Literature DB >> 35020007

Interventional recanalization therapy in patients with non-cirrhotic, non-malignant portal vein thrombosis: comparison between transjugular versus transhepatic access.

Nabeel Mansour1, Osman Öcal1, Mirjam Gerwing2, Michael Köhler2, Sinan Deniz1, Hauke Heinzow3,4, Christian Steib5, Martin K Angele6, Max Seidensticker1, Jens Ricke1, Moritz Wildgruber7,8.   

Abstract

PURPOSE: To compare the safety and outcome of transjugular versus percutaneous technique in recanalization of non-cirrhotic, non-malignant portal vein thrombosis.
METHODS: We present a retrospective bicentric analysis of 21 patients with non-cirrhotic, non-malignant PVT, who were treated between 2016 and 2021 by interventional recanalization via different access routes (percutaneous [PT] vs. transjugular in transhepatic portosystemic shunt [TIPS] technique). Complication rates with a focus on periprocedural bleeding and patency as well as outcome were compared.
RESULTS: Of the 21 patients treated (median age 48 years, range of 19-78), seven (33%) patients had an underlying prothrombotic condition. While 14 (57%) patients were treated for acute PVT, seven (43%) patients had progressive thrombosis with known chronic PVT. Nine patients underwent initial recanalization via PT access and twelve via TIPS technique. There was no significant difference in complete technical success rate according to initial access route (55.5% in PT group vs. 83.3% in TIPS group, p = 0.331). However, creation of an actual TIPS was associated with higher technical success in restoring portal venous flow (86.6% vs. 33.3%, p = 0.030). 13 (61.9%) patients received thrombolysis. Nine (42.8%) patients experienced hemorrhagic complications. In a multivariate analysis, thrombolysis (p = 0.049) and PT access as the first procedure (p = 0.045) were significant risk factors for bleeding.
CONCLUSION: Invasive recanalization of the portal vein in patients with PVT and absence of cirrhosis and malignancy offers a good therapeutic option with high recanalization and patency rates. Bleeding complications result predominantly from a percutaneous access and high amounts of thrombolytics used; therefore, recanalization via TIPS technique should be favored.
© 2022. The Author(s).

Entities:  

Keywords:  Portal vein thrombosis; Recanalization; Thrombolysis; Transjugular intrahepatic portosystemic shunt

Mesh:

Year:  2022        PMID: 35020007      PMCID: PMC8863683          DOI: 10.1007/s00261-022-03411-w

Source DB:  PubMed          Journal:  Abdom Radiol (NY)


Introduction

Portal vein thrombosis (PVT) is a rare condition with a reported prevalence of 3.7 per 100.000 population, and half of the cases occur in a patient without liver cirrhosis or malignancy [1]. In contrast to cases with malignancy or cirrhosis, were the outcome is primarily dependent on the underlying disease, non-cirrhotic and non-malignant PVT have a different pathogenesis and the PVT itself is decisive for the prognosis of the patient [2]. Similar to thrombosis in other vessels, non-cirrhotic and non-malignant PVT is related to one or more features of the Virchow’s triad [3-5]. Although PVT without has better survival rates than PVT in patients with cirrhosis or malignancy [1], it is associated with a significant risk of venous congestion of the gut in the acute period and complications related to portal hypertension in the long term, especially life-threatening variceal bleeding, requiring lifelong specialized care [6, 7]. The rarity of this condition precludes large-scale controlled trials, and the treatment algorithm of non-cirrhotic and non-malignant PVT has not been standardized. The American Association For Study of Liver Diseases currently (AASLD) recommends the consideration of interventional portal vein recanalization (PVR) in patients with acute PVT and impending intestinal ischemia [2]. In patients with chronic PVT and recurrent bleeding and/or refractory ascites not manageable medically or endoscopically, interventional PVR followed by TIPS is also currently recommended [2]. Anticoagulation for six months is recommended in patients with reversible etiologies of PVT, life-long in patients with thrombophilia [8]. Several case series have shown that interventional recanalization with thrombolysis via superior mesenteric artery, percutaneous transhepatic portal vein thrombolysis [9] or thrombectomy [10], and recanalization via TIPS access with additional TIPS placement [11, 12] have high technical and clinical success rates, especially in patients with a deteriorating clinical condition and persistent symptoms of portal hypertension despite anticoagulation (impending bowel ischemia or infarction). Recently, a multicenter study has compared the outcome of medical and interventional therapies in non-cirrhotic and non-malignant PVT and showed significantly higher recanalization rates after interventional treatment (37% vs. 71%, p < 0.001), despite the higher thrombus burden in the interventional arm at baseline [13]. These results suggest a wider use of interventional procedures in patients with non-cirrhotic and non-malignant PVT. However, further investigation of the optimal approach and technique for interventional recanalization still needs to be clarified, as severe complications including periprocedural bleeding have been reported. The aim of this retrospective, bicentric cohort study was to evaluate the outcome of interventional therapies in patients with non-cirrhotic and non-malignant PVT, and thereby compare the safety and efficacy of different portal vein access routes.

Materials and methods

Study design

This observational study includes a retrospective bicentric analysis of the clinical course in a total of 21 patients with non-cirrhotic and non-malignant PVT, who were treated at two tertiary care university hospitals with experience of > 50 TIPS procedures annually from the year 2016 to 2021. Preliminary results of the cohort treated at Center 1 have already been published in a first case series [14]. The study was approved by the institutional review board (Protocol number 2016-046-f-S). Informed consent was waived due to the retrospective character of the study.

Diagnosis and definitions

PVT was confirmed by contrast-enhanced CT in all patients and was graded according to the previously published grading system [13]: grade 1: incomplete occlusion of the vessel lumen; grade 2: complete occlusion or extended thrombosis; grade 3: the presence of cavernous transformation. PVT was considered acute when symptoms developed less than 60 days before presentation, and there is no radiological or endoscopic evidence of collateral circulation [2, 15–17]. Clinical and laboratory investigations were completed to identify the etiology of PVT, including screening for prothrombotic disorders. All patients were discussed in multidisciplinary rounds, including gastroenterology, interventional radiology, and liver/transplant surgery, and treatment decision was made by consensus in every case. All patients with grade 2 thrombosis were heparinized with the aim of partial thromboplastin time (PTT) of 60–80 s after the establishment of the diagnosis. Portal vein recanalization procedures, either percutaneous (PT) or via TIPS access, were done under general anesthesia. PT access was preferred for recanalization in the initial procedure, except for the cases with ascites. Transjugular access as the first choice instead was performed in case of technical or clinical failure of PT access or in the presence of ascite due to increased risk of abdominal bleeding. Technical success was described as complete recanalization of the entire portal venous system or complete bypass of the thrombus via a TIPS. In patients with residual thrombus causing less than a 25% decrease in the lumen, the outcome was described as a partial technical success and the rest of the cases as technical failure.

Interventional technique and concomitant treatments

Portal vein interventions were performed by interventional radiologists with > 5 years of experience in portal venous interventions. Puncture of the thrombosed portal vein was performed under ultrasound guidance either percutaneously (PT) or via the transjugular route in TIPS technique [11]. In case of inadequate visualization of the portal vein in ultrasound to guide TIPS puncture (n = 1), a guidewire was advanced as a fluoroscopic target into the portal vein via percutaneous puncture of the splenic vein. In case of percutaneous access, a 9F sheath was introduced into the portal vein, in case of TIPS access a 10F sheath was inserted. Aspiration thrombectomy was done in all patients with a large-bore aspiration catheter (CAT-8 Indigo Catheter, Penumbra Inc., Alameda, California, USA). In both centers, aspiration thrombectomy was performed as the initial step and proceeded to local thrombolysis in case of incomplete recanalization. Pulse spray thrombolysis was done using dedicated 4F spray lysis catheters with 10–20 cm side holes at a dose of 1 mg/h rt-PA. If overnight thrombolysis was performed, patients were monitored on intensive care units, and control angiography was done on the following day. Balloon angioplasty and additional stenting of the portal vein, superior mesenteric and splenic vein were performed when needed to establish or maintain portal venous flow. This step was followed by the creation of TIPS in patients with transjugular access, and in patients with insufficient recanalization after percutaneous thrombus aspiration, local thrombolysis and repeated aspiration were performed. This step was combined with rheolytic thrombolysis using the AngioJet rheolytic thrombectomy system in the power pulse mode (Boston Scientific, Marlborough, MA, USA) in some patients. Thrombolysis was also performed in patients with an inadequate flow after TIPS creation. In patients with insufficient inflow due to thrombosis in SMV or SV, visceral stenting was performed. In case of failed complete recanalization in patients with initial percutaneous access, secondary TIPS was created (Fig. 1).
Fig. 1

Algorithm of interventional therapy in patients with non-cirrhotic, non-malignant portal vein thrombosis

Algorithm of interventional therapy in patients with non-cirrhotic, non-malignant portal vein thrombosis All patients received therapeutic anticoagulation with unfractionated heparin during treatment (target PTT 60–80 s). Following complete or partial recanalization heparinization was switched to oral anticoagulation with phenprocoumon for at least six months followed by 100 mg/day aspirin monotherapy for lifetime. For patients with an underlying prothrombotic mutation, lifelong oral anticoagulation was initiated. In these cases, novel oral anticoagulants were applied instead of phenprocoumon.

Statistical analysis

Preprocedural patient characteristics and technical details were grouped as categorical or nominal variables. The total dose of lysis in patients with PT and TIPS access were compared using the non-parametric Mann–Whitney U test. Univariate analysis of the relationship between periprocedural characteristics and technical success and bleeding was performed. Factors with a p-value < 0.1 were included in multivariate analysis using binary logistic regression. A p-value < 0.05 was considered significant. Statistical analysis was performed using R statistical software (R version 3.6.3).

Results

Study population

21 patients presenting with non-cirrhotic, non-malignant PVT were treated according to the interventional recanalization scheme described in Fig. 1. Baseline characteristics of the patients are summarized in Tables 1 and 2. The 21 patients included were a median of 48 years, ranging from 19 to 78 years at the time of treatment. An underlying prothrombotic condition was identified in seven patients (33%), of these three had a Janus kinase 2 (JAK2) mutation (14%). In total, 14 patients were treated for acute PVT (57%) with median symptom onset to first intervention of 13 days (range of 3–49). Seven patients had chronic PVT with presence of cavernous transformation of the portal vein and were treated electively due to progressive thrombosis and escalating symptoms related to the increase of portal venous pressure, refractory to medical therapy (grade 3). Clinical presentations consisted of one or a combination of symptoms including abdominal pain (n = 12), esophageal varices (n = 7) leading to hematemesis (n = 3), ascites (n = 9), and paralytic ileus (n = 1). In the n = 7 patients with accompanying ascites treated at Center 1, the ascites was compensated in five patients, allowing for a percutaneous approach. Most of the patients treated in Center 1 underwent portal vein recanalization via percutaneous access (75%). In Center 2, the transjugular recanalization route in TIPS technique was performed in 77% of the cases. Two patients with acute PVT and venous congestion had to undergo open surgery before initiation of interventional treatment, one patient with resection of a gangrenous ileum segment, the other patient underwent emergent splenectomy due to rupture of the splenic capsule [18].
Table 1

Patient characteristics and extent of thrombosis

PT accessTIPS access
Age (median years)46 (24–78)51 (19–74)
Sex (male/female)7/28/4
Onset
 Acute (grade 2 PVT)68
 Chronic (grade 3 PVT)34
Etiology
 Septic/inflammatory22
 JAK2-mutation/MPN12
 Other prothrombotic conditions22
 Others/unknown46
Clinical manifestation
 Ascites63
 Abdominal pain66
 Esophageal varices16
 Hematemesis12
 Paralytic ileus10
Extent of thrombosis
 Intrahepatic + extrahepatic occlusion of PV68
 Only intrahepatic00
 Only extrahepatic34
 Involvement of VMS89
 Involvement of SV48

PT percutaneous access, TIPS transjugular intrahepatic portosystemic shunt, JAK2 janus kinase 2, MPN myeloproliferative neoplasm, CT computed tomography, PV portal vein, SMV superior mesenteric vein, SV splenic vein

Table 2

Patient history

Patient numberAge (years)/sexRoute of interventionOnsetInitial symptomsEtiology and risk factorsTime of symptoms to admission (days)Time of symptoms to Intervention (days)Length of hospital stay (days)Last Follow-up (days)Patency reached
148/FPTAcuteAbdominal pain, paralytic ileus, ascitesHeterozygotic prothrombin mutation2326776Yes
243/MPTAcuteAbdominal painNone71756663Yes
325/MPTAcuteAbdominal painHeterozygotic factor V Leiden mutation41532610Yes
448/MPTAcuteabdominal painSplenectomy, hemophagocytic lymphohistiocytosis141857594No
574/MPTAcuteNoneInflammation11919n.aYes
619/FPTAcuteAbdominal pain, diarrhea, vomitingOral contraceptives, exsiccosis101158451No
757/FTIPSAcuteMild abdominal painDiabetes424917399Yes
826/MTIPSAcuteVariceal bleedingPortal hypertension1527922Yes
957/FTIPSAcuteAbdominal pain, vomitingJAK2 mutation4456750No
1060/MPTChronicPortal hypertensive gastropathy, epigastric painAntiphospholipid syndromeElective5113Yes
1173/MPTChronicTherapy resistant ascites, spontaneous bacterial peritonitis, esophageal varicesJAK2 mutationElective212420No
1251/MTIPSAcuteGastric varicesdisseminated intravascular coagulation (DIC)066845Yes
1351/MTIPSAcuteAbdominal painNone3211330Yes
1478/MTIPSChronicTherapy resistant ascites, spontaneous bacterial peritonitis, esophageal varicesNoneElective78530No
1556/FTIPSChronicEsophageal varices, hematemesisMedicinal3226614Yes
1668/MPTChronicAbdominal pain, esophageal varices, hematemesisChronic pancreatitis11217480Yes
1741/FTIPSChronicPortal hypertensive gastropathy, epigastric pain, nausea, vomitingIgG4-Related Sclerosing CholangitisElective2127Yes
1841/MTIPSAcuteAbdominal pain, nausea, ConstipationHomozygotic Factor V Leiden mutation2919270Yes
1924/MTIPSChronicesophageal varices, hematemesisJAK2 mutation1101842Yes
2029/MTIPSAcuteAbdominal painHeterozygotic prothrombin mutation0163355Yes
2141/MTIPSAcuteAbdominal painVaccine related thrombosis072954Yes

n.a., not applicable (patient died in the course of therapy); JAK2, janus kinase 2; PT, percutaneous access; TIPS, transjugular intrahepatic portosystemic shunt

Patient characteristics and extent of thrombosis PT percutaneous access, TIPS transjugular intrahepatic portosystemic shunt, JAK2 janus kinase 2, MPN myeloproliferative neoplasm, CT computed tomography, PV portal vein, SMV superior mesenteric vein, SV splenic vein Patient history n.a., not applicable (patient died in the course of therapy); JAK2, janus kinase 2; PT, percutaneous access; TIPS, transjugular intrahepatic portosystemic shunt

Outcomes

Median time from symptom onset to first intervention in patients with acute grade 2 PVT was 13 days (range of 3–49 days). Nine (42.8%) patients had initial recanalization via PT access, and twelve (57.2%) patients via TIPS access. Procedural details of each patient are given in Table 3. Three patients with initial PT access underwent sequential recanalization via transjugular access with secondary TIPS placement due to initially insufficient recanalization via the percutaneous access (defined as > 25% residual thrombosis of the portal vein or intrahepatic branches) (Table 4). The complete technical success rate was 55.5% in patients with initial PT access and 83.3% in patients with initial TIPS access (p = 0.331). However, the creation of a TIPS was significantly associated with higher technical success (86.6% vs. 33.3%, p = 0.030). None of the other procedure-related parameters correlated with technical success (Table 5). One patient in the percutaneous group had partial recanalization only. Due to poorer flow restoration via the percutaneous access, higher amounts of thrombolytics [recombinant tissue-Plasminogen Activator (rt-PA)] were required to restore flow via percutaneous access as the first procedure (mean 77.3 mg vs. 25.6 mg, p = 0.037) (Fig. 2).
Table 3

Procedural characteristics

Patient numberRoute of interventionLysisRheolytic thrombolysisVisceral stentingTIPS creationAdditional measures
1PTYesNoNoNo
2PTYesNoSMV, VSYes
3PTYesYesVMSNo
4PTYesYesNoYes
5PTYesNoVSNo
6PTYesYesNoNo
7TIPSYesYesVSYes
8TIPSYesYesNoYes
9TIPSYesNoNoYes
10PTNoNoPVNo
11PTNoNoNoNo
12TIPSNoNoSMV, VSYes
13TIPSYesNoNoYes
14TIPSNoNoSVYes
15TIPSNoNoNoYes
16PTNoNoSMVYes
17TIPSNoNoNoYes
18TIPSYesNoSMVYes
19TIPSNoNoNoYes
20TIPSYesNoYesYesSplenic vein puncture to guide TIPS creation
21TIPSYesNoNoYes

PT, percutaneous access; TIPS, transjugular intrahepatic portosystemic shunt; SMV, superior mesenteric vein; SV, splenic vein

Table 4

Comparison of procedural details

PT accessTIPS accessp-value
Primary TIPS placement0/912/12
Secondary TIPS placement3/90/12
Stenting5/95/120.669
PV stenting2/92/12
SMV stenting3/93/12
VS stenting2/93/12
Complete technical success5/910/120.331
Thrombolysis6/95/120.386
Mean rt-PA-lysis (mg)77,325.60.037*

PT percutaneous, TIPS transjugular intrahepatic portosystemic shunt, PV portal vein, SMV superior mesenteric vein, VS splenic vein, rt-PA recombinant tissue-Plasminogen Activator

Table 5

Factors associated with technical success

n = 21Yes (n = 15)No (n = 6)p-value
Gender (male)11/154/6> 0.99
Myeloproliferative etiology (yes)6/153/6> 0.99
Acute PVT12/154/60.597
First approach (Percutaneous)5/154/60.331
Extension into intrahepatic portal branches10/154/6> 0.99
Involvement of SMV11/156/60.280
Involvement of SV8/154/60.659
Thrombolysis (yes)8/154/60.659
TIPS (yes)13/152/60.030*
Rheolytic thrombolysis (yes)3/152/60.597
Visceral stenting (yes)8/153/6> 0.99
Fig. 2

Exemplary cases of two patients with PVT included in this study who were treated with different recanalization techniques that include two interventional access routes (PT- and TIPS access). The first patient aged 50 (patient number 12/a–c) developed acute 2 PVT due to sepsis. a Initial CT with complete thrombotic obstruction of the extra- and intrahepatic portal venous system (white arrow). b Initial angiogram after TIPS access (asterisk) showing obstruction of the portal vein and the subsequent collateralization. c Angiogram showing successful patency of the portal vein achieved after thrombectomy, TIPS-Implantation and stenting up into the superior mesenteric vein (white arrowhead). The second patient aged 60 (patient number 10/d-f) with chronic portal vein thrombosis first diagnosed in 2011 and subsequent cavernous transformation (grade 3). Interventional recanalization was performed due to unsuccessful anticoagulation therapy and escalating portal hypertensive hemorrhagic gastropathy. d CT scan showing complete thrombotic obstruction of the portal vein with subsequent cavernous transformation. e Initial angiogram after percutaneous transhepatic access (asterisk) showing the cavernous transformation of the portal vein (black arrowhead). f Angiogram showing the successful patency of the portal vein achieved after porto-mesenteric stenting (white arrowhead). CT computed tomography, PVT portal vein thrombosis, TIPS transjugular intrahepatic portosystemic shunt

Procedural characteristics PT, percutaneous access; TIPS, transjugular intrahepatic portosystemic shunt; SMV, superior mesenteric vein; SV, splenic vein Comparison of procedural details PT percutaneous, TIPS transjugular intrahepatic portosystemic shunt, PV portal vein, SMV superior mesenteric vein, VS splenic vein, rt-PA recombinant tissue-Plasminogen Activator Factors associated with technical success Exemplary cases of two patients with PVT included in this study who were treated with different recanalization techniques that include two interventional access routes (PT- and TIPS access). The first patient aged 50 (patient number 12/a–c) developed acute 2 PVT due to sepsis. a Initial CT with complete thrombotic obstruction of the extra- and intrahepatic portal venous system (white arrow). b Initial angiogram after TIPS access (asterisk) showing obstruction of the portal vein and the subsequent collateralization. c Angiogram showing successful patency of the portal vein achieved after thrombectomy, TIPS-Implantation and stenting up into the superior mesenteric vein (white arrowhead). The second patient aged 60 (patient number 10/d-f) with chronic portal vein thrombosis first diagnosed in 2011 and subsequent cavernous transformation (grade 3). Interventional recanalization was performed due to unsuccessful anticoagulation therapy and escalating portal hypertensive hemorrhagic gastropathy. d CT scan showing complete thrombotic obstruction of the portal vein with subsequent cavernous transformation. e Initial angiogram after percutaneous transhepatic access (asterisk) showing the cavernous transformation of the portal vein (black arrowhead). f Angiogram showing the successful patency of the portal vein achieved after porto-mesenteric stenting (white arrowhead). CT computed tomography, PVT portal vein thrombosis, TIPS transjugular intrahepatic portosystemic shunt Nine (42.8%) patients experienced hemorrhagic complications. Of these, five patients had bleeding from the liver, one from spleen due to additional splenic access, one from the stump of the splenic artery, and the other one had disseminated abdominal bleeding without localized arterial extravasation. In univariate analysis, thrombolysis was significantly associated with bleeding (88.8% vs. 33.3%, p = 0.024). Also, the PT group had higher bleeding than the TIPS group (66.6% vs. 25%, p = 0.087). Multivariate analysis showed both thrombolysis (p = 0.049) and PT access (p = 0.045) were independent significant risk factors of bleeding (Table 6). Three patients in the PT group and one patient in TIPS group underwent further surgery with packing and evacuation of hematoma (p = 0.272). No significant difference was observed in technical success (p = 0.597) or bleeding complications (p = 0.338) between acute grade 2 and chronic grade 3 PVT with presence of cavernous transformation (Table 5).
Table 6

Risk factors for bleeding

n = 21BleedingNo bleedingp-valueMultivariate analysis
Gender (male)6/99/12> 0.99
Myeloproliferative etiology (yes)5/94/120.396
Acute PVT8/98/120.338
First approach (Percutaneous)6/93/120.0870.045*
Extension into intrahepatic portal branches7/97/120.642
Involvement of SMV9/98/120.103
Involvement of SV7/95/120.184
Thrombolysis (yes)8/94/120.0240.049*
TIPS (yes)5/910/120.331
Rheolytic thrombolysis (yes)2/93/12> 0.99
Visceral stenting (yes)3/97/120.387

PT percutaneous, TIPS transjugular intrahepatic portosystemic shunt, PV portal vein, SMV superior mesenteric vein, VS splenic vein, rt-PA recombinant alteplase

Risk factors for bleeding PT percutaneous, TIPS transjugular intrahepatic portosystemic shunt, PV portal vein, SMV superior mesenteric vein, VS splenic vein, rt-PA recombinant alteplase One patient from Center 1 with failed recanalization had bowel perforation and underwent resection of 20 cm of ileum. Three patients (14.2%) died during hospitalization. One patient died due to multiorgan failure and sepsis despite complete recanalization of PVT. One patient was lost due to intracerebral hemorrhage and hemorrhagic shock after hepatic bleeding. The other patient died after failed recanalization attempts due to sepsis.

Patency

Primary patency (complete or partial) of the portal vein was reached in 16 patients (76.2%). The median follow-up was 365 days (range of 3–922 days). Two patients showed recurrence of PVT approximately after 30 weeks (one from each group). The patient from the TIPS group with recurrent PVT displayed minor thrombotic deposits after TIPS and stenting on invasive angiography and was treated with balloon angioplasty and local thrombolysis without any additional complications. All patients with a failed recanalization developed a chronic PVT with a subsequent cavernous transformation. None of the treated patients suffered from major long-term complications during the follow-up period; only one patient revealed mild gastroesophageal varices (grade I) on endoscopy. Follow-up laboratory values, clinical assessment, and ultrasound revealed no signs of cirrhosis formation.

Discussion

Non-malignant, non-cirrhotic portal vein thrombosis is a rare but potentially fatal condition requiring rapid and efficient treatment. Although systemic anticoagulation is recommended throughout different therapy guidelines as the method of choice in treating portal vein thrombosis [8, 19], complete recanalization is only achieved in around 35% of the cases [20, 21]. Recent case series have shown that interventional therapies, such as thrombectomy, thrombolysis or TIPS, are effective in patients with acute [22, 23] or chronic PVT [24-29]. A systematic review of studies using TIPS in portal vein thrombosis showed a high rate of recanalization and long-term patency [30]. A recent multicentric study from Rössle et al. [13] comparing medical and interventional treatment in 65 patients showed low procedure-related mortality (2.9%) and a high success rate of the interventional treatment (17% vs. 54%). However, several techniques have been utilized in these studies, and the optimal interventional method needs to be defined. Our results have shown that the creation of TIPS resulted in significantly higher technical success, and percutaneous approach and thrombolysis are significantly associated with increased bleeding. Non-malignant, non-cirrhotic portal vein thrombosis constitute a special entity, because in patients with underlying cirrhosis or malignancy, portal vein thrombosis usually develops in the long term, which allows more time to develop collaterals. Additionally, the treatment of the underlying disease is the mainstay in management of these patients, and thrombosis-directed therapy is mostly restricted to systemic heparin. It is also important to view cirrhosis of the liver as an independent risk factor for thrombosis, mainly because loss of liver function impacts both procoagulant and anticoagulant factors; therefore, a differential approach of therapy in the presence of cirrhosis is required [8]. To avoid acute and long-term complications, patients who do not benefit adequately from initial anticoagulation need to be offered more aggressive therapy options. In this study we describe an escalating invasive therapy regime, starting with thrombaspiration, followed by local thrombolysis (bolus and overnight lysis), rheolysis, balloon angioplasty, stenting, and possibly TIPS implantation, if the latter methods did not lead to adequate flow restoration. In the treatment of non-cirrhotic, non-malignant PVT, multiple studies with small cohorts have shown higher success rates for combined surgical/interventional and isolated interventional therapy than isolated anticoagulation therapy with recanalization rates ranging from 75% to 80%, respectively [11, 14, 31]. However, invasive recanalization is associated with significantly higher rates of major hemorrhagic complications, especially in patients who underwent invasive recanalization through a percutaneous transhepatic access [14]. In our case series, we compared two different access routes (PT vs. TIPS access) for PVT recanalization. In the past percutaneous access was predominantly used especially in case of one branch of the portal vein still being patent, facilitating the percutaneous puncture and allowing some degree of flow, whereas in extensive thrombosis of the entire portal venous system, TIPS is needed to achieve adequate flow restoration in order to maintain patency. These recanalization routes offer different advantages and disadvantages. While recanalization of the portal vein through a percutaneous access allows the preservation of the endothelial wall and blood flow through the native portal vein and intrahepatic branches, recanalization via TIPS access requires the creation of an artificial connection. In patients with occluded intrahepatic branches, PT recanalization is more challenging, especially due to limited flow. In contrary, TIPS technique allows access to the portomesenteric system despite extension of thrombus in the intrahepatic branches, as seen in many PVT cases. Additionally, TIPS allows an easy access for further interventional procedures of the portal vein. In this study, interventional recanalization of the portal vein through a transjugular approach showed significantly lower rates of major hemorrhagic complications. In this group, a significantly lower amount of thrombolysis was required to restore flow, while other procedural details such as use of additional stenting or rheolytic therapy were not associated with outcome. Percutaneous access requiring perforation of the liver capsule together with the increased amount of thrombolytics led to increased rates of major hemorrhagic complications. Previous studies of patients with impaired coagulation needing liver biopsy also showed higher complication rates after percutaneous access compared to the transjugular route [32]. Furthermore, probably due to stable outflow after TIPS, patients with TIPS had significantly higher clinical success. Limitations of this analysis include the retrospective character of the study and a certain selection and procedural bias between the two centers. The yet limited follow-up time may underrepresent long-term benefits of PVT recanalization. Heterogeneity of onset of PVT poses another limitation, since acute on chronic PVT offers different challenges in management, yet with the focus of this study on the route to restore blood flow, the inclusion of both groups seems feasible. Additionally, low enrollment rates mainly due to interventional therapy not being the first-line therapy method in patients with non-cirrhotic, non-malignant PVT contribute to smaller study populations. With current guidelines increasingly recommending escalating recanalization therapy in patients affected by acute or chronic PVT and impending serious complications that are not manageable conservatively [2], further research and a greater sample size may be desirable.

Conclusion

Invasive recanalization of the portal vein in carefully selected patients with PVT and absence of cirrhosis and malignancy offers a good therapeutic option with high recanalization and patency rates, compared to the moderate recanalization rates achieved by anticoagulation alone. The aim of invasive therapy is to avoid severe complications, both acute such as venous congestion of the gut, as well as chronic such as complications arising from portal hypertension, especially variceal bleeding. Although acute and chronic PVT offer different technical challenges, no significant difference in recanalization rates or periinterventional complications between the two forms of PVT were observed. Present data suggest that bleeding complications result predominantly from the percutaneous access and increased amounts of thrombolytics applied to restore proper flow. With low periinterventional morbidity and mortality and simultaneous high technical success rates and patency, portal vein recanalization in the TIPS technique is favorable and should be considered as the interventional treatment of choice.
  31 in total

1.  Thrombolytic treatment of portal thrombosis.

Authors:  Piotr Malkowski; Jacek Pawlak; Bogdan Michalowicz; Jerzy Szczerban; Tadeusz Wroblewski; Elzbieta Leowska; Marek Krawczyk
Journal:  Hepatogastroenterology       Date:  2003 Nov-Dec

2.  Transjugular intrahepatic portosystemic shunt, mechanical aspiration thrombectomy, and direct thrombolysis in the treatment of acute portal and superior mesenteric vein thrombosis.

Authors:  Carlo Ferro; Umberto G Rossi; Giulio Bovio; M'hamed Dahamane; Monica Centanaro
Journal:  Cardiovasc Intervent Radiol       Date:  2007-08-09       Impact factor: 2.740

Review 3.  Management of acute non-cirrhotic and non-malignant portal vein thrombosis: a systematic review.

Authors:  T C Hall; G Garcea; M Metcalfe; D Bilku; A R Dennison
Journal:  World J Surg       Date:  2011-11       Impact factor: 3.352

Review 4.  Noncirrhotic nontumoral portal vein thrombosis.

Authors:  Susana Seijo; Aurelie Plessier
Journal:  Clin Liver Dis (Hoboken)       Date:  2014-06-25

5.  A prospective, multicentre study in acute noncirrhotic, nonmalignant portal vein thrombosis: comparison of medical and interventional treatment.

Authors:  Martin Rössle; Dominik Bettinger; Jonel Trebicka; Christoph Klinger; Michael Praktiknjo; Lukas Sturm; Karel Caca; Victoria Therese Mücke; Klaus Radecke; Cornelius Engelmann; Alexander Zipprich; Hauke Heinzow; Carsten Meyer; Ulrich Tappe; Beate Appenrodt; Arthur Schmidt; Christian Lange; Christian Strassburg; Stefan Zeuzem; Daniel Grandt; Hartmut Schmidt; Joachim Moessner; Thomas Berg; Frank Lammert; Robert Thimme; Michael Schultheiß
Journal:  Aliment Pharmacol Ther       Date:  2020-06-07       Impact factor: 8.171

6.  Escalating interventional recanalization therapy in non-cirrhotic, non-malignant acute portal vein thrombosis.

Authors:  Mirjam Gerwing; Christian Wilms; Hauke Heinzow; Peter B Sporns; Walter Heindel; Hartmut Schmidt; Moritz Wildgruber; Michael Köhler
Journal:  Eur J Gastroenterol Hepatol       Date:  2019-12       Impact factor: 2.566

7.  Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study.

Authors:  Aurelie Plessier; Sarwa Darwish-Murad; Manuel Hernandez-Guerra; Yann Consigny; Federica Fabris; Jonel Trebicka; Jorg Heller; Isabelle Morard; Luc Lasser; Philippe Langlet; Marie-Hélène Denninger; Dominique Vidaud; Bertrand Condat; Antoine Hadengue; Massimo Primignani; Juan-Carlos Garcia-Pagan; Harry L A Janssen; Dominique Valla
Journal:  Hepatology       Date:  2010-01       Impact factor: 17.425

8.  Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.

Authors:  Maria Assunta Zocco; Enrico Di Stasio; Raimondo De Cristofaro; Marialuisa Novi; Maria Elena Ainora; Francesca Ponziani; Laura Riccardi; Stefano Lancellotti; Angelo Santoliquido; Roberto Flore; Maurizio Pompili; Gian Lodovico Rapaccini; Paolo Tondi; Giovanni Battista Gasbarrini; Raffaele Landolfi; Antonio Gasbarrini
Journal:  J Hepatol       Date:  2009-04-23       Impact factor: 25.083

9.  Long-term results of variceal bleeding management in 302 patients with chronic extrahepatic portal vein obstruction.

Authors:  Hui Chen; Chuangye He; Yong Lv; Jiahao Fan; Shihao Tang; Jing Niu; Jie Yuan; Bohan Luo; Wengang Guo; Zhanxin Yin; Guohong Han
Journal:  J Gastroenterol Hepatol       Date:  2019-12-06       Impact factor: 4.029

10.  Portal vein thrombosis associated with ChAdOx1 nCov-19 vaccination.

Authors:  Osman Öcal; Stephanie-Susanne Stecher; Moritz Wildgruber
Journal:  Lancet Gastroenterol Hepatol       Date:  2021-06-09
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