Revisiting gastric varix Transjugular intrahepatic portosystemic shunt for gastric variceal bleeding Young Hwan Kim Department of Radiology, Dongsan Medical Center, Keimyung University School of Medicine, Korea Gastric variceal bleeding is a life-threatening condition that requires a multidisciplinary approach for effective therapy. Most of variceal bleeding can be successfully controlled by endoscopy. Nevertheless, the role of interventional radiology is necessary if hemostasis is not achieved by endoscopy. Interventional treatment for variceal bleeding can be roughly classified into two types: shunt creation (TIPS) and shunt occlusion (Balloon Occluded Retrograde Transvenous Obliteration, BRTO). TIPS procedure involves establishment of a direct pathway between the hepatic vein and the portal vein to decompress the portal hypertension that is the source of the patient s hemorrhage. The role of TIPS in the management of gastric variceal bleeding that is refractory to endoscopic therapy as well as secondary prophylaxis of variceal bleeding is well established. Although TIPS is highly effective in controlling variceal bleeding, it carries a risk of hepatic encephalopathy and poor shunt patency. Recently, TIPS procedure has been revolutionized by the introduction of PTFE-covered stent graft, which dramatically improves long-term shunt patency compared to bare metal stent. Moreover, shunt occlusion therapy such as BRTO has been a valuable alternative to TIPS in patient with severe hepatic encephalopathy or poor hepatic reserve. Index words: Gastric varices, Variceal bleeding, Transjugular intrahepatic portosystemic shunt 서론 위정맥류는문맥고혈압환자중 30% 에서발생하는합병증으로출혈률은 10-36% 정도로식도정맥류에비하면적지만한번출혈을하면사망률이 14-45% 로식도정맥류출혈보다위험하다. 1,2 또한위정맥류는위신단락 (gastrorenal shunt) 을동반한경우가많아문맥과전신정맥사이의압력차이 (portosystemic pressure gradient) 가 12 mmhg 이하에서도출혈을할수있다. 위정맥류출혈의치료방법으로는내과적약물치료, 경화술과결찰술을포함한내시경적치료, 중재적시술, 수술적단락형성등이있다. 수술적단락술은응급으로시행할경우시술과관련된사망률이높은단점이있어점차감소되고있다. 따라서위정맥류출혈의 1차적치료는내시경적치료와내과적약물치료이며지혈에실패하였을때중재적치료가이용될수있다. 또한 TIPS와같은중재적치료는내시경에비해재출혈의빈도가낮기때문에일차적출혈후이차재출혈을막기위해서도시행될수있다. 3 문맥압항진증에의한정맥류출혈의중재적치료방법에는 TIPS, 역행성경정맥위정맥류폐색술 (Balloon-Occluded Retrograde Transvenous Obliteration for Gastric Variceal 88 대한간학회
김영환 Transjugular intrahepatic portosystemic shunt for gastric variceal bleeding Bleeding, BRTO), 피부간경유정맥류색전술 (Percutaneous Transhepatic Variceal Obliteration, PTVO) 등이있다. PTVO 는문맥고혈압을감압시키지못하여재출혈이흔하고장기간의생존연장에는크게도움이되지않아현재사용이제한적이다. 4 하지만최근경화제로 N-butyl cyanoacrylate가소개되면서재출혈의빈도를낮출수있을것으로기대되어 TIPS나 BRTO의시행이기술적으로나임상적으로어려운환자에서시행이되고있다. 5,6 TIPS는위정맥류출혈의원인인문맥압을낮출수있고동반된문맥고혈압의합병증을동시에치료할수있기때문에내시경적경화술이실패하거나특히위정맥류와같이내시경적경화술이어려운경우많이이용되고있다. 최근에는 BRTO가소개되면서 TIPS에비해안전하며재출혈의빈도가적고간성뇌병증 (hepatic encephalopathy) 도치료할수있는장점이있어위정맥류출혈의중재적치료방법으로많이이용되고있다. 7,8 TIPS의기본원리는외과적문맥하대정맥단락술과동일하며간문맥과간정맥사이에스텐트를설치하여문맥전신션트 (portosystemic shunt) 를만들어문맥전신정맥압차이를 12 mmhg 이하로문맥압을감압시키는것이목적이다. 이로인해정맥류혈류를감소시켜출혈을조절하며출혈이외의문맥고혈압의합병증들을치료하여주는것이다. 그러나인위적인문맥전신션트에따른합병증들이발생할수있다는문제점도있다. TIPS 후의혈역학적변화양상은문맥전신션트로인한문맥관류 (portal perfusion) 의감소를보상하기간동맥혈류 (hepatic artery blood flow) 가보상적으로증가하여전체적인간관류 (hepatic perfusion) 에는큰변화가없으나 9 일시적인간세포손상 (transient hepatocellular damage) 으로인해 bilirubin, transaminase, prothrombin time, ammonia 등이증가할수있다. 특히간동맥혈류의보상작용이불충분할경우간으로의혈류감소로인해점진적인간부전 (progressive hepatic failure) 이발생할수있고간성뇌병증이올수있다. 또한문맥전신션트를통해체정맥으로의혈류가증가하여중심정맥압이증가한다. 이러한 TIPS후의혈역학적변화를이해하면적응증과비적응증을쉽게이해할수있다. 적응증 TIPS의적응증은 1) 내시경적치료로지혈되지않는정맥류출혈, 2) 위정맥류출혈후재출혈예방 (secondary prevention of variceal bleeding), 3) 조절이되지않는복수, 4) Budd-Chiari 증후군, 5) 문맥고혈압성위병증 (Portal hypertensive gastropathy), 6) 간성수흉증 (hepatic hydrothorax), 7) 간폐증후군 (hepatopulmonary syndrome), 8) 간신증후군 (hepatorenal syndrome) 등이다. 10-13 비적응증 절대적금기로는출혈하지않은정맥류의출혈예방 (primary prevention of variceal bleeding), 우측심부전, 심한폐동맥고혈압, 심한삼천판역류 (severe tricuspid regurgitation, 조절되지않은담폐혈증등이다. 13 심한 www.kasl.org 89
제 22 차대한간학회추계학술대회 간부전 (Child Pugh class C, model for end-stage liver disease score > 22, serum bilirubin > 3 mg/dl) 을가진환 자에서 TIPS가생존에도움이되는지는여전히불명확하다. 14 그외상대적금기로는감염, 만성문맥혈전, 간성뇌병증, 낭포성간질환 (cystic liver disease) 등이다. 10-12,14 시술방법 TIPS 시술전초음파검사나컴퓨터단층촬영 (Computed Tomography, CT) 을통해간문맥과간정맥의해부 학적관계와간문맥혈전여부, 천자경로에간암존재여부에대한평가를한다. 시술방법은우측내경정 맥 (internal jugular vein) 을천자하여 ring transjugular intrahepatic access set (Cook, Bloomington, IN, USA) 내에 있는 9-F 안내도관 (introducer) 을삽입한다음 5-F 카테타로우간정맥을선택한다. 16-G transjugular needle 로 우간정맥에서우측주문맥을천자하여 5-F 카테타를비장정맥에삽입한후문맥조영술과문맥압을측정 한다. 우간정맥을이용하는이유는직경이크고우측문맥과가장가까이있고일정하게문맥의상후방에 위치하고있기때문에우간정맥에서전하방을향해천자를하면문맥천자를쉽게할수있다. 15 경우에따 라서는중간정맥이나좌간정맥을이용할수있으며문맥분지나좌측문맥을천자하는경우도있다. 가급 적이면술후조기단락폐쇄의원인인급성혈전형성을예방하기위해서간내천자경로가직선이되며 천자경로를짧게하는것이필요하다. 문맥천자시가장주의해야할것은간피막외문맥을천자하여 풍선으로확장시킨후에발생하는복강내출혈이다. Schultz 등 16 은사체에서주문맥분지부위가간피막 외에존재하는경우가 48%, 피막에존재하는경우가 25% 이며좌우주문맥이피막외에존재하는최장길 이가각각 2.5 cm, 3 cm 으로보고하였다. 그러나이는개인에따라변이가있으므로시술도중반드시확인 하여야한다. 적절한문맥이천자되었으면천자경로를풍선카테타로확장시킨후적절한직경 (8-10 mm) 의스텐트를삽입한다. 스텐트삽입시유의할점은간정맥벽의협착이지연단락폐쇄부위중가장많기 때문에하대정맥근처의간정맥까지스텐트를연장하여위치시키는것이스텐트의개통성을오래유지시키 는데도움이된다. 17 또한간이식수술의가능성이있는환자의경우하대정맥내나주문맥내에는스텐트 를삽입하지않는것이적절하다. 정맥류출혈의경우시술후문맥전신정맥압력차이를 12 mmhg 이하로 조절해주어야재출혈을예방할수있으며, 조절되지않은복수의경우이론의여지가있지만 8 mmhg이하로낮추어줄것을권장하고있다. 10 TIPS시술만으로도대부분의경우혈류역학적으로현저한개선이이루 어지나, 시술자에따라서 TIPS시술중지속적인저명한정맥류혈류가보이는경우충분한지혈과위정맥류 10, 18, 19 재출혈빈도를낮추기위해다양한색전물질을이용한정맥류색전술을시행하기도한다. 합병증 TIPS 의합병증은시술과연관되어생길수있는합병증, 스텐트자체에의한합병증, 문맥전신션트효과 90 대한간학회
김영환 Transjugular intrahepatic portosystemic shunt for gastric variceal bleeding 에의한합병증등으로나누어볼수있다. 20 시술과관련되어생길수있는합병증으로는우측내경정맥천자시경동맥천자나기관천자그리고천자부위의혈종형성, 출혈등이있을수있으며간정맥을통한간내문맥으로의접근과정중간내담도천자로인한혈액담즙증과조기단락폐색, 담낭천자, 우측신장천자, 심부정맥, 간동맥손상, 간외문맥천자등이발생할수있고, 또한조영제에의한과민반응, 급성신부전, 폐혈증, 일시적간기능효소치증가등이있을수있다. 이중가장위험한합병증은간외문맥의천자와이의풍선확장술에의한대량의복강내출혈이다. 그러므로시술중이를반드시확인하여야한다. 또한천자경로에간세포암이존재하는경우시술의상대적금기사항이므로초음파나 CT를통해혈관해부학적위치와경로에간세포암존재에대해미리확인을하여야합병증을줄일수있다. 스텐트와연관된합병증으로는급성또는지연성스텐트내강의폐쇄혹은협착, 스텐트의부적절한위치선정, 스텐트의위치이동, 길이단축등이있다. 문맥전신션트효과에의한합병증으로는간성뇌병증의발생또는기존의간성뇌병증의악화, 간기능부전의악화등이있다. 간성뇌병증의빈도는진단기준에따라다양하며 25-30% 에서발생또는악화되는것으로보고되고있다. 12 간성뇌병증은고식적치료로대부분호전되나 3-7% 에서는내과적치료에반응하지않는경우도있다. 이러한경우코일이나혈관플러그 (vascular plug) 를스텐트내부에위치시킴으로서스텐트내부에혈전을유발하여단락을인위적으로폐색시키거나스텐트그라프트 (stent graft) 를이용하여단락의직경을감소시킬수있다. 21 결과 TIPS 의기술적성공률은시술의숙련도에따라다르나 93-100% 로되어있으며시술과관련된사망률은 0-2%, 30 일사망률은 3-15% 로보고되고있다 (12, 22-28). 30 일사망률 (early mortality) 에영향을미치는요소 들로는응급 (emergent) TIPS, Child-Pugh score 12 점이상, alanine aminotransferase 100 IU/L 이상, total bilirubin 3.0 mg/dl 이상, TIPS 전 encephalopathy history 있는경우, APACHE(acute physiology and chronic health evaluation) II score 18 이상, model for end-stage liver disease (MELD) score 18 이상등이있다. 13, 26-28 시술후 추적관찰에서사망의원인으로는악화된간부전이가장많으며급성호흡부전증후군, 신부전, 정맥류재출 혈등이있다. TIPS 시술후 1년, 2년, 3년, 5년생존율은각각 61-71%, 51-60%, 49-50%, 41-42% 로보고되어 22, 29-31 있으며 Child A, B와 C군간에는생존율에있어서통계학적으로유의한차이를보인다. TIPS 후장기추적관찰에서중요한문제점은단락의폐색또는협착으로인한정맥류의재출혈이다. TIPS 후 1 년, 2 년, 4 년, 5 년일차개통률 (primary patency rate) 은각각 22-66%, 17-42%, 12-13%, 12-13% 이며일 차보조개통률 (primary assisted patency rate) 은각각 67-83%, 61-79%, 42-51%, 36-46% 이며이차개통률 (secondary patency rate) 은각각 85-96%, 64-90%, 55-83%, 55-83% 로보고되어있는반면 22, 29, 30, TIPS 후 1년, 2 22, 29, 31 년정맥류재출혈률의경우각각 20-26%, 21-32% 로보고되어있다. 그러므로정맥류재출혈이나복 수의증가등이단락의기능장애를시사하는증상이지만단락의협착이있다하더라도항상재출혈이일 어나는것은아니다. 따라서증상이나타나기전에추적도플러초음파검사를시행하여야단락의이상을 www.kasl.org 91
제 22 차대한간학회추계학술대회 조기에진단할수있으며이때재개통술을시행함으로써재출혈의빈도를줄일수있다. 시술후 30일이내의단락폐색은단락내혈전폐색이원인이며부적절한스텐트설치와같은기술적인결함으로인한경우가많고담도손상에의한담즙누출로인해발생할수도있다. 30일이후의협착이나폐색은조직학적으로가성내막증식 (pseudointimal hyperplasia) 에의해발생한다. 협착은주로단락의간정맥끝부위에서가장흔히발생하고단락내부에서두번째로흔히발생한다. 32 특히스텐트의위치를간정맥내에위치시킬경우잘올수있으며이는스텐트의길이감소 (shortening) 로인해스텐트끝이간실질경로 (parenchymal tract) 내로들어가거나, 간문맥의높은혈속의혈류가간정맥에서와류 (tuberlent flow) 를형성하여전단력 (shear stress) 을간정맥측에서받기때문이며이로인해가성내막증식이발생한다. 17 또한스텐트내폐쇄를일으키는가성내막증식의주요한원인이문맥천자도중의담도손상이라는증거들이발견되고있으며 33, 34, 담도천자는가성내막증식의주요한원인일뿐아니라담즙의성분인점액 (mucin) 과음이온담즘산염 (anionic bile salt) 이그자체로써혈전형성을촉진하여급성 TIPS 스텐트폐쇄혹은협착을일으킬수있다. 이러한시술과정중의담도천자가단락술경로폐쇄를일으킬수있다는사실은스텐트그라프트에대한연구를촉진하게되었으며여러다양한그라프트재료들이임상과동물실험에사용되어근래에는 PTFE 피복 (polytetrafluoroethylene covered) 스텐트그라프트개발로담즙의혈관내유입을막아스텐트의개존성을높일수있다는보고들이나오고있다. 35-39 2007년보고된 PTFE 피복스텐트그라프트와노출금속스텐트 (bare metal stent) 를비교해서 2년추적관찰이된무작위대조군연구에의하면일차개존율이각각 76% 와 36% 이며임상증상의재발은 10% 와 29%, 간성뇌병증의발생은 33% 와 49% 로 PTFE 피복스텐트그라프트가개존률이높고간성뇌병증의발생이적은것으로알려져있다. 40 최근보고된메타분석 (meta-analysis) 에서도피복스텐트그라프트가노출금속스텐트에비해사망률이낮으며간성뇌병증발생도적은것으로밝혀져 TIPS시술시 PTFE 피복스텐트그라프트를권장하고있다. 41 단락폐색이나협착에의한재출혈의경우부가적스텐트또는풍선확장술등으로재개통시술을할수있으며재개통이어려울때는재시술을시행할수있다. 42 결론 TIPS는 BRTO와더불어내과적치료에실패한정맥류출혈의치료에상호보완적으로시행할수있는안전하고효과적인치료방법이다. 특히 BRTO를시행하기어려운위신단락이없는경우나위정맥류출혈과동반된문맥압항진증에의한합병증등이있을때유용한방사선적중재술이다. 43 최근 PTFE 피복스텐트그라프트의개발로인해그동안문제가되었던잦은단락협착에의한재출혈의빈도와간성뇌병증의발병이줄어들고있어위정맥류출혈의재발방지를위해서도여전히효과적인시술이라할수있다. 92 대한간학회
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