response (defined as not requiring extended paracentesis) in 68% of patients, 17 while a decreased survival in case of persistent ascites after TIPS-placement has been reported for a cohort of patients receiving bare metal stents. 18 The reason why ascites control fails in some patients after TIPS, despite a standardized patient selection following current guidelines, remains elusive. Thus, additional factors that improve patient selection need to be identified. In this study, we aimed to assess predictors of persistent ascites after TIPS by analyzing a wide range of demographic, laboratory, ultrasound and invasive hemodynamic variables. In addition, the effect of unsuccessful ascites control on transplant-free survival was assessed in our well-characterized cohort.

Mean and median values with the corresponding standard deviation or interquartile range (IQR) were calculated for continuous data using Excel 2016 (Microsoft Inc., Redmond, WA) and SPSS Statistics Version 25 (IBM Corp., Armonk, NY), percentages and counts are given for categorical data. A univariable logistic regression was conducted to identify possible predictors of persistent ascites after TIPS-placement, followed by a multivariable logistic regression in which all parameters with a p value < 0.1 in the univariable regression were included. The area under the receiver operating characteristic (AUROC) curve was calculated for metric variables selected by the multivariable logistic regression to determine an optimal cut-off point. Additionally, a multivariable Cox regression for covariate adjustment for the composite endpoint liver transplantation and death followed by a cause-specific analysis and a Fine and Grey competing risk regression model was carried out. For these analyses, variables that showed differences in the group-wise comparison (persistent ascites vs. ascites control after TIPS) or were considered relevant for patient outcome according to the literature were included as covariates. Given the exploratory character of these analyses, no adjustment for multiple testing was conducted and the significance level was set to be 0.05 for all calculations. Adjusted survival curves for the composite endpoint were calculated based on the multivariable Cox model adjusting for mean MELD, mean CLIF-C AD, and mean PSPG post-TIPS. Figure design and statistical testing was carried out using SPSS Version 25 and R Version 3.5.1 (R Core Team, 2018).

All TIPS insertions were carried out by experienced interventional radiologists trained for this procedure. In order to optimize conditions, a paracentesis was performed before TIPS-placement. During the intervention, local anesthesia in combination with midazolame (Hofmann-La Roche, Basel, Switzerland) and piritramide (Hameln pharma plus GmbH, Hameln, Germany) was administered in most patients, but a minority received additional propofol sedation. The portosystemic pressure gradient (PSPG) was invasively acquired by measurement of the pressure gradient in the portal vein and the intra-abdominal portion of the vena cava. In all patients, a 10 mm expanded polytetrafluoroethylene (ePTFE) coated stentgraft (VIATORR®, W.L. Gore & Associates Inc., AZ) was used and dilated to 8 mm using an 8/40 mm balloon dilatation catheter (Boston Scientific, Marlborough, MA). If variceal flow was present after TIPS-placement, variceal embolization was additionally carried out using a 2:1 mixture of N-butyl cyanoacrylate (B. Braun Melsungen AG, Melsungen, Germany) and lipiodol (Guerbet, Villepinte, France).

The following outcome parameters were retrospectively collected: the need for paracentesis after TIPS-placement, the number of TIPS revisions performed, dates of complicating events (bleeding, diagnosis of a hepatocellular carcinoma [HCC], spontaneous bacterial peritonitis [SBP]), the date of liver transplantation or death, and the date of the last clinical visit/contact. Patients that had not presented to our outpatient clinic for > 6 months (cut-off date 01.01.2018) were followed up by phone. Persistent ascites was defined as the ongoing need for paracentesis > 3 months after TIPS-placement as described before. 18 The study was approved by the local ethics committee (reference number PV5580) in accordance with the principles of the declaration of Helsinki.

All patients receiving a TIPS for refractory ascites at the University Medical Center Hamburg-Eppendorf between January 2011 and December 2016 were screened for this retrospective analysis. The following baseline parameters were collected: demographic data, a detailed disease history including the timepoint of the first ascitic decompensation and the monthly paracentesis frequency, medication pre-TIPS, and the results of the last analysis of the composition of the ascitic fluid. Before TIPS-placement, all patients received an echocardiography as well as a standardized abdominal ultrasound before and after TIPS. For this study, all echocardiograms and abdominal ultrasounds were re-evaluated and rescored if necessary. Available pre-TIPS CT scans/MRIs were additionally analyzed for collateral flow. Routine laboratory parameters including Child-Pugh score, model for end-stage liver disease (MELD) score and Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD) score were assessed at baseline and shortly after (mean 12 ± 18 days) TIPS-placement. Alcohol consumption post-TIPS was evaluated by review of the clinical records and defined as “any” alcohol consumption either reported by the patient or detected by alcohol markers (usually ethyl glucuronide in urine). Changes in cardiac function post-TIPS were systematically investigated by evaluation of available post-TIPS echocardiograms.

During follow-up, 12 TIPS revisions were performed in patients with persistent ascites, including 3 TIPS reductions and 9 dilatations without an improvement of ascites. Reasons why the other patients were not considered for a stent dilatation include HE (4 patients), fear of exhaustion of cardiac reserve (3), blood stream infection (2), liver transplantation shortly after TIPS-placement (2), late-onset recompensation with diuretics (1) and an unstructured follow-up (9).

A total of 52 out of 128 patients underwent follow-up echocardiographies, of which 32 were performed in patients with ascites control and 20 in patients with persistent ascites. When stratified according to ascites clearance, changes in cardiac parameters were similar between groups, especially an increase in atrial diameters (Table S4). A deterioration of diastolic dysfunction defined as a diastolic dysfunction grade II or III was observed in 5/32 (16%) patients with ascites control and 2/20 (10%) patients with persistent ascites after TIPS. In patients with ascites control, 1 patient with a diastolic dysfunction II° developed an additional moderate tricuspid insufficiency, 2 patients developed either a moderate mitral or tricuspid insufficiency and 1 patient developed pulmonary arterial hypertension. In patients with persistent ascites after TIPS, 1 patient developed a moderate tricuspid insufficiency and 2 patients presented with cardiac failure due to a newly developed dilatative cardiomyopathy and a high-grade tricuspid insufficiency.

The development of the underlying liver disease may affect ascites control and prognosis of patients with decompensated liver cirrhosis. Chronic alcohol abuse, viral liver disease or the combination of both were the main etiologies of liver cirrhosis in this cohort ( ). Data on alcohol consumption after TIPS-placement were available in 77/92 (84%) patients with alcoholic liver disease (ALD) and in 104/128 (81%) patients irrespective of disease etiology (Table S3). When stratified according to ascites clearance, the rate of post-TIPS alcohol consumption was similar for patients with ALD (19/70, 27% in the ascites control group vs. 7/22, 31% in patients with persistent ascites) and for all patients irrespective of disease etiology (22/95, 23% vs. 8/33, 24%). All 3 patients with a chronic hepatitis B infection were already under treatment before TIPS-placement, and in case of chronic hepatitis C virus (HCV) infection, 2/15 patients were treated before TIPS, 1/15 patients was treated after TIPS and 12/15 patients did not receive antiviral therapy and therefore had a stable underlying liver disease.

During follow-up, 8 patients (6%) suffered from portal hypertensive bleeding complications, HCC developed in 11 patients (8%) and 16 patients (13%) were treated for SBP. After stratification for ascites control, the event rate for HCC and bleeding was similar between groups, but more patients with persistent ascites developed SBP (4/95, 4% vs. 12/33, 36%, ). Patients with ascites control after TIPS presented with a lower event rate of liver transplantations or death (28/95, 29% vs. 23/33, 70%), corresponding to a longer transplant-free survival (median 25.8 vs. 10.0 months, and ). In a multivariable Cox regression including baseline creatinine, baseline MELD score, baseline CLIF-C AD score, post-TIPS PSPG values and group stratification according to ascites control or persistent ascites after TIPS, only persistent ascites was identified as an independent predictor of the composite endpoint liver transplantation/death (hazard ratio [HR] 5.654; CI 3.019–10.59; ), which was confirmed both in the cause-specific analysis (not shown) and the Fine and Grey competing risk regression for each endpoint (death or liver transplantation). In the cause-specific analysis, the baseline CLIF-C AD score was also predictive of the endpoint “death” (HR 1.068; CI 1.01–1.13; p = 0.02; data not shown), whereas baseline MELD score was an additional independent predictor of the endpoint “liver transplantation” (HR 1.323; CI 1.024–1.71; p = 0.03; data not shown). In the Fine and Grey competing risk regression, baseline CLIF-C AD score was an additional independent predictor of death (HR 1.058; CI 1.001–1.12; see ).

Variables from all pre-TIPS assessments were first analyzed with an univariable logistic regression model, but only the pre-TIPS paracentesis frequency, the left atrial diameter, baseline creatinine values, PSPG post-TIPS and the absolute PSPG decrease (ΔPSPG) had a p value < 0.1 and were therefore included in the multivariable regression model ( ). On multivariable analysis, the paracentesis frequency pre-TIPS (odds ratio [OR] 1.672; 95% CI 1.253–2.355), ΔPSPG (OR 1.164; CI 1.027–1.340) and baseline creatinine values (OR 2.640; CI 1.201–6.607) were identified as independent predictors of persistent ascites after TIPS. However, an additional AUROC calculation showed a poor discriminating power of baseline creatinine with an area under the curve of 0.661 and an optimal cut-off value of 1.5 mg/dl with a mediocre sensitivity (0.758) and a poor specificity (0.515, see Fig. S1 and Table S2).

After a mean of 12 ± 18 days, a routine laboratory follow-up was carried out. In the whole cohort, bilirubin increased significantly (from 1.4 ± 0.9 to 1.9 ± 1.2 mg/dl) after TIPS, whereas creatinine values decreased to a significant extent (from 1.4 ± 0.7 to 1.1 ± 0.4 mg/dl), resulting in stable MELD and CLIF-C AD scores. Changes in laboratory parameters were also comparable between the groups of patients with ascites control and persistent ascites after TIPS ( ).

The follow-up abdominal Doppler ultrasound was performed after a median of 3 days (IQR 1) following TIPS-placement. Portal venous flow increased significantly from 19.1 ± 5.4 to 37.3 ± 13.3 cm/sec, accompanied by an increase in hepatic arterial flow ( ). All but 2 patients presented with a retrograde intrahepatic portal venous flow, intra-TIPS flow amounted to a mean of 115 ± 33 cm/sec, and all flow parameters were comparable between the groups ( ).

Baseline portal and central venous pressure values with the corresponding PSPG before TIPS-placement were similar in both groups ( ). A stent was successfully placed in all patients, resulting in a decrease of mean PSPG values from 21.0 ± 4.5 to 8.7 ± 2.9 mmHg in the whole cohort. Patients with ascites control after TIPS showed a trend towards lower post-TIPS PSPG values compared to patients with persistent ascites (8.4 ± 2.8 mmHg vs. 9.4 ± 2.8 mmHg) and a higher absolute decrease in PSPG brought about by the intervention (ΔPSPG 12.9 ± 4.1 vs. 10.5 ± 4.1 mmHg). During angiography, collateral flow before TIPS-creation was present in 27/128 (21%) of patients with a higher prevalence in the group of patients with ascites control (22/95, 23% vs. 5/33, 15%), and an additional variceal embolization was only carried out in 6 patients.

When stratifying the patient cohort according to ascites clearance, neither group differed with regard to baseline demographics and disease history including pre-TIPS medication (Table S1), but patients with ascites control after TIPS-placement had a lower paracentesis frequency pre-TIPS (2.2 ± 1.2 vs. 3.6 ± 2.2 per month, ). Abdominal ultrasound studies at baseline indicated similar flow rates in the portal vein and the hepatic artery, but collaterals and shunts evaluated either by ultrasound or abdominal CT scan/MRI (additionally available in a subgroup of 36 patients) were more prevalent in patients with persistent ascites after TIPS (18/33, 55% vs. 28/95, 29% in patients with ascites control, ). Baseline echocardiography including an assessment of the diastolic dysfunction, tricuspid annular plane systolic excursion, E/A, E/E’, diameter of the right atrium and the left ventricular ejection fraction also yielded comparable results, but patients with ascites control after TIPS presented with a smaller left atrium (18.8 ± 5.1 vs. 21.8 ± 8.9 cm 2 , ). The composition of the ascitic fluid and routine laboratory parameters at baseline were similar between the group of patients with ascites control and persistent ascites, including MELD (12.3 ± 3.5 vs. 13.5 ± 4.4) and CLIF-C AD (50.3 ± 6.5 vs. 52.2 ± 6.4) scores ( ). However, patients with ascites control after TIPS presented with lower creatinine values at baseline (1.3 ± 0.5 vs. 1.7 ± 1.0 mg/dl).

In total, 222 patients receiving a TIPS for refractory ascites were identified, of which 131 patients had a complete documented work-up and were therefore included in this study. However, 1 patient was lost to follow-up and 2 patients suffered acute complications (fatal bleeding and immediate post-TIPS liver failure), resulting in a total of 128 patients in the final analysis. General characteristics are given in . The main etiology of liver disease was chronic alcohol abuse (92/128, 72%) and most patients presented with a liver cirrhosis Child-Pugh B (103/128, 80%). Before TIPS insertion, the mean PSPG amounted to 21.0 ± 4.5 mmHg ( ) and the mean MELD and CLIF-C AD score were 12.6 ± 3.8 and 50.8 ± 6.5 points, respectively ( ). During follow-up, a total of 95/128 patients (74%) showed ascites control, of which 58 patients (61%) needed no additional paracentesis at all, and ascites persisted in 33/128 patients (26%) with the ongoing need for paracentesis > 3 months post-TIPS. A TIPS revision was carried out in 20/128 patients (15%), of which 14 (70%) underwent recanalization/dilatation and 6 (30%) a stent diameter reduction due to prolonged HE. In total, 11 patients (8%) underwent liver transplantation and 40 patients (31%) died during follow-up, resulting in an overall median transplant-free survival of 20.3 months ( ). None of the patients who underwent liver transplantation was prioritized on the waiting list due to refractory ascites.

Discussion

Despite careful patient selection, ascites persists in a relevant proportion of patients receiving a TIPS for refractory ascites. In this study, we demonstrate that lower pre-TIPS paracentesis frequency and creatinine levels are associated with superior ascites control and that TIPS-non-response with persistent ascites predicts impaired transplant-free survival.

As patients were selected according to widely accepted recommendations, the patient cohort presented in this study is rather homogeneous and baseline characteristics including MELD and Child-Pugh scores and pre- and post-TIPS ultrasound, laboratory and PSPG values are comparable to the published literature.[6], [8], [14], [15], [19], [20] All TIPS-placements were technically successful with an adequate decrease in portal pressure, leading to ascites control in 74% and persistent ascites with the ongoing need for paracentesis > 3 months after TIPS in 26% of patients, which is also in line with previous reports.17

On multivariable analysis, paracentesis frequency pre-TIPS, baseline creatinine and the absolute decrease of PSPG (ΔPSPG) were independent predictors of persistent ascites post-TIPS. However, the clinical importance of the difference in ΔPSPG is questionable, as it only amounted to approximately 1.5 mmHg with a lower limit of the odds ratio close to 1. To our surprise, the post-TIPS PSPG was not associated with ascites control in our cohort, even though some patients presented with post-TIPS PSPG values > 12 mmHg which is not considered optimal. In this context, the timing of the PSPG measurement immediately after TIPS-creation could have influenced our results, as values change over time.21 Furthermore, recent studies[22], [23] have reported a passive dilatation of the TIPS-stent after its placement, which might also contribute to further changes in PSPG values. Therefore, defining an optimal PSPG cut-off for patients with refractory ascites remains a matter of debate,24 especially in light of the potentially deleterious effect of overly aggressive pressure reduction.25

Similar to our results, several other studies have reported that higher creatinine values at baseline are associated with an unfavorable outcome after TIPS for refractory ascites.[6], [19], [26] However, guiding therapeutic decisions based on creatinine values alone is difficult, as a TIPS itself improves renal function,15 as also seen in our cohort, so that renal insufficiency/hepatorenal syndrome (HRS) can be considered an indication for TIPS itself.27 Importantly, the rate and type of HRS was similar between groups in our cohort, which otherwise would have been an important confounder, as the type of HRS has also been shown to have an impact on post-TIPS survival.[28], [29]

Besides lower creatinine values, a lower pre-TIPS paracentesis frequency was also identified as an independent predictor of ascites control post-TIPS. Taking these 2 findings together, our data support the idea that a TIPS should be inserted “early” in ascitic decompensation and not be reserved for patients with an extremely high paracentesis frequency.30 Even though there are a multitude of reasons for renal impairment in liver cirrhosis, long-term diuretic therapy with a consecutive increase in creatinine values is a key contributor. Therefore, an “early” TIPS in refractory ascites may help to break the vicious circle of attempting to increase diuretics to mobilize ascites, causing further renal impairment which in turn makes pharmaceutical control of ascites impossible. This approach is also supported by the latest prospective, randomized trial comparing TIPS to LVP8 in patients with only recurrent ascites and a limited paracentesis frequency, which demonstrated a survival benefit in TIPS-treated patients. Therefore, we suggest that a TIPS should be considered early in patients with a stable underlying liver disease whose kidney function is beginning to be impaired, whereas in patients with an HCV-associated liver cirrhosis, treatment of the underlying disease with direct-acting antivirals should be considered first31 to improve liver function.

Furthermore, our data clearly indicate that patients with persistent ascites after TIPS have a decreased transplant-free survival. Interestingly, neither the MELD nor the CLIF-C AD score was predictive of the composite endpoint transplantation and death, and neither score changed to a statistically significant extent on short-term follow-up (even though these scores can be inaccurate on short-term follow-up due to procedure-related changes in e.g. bilirubin). In this regard, our study highlights another issue regarding patient selection for TIPS and a possible liver transplantation. While patients with persistent ascites after TIPS have an impaired transplant-free survival, this is not adequately reflected by current clinical scores used for organ allocation in some countries, like the MELD score, especially as its main driver – serum creatinine – may improve after TIPS-placement. Therefore, prioritized organ allocation for patients with persistent ascites after TIPS awaiting liver transplantation should be systematically evaluated and considered as a standard strategy.

Despite a thorough analysis, we did not find any additional predictive marker among the routinely assessed parameters that may help in the patient selection for TIPS. In this present study, the CLIF-C AD score that has shown to improve the prediction of prognosis in acutely decompensated patients32 has been evaluated in TIPS patients for the first time. However, it did not yield any further predictive power despite incorporating age and white blood cell count – factors that have been described as relevant for patient outcome after TIPS.[33], [34], [35] Considering the impact of systemic inflammation on patient outcome after TIPS,33 further prospective studies are warranted to dissect the crosstalk between portal hypertension and immunity. In this context, elastography techniques to measure liver and spleen stiffness may also help to anticipate patient outcome after TIPS-placement, as both parameters quickly respond to pressure changes[36], [37], [38] and a beneficial effect of a decrease in liver stiffness after TIPS or non-selective betablocker treatment have been reported.[39], [40]

The strength of this study lies within the exhaustive in-depth analysis and a highly standardized patient selection and treatment, particularly the exclusive use of ePTFE-covered stentgrafts. However, it also has several limitations, like its retrospective nature, a limited sample size and a high confidence interval on multivariable analysis due to the limited number of events. In this context, recompensation after TIPS itself poses a potential bias as it allows for a more aggressive treatment of potentially life-limiting liver-related and unrelated medical conditions. In addition, not all patients with persistent ascites post-TIPS underwent a stent re-dilatation for various reasons, even though some of these patients might arguably have benefited from a further stent dilatation. Another limitation is, that due to the study design, the evaluation of alcohol consumption only represents an approximation, as no details on drinking habits (e.g. amount consumed, frequency, etc.) can be provided. On the other hand, the data at hand indicate that most patients remained under stable conditions with respect to their underlying liver disease, which is important as interventions like alcohol withdrawal and viral eradication have a direct impact on liver function and portal hypertension.41 Similarly, the data of follow-up echocardiography and the association of spontaneous shunts on TIPS function can only be regarded as preliminary. Even though changes in cardiac parameters were similar between groups and cardiac failure was only observed in 2 patients in this cohort, the limited availability of follow-up echocardiograms preclude a generalization, so that post-TIPS heart failure might have been overlooked as a factor contributing to the persistence of ascites. In addition, abdominal imaging pre-TIPS revealed a higher number of shunts in patients with persistent ascites post-TIPS, which is in line with a previous report on the association of spontaneous shunts and outcome in patients in liver cirrhosis.42 However, as only a fraction of patients were evaluated by a CT or MRI scan, and as more collaterals were detected in patients with ascites control during angiography, these results cannot be generalized. However, the association between spontaneous shunts and post-TIPS outcome should be investigated in prospective studies if possible.

In conclusion, our results suggest that TIPS-placement should not be restricted to patients with a high paracentesis frequency and renal impairment, but that it should already be considered early during ascitic decompensation in patients with refractory ascites and a lower paracentesis frequency. Persistent ascites after TIPS is associated with a poor prognosis, so that prioritized liver transplant allocation should be considered.