PG 1 PG Course 2012 Portal Hypertension 문맥압항진증의영상시술치료 서울대학교의과대학분당서울대학교병원영상의학과 윤창진 Radiologic Intervention of Portal Hypertension Chang Jin Yoon Seoul

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PG 1 PG Course 2012 Portal Hypertension 문맥압항진증의영상시술치료 서울대학교의과대학분당서울대학교병원영상의학과 윤창진 Radiologic Intervention of Portal Hypertension Chang Jin Yoon Seoul National University College of Medicine, Seoul

1 PG 1 PG Course 2012 Portal Hypertension 문맥압항진증의영상시술치료 서울대학교의과대학분당서울대학교병원영상의학과 윤창진 Radiologic Intervention of Portal Hypertension Chang Jin Yoon Seoul National University College of Medicine, Seoul National University Bundang Hospital, Bundang, Korea During recent decades, many image-guided procedures for portal hypertension have been developed, and today, interventional radiology has evolved to become an integral part of therapy. Various procedures are currently available, the choice depending on the etiology and location of disease, the pathoanatomy, and the symptomatology. Those procedures can be categorized into two groups. 1) Interventions to reduce the portal pressure by either direct or indirect methods. This can be achieved with transjugular intrahepatic portosystemic shunt (TIPS), recanalization of the hepatic vein outflow, recanalization of the portal vein and its tributaries, partial splenic embolization, and embolization of arterioportal shunts. 2) Interventions to embolize bleeding varices without altering portal pressure. This can be performed percutaneously or transvenously. This article briefly describes the procedures, their results, and their current status in the treatment of portal hypertension. Key words: Interventional radiology, Portal hypertension 간문맥의영상의학적인터벤션은 1970년대위및식도정맥류출혈의경간색전술 (transhepatic embolization) 로부터시작되었으며, 1980년대경목정맥경간문맥단락술 (transjugular intrahepatic portosystemic shunt; TIPS) 이개발되어내시경적치료가어려운상부위장관정맥류출혈의치료에사용되면서획기적발전을이루었다. 이후문맥재개통술 (portal vein recanalization), balloon-occluded retrograde transvenous obliteration of varices (BRTO), 간정맥혈관성형술 (hepatic venous outflow angioplasty) 등다양한시술이차례로개발되어현재인터벤션영상의학의한분야로확립되었다. Interventions in portal hypertension 간문맥고혈압의인터벤션치료는두가지로나눌수있다. 1) 문맥압자체를감압하는시술로 variceal bleeding, congestive gastroenteropathy, ascites, hydrothorax, hepatorenal syndrome 등문맥고혈압의합병증을줄이는방법과 2) 문맥압을감압하지않고출혈정맥류를색전하여지혈하는치료방법이있으며, 다음과같은다양한시술이있다. 38

2 윤창진 문맥압항진증의영상시술치료 1. Interventions to reduce portal blood pressure a. Transjugular intrahepatic portosystemic shunts (TIPS) b. Recanalization of hepatic venous outflow c. Recanalization of the occluded portal vein and its tributaries d. Embolization of arterioportal fistula e. Partial splenic embolization 2. Interventions to embolize bleeding varices (without altering the portal blood pressure) a. Percutaneous transhepatic variceal embolization b. Balloon-occluded retrograde obliteration of gastric varices (BRTO) Transjugular intrahepatic portosystemic shunt (TIPS) TIPS는문맥과간정맥사이의간실질내에 portosystemic shunt를만드는시술로 (1) 목정맥천자, (2) 간정맥삽관, (3) 간정맥으로부터간실질을지나문맥천자, (4) 풍선확장술로 parenchymal tract 형성, (5) 형성된 portosystemic shunt의 patency 유지를위한 stent 삽입의과정으로시행된다. 대부분의경우직경 8-10 mm stent가사용되며, portosystemic gradient 12 mm Hg 이하의문맥압감소를목표로하는것이일반적이다. 일반적으로인정되는적응증은 Table 1과같다. 1 TIPS의금기증으로는 congestive heart failure, severe pulmonary hypertension, severe tricuspid regurgitation, hepatic failure, preexisting encephalopathy, unrelieved biliary obstruction, multiple hepatic cysts, and uncontrolled systemic infection 등이며, presence of large liver tumors, hepatic vein thrombosis, portal vein thrombosis, thrombocytopenia (< 20,000/cm 3 ) and severe coagulopathy (INR >5) 도상대적금기증으로간주된다 1. TIPS는기술적성공율이 95% 로매우높으며, 시술연관사망률은 1% 이하인안전한시술이다. 그러나, 대부분전신상태가매우불량한환자들에서시행되므로시술후 1개월사망률은상대적으로높고, 특히간기능저하 Table 1. Indications of transjugular intrahepatic portosystemic shunt 1. Acute variceal bleeding unresponsive to medical and endoscopic therapy 2. Recurrent variceal bleeding unresponsive to medical and endoscopic therapy 3. Ectopic variceal bleeding (e.g., bleeding from duodenal varices, rectal varices, stomal varices, and caput medusae) 4. Nonvariceal bleeding secondary to hypertensive gastropathy/enteropathy 5. Ascites resistant or intolerant to optimal medical therapy 6. Hepatic hydrothorax resistant or intolerant to optimal medical therapy 7. Budd-Chiari syndrome 8. Hepatorenal syndrome 9. Hepatopulmonary syndrome 39

3 Postgraduate Course 2012 정도에따라 40% 까지보고되고있어대상환자선정에주의가필요하다. 현재까지보고된예후인자로 serum bilirubin (>3 mg/dl), Child-Pugh score (>12), modified MELD score (>25), APACHE II score (>18), Emory risk score (>3) 등이있다. 2 TIPS의단기치료효과는정맥류출혈의적응증일경우 90% 이상, ascites나 hydrothorax의경우 70% 이상으로내시경적지혈술이나반복적복수천자와비교하여우월하다 (Tables 2, 3) 그러나, TIPS 시행후 intimal hyperplasia 에의한 shunt dysfunction이빈번히발생하여 shunt tract의일차개통율은 3년 20%, 5년 10% 정도로장기개통율이매우낮다. 정기적인 Doppler검사로 shunt stenosis를조기진단하여풍선 Table 2. Results of randomized trials of transjugular intrahepatic portosystemic shunt vs. endoscopic therapy Author No of patients Type of ET Rebleed rate Mortality rate Encephalopathy TIPS ET TIPS ET TIPS ET TIPS ET GEAIH * Sclerotherapy NA NA Cabrera Sclerotherapy Rossle Sclerotherapy/ligation+ propranolol Sanyal Sclerotherapy Cello Sclerotherapy Sauer Sclerotherapy+ propanolol Jalan Band ligation Merli Sclerotherapy Sauer Band ligation Garcia-Villareal Sclerotherapy Pomier-Layrargues Band ligation Narahara Sclerotherapy Gulberg Band ligation Mean * Grouped'Etude des Anastomoses Intra-Hepatiques, TIPS: Transjugular intrahepatic portosystemic shunt, ET: Endoscopic therapy. Table 3. Results of randomized trials comparing transjugular intrahepatic portosystemic shunt with repeated large-volume paracentesis Author No of patients Control of ascites (at 4 months) Survival (at 12 months) Encephalopathy TIPS LVP TIPS LVP TIPS LVP TIPS LVP Rossle Gines Sanyal Salerno Mean TIPS: Transjugular intrahepatic portosystemic shunt, LVP: Large-volume paracentesis 40

4 윤창진 문맥압항진증의영상시술치료 확장술이나 re-stenting 등적극적인재시술이권장되며, 이경우 5년이차개통율을 50% 정도로유지할수있다. 최근 stent-graft의사용이기존의 bare stent에비하여유의하게 shunt patency를향상시킬수있음이증명되어향후 stent-graft 사용이표준으로인정될전망이다. 21 다른자연발생적 portosystemic shunt와마찬가지로 TIPS는 encephalopathy의발생, 악화를유발할수있으며, 50% 까지보고된다. 대부분은내과적치료로조절이가능하나, 3-7% 에서는 shunt reduction이필요하다. Recanalization of Hepatic Venous Outflow Budd-Chiari syndrome은간정맥및하대정맥수준에서의모든 hepatic vein outflow의장애를포함하며, 이로인한간울혈은간실질괴사, 섬유화로진행하게된다. 치료의목표는간정맥유출의 physiological flow를회복하는것으로, 간정맥및하대정맥의폐쇄부위가짧은경우폐쇄부위를풍선혈관성형술이나 stenting으로개통시킴으로써간울혈을해소하고간실질손상의진행을막을수있다. 그러나, 간정맥전체가폐쇄되어있는경우간정맥의재개통은기술적으로어려울뿐만아니라재폐쇄될가능성이매우높다. Budd-Chiari syndrome 환자에서의수술적 portocaval shunt는비대되어있는미상엽 (caudate lobe) 으로인하여간문맥으로의접근이제한되어기술적으로어려우며, 미상엽에의하여눌린하대정맥내압력이높아 portocaval shunt의효과가적다. TIPS는수술적치료에비하여안전하고, 하대정맥상부로 shunt flow를연결하므로치료효과도우수하다. 최근의보고에의하면복수조절효과는 100% 에가까우며, 대부분의환자에서간기능이호전되었다. 22 Recanalization of portal vein 간외간문맥의국소적패색에의한문맥고혈압은전체문맥고혈압의 5-10% 를차지한다. 원인은문맥혈전증, 수술후양성협착, 악성종양에의한협착등다양하며, 정맥류출혈, 복수, 복통등모든문맥고혈압증상이발생할수있다. 경간적 (transhepatic) 혹은경목정맥 (transjugular) 접근으로문맥협착혹은폐색에대하여혈관성형술및 stenting을시행할수있고기술적 / 임상적성공율은 95% 이상이다. 23 Embolization of Arterioportal fistulae Arterioportal fistulae도드물지만문맥고혈압의원인이될수있으며, 선천성일수있으나외상, 생검, 간종양등이차적인원인일경우가많다. 대부분의경우 fistula를통한혈류량이적어임상적으로의미있는문맥고혈압을일으키지않으나, 혈류량이많을경우드물게출혈, 복수, 비장비대등문맥고혈압증상이발생할수있다. 원인이되는간동맥의색전술 (transhepatic arterial embolization) 이가장선호되는치료방법이며색전물질로는 coil, detachable balloons, glue등이사용된다

5 Postgraduate Course 2012 Partial splenic embolization Splenic artery embolization은문맥으로의유입혈류를감소시켜문맥압을간접적으로줄이려는목적으로시행된다. 이시술은 splenic artery의가지를초선택적으로색전하는것으로 polyvinyl alcohol particle을사용한다. 문맥압감소, 비장의크기감소및비장비대로인한thrombocytopenia의호전을기대할수있다. 25 드물게비장농양, 패혈증등합병증이발생할수있다. Percutaneous transhepatic variceal embolization (PTE) PTE는내과적치료에반응하지않는정맥류출혈을치료하기위하여 1974년 Lunderquist 등에의해처음시도되었으며, 문맥고혈압의인터벤션치료중가장먼저개발된시술이다. 26 경피적으로간문맥을접근하여위정맥에삽관하고, 위정맥류를 ethanol, coil, cyanoacrylate 등으로색전술을시행한다. PTE는출혈정맥류를직접색전함으로서 70-90% 의높은지혈성공율을기대할수있으나, 문맥고혈압자체를낮추지는못하는한계가있어 38-70% 의환자에서 6개월내재출혈이발생하는단점이있고, 문맥혈전증이나심한복수가있는경우정맥류로의접근이어려운어려움이있다. 27 Balloon-occluded retrograde transvenous obliteration of varices (BRTO) BRTO는 gastrorenal shunt를통하여위정맥류에대하여경화요법 (sclerotherapy) 을시행하는것으로 2000년대일본에서개발, 발전되었다. 시술은대퇴정맥이나목정맥으로접근하여좌신정맥-gastrorenal shunt에삽관하고풍선카테터로 shunt내의 portosystemic flow를일시적으로막은후 sclerosant (5% ethanolamine oleate) 를주입하여위정맥류를 retrograde filling시킴으로서위정맥류내혈전을유발하여색전한다. 위정맥류출혈에서지혈효과는 TIPS 와비슷한정도로우수하나, portosystemic shunt를차단함으로써 TIPS와는반대로간문맥내의 hepatopetal flow를증가시켜간경화환자에서간기능호전및간성혼수를방지하는효과를기대할수있다. 28 그러나, gastrorenal shunt의폐쇄는식도정맥류의발생, 악화의원인이되기도한다. 맺는말 지난수십년간문맥고혈압및연관합병증을치료하기위한인터벤션치료법들이지속적으로개발, 발전되어왔다. 현재다양한인터벤션치료법들이임상적으로사용되고있으며, 문맥고혈압의치료에있어일차적혹은내시경 / 수술적치료의보조적치료법으로서중요한역할을하고있다. 각시술들은고유의적응증, 장단점, 한계가있으므로대상환자의선정에있어문맥고혈압의원인, 증상, 임상상태, 영상검사소견등을종합하여신중히선택되어야한다. 42

6 윤창진 문맥압항진증의영상시술치료 참고문헌 1. Boyer TD, Haskal ZJ. American Association for the Study of Liver Diseases practice guidelines: The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology 2005;41: Ferral H, Patel NH. Selection criteria for patients undergoing transjugular intrahepatic portosystemic shunt procedures: Current status. J Vasc Interv Radiol 2005;16: Cabrera J, Manyar M, Granados R, et al. Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage. Gastroenterology 1996;110: Rossle M, Deibert P, Haag K, et al. Randomised trial of transjugular intrahepatic portosystemic shunt versus endoscopy plus propranolol for prevention of varicealrebleeding. Lancet 1997;249: Sauer P, Theilmann L, Stremmel W, Benz C, Richter GM, Stiehl A. Transjugular intrahepatic portosystemic stent versus sclerotherapy plus propranolol for rebleeding. Gastroenterology 1997;113: Sanyal AJ, Freedman AM, Luketic VA, et al. Transjugular intrahepatic portosystemic shunt -compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage: a randomized, controlled trial. Ann Intern Med 1997;126: Cello JP, Ring EJ, Olcott EW, et al. Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage: A randomized, controlled trial. Ann Int Med 1997;126: Jalan R, Forrest EH, Stanley AJ, Redhead DN, Forbes J, Dillon JF. A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices. Hepatology 1997;26: Merli M, Salerno F, Riggio O, et al. Transjugular intrahepatic portosystemic shunt versus -endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: A randomized multicenter trial. GruppoItaliano Studio TIPS (GIST) Hepatology1998;27: Grouped'Etude des Anastomoses Intra-Hepatiques TIPS vssclerotherapy + propranolol in the prevention of varicealrebleeding: Preliminary results of a multicenter randomized trial. Hepatology1995;22:A Garcia-Villareal L, Martinez-Lagares F, Sierra A, et al. Transjugular intrahepatic portosystemic shunt versus sclerotherapy for the prevention of varicealrebleeding after recent variceal hemorrhage. Hepatology 1999;29: Sauer P, Benz C, Thielmann L, Richter G, Stermmel W, Stiehl A. Transjugular intrahepatic portosystemic stent shunt (TIPS) vs endoscopic banding in the prevention of varicealrebleeding: Final results of a randomized study. Gastroenterology 1998;114:A Pomier-Layrargues G, Villeneuve JP, Deschenes M, et al. Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of varicealrebleeding in patients with cirrhosis: A randomized trial. Gut 2001;48: Narahara Y, Kanawaza H, Kawamata H, et al. A randomized clinical trial comparing transjugular intrahepatic portosystemic shunt with endoscopic sclerotherapy in the long-term management of patients with cirrhosis after recent variceal hemorrhage. Hepatol Res 2001;21: Gulberg V, Schepke M, Geigenberger G, et al. Transjugular intrahepatic portosystemic shunting is not superior to endoscopic variceal band ligation for prevention of varicealrebleeding in cirrhotic patients: A randomized controlled trial. Scand J Gastroenterol 2002;37: Rossle M, Ochs A, Gulberg V, et al. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites. N Engl J Med 2000;342: Gines P, Uriz J, Calahorra B, et al. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology 2002;123: Sanyal AJ, Genning C, Reddy KR, et al. The North American study for the treatment of refractory ascites. Gastroenterology 2003;124: Salerno F, Merli M, Riggio O, et al. Randomized control study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites. Hepatology 2004;40: Siegerstetter V, Deibert P, Ochs A, Olschewski M, Blum HE, Rossle M. Treatment of refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt: Long-term results in 40 patients. Eur J GastroenterolHepatol 2001;13: Bureau C, Garcia-Pagan JC, Pomier-Layrargues G, et al. A randomized study comparing the use of polytetrafluoroethane (PTFE) covered stents and uncovered stents for TIPS: Long term patency. Hepatology 2004;40:186A. 22. Khuroo MS, Al-Suhabani H, Al-Sebayel M, et al. Budd-Chiari syndrome: Long term effect on outcome with transjugular intrahepatic portosystemic shunt. J GastroenterolHepatol 2005;20: Yamakado K, Nakatsuka A, Tanaka N, et al. Portal venous stent placement in patients with pancreatic and biliary neoplasms invading 43

7 Postgraduate Course 2012 portal veins and causing portal hypertension: Initial experience. Radiology 2001;220: Vauthey JN, Tomczak RJ, Helmberger T, et al. The arterioportal fistula syndrome: Clinicopathologic features, diagnosis and therapy. Gastroenterology1997;113: Koconis KG, Singh H, Soares G. Partial splenic embolization in the treatment of patients with portal hypertension: A review of the English language literature. J Vasc Interv Radiol 2007;18: Lunderquist A, Simert G, Tylen U, Vang J. Follow-up of patients with portal hypertension and esophageal varices treated with percutaneous obliteration of gastric coronary vein. Radiology1977;122: L'Hermine C, Chastanet P, Delemazure O, Bonniere PL, Durieu JP, Paris JC. Percutaneous transhepatic embolization of gastroesophagealvarices: Results in 400 patients. Am J Roentgenol1989;152: Ninoi T, Nishida N, Kaminou T, et al. Balloon-occluded retrograde transvenous obliteration of gastric varices with gastrorenal shunt: Long-term follow-up in 78 patients. Am J Roentgenol 2005;184:

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<30322E535453BABBB9AE2DC6EDC1FD2E687770> 정맥류출혈의치료를위한중재방사선학적시술 Interventional Procedures for the Treatment of Variceal Bleeding 울산의대서울아산병원영상의학과 권동일 Two common interventional procedures for the treatment of gastric variceal bleeding were TIPS (transjugular