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Achieving an effective pressure reduction after TIPS: The need for a new target

  • Xiaoze Wang
    Affiliations
    Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
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  • Xuefeng Luo
    Affiliations
    Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
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  • Li Yang
    Correspondence
    Corresponding author. Address: Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, Sichuan, China; Tel.: +86 18980601276, fax: 028-85553329.
    Affiliations
    Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, West China Hospital, Sichuan University, Chengdu, China
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Published:February 20, 2021DOI:https://doi.org/10.1016/j.jhep.2021.02.010

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      • Small diameter shunts should lead to safe expansion of the use of TIPS
        Journal of HepatologyVol. 74Issue 1
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          Transjugular intrahepatic portosystemic shunt (TIPS) is increasingly used worldwide to treat the complications of portal hypertension in patients with advanced cirrhosis. However, its use is hampered by the risk of causing hepatic encephalopathy and of worsening liver function. The reported haemodynamic targets used to guide TIPS are too narrow to be achieved in most cases and are perhaps not entirely adequate nowadays as they were obtained in the pre-covered stent era. We propose that small diameter TIPS – alone or combined to pharmacological therapy or ancillary interventional radiology procedures – may overcome these limitations while maintaining the beneficial effects of the procedure.
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      • Reply to: “Achieving an effective pressure reduction after TIPS: The need for a new target”
        Journal of HepatologyVol. 75Issue 1
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          I thank Drs Wang et al.1 for their kind comments on my paper. As I emphasized, hemodynamic targets for TIPS are largely based on studies from the pre-covered stent era, when TIPS dysfunction was extremely common.2 At that time, we showed that reducing the portal pressure gradient (PPG, the difference between portal vein and hepatic vein pressure) to values below 12 mmHg was necessary to prevent rebleeding or ascites, but that reductions below 10 mmHg were associated with an increased risk of encephalopathy.
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      To the Editor:
      We read with great interest the recent article by Jaume Bosch, proposing new insights into the hemodynamic target used to guide transjugular intrahepatic portosystemic shunt (TIPS).
      • Bosch J.
      Small diameter shunts should lead to safe expansion of the use of TIPS.
      The author also suggested small diameter TIPS, combined with other procedures or pharmacological therapy when necessary, might help avoid hepatic encephalopathy (HE). We would like to compare the outcomes of patients with portal pressure gradient (PPG) >12 mmHg and those with PPG ≤12 mmHg after TIPS creation.
      Two hundred and sixteen cirrhotic patients who underwent de novo TIPS placement due to variceal bleeding between June 2015 and April 2019 in our department were retrospectively reviewed. Written informed consent was obtained from each patient, and the study protocol was approved by the ethics committee of our hospital. The TIPS procedure was performed under local anesthesia. The intrahepatic tract was dilated with an 8×60 mm angioplasty balloon, followed by the placement of an 8-mm Fluency ePTFE-covered stent (Bard, Murray Hill, USA). The stent lengths used were 6 cm (n = 163, 75.5%) and 8 cm (n = 53, 24.5%). Persistent visualized collaterals on post-TIPS portography were embolized. PPG was measured after the embolization. The haemodynamic success of TIPS (final PPG ≤12 mmHg) was not achieved in 37 patients (17.1%). The baseline characteristics of patients in group 1 (PPG >12 mmHg) and group 2 (PPG ≤12 mmHg) are summarized in Table 1. In group 1, the median PPG was reduced from 27 mmHg (IQR, 25-30 mmHg) to 15 mmHg (IQR, 14-19 mmHg). In group 2, the median PPG was reduced from 20 mmHg (IQR, 17-23 mmHg) to 8 mmHg (IQR, 6-10 mmHg). The median percentage reduction of PPG was 44% (IQR, 31%-51.5%) in group 1 and 60% (IQR, 51.2%-68.5%) in group 2.
      Table 1Demographics and clinical outcomes of patients in 2 groups.
      VariablesGroup 1 (n = 37)Group 2 (n = 179)
      Age, years47.0 (42.0, 52.0)49.0 (43.0, 59.0)
      Sex, male/female28/9132/47
      Cause of liver disease, n
       Chronic HBV infection25 (67.6%)117 (65.4%)
       Alcohol6 (16.2%)28 (15.6%)
       Others6 (16.2%)34 (19.0%)
      Child-Pugh score8 (7, 8)7 (6, 8)
      MELD score9.8 (9.0, 12.6)9.9 (8.6, 11.6)
      Indication of TIPS, n (%)
       Acute variceal bleeding4 (10.8%)9 (5.0%)
       Second prophylaxis of variceal bleeding33 (89.2%)170 (95.0%)
      Variceal embolization, n (%)36 (97.3%)145 (81.0%)
      PPG before TIPS, mmHg27 (25, 30)20 (17, 23)
      PPG after TIPS, mmHg15 (14, 19)8 (6, 10)
      Percentage of PPG reduction, %44.0% (31.0%, 51.5%)60.0% (51.2%, 68.5%)
      Duration of follow-up, days433 (252, 627)419 (292, 643)
      Outcomes
       Variceal rebleeding623
       TIPS dysfunction944
       Hepatic encephalopathy1154
       Death68
      MELD, model for end-stage liver disease; PPG, portal pressure gradient; TIPS, transjugular intrahepatic portosystemic shunt.
      There was no significant difference between group 1 and 2 in terms of 1-year probability of remaining free of variceal rebleeding (91.8% vs. 90.1%), 1-year probability of HE (29.1% vs. 29.5%), 1-year probability of shunt dysfunction (14.5% vs. 17%) and 1-year probability of survival (91.9% vs. 97.8%). In group 1, variceal rebleeding occurred in 6 patients. TIPS dysfunction was confirmed in each patient. Five patients received shunt revision, and 1 underwent endoscopic treatment. Still, 3/6 patients died of variceal rebleeding after discharge. During follow-up, another 3 patients died due to liver failure 56, 112 and 480 days after TIPS placement, respectively. None of them had an acute-on-chronic liver failure before TIPS.
      Previous studies have demonstrated that variceal rebleeding rarely occurred in patients with a PPG of less than 12 mmHg.
      • Bosch J.
      • Garcia-Pagan J.C.
      Prevention of variceal rebleeding.
      ,
      • Garcia-Tsao G.
      • Groszmann R.J.
      • Fisher R.L.
      • Conn H.O.
      • Atterbury C.E.
      • Glickman M.
      Portal pressure, presence of gastroesophageal varices and variceal bleeding.
      Therefore, the final PPG ≤12 mmHg was generally considered the threshold of hemodynamic success of TIPS.
      • Krajina A.
      • Hulek P.
      • Fejfar T.
      • Valek V.
      Quality improvement guidelines for Transjugular Intrahepatic Portosystemic Shunt (TIPS).
      However, patients who had a reduction by 25-50% may still have a favorable outcome compared with a widely used threshold value of 12 mmHg after TIPS creation.
      • Thalheimer U.
      • Leandro G.
      • Samonakis D.N.
      • Triantos C.K.
      • Senzolo M.
      • Fung K.
      • et al.
      TIPS for refractory ascites: a single-centre experience.
      In our cohort, the cumulative rates of variceal rebleeding, HE and mortality were similar between the 2 groups and were consistent with patients who had a final PPG ≤12 mmHg in previous reports.
      • Weber C.N.
      • Nadolski G.J.
      • White S.B.
      • Clark T.W.
      • Mondschein J.I.
      • Stavropoulos S.W.
      • et al.
      Long-term patency and clinical analysis of expanded polytetrafluoroethylene-covered transjugular intrahepatic portosystemic shunt stent grafts.
      The relatively high TIPS dysfunction rate may be due to non-dedicated stent use because the dedicated stent was not available during that time in our institution.
      In addition, the use of 8-mm stents may cause less reduction of PPG. Our previous study found that 8-mm TIPS in the Chinese population was sufficient to decompress the portal venous system, prevent variceal rebleeding and reduce HE incidence compared with 10-mm TIPS.
      • Luo X.
      • Wang X.
      • Zhu Y.
      • Xi X.
      • Zhao Y.
      • Yang J.
      • et al.
      Clinical efficacy of transjugular intrahepatic portosystemic shunt created with expanded polytetrafluoroethylene-covered stent-grafts: 8-mm versus 10-mm.
      One randomized controlled trial also confirmed that 8-mm stents could reduce the risk of post-TIPS HE and liver function impairment.
      • Wang Q.
      • Lv Y.
      • Bai M.
      • Wang Z.
      • Liu H.
      • He C.
      • et al.
      Eight millimetre covered TIPS does not compromise shunt function but reduces hepatic encephalopathy in preventing variceal rebleeding.
      More recently, Trebicka and his colleagues demonstrated that 8-mm stents were associated with prolonged survival compared with 10-mm stents.
      • Trebicka J.
      • Bastgen D.
      • Byrtus J.
      • Praktiknjo M.
      • Terstiegen S.
      • Meyer C.
      • et al.
      Smaller-diameter covered transjugular intrahepatic portosystemic shunt stents are associated with increased survival.
      In light of this, a smaller TIPS, despite a possible higher post-TIPS PPG may lead to a better outcome.
      Spontaneous portosystemic shunt (SPSS) increased the risk of HE and a chronic course in patients with cirrhosis.
      • Simón-Talero M.
      • Roccarina D.
      • Martínez J.
      • Lampichler K.
      • Baiges A.
      • Low G.
      • et al.
      Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis.
      Whether or not SPSS should be embolised during TIPS placement remains controversial. The impact of TIPS in combination with embolization of SPSS on long-term outcomes in patients with cirrhosis requires further studies. Theoretically, PPG would be increased following embolization. PPG was also influenced by the diameter of the shunt, the timing of the measurement, the type of anesthesia and the patients' level of awareness etc. Therefore, the measurement of PPG needs to be standardized among different centers. The optimal final PPG after TIPS creation also requires validation using dedicated TIPS stents. Further studies are required to assess the efficacy of a small diameter TIPS which may lead to a PPG >12 mmHg, complemented by drugs, endoscopic or interventional procedures.

      Financial support

      Xiaoze Wang received fund (No. 2019HXBH070) from Post-Doctor Research Project, West China Hospital, Sichuan University. Li Yang received fund (ZYGD20012) from the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

      Authors’ contributions

      Concept and design: Xuefeng Luo and Li Yang. Data collection and interpretation: Xiaoze Wang and Xuefeng Luo. Manuscript drafting: Xiaoze Wang. Manuscript revising: Xuefeng Luo and Li Yang. All authors approved the final version of the article and the authorship list.
      Please refer to the accompanying ICMJE disclosure.

      Conflict of interest

      The authors declare no conflicts of interest that pertain to this work.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following is the supplementary data to this article:

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