Should the Presence of Spontaneous Portosystemic Shunts Be Implemented to the Model for End-Stage Liver Disease Score for a Better Prediction of Outcome?
2018; Elsevier BV; Volume: 154; Issue: 6 Linguagem: Inglês
10.1053/j.gastro.2018.03.035
ISSN1528-0012
AutoresMaéva Guillaume, Christophe Bureau,
Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoSee “Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis,” by Simón-Talero M, Roccarina D, Martínez J, et al, on page 1694. See “Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis,” by Simón-Talero M, Roccarina D, Martínez J, et al, on page 1694. Portal hypertension (PHT) in cirrhosis is the result of increased intrahepatic vascular resistance to portal blood flow owing to both structural changes in the liver and increased hepatic vascular tone.1Garcia-Tsao G. Abraldes J.G. Berzigotti A. et al.Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases.Hepatology. 2017; 65: 310-335Crossref PubMed Scopus (706) Google Scholar, 2Iwakiri Y. Groszmann R.J. Vascular endothelial dysfunction in cirrhosis.J Hepatol. 2007; 46: 927-934Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar Consequently, 2 mechanisms concomitantly occur: a splanchnic vasodilatation and the development of portosystemic collaterals. Spontaneous portosystemic shunts (SPSS) are probably the result of both dilatation of preexisting vascular channels and formation of new vessels.3Fernandez M. Semela D. Bruix J. et al.Angiogenesis in liver disease.J Hepatol. 2009; 50: 604-620Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar They represent communications between the portal or splanchnic venous system and the systemic venous system (Figure 1). This supposed “compensatory” mechanism is insufficient to adequately decrease portal pressure and could further contribute to increase splanchnic blood flow and resistance, worsening PHT and decreasing hepatocyte perfusion.3Fernandez M. Semela D. Bruix J. et al.Angiogenesis in liver disease.J Hepatol. 2009; 50: 604-620Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar The extensive network of SPSS was explored in this issue of Gastroenterology by Simón-Talero et al,4Simón-Talero M. Roccarina D. Martínez J. et al.Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis.Gastroenterology. 2018; 154: 1694-1705Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar with the aim of assessing the prevalence of SPSS in cirrhotics, and the association between the presence of SPSS and liver-related complications. The prevalence has been mainly explored in old studies using angiography. Reassessing this using modern imaging that provides an overview of multiple organ systems is of high interest. Moreover, it has thus far been unclear as to whether the presence and size of SPSS are able to predict liver complications and mortality.5Aseni P. Beati C. Brambilla G. et al.Does large spontaneous portal systemic shunt in cirrhosis protect from the risk of gastroesophageal bleeding?.J Clin Gastroenterol. 1986; 8: 235-238Crossref PubMed Scopus (18) Google Scholar The authors investigated the prevalence of SPSS in 1729 patients using abdominal computed tomography or magnetic resonance imaging, and the incidence of cirrhosis complications and mortality according to whether or not SPSS was present. They classified patients with SPSS according to size: large (≥8 mm) or small (<8 mm). They found a prevalence of 60% of SPSS (32% small and 28% large), the most common shunts being the splenorenal and paraumbilical. The presence and size of SPSS increased with liver dysfunction and with the severity of PHT. During follow-up, the incidence of hepatic encephalopathy (HE) increased with the presence and size of SPSS (48% and 34% of patients with large and small SPSS vs 20% of patients without SPSS). In addition, the presence of SPSS was associated with a higher risk of PHT-related complications (variceal bleeding and ascites) and a lower rate of transplant-free survival. Interestingly, this observation was significant in the subset of patients with preserved liver function (Model for End-Stage Liver Disease [MELD] score 6-9 or Child-Pugh class A). In patients with clinically significant PHT and a MELD score of <10, having SPSS increased the risk of decompensating events compared with those without SPSS (68% vs 44%). This is the largest study reported so far, coming from several expert centers and countries. The most clinically relevant information is that the presence of SPSS may identify a subgroup of patients with compensated liver cirrhosis without liver failure, who are at risk of developing HE and PHT complications, and thus who would require close monitoring and follow-up. The interpretation of some data must be taken cautiously, especially when retrospectively assessing a subjective outcome such as encephalopathy. Likewise, including only patients with computed tomography scan or magnetic resonance imaging could have induced a selection bias leading to an overestimation of SPSS prevalence. The interobserver and interobserver variabilities are not known and a standardized lecture protocol is awaited (no double-blind lecture and a clear center effect in the present study). The optimal size for splitting large versus small also remains to be elucidated. In addition, it would be relevant to prospectively compare the predictive value of SPSS with the other usual hallmarks of PHT (liver stiffness, platelet count, etc) in a large population. Otherwise, it is still unclear whether etiology plays a role in the development of SPSS, because patients with hepatitis C virus infection are often diagnosed earlier than alcoholic patients. Treatment with β-blockers or band ligation may induce a bias acting as a confounding factor in the prevalence and the size of the SPSS. Further longitudinal studies with sequential evaluation are warranted to confirm these data as well as explore the influence of etiological treatment. Finally, we can assume that not all patients need to be explored, as recommended for the screening of varices using the “Baveno criteria.”6de Franchis R. Baveno V.I.F. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.J Hepatol. 2015; 63: 743-752Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Nevertheless, Simón-Talero et al4Simón-Talero M. Roccarina D. Martínez J. et al.Association between portosystemic shunts and increased complications and mortality in patients with cirrhosis.Gastroenterology. 2018; 154: 1694-1705Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar described a high prevalence of SPSS in cirrhotics, which increased with liver dysfunction, and observed an association between the presence of SPSS and worse outcomes. This association is particularly relevant in patients with preserved liver function, because the presence of SPSS independently increases the risk of developing HE, variceal bleeding and ascites, and decreases transplant-free survival. It is well-established that HE is related to the severity of liver insufficiency and/or SPSS.7Vilstrup H. Amodio P. Bajaj J. et al.Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.Hepatology. 2014; 60: 715-735Crossref PubMed Scopus (837) Google Scholar, 8Sherlock S. Summerskill W.H. White L.P. et al.Portal-systemic encephalopathy; neurological complications of liver disease.Lancet. 1954; 267: 454-457PubMed Google Scholar However, only a few small studies have previously described an association between the presence and size of SPSS and an increased incidence of HE.9Ohnishi K. Sato S. Saito M. et al.Clinical and portal hemodynamic features in cirrhotic patients having a large spontaneous splenorenal and/or gastrorenal shunt.Am J Gastroenterol. 1986; 81: 450-455PubMed Google Scholar, 10Riggio O. Efrati C. Catalano C. et al.High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study.Hepatology. 2005; 42: 1158-1165Crossref PubMed Scopus (128) Google Scholar Futures studies should evaluate if SPSS persists after portal decompression with transjugular intrahepatic portosystemic shunt (TIPS), and whether their presence before TIPS increases the risk of post-TIPS HE, as already suggested.11Borentain P. Soussan J. Resseguier N. et al.The presence of spontaneous portosystemic shunts increases the risk of complications after transjugular intrahepatic portosystemic shunt (TIPS) placement.Diagn Interv Imaging. 2016; 97: 643-650Crossref PubMed Scopus (16) Google Scholar Likewise, future studies should aim to evaluate the influence of SPSS on complications occurring during or immediately after liver transplantation. This issue has rarely been addressed and has a potential therapeutic implication. Indeed, embolization of large SPSS has been proposed as a potential treatment option for patients with refractory HE,12Laleman W. Simon-Talero M. Maleux G. et al.Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy.Hepatology. 2013; 57: 2448-2457Crossref PubMed Scopus (140) Google Scholar, 13Singh S. Kamath P.S. Andrews J.C. et al.Embolization of spontaneous portosystemic shunts for management of severe persistent hepatic encephalopathy.Hepatology. 2014; 59: 735-736Crossref PubMed Scopus (11) Google Scholar, 14An J. Kim K.W. Han S. et al.Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy.Aliment Pharmacol Ther. 2014; 39: 1418-1426Crossref PubMed Scopus (41) Google Scholar showing promising results in carefully selected patients.12Laleman W. Simon-Talero M. Maleux G. et al.Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy.Hepatology. 2013; 57: 2448-2457Crossref PubMed Scopus (140) Google Scholar, 14An J. Kim K.W. Han S. et al.Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy.Aliment Pharmacol Ther. 2014; 39: 1418-1426Crossref PubMed Scopus (41) Google Scholar In addition, embolization of SPSS has been evaluated to treat post-TIPS HE.15Wu W. He C. Han G. Embolization of spontaneous splenorenal shunt for after-TIPS hepatic encephalopathy in a patient with cirrhosis and variceal bleeding.Hepatology. 2015; 61: 1761-1762Crossref PubMed Scopus (13) Google Scholar, 16Doshi M. Pereira K. Carrion A. et al.Antegrade embolization of spontaneous splenorenal shunt for post-transjugular intrahepatic portosystemic shunt refractory hepatic encephalopathy.Hepatology. 2016; 64: 314-315Crossref PubMed Scopus (3) Google Scholar Balloon-occluded retrograde transvenous obliteration, as an alternative to or combined with TIPS, is a procedure for treatment of fundal varices that could also be an option to treat refractory HE.17Fukuda T. Hirota S. Sugimura K. Long-term results of balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy.J Vasc Interv Radiol. 2001; 12: 327-336Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar, 18Gwon D.I. Kim Y.H. Ko G.Y. et al.Vascular plug-assisted retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy: a prospective multicenter study.J Vasc Interv Radiol. 2015; 26: 1589-1595Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar It has been shown that SPPS occlusion is associated with increased hepatic blood flow and improvement of liver metabolic profile,19Kako Y. Yamakado K. Jomoto W. et al.Changes in liver perfusion and function before and after percutaneous occlusion of spontaneous portosystemic shunt.Jpn J Radiol. 2017; 35: 366-372Crossref PubMed Scopus (6) Google Scholar but with a risk of worsening PHT. SPSS should not be interpreted as a compensatory mechanism, but rather as a feature of severe PHT and a prognosis marker of a poor outcome. Because the MELD score does not perfectly reflect the severity of liver disease, neither taking into account PHT nor encephalopathy, the presence of SPSS might be evaluated to implement the MELD scoring system. Whether adding the presence of SPSS to MELD in a new score would improve prognostic prediction is an important issue raised by the present study. Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With CirrhosisGastroenterologyVol. 154Issue 6PreviewSpontaneous portosystemic shunts (SPSS) have been associated with hepatic encephalopathy (HE). Little is known about their prevalence among patients with cirrhosis or clinical effects. We investigated the prevalence and characteristics of SPSS in patients with cirrhosis and their outcomes. Full-Text PDF
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