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Treatment Options for Hepatic Venous Outflow Tract Obstruction: Is the Scale Tipping in Favor of TIPS?

  • Anshuman Elhence
    Affiliations
    Department of Gastroenterology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
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  • Shalimar
    Correspondence
    Address for correspondence: Shalimar, Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, Room number 127, Old OT block, Delhi, India.
    Affiliations
    Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Delhi, India
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Published:September 27, 2022DOI:https://doi.org/10.1016/j.jceh.2022.09.005

      Abbreviations:

      BCS (Budd-Chiari Syndrome), HV (hepatic veins), INR (international normalized ratio), IVC (inferior vena cava), LT (liver transplantation), MELD (model for end-stage liver disease), TIPS (transjugular intrahepatic portosystemic shunt)
      Hepatic venous outflow tract obstruction or Budd-Chiari Syndrome (BCS) entails obstruction of the hepatic veins (HV) and/or the inferior vena cava (IVC), leading to a syndrome characterized by hepatic congestion and portal hypertension and its consequences.
      • Shalimar
      • Kumar A.
      • Kedia S.
      • et al.
      Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.
      The entity, by definition, excludes sinusoidal obstruction syndrome and similar changes arising as a result of right heart failure.
      • Janssen H.L.A.
      • Garcia-Pagan J.C.
      • Elias E.
      • et al.
      Budd-Chiari syndrome: a review by an expert panel.
      The vast majority of cases are primary, which arise as a result of occlusion arising from endoluminal causes, such as thrombosis or web, whereas secondary BCS resulting from external invasion or compression constitutes a minority of cases.
      • Janssen H.L.A.
      • Garcia-Pagan J.C.
      • Elias E.
      • et al.
      Budd-Chiari syndrome: a review by an expert panel.
      The clinical features, natural history and treatment choices are dependent on the anatomy and the acuity of presentation. There is a wide geographical variation in the anatomy and acuity of block as well as the accepted treatment strategies. In view of rarity of the disease and the absence of large prospective data comparing the various treatment strategies, these are often predicated on the basis of local expertise and available treatment options.
      • Gamanagatti S.
      • Hemachandran N.
      Hepatic venous outflow tract obstruction: causes, natural history, and treatment.
      In this issue of the journal, Wongjarupong et al. report the long-term outcomes and effect of the transjugular intrahepatic portosystemic shunt (TIPS) on liver function in patients with BCS from the west.
      • Wongjarupong N.
      • Young S.
      • Huynh R.K.
      • Lake J.
      • Lim N.
      Long-term improvement in liver function following transjugular intrahepatic portosystemic shunt in patients with budd–chiari syndrome.
      To put the results of the study in appropriate perspective, we delve into the background of BCS.
      In the west, isolated involvement of HV—more commonly a long-segment occlusion—is frequent, whereas in the east, HV and IVC combined involvement—often a short-segment block—is commonly seen.
      • Gamanagatti S.
      • Hemachandran N.
      Hepatic venous outflow tract obstruction: causes, natural history, and treatment.
      ,
      • Hemachandran N.
      • Shalimar
      • Acharya S.
      • et al.
      Long-term outcomes of endovascular interventions in more than 500 patients with budd-chiari syndrome.
      ,
      • Valla D.C.
      Hepatic venous outflow tract obstruction etiopathogenesis: Asia versus the West.
      In the Indian subcontinent, an isolated intrahepatic IVC block attributed to IVC web (arising as result of multiple episodes of subclinical phlebitis and thrombosis secondary to infection) had been described previously. But this profile has changed over the last decade or so to resemble that seen in the rest of the Asia, probably related to better imaging of the HVs.
      • Hemachandran N.
      • Shalimar
      • Acharya S.
      • et al.
      Long-term outcomes of endovascular interventions in more than 500 patients with budd-chiari syndrome.
      ,
      • Shrestha S.M.
      • Okuda K.
      • Uchida T.
      • et al.
      Endemicity and clinical picture of liver disease due to obstruction of the hepatic portion of the inferior vena cava in Nepal.
      Those with HV involvement are more likely to present with a shorter and acute course with jaundice, ascites, and variceal bleed, whereas those with IVC involvement often have a long history of pedal edema along with subcutaneous abdominal wall collaterals and are less likely to have jaundice or variceal bleed.
      • Eapen C.E.
      • Mammen T.
      • Moses V.
      • Shyamkumar N.K.
      Changing profile of Budd Chiari syndrome in India.
      There is much debate on the appropriate treatment of BCS, with different strategies proposed. A school of thought proposes the “step-up” strategy comprising anticoagulation first followed by endovascular interventions in nonresponders and liver transplantation (LT) to those who do not respond to endovascular interventions.
      • Janssen H.L.A.
      • Garcia-Pagan J.C.
      • Elias E.
      • et al.
      Budd-Chiari syndrome: a review by an expert panel.
      ,
      • Elhence A.
      • Anand A.
      • Shalimar
      Authors’ reply: Re: clinical utility of transient elastography in the management of patients with Budd-Chiari syndrome undergoing endovascular intervention.
      On the other hand is the opinion of “upfront” endovascular intervention along with anticoagulation and offering LT to nonresponders.
      • Shalimar
      • Kumar A.
      • Kedia S.
      • et al.
      Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.
      With evolving experience in endovascular interventions and data suggesting that less than 20% of patients do well with anticoagulation alone, the treatment paradigm is shifting toward upfront endovascular interventions.
      Even among the endovascular interventions, there is a choice between native vein recanalization procedures such as angioplasty, with or without stenting, and TIPS. Owing to the differences in the anatomy of block in BCS in the east, a lot of centers prefer angioplasty, with or without stenting, as the preferred endovascular intervention.
      • Shalimar
      • Kumar A.
      • Kedia S.
      • et al.
      Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.
      TIPS is only considered for patients with inadequate response to these native vein recanalization procedures and those with long-segment occlusion of all three HVs.
      • Shalimar
      • Kumar A.
      • Kedia S.
      • et al.
      Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.
      However, in the west, there is more experience with TIPS, which remains the preferred endovascular approach to create a shunt between the IVC and portal vein.
      • Janssen H.L.A.
      • Garcia-Pagan J.C.
      • Elias E.
      • et al.
      Budd-Chiari syndrome: a review by an expert panel.
      At times, when the HV notch is not well visualized, a direct shunt between the IVC and the portal vein may be created using percutaneous assistance; this variation is called direct intrahepatic portosystemic shunt.
      • Gamanagatti S.
      • Hemachandran N.
      Hepatic venous outflow tract obstruction: causes, natural history, and treatment.
      Choice of one endovascular intervention over the other depends on local expertise apart from the anatomical concerns. Our data supports that 5-year survival rates are better in the native vein recanalization group compared with the TIPS group (89% vs 76%).
      • Hemachandran N.
      • Shalimar
      • Acharya S.
      • et al.
      Long-term outcomes of endovascular interventions in more than 500 patients with budd-chiari syndrome.
      The caveat in interpreting this is that we performed TIPS selectively for those who have failed native vein recanalization procedures and those with all the HVs involved, which by definition constitute a sicker group. The inherent advantage of native vein recanalization procedures is that they have been shown to have a similar survival and patency rate with lesser periprocedural complications and risk of hepatic encephalopathy when done for appropriately chosen patients with a short-segment HV and/or IVC block.
      • Tripathi D.
      • Sunderraj L.
      • Vemala V.
      • et al.
      Long-term outcomes following percutaneous hepatic vein recanalization for Budd–Chiari syndrome.
      With this backdrop, Wongjarupong et al., in this journal issue, present their retrospective data on the long-term outcome of TIPS for BCS in 20 patients aged >20 years from a quaternary care medical center in North America.
      • Wongjarupong N.
      • Young S.
      • Huynh R.K.
      • Lake J.
      • Lim N.
      Long-term improvement in liver function following transjugular intrahepatic portosystemic shunt in patients with budd–chiari syndrome.
      Furthermore, they did a time to event analysis at 6 months, 1 year, 2 years, 5 years and 10 years posttransplant with censoring for death, liver transplant or loss to follow-up. Of these 20 patients, 80% had a hypercoagulable state with HV block in 70%, HV with IVC block in 15%, and the rest had no information on the anatomy of the block. As the study extended over two decades, patients undergoing TIPS in the earlier part of the study (before 2004) presumably received uncovered stents, which are not the current standard of care. Because, as discussed, the management of BCS needs to be highlighted in the right perspective, it will be pertinent to know what number of patients sought treatment for BCS at the authors’ institution during the study period and their management strategy for BCS—“step-up” versus “upfront” recanalization. Moreover, more clarity is needed about the detailed anatomy of the block: were the HV blocks long-segment or ostial? What was the number of HVs involved? Were some of these patients offered a native vein recanalization intervention initially?
      About 75% of patients required a TIPS revision at follow-up, a quarter of them within 30 days from the first intervention. There was a definite decrease in severe ascites and improvement in serum albumin levels over the period of follow-up. At 10-year follow-up, there was no significant change in bilirubin, creatinine, international normalized ratio (INR), model for end-stage liver disease (MELD) and MELD-Na scores, probably because the INR was fallaciously raised due to oral anticoagulants and there was no effect of the procedure on serum creatinine. An important observation is that 40% of the patients still required LT after TIPS, most commonly due to symptom recurrence or TIPS block. We have previously published our retrospective data on long-term outcomes of TIPS in BCS of 80 patients accrued over 7 years at our center.
      • Shalimar
      • Gamanagatti S.R.
      • Patel A.H.
      • et al.
      Long-term outcomes of transjugular intrahepatic portosystemic shunt in Indian patients with Budd-Chiari syndrome.
      Of these 80 patients, most had a long-segment block involving all the HVs (74%). The 5-year stent patency rate was 81%, and the 5-year post-TIPS survival was 84%. Post-TIPS survival was predicted by a decrease in symptoms and Child-Pugh stage after the intervention, even among those with Child-Pugh C cirrhosis. Hence, we had proposed TIPS as an effective treatment even for this subset of patients and advocated consideration of early LT for nonresponders. However, it is important to know that we offered TIPS only to patients with long-segment block of all HVs or those having failed previous native vein recanalization procedures at our center. Similar long-term outcomes post-TIPS have been reported from other centers also.
      • Sonavane A.D.
      • Amarapurkar D.N.
      • Rathod K.R.
      • Punamiya S.J.
      Long term survival of patients undergoing TIPS in Budd-Chiari syndrome.
      • Eapen C.E.
      • Velissaris D.
      • Heydtmann M.
      • Gunson B.
      • Olliff S.
      • Elias E.
      Favourable medium term outcome following hepatic vein recanalisation and/or transjugular intrahepatic portosystemic shunt for Budd Chiari syndrome.
      • Garcia-Pagán J.C.
      • Heydtmann M.
      • Raffa S.
      • et al.
      TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124 patients.

      Giri S, Kale A, Shukla A. Efficacy and safety of transjugular intrahepatic portosystemic shunt in Budd-Chiari syndrome: a systematic review and meta-analysis. J Vasc Intervent Radiol. Published online August 5, 2022:S1051-0443(22)1092-2. https://doi.org/10.1016/j.jvir.2022.07.022

      Notwithstanding the convincing data in support of TIPS from this study and others, its place in the management algorithm of BCS needs to be reassessed.

      Giri S, Kale A, Shukla A. Efficacy and safety of transjugular intrahepatic portosystemic shunt in Budd-Chiari syndrome: a systematic review and meta-analysis. J Vasc Intervent Radiol. Published online August 5, 2022:S1051-0443(22)1092-2. https://doi.org/10.1016/j.jvir.2022.07.022

      The appeal of native vein recanalization procedures such as venoplasty and stenting lies in their less invasive nature, reduced costs, and reestablishment of physiological drainage of the hepatic parenchyma with a lesser rate of complications compared with TIPS, which entails a nonphysiologic portosystemic shunt with risk of hepatic failure and encephalopathy.
      • Wang Q.
      • Han G.
      Image-guided treatment of Budd-Chiari syndrome: a giant leap from the past, a small step towards the future.
      Hence, we believe that the way forward will be to offer venoplasty ± stenting as the endovascular intervention of choice in patients with a suitable anatomy and offer TIPS to those failing native vein recanalization procedures, as well as “upfront” in a subset of patients with anatomy not amenable to venoplasty/stenting. Undisputedly, anticoagulation, management of portal hypertension-related complications and offering LT to those not responding to these endovascular interventions remain an equally important part of the management strategy (Figure 1).
      Figure 1
      Figure 1Management of BCS: an algorithmic approach. BCS, Budd-Chiari Syndrome; HTN, hypertension; HV, hepatic veins; IVC, inferior vena cava; TIPS, transjugular intrahepatic portosystemic shunt.

      Credit authorship contribution statement

      Anshuman Elhence and Shalimar drafted the article.

      Conflicts of interest

      The authors have none to declare.

      Acknowledgments

      None.

      References

        • Shalimar
        • Kumar A.
        • Kedia S.
        • et al.
        Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score.
        Aliment Pharmacol Ther. 2016; 43: 1154-1167https://doi.org/10.1111/apt.13604
        • Janssen H.L.A.
        • Garcia-Pagan J.C.
        • Elias E.
        • et al.
        Budd-Chiari syndrome: a review by an expert panel.
        J Hepatol. 2003; 38: 364-371https://doi.org/10.1016/s0168-8278(02)00434-8
        • Gamanagatti S.
        • Hemachandran N.
        Hepatic venous outflow tract obstruction: causes, natural history, and treatment.
        Clin Liver Dis (Hoboken). 2021; 18: 117-121https://doi.org/10.1002/cld.1126
        • Wongjarupong N.
        • Young S.
        • Huynh R.K.
        • Lake J.
        • Lim N.
        Long-term improvement in liver function following transjugular intrahepatic portosystemic shunt in patients with budd–chiari syndrome.
        J Clin Exp Hepatol. 2022; 12: 1474-1479https://doi.org/10.1016/j.jceh.2022.07.251
        • Hemachandran N.
        • Shalimar
        • Acharya S.
        • et al.
        Long-term outcomes of endovascular interventions in more than 500 patients with budd-chiari syndrome.
        J Vasc Intervent Radiol. 2021; 32: 61-69.e1https://doi.org/10.1016/j.jvir.2020.08.035
        • Valla D.C.
        Hepatic venous outflow tract obstruction etiopathogenesis: Asia versus the West.
        J Gastroenterol Hepatol. 2004; 19: S204-S211https://doi.org/10.1111/j.1440-1746.2004.03642.x
        • Shrestha S.M.
        • Okuda K.
        • Uchida T.
        • et al.
        Endemicity and clinical picture of liver disease due to obstruction of the hepatic portion of the inferior vena cava in Nepal.
        J Gastroenterol Hepatol. 1996; 11: 170-179https://doi.org/10.1111/j.1440-1746.1996.tb00056.x
        • Eapen C.E.
        • Mammen T.
        • Moses V.
        • Shyamkumar N.K.
        Changing profile of Budd Chiari syndrome in India.
        Indian J Gastroenterol. 2007; 26: 77-81
        • Elhence A.
        • Anand A.
        • Shalimar
        Authors’ reply: Re: clinical utility of transient elastography in the management of patients with Budd-Chiari syndrome undergoing endovascular intervention.
        J Vasc Intervent Radiol. 2022; 33: 617https://doi.org/10.1016/j.jvir.2022.02.014
        • Tripathi D.
        • Sunderraj L.
        • Vemala V.
        • et al.
        Long-term outcomes following percutaneous hepatic vein recanalization for Budd–Chiari syndrome.
        Liver Int. 2017; 37: 111-120https://doi.org/10.1111/liv.13180
        • Shalimar
        • Gamanagatti S.R.
        • Patel A.H.
        • et al.
        Long-term outcomes of transjugular intrahepatic portosystemic shunt in Indian patients with Budd-Chiari syndrome.
        Eur J Gastroenterol Hepatol. 2017; 29: 1174-1182https://doi.org/10.1097/MEG.0000000000000945
        • Sonavane A.D.
        • Amarapurkar D.N.
        • Rathod K.R.
        • Punamiya S.J.
        Long term survival of patients undergoing TIPS in Budd-Chiari syndrome.
        J Clin Exp Hepatol. 2019; 9: 56-61https://doi.org/10.1016/j.jceh.2018.02.008
        • Eapen C.E.
        • Velissaris D.
        • Heydtmann M.
        • Gunson B.
        • Olliff S.
        • Elias E.
        Favourable medium term outcome following hepatic vein recanalisation and/or transjugular intrahepatic portosystemic shunt for Budd Chiari syndrome.
        Gut. 2006; 55: 878-884https://doi.org/10.1136/gut.2005.071423
        • Garcia-Pagán J.C.
        • Heydtmann M.
        • Raffa S.
        • et al.
        TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124 patients.
        Gastroenterology. 2008; 135: 808-815https://doi.org/10.1053/j.gastro.2008.05.051
      1. Giri S, Kale A, Shukla A. Efficacy and safety of transjugular intrahepatic portosystemic shunt in Budd-Chiari syndrome: a systematic review and meta-analysis. J Vasc Intervent Radiol. Published online August 5, 2022:S1051-0443(22)1092-2. https://doi.org/10.1016/j.jvir.2022.07.022

        • Wang Q.
        • Han G.
        Image-guided treatment of Budd-Chiari syndrome: a giant leap from the past, a small step towards the future.
        Abdom Radiol (NY). 2018; 43: 1908-1919https://doi.org/10.1007/s00261-017-1341-y