Transjugular Intrahepatic Portosystemic Shunt Reduction Techniques

Abstract

Transjugular intrahepatic portosystemic shunt (TIPS) creation treats complications of portal hypertension in appropriately selected patients by lowering the portal venous pressure. While this can be a lifesaving intervention, portal venous flow diversion is not without potential consequences. Overshunting can lead to hepatic decompensation and encephalopathy. TIPS reduction and TIPS occlusion are therapeutic options used to mitigate overshunting, with reduction being the initial alternative due to retained shunt patency and lower potential for venous thrombosis. Patient selection, techniques for TIPS reduction, and patient outcomes are reviewed in this article.

Transjugular intrahepatic portosystemic shunt (TIPS) creation is a minimally invasive procedure used to treat complications of portal hypertension in patients with variceal hemorrhage, refractory ascites, hepatorenal syndrome, Budd-Chiari syndrome, hepatic veno-occlusive disease, hepatic hydrothorax, portal hypertensive gastropathy, hepatopulmonary syndrome, and portal vein thrombosis. ¹ Complications following TIPS creation are most often attributed to overshunting of splanchnic blood bypassing hepatic parenchyma filtration, which can result in hepatic encephalopathy, acute liver failure, and pulmonary hypertension. ^{2 3}

Most patients with encephalopathy can be treated conservatively by limiting protein in the diet, increasing fiber intake, and minimizing gut microflora neurotoxin production and absorption with antibiotics and disaccharides. However, up to 8% of patients will develop refractory encephalopathy and may benefit from further intervention and TIPS reduction. ⁴ Debilitating hepatic encephalopathy refractory to medical optimization is the most common indication for TIPS reduction, which is generally defined by West Haven criteria of grade 2, 3, or 4 and collectively referred to as overt hepatic encephalopathy (OHE). ^{5 6 7} These grades feature varying degrees of cognitive disorientation and asterixis and are utilized to evaluate clinical symptoms pre- and postprocedure. Severe or refractory hepatic encephalopathy typically develops within 1 to 3 months after TIPS. ^{6 8 9} Predictive factors of post-TIPS encephalopathy include nonalcoholic causes of cirrhosis with hypoalbuminemia, Child-Pugh class B or C disease, prior episodes of encephalopathy, large TIPS diameter, a high change in portosystemic gradient reduction, and age less than 65 years. ^{10 11}

Per the PEARL trial featuring 238 patients who received prophylactic medical management prior to undergoing TIPS, new or worsening hepatic encephalopathy was observed in 33% of patients within 30 days after the procedure, while 17% of those patients still had hepatic encephalopathy after 90 days. ⁸ Other studies described hepatic encephalopathy occurring in 22 to 50% of patients after TIPS creation. ¹² When bare metal stents were used, there was a progressive decrease of hepatic encephalopathy incidence and severity after the first month secondary to the spontaneous reduction of the TIPS diameter, which has been demonstrated via increased portosystemic gradient index and decreased ammonia levels on follow-up. ¹³

Hepatic encephalopathy frequently coincides with a decline in hepatic function. Acute liver failure is the second most common indication for TIPS reduction and is defined as a change of more than threefold bilirubin and/or twofold international normalized ratio (INR) with clinical symptoms. ¹⁴ Symptoms develop more rapidly than hepatic encephalopathy, occurring within days to weeks after TIPS creation. While defined with bilirubin and INR, acute liver failure treatment response is subsequently monitored by liver transaminase trends and clinical symptoms. A lesser reported indication for TIPS modification is pulmonary hypertension, where elevated pulmonary pressures are observed after TIPS creation and diuretic therapy is unsuccessful in managing symptoms. Onset of symptoms varies as literature on TIPS reduction for pulmonary hypertension alone is limited. ⁶

TIPS reduction techniques and outcomes have evolved over the past several decades with the advent of new devices. Historical and current techniques and short-term clinical outcomes are reviewed herein.

Techniques

Percutaneous interventional options for reducing blood flow through the shunt are TIPS occlusion and TIPS reduction. Early reports of TIPS closure described the use of coils. ^{15 16} Another occlusion technique involved temporarily inflating an angioplasty balloon within the TIPS and creating in-stent thrombosis, potentially allowing for later recanalization and placement of a smaller internal stent. ^{17 18} Acute shunt occlusion is not favored because it can lead to progressive liver failure, recurrent variceal hemorrhage, and fatal hemodynamic alterations. ^{19 20}

TIPS reduction aims to decrease the luminal size of the shunt while maintaining shunt patency. Early techniques featured bare metal stents partially dilated at the portal end and completely dilated and anchored at the hepatic end. These stents could be constrained in the mid-portion with silk to decrease the diameter, and Ethibloc could be injected into the space between the original TIPS and reducing stent. ^{21 22} While novel at the time, these initial techniques were limited by the unpredictability of reduction and portal pressure elevation. The rise of the commercial stent-grafts allowed for greater control of TIPS in both creation and reduction, leading to longer patency and lower dysfunction rates. ²³

Taylor et al collectively details three main techniques of TIPS reduction with stent-grafts: the parallel stent technique where a short balloon-expandable bare metal stent is deployed at the hepatic end parallel to a stent-graft spanning both ends ( Fig. 1a ); the hourglass configuration technique where a constrained self-expandable stent-graft or incompletely dilated balloon-expendable stent-graft is deployed within the TIPS ( Fig. 1b ); and the tapered stent-graft technique where a commercially available tapered stent-graft is fully expanded at the portal end ( Fig. 1c ). ⁹

Fig. 1.

Three main techniques of TIPS reduction using stent-grafts, adapted from Taylor et al. ( a ) Parallel stents technique: A short balloon-expandable bare metal stent at the hepatic end is deployed parallel to a stent-graft spanning both ends. ( b ) Hourglass configuration technique: A constrained self-expandable or incompletely dilated balloon-expandable stent-graft is dilated to the size of the TIPS, first at the portal vein end and subsequently at the hepatic vein end. The mid-portion of the stent-graft is then partially dilated. ( c ) Tapered stent-graft technique: A commercially available tapered stent-graft is fully expanded at the portal vein end and partially expanded at the hepatic vein end. HV, hepatic vein; IVC, inferior vena cava; MPV, main portal vein.

TIPS reduction utilizing an hourglass configuration technique is preferred at our institution. Initial clinical data on three patients who underwent TIPS reduction are summarized in Table 1 . All patients were middle-aged males with cirrhosis who underwent TIPS creation for variceal bleeding or refractory ascites. Patients later developed new onset or worsening OHE refractory to conventional medical therapy.

Table 1. Clinical data on patients who underwent initial TIPS creation.

Patient	Age (years), sex	Hepatic disease	MELD	TIPS Indication	Pre-TIPS HE grade	TIPS Stent (cm)	PSG (mm Hg), before/after TIPS
1	46 M	EtOH cirrhosis	30	Variceal bleeding	I–II	1 × 8	N/A	11
2	69 M	HCV	14	Refractory ascites	0	1 × 6	20	4
3	51 M	EtOH cirrhosis	24	Variceal bleeding	N/A	1 × 6	35	12

Abbreviations: EtOH, alcoholic; HCV, hepatitis C virus infection; HE, hepatic encephalopathy; M, male; MELD, model for end-stage liver disease; N/A, not applicable; PSG, portosystemic gradient; TIPS, transhepatic portosystemic shunt.

For the TIPS reduction procedure, right internal jugular vein access was obtained, and a contrast portal venogram was performed to confirm positioning and anatomy. Pre-reduction hemodynamic pressures were obtained in the portal vein and right atrium. A 10-Fr by 40-cm sheath was advanced into the TIPS stent. An 8-mm diameter by 5.9-cm length Gore VBX balloon-expandable polytetrafluoroethylene (PTFE)-covered stent-graft (Gore Medical, Newark, DE) was partially deployed inside the 10-mm Viatorr TIPS ( Fig. 2 ). After the ends of the stent-graft were partially expanded, the deployment balloon was deflated as the sheath was slowly advanced forward until the tip of sheath rested against the central nondilated portion of the stent-graft. A sheath-buttressing technique was then used, where forward pressure on the sheath and the curvature of the TIPS were used to maintain stability and prevent the partially expanded stent-graft from migrating. The mid-portion of the stent-graft was dilated using a 5-mm angioplasty balloon. Lastly, the stent-graft ends were fully expanded with a 12-mm-diameter angioplasty balloon first at the portal vein end and then at the hepatic vein end. Post-stent reduction hemodynamic pressures were obtained in the portal vein and right atrium, and a final contrast portal venogram was performed.

Fig. 2.

TIPS reduction Gore VBX stent-graft deployment. ( a ) Over a stiff guidewire, an 8 mm × 5.9 cm Gore VBX PTFE-covered stent graft was partially expanded within the 10 mm × 8.0 cm Viatorr TIPS. ( b ) With the assistance of the sheath and curvature of the TIPS to keep the incompletely expanded stent-graft in place, the stent-graft was expanded to a diameter of 5 mm along its entire length. ( c ) Using a 12 × 40 mm angioplasty balloon, the portal vein end was fully expanded to the diameter of the TIPS stent, followed by subsequent expansion of the hepatic vein end (not shown). ( d ) The final configuration resembles that of an hourglass where the stent was secured on both ends and reduced at the mid-portion, resulting in controlled reduction of the overall shunting. The portosystemic gradient was increased from 13 to 23 mm Hg in this case.

Fig. 3 illustrates an additional hourglass TIPS reduction stent-graft utilizing an iCast (Atrium Medical Corp., Merrimack, NH) as opposed to a Gore VBX. Unlike the VBX deployment, the iCast stent-graft has slightly more differential inflation at the ends of the balloon-mounted stent rather than the center, referred to as the dog bone configuration. Taking advantage of this characteristic, the 10-mm iCast was partially deployed within the TIPS until the portal and hepatic vein ends were anchored. The balloon was then deflated and used to maximally dilate the portal vein end to ensure complete anchoring, followed by dilation of the hepatic vein end.

Fig. 3.

TIPS reduction iCast stent-graft deployment. ( a ) Over a stiff guidewire, a 10 mm × 5.9 cm PTFE-covered iCast stent-graft was partially expanded within the TIPS (dog bone effect). ( b ) After expanding the stent-graft to a diameter of 5 mm along its entire length, both the portal vein end and subsequent hepatic vein end were dilated using a 12 × 40 mm angioplasty balloon. ( c ) The final hourglass configuration (arrows) stent-graft reduction resulted in the portosystemic gradient increasing from 10 to 22 mm Hg.

The patient in Fig. 2 had a portosystemic gradient change of 13 to 23 mm Hg post-reduction, while the patient in Fig. 3 had a change of 10 to 22 mm Hg. All patients demonstrated an immediate improvement in hepatic encephalopathy. Patient 1 demonstrated TIPS occlusion on follow-up CT abdomen/pelvis 193 days after TIPS reduction. His ascites worsened to the point of him requiring weekly paracenteses after not requiring any TIPS creation. However, given his clinical status and laboratory values, no further intervention was required. Patient 2 was undergoing weekly paracentesis for refractory ascites, which resolved to none after TIPS creation but increased to once per month after TIPS reduction. Patient 3 required infrequent paracenteses and was later treated for recurrent variceal hemorrhage at an outside hospital 4 months after TIPS reduction. A complete summary of clinical status, characteristics, and outcomes of patients who underwent TIPS reduction is outlined in Table 2 .

Table 2. Clinical status, characteristics, and outcomes of patients who underwent TIPS reduction.

Patient	Interval between TIPS and reduction (days)	Pre-/Post-reduction HE grade		Mid-stent dilation diameter (mm)	PSG (mm Hg), before/after reduction		Follow-up interval (days)	Outcomes
1	56	II–III	0–I	5	10	22	2,300	Alive; shunt occlusion, ascites
2	132	III	0–I	5	8	19	315	Alive; ascites
3	78	II–III	0–IV	5	13	23	238	Death due to liver failure; recurrent variceal hemorrhage

Abbreviations: HE, hepatic encephalopathy; PSG, portosystemic gradient; TIPS, transhepatic portosystemic shunt.

Discussion

Given the varying flow dynamics in the three main methods of TIPS reduction, the hourglass configuration technique is favored at our institution because of the controlled method of mid-stent constraint in addition to the stability provided at both the portal and hepatic vein ends. After deployment, forward pressure is maintained on the sheath, and the stiff guidewire and angle of the hepatic vein help prevent the stent-graft from migration. The portal vein end is elected to be dilated first because of the direction of the shunted blood flow through the TIPS. If the hepatic vein ends were to be dilated first instead, blood flow could theoretically pressurize past the nondilated hepatic vein stent end and into the space between the TIPS and stent-graft, causing thrombosis and/or migration. Additionally, the new unused balloon has the smallest crossing profile with the lowest chance of getting caught in the central nondilated stent.

While the sheath-buttressing technique is effective, the sheath control technique provides more stent-graft control and security in less procedural steps. Blue et al detailed TIPS reduction with the sheath control technique for the hourglass configuration method. In the study, 10 consecutive patients underwent an iCast stent-graft TIPS reduction with a 100% technical success, and all patients experienced improvement in hepatic encephalopathy. ²⁴ Upon introduction of the stent-graft within the TIPS, the sheath was retracted approximately 1.5 to 2.0 cm from the portal vein end, uncovering a portion of the stent-graft. The deployment balloon was inflated, securing the stent-graft at the portal vein end and creating the distal half of the hourglass shape. The deployment balloon was exchanged for a larger balloon positioned in the hepatic vein end of the stent graft. The sheath was withdrawn over the remaining unexpanded stent and the hepatic vein end was dilated to the size of the TIPS in order to secure both ends of the stent-graft and complete the hourglass configuration.

The hourglass configuration technique requires only one stent-graft, which lowers both the cost and complexity of the procedure as well as the risks of a second stent failure or migration. The mid-stent stenosis can be easily decreased in a stepwise fashion and individually tailored via intraprocedural hemodynamic pressure measurements to appropriately lower the portosystemic gradient according to the patient's clinical condition. This step can be performed during the reduction procedure or in a separate procedure if the patient manifests signs of recurrent portal hypertension.

Accepted ranges of stent-graft diameter, length, and magnitude of increased portosystemic gradient exist in the literature but still vary on a case-by-case basis. ²⁵ Fanelli et al presented procedural details and outcomes of 12 patients who underwent TIPS reduction with an hourglass stent-graft. Their technique involved tying an absorbable 3–0 polyglactin 910 suture in the middle of a 10 × 40 mm angioplasty balloon and then mounting an expandable PTFE stent-graft before insertion. Once in the TIPS, the balloon was inflated to a nominal pressure of 8 atmospheres (atm), allowing for the proximal and distal ends of the stent-graft to expand to the full 10 mm but restricting a small segment of the central portion due to the tied suture. Based on the desired portosystemic gradient changes, the central portion was adjusted accordingly. A balloon dilatation diameter of 6 mm was used in 75% of patients (range: 5–7 mm), and no stent-graft occlusion was observed in any patients (follow-up range of 1.2–172.0 weeks). Portosystemic gradients ranged from 13 to 21 mm Hg after reduction. ²⁶

As demonstrated in each of our three cases, patients generally experience an immediate improvement in OHE after TIPS reduction with an hourglass configuration PTFE balloon-expandable stent-graft. ²⁶ The parallel stents and tapered stent-graft techniques incorporate variables that may be more challenging and lead to less customizable reductions. The parallel stent technique requires the appropriate placement and expansion of two side-by-side stents at the hepatic vein end. Having two stents increases the risk of stent failure, alongside additional costs and procedural time. The advantage of the parallel stents technique is the ability to dilate either stent, theoretically resulting in unlimited attempts to achieve optimal portosystemic gradient. The tapered stent-graft technique relies on the prebuilt tapered configuration and self-expending covered stent, which was initially built for arteriovenous graft anastomoses. Dilation at the portal vein end only results in less modification of blood flow and less stent-graft stability at the hepatic vein end, which could potentially lead to migration.

While serum ammonia level and liver function tests provide quantitative data for TIPS reduction on follow-up, improvement in the patient's hepatic encephalopathy is the most meaningful outcome and drives further decision making. This improvement is generally observed within 24 hours after TIPS reduction, and medical management of hepatic encephalopathy including limiting protein intake, increasing fiber intake, and maintaining nonabsorbable antibiotic and disaccharide therapy should be continued. These patients are at an increased risk of ascites reaccumulation and variceal hemorrhage, both of which were observed in our patients, and continuing medical measures such as diuretic therapy and beta-blockade are often necessary. ⁹

Although the evolution and success of TIPS reduction technique have been reported in a majority of patients across multiple institutions, there still exists unclear procedural standards regarding ideal TIPS reduction sizes and resulting portosystemic shunt gradients. ^{9 24 26} Even with successful TIPS reduction, patients may have only temporary resolution or improvement in clinical symptoms. TIPS reduction aims to alleviate OHE at the cost of re-elevating the portosystemic gradient, which increases the risks of ascites, liver failure, and variceal hemorrhage. Sarwar et al detailed a retrospective review on the clinical outcomes of 26 patients who underwent TIPS reduction. While 96% of patients had worsening OHE after TIPS creation, 96% of patients demonstrated improvement of OHE after TIPS reduction. Right heart failure improved in two of the three patients, and no patients experienced recurrent variceal hemorrhage. Of the 14 patients who underwent TIPS creation for refractory ascites, 43% had a decreased frequency of paracentesis compared to pre-TIPS creation. ²⁵

Narrowing of any stent, whether intentional or not, increases the risk of occlusion. This was observed in Patient 1 on the follow-up imaging performed 6.5 months after TIPS reduction. As with TIPS occlusion, reducing stent-graft occlusion can lead to fatal outcomes from progressive liver failure, recurrent variceal hemorrhage, and acute hemodynamic alterations. ²⁰

Overshunting refractory to conservative therapy remains a relatively rare entity in considerably ill patients, and the optimal management remains to be elucidated. With the advent of new balloon-expandable stent-grafts, TIPS reduction techniques have evolved from the complex procedures described herein with variable technical results. A vast majority of authors on TIPS reduction in the last decade have favored some variation of the hourglass technique given the reduced complexity and cost. However, the literature remains limited on the appropriate gradient endpoints which will drive meaningful clinical improvement while minimizing risks of recurrent portal hypertension.

Conclusion

TIPS reduction is an interventional procedure with high technical and clinical success for patients with complications of overshunting. While multiple techniques exist, the hourglass configuration method allows for efficient and tailored stent-graft modification and is effective at reducing shunt flow and improving OHE. Further studies evaluating procedural data in conjunction with patient outcomes could assist in establishing technical guidelines and ideal portosystemic shunt gradients to balance the complications of overshunting after TIPS creation.