정우진 문맥압항진성위병증및기타출혈관리 류출혈은전체상부위장관출혈 의 30-40% 정도를차지하는것으로 보고되며위또는십이지장궤양에 의한것으로보고되고있다. 5,6 2010년 1월에서 2011년 12월까지계명대학교동산병원응급실로토혈또는흑색변을주소로위장관출혈로평가받은 227명의환

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PG 2 PG Course 2012 Portal Hypertension 문맥압항진성위병증및기타출혈관리 계명대학교의과대학내과학교실 정우진 Management of Portal Hypertensive Gastropathy and Other Bleeding Woo Jin Chung Department of Internal Medicine, Keimyung

1 PG 2 PG Course 2012 Portal Hypertension 문맥압항진성위병증및기타출혈관리 계명대학교의과대학내과학교실 정우진 Management of Portal Hypertensive Gastropathy and Other Bleeding Woo Jin Chung Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea A major cause of cirrhosis related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Less common causes of gastrointestinal bleeding are peptic ulcers, malignancy, angiodysplasia, etc. Upper gastrointestinal bleeding has been classified according to the presence of a variceal or non-variceal bleeding. Althought non-variceal gastrointestinal bleeding is not uncommon in cirrhotic patients, gastroduodenal ulcers may develop as often as non-cirrhotic patients. Ulcers in cirrhotic patients may be more severe and less frequently associated with chronic intake of non-steroidal anti-inflammatory drugs, and may require more frequently endoscopic treatment. Portal hypertensive gastropathy (PHG) refer to changes in the mucosa of the stomach in patients with portal hypertension. Patients with portal hypertension may experience bleeding from the stomach, and pharmacologic or radiologic interventional procedure may be useful in preventing re-bleeding from PHG. Gastric antral vascular ectasia (GAVE) seems to be different disease entity from PHG, and endoscopic ablation can be the first-line treatment. Key words: Liver cirrhosis, Portal hypertensive gastropathy, Gastric antral vascular ectasia 서 론 위장관출혈은그사망률이 4-15% 까지도보고되는생존을위협하는요소인데, 1-4 간경변증환자에서는간경변증이없는경우에서와비교하였을때좀더높은출혈의가능성을가지게된다. 그원인중상당부분은식도정맥류와위정맥류에서의출혈이주요한요인으로차지하고있고정맥류이외의출혈의원인으로는간경변증이없는경우에서와마찬가지로위, 십이지장궤양출혈이주요한부분을차지하고있으며, 그외문맥압항진성위병증, 위전정부혈관확장증등이원인으로차지하고있다. 문맥압항진성위병증이나위전정부혈관확장증등의기전은아직까지분명치않으며치료또한원인에따라다를수있어서이러한상태에대한좀더명확한이해가요구된다. 1. 간경변증환자에서의위장관출혈 간경변증환자에서의위장관출혈은크게정맥류출혈과비정맥류출혈로분류되어질수있으며, 비정맥 66

정우진 문맥압항진성위병증및기타출혈관리 류출혈은전체상부위장관출혈 의 30-40% 정도를차지하는것으로 보고되며위또는십이지장궤양에 의한것으로보고되고있다. 5,6 2010년 1월에서 2011년 12월까지계명대학교동산병원응급실로토혈또는흑색변을주소로위장관출혈로평가받은 227명의환자를대상으로분석하였을때 26.

Prevalence of gastrointestinal bleeding patients with or without accompanying liver cirrhosis who visited emergency room at Keimyung university Dongsan hospital between Jan. 2010 and Dec.2011.

4%). 혈관이형성 (1.2%) 등이었다. 간경변증환자에서는식도정맥류출혈 (50%), 위궤양 (24.2%), 십이지장궤양 (7.6%), 위정맥류 (4.5%) 등이었으며, 정맥류출혈을배제했을경우위궤양 (64%), 십이지장궤양 (20%), Mallory-Weiss syndrome (4%), 위와십이지장궤양 (4%) 등이원인이었다 (Figure 2).

2% Causes of GI bleeding Prevalence Esophageal varix 50% Gastric ulcer 24.2% Duodenal ulcer 7.6% Gastric varix 4.5% others 13.7% others 4.

2 정우진 문맥압항진성위병증및기타출혈관리 류출혈은전체상부위장관출혈 의 30-40% 정도를차지하는것으로 보고되며위또는십이지장궤양에 의한것으로보고되고있다. 5,6 2010년 1월에서 2011년 12월까지계명대학교동산병원응급실로토혈또는흑색변을주소로위장관출혈로평가받은 227명의환자를대상으로분석하였을때 26.8% 의 Patients Prevalence Liver cirrhosis 26.8% Non-LC 73.2% Figure 1. Prevalence of gastrointestinal bleeding patients with or without accompanying liver cirrhosis who visited emergency room at Keimyung university Dongsan hospital between Jan and Dec 환자는간경변증환자였으며나머지 73.2% 의환자는간경변증을동반하지않은환자들이었다 (Figure 1). 간경변증이동반되지않은환자에서의출혈의원인을분석해보면위궤양 (54.2%), 십이지장궤양 (12.7%), Mallory-Weiss syndrome (12.7%), 위암 (10.8%), 위와십이지장궤양 (5.4%), 그리고 Dieulafoy s lesion (2.4%). 혈관이형성 (1.2%) 등이었다. 간경변증환자에서는식도정맥류출혈 (50%), 위궤양 (24.2%), 십이지장궤양 (7.6%), 위정맥류 (4.5%) 등이었으며, 정맥류출혈을배제했을경우위궤양 (64%), 십이지장궤양 (20%), Mallory-Weiss syndrome (4%), 위와십이지장궤양 (4%) 등이원인이었다 (Figure 2). Causes of GI bleeding Prevalence Gastric ulcer 54.2% Duodenal ulcer 12.7% Mallory-Weiss Syndrome 12.7% Gastric cancer 10.8% G. ulcer & D. ulcer 5.4% others 4.2% Causes of GI bleeding Prevalence Esophageal varix 50% Gastric ulcer 24.2% Duodenal ulcer 7.6% Gastric varix 4.5% others 13.7% others 4.2% Causes of GI bleeding Prevalence Gastric ulcer 64% Duodenal ulcer 20% Mallory-Weiss Syndrome 4% G. ulcer & D. ulcer 4% others 8% others 4.2% Figure 2. Analysis of gastrointestinal bleeding causes of patients with or without accompanying liver cirrhosis who visited emergency room at Keimyung university Dongsan hospital between Jan and Dec Prevalence of bleeding causes in patients without liver cirrhosis (A) and with liver cirrhosis (B). Prevalence of non-variceal bleeding causes in patients with liver cirrhosis (C). 67

3 Postgraduate Course 2012 간경변증환자에서의위또는십이지장궤양의기전은간경변증을동반하고있지않은경우에서와비교하여서로다른기전에의한것으로보고되는데, 간경변증을동반하고있지않은경우노령, 만성적인비스테로이드성소염진통제의복용, Helicobacter pylori의감염등이주요한원인으로작용하지만, 간경변증환자에서는알코올의섭취나문맥압항진이주요한원인으로보고된다. 7,8 그이외에도문맥압항진성위병증 (Portal hypertensive gastropathy, PHG) 과위전정부혈관확장증 (Gastric antral vascular ectasia, GAVE) 에의해서도출혈이가능하다. 2. 간경변증환자에서의소화성궤양간경변증환자에서의소화성궤양유병률은 4.3% 에서 49% 까지보고되기도하며, 9,10 국내연구에서는 24.3% 에서 38.3% 로서양의보고들보다높게보고되었다. 11,12 간경변증이진행되어잔여간기능이감소할수록소화성궤양의발생빈도는더증가되며, H2 수용체길항제로치료시에치료속도가늦고치료중단시뿐만아니라치료중에도간경변증이없는경우와비교하여높은 1년이내의높은재발률이보고된다 (17-20% vs %). 9 간경변증환자에서는문맥고혈압에의한위점막미세순환의변화에의한울혈및신생혈관생성의장애가동반되면서위산이나담즙등의공격인자에대한방어기전의약화가된다. 13,14 간경변증환자에서 Helicobacter pylori 의감염이소화성궤양의발생위험인자로주요한역할을하는것으로보고된다. 10 하지만, 제균이후의재발에관하여서는간경변증이없는경우와좀다른결과를보여주는데, 십이지장궤양을가진간경변증환자에서제균치료 1 년후 58% 의재발을보여주었고 15 또다른연구에서도 소화성궤양을가진간경변증환자에서제균치료 2 년내에 41% 에서궤양의재발을보고하여간경변증을가 진경우에서소화성궤양의재발은제균치료의성공보다는잔존간기능의정도나정맥류출혈유무가위험 인자일수있음을보고하였다 간경변증환자에서의문맥압항진성위병증문맥압항진성위병증이란문맥고혈압을가진환자의위장점막의변화를언급하는것으로이러한점막의변화로는점막의 friability와점막표면으로확장된혈관들의존재로나타날수있다 (Figure 3). 이러한문맥압항진성위병증의빈도는통일된진단기준이마땅치않아보고자에따라 9% 에서 80% 에까지다양하게보고하고있는데, 위병증은질병의유병기간, 식도, 위정맥류의존재여부와크기, 이전식도정맥류에의경화치료병력과상호비례관계를보이는것으로보고되기도하는데, 실제로위병증에서출혈을하는경우는상대적으로흔하지않으며, 심한출혈을유발하는경우는드문것으로언급된다. 21 최근에는문맥압항진성위병증의진단또는중증도를분류하는방법으로 Baveno consensus workshop에서 제안된 2 단계분류가주로이용되고있는데 (Table 1), 22 평균 18 개월가량의추적관찰을하였을때 29% 정도 에서는변화없이유지되었고, 23% 에서는좀더악화를, 23% 에서는호전이, 그리고 25% 정도에서는상황에 68

Portal Hypertensive Gastropathy Scoring System Proposed by Baveno III Consensus Workshop Parameter 1. Mucosal mosaic pattern Mild Severe 2. Red markings Isolated Confluent 3.

4 정우진 문맥압항진성위병증및기타출혈관리 A B Figure 3. Representative images of mild (A) and severe (B) portal hypertensive gastropathy. 따라악화또는완화됨이보고되었다. 21 문맥압항진증이발생하면문맥으로의혈류가위장쪽으로역류가발생하여혈류의정체가일어나게됨이문맥압항진성위병증발생의일차적인원인으로평가된다 하지만, 문맥압의항진의정도와문맥압항진성위병증의중증도와의관련에관하여서는아직도명확하지않으며, 17,18,23 실제임상적인의미가있는위장관출혈과관련된발생원인에관해서는위장점막의혈역학적변화 Table 1. Portal Hypertensive Gastropathy Scoring System Proposed by Baveno III Consensus Workshop Parameter 1. Mucosal mosaic pattern Mild Severe 2. Red markings Isolated Confluent 3. Gastric antral vascular ectasia Absence Presence Mild portal hypertensive gastropathy 3. Severe portal hypertensive gastropathy 4. Score 로인한위장점막공격인자의증가와방어인자의감소가출혈을조장하는또다른요소일것으로추정되고있다. 18 문맥압항진성위병증의경우에서약 10% 정도에서는만성출혈로인한빈혈을유발하는것으로보고되며, 급성출혈을경험하는경우는 2.5% 정도로보고되고, 출혈과관련된사망률은 12.5% 정도로보고된다. 21 따라서일부의환자에서는문맥압을낮추어주기위한약물치료등이요구되어질수있다. 비선택적베타차단제는문맥압항진성위병증의중증도를낮추고재출혈을방지함으로써환자의삶의질을개선시킬수있는것으로보고되며 24 급성출혈의경우에서는문맥압항진증의치료에사용되는 octreotide와 somatostatin 등의약물이매우효과적인것으로보고된다. 25 그외에문맥압을낮추는경경정맥간내문맥정 맥단락술도문맥압항진성위병증의중증도를호전시키며, 이로인한재출혈의빈도를감소시키는것으로보고된다. 26 Helicobacter pylori 의존재와문맥압항진성위병증과의상관관계는명확지않기때문에문맥압항진성위병증의치료에있어서제균치료의필요성에대한근거는아직명확지않고 27 PPI의사용이문맥압항진성위병증에의한궤양의발생및출혈의발생을줄여줄수있는지에대한근거또한명확하지않다

5 Postgraduate Course 간경변증환자에서의위전정부혈관확장증위전정부혈관확장증은위전정부등에서의작은혈관확장과연관되어만성적인위장관출혈과철분결핍성빈혈을유발할수있는질환이다. 이러한질환은내시경검사소견에서전정부에의붉은선상으로의혈관확장소견이관찰되며, 병리학적으로는확장된모세혈관, 섬유근조직이형성, 섬유소혈전, 섬유유리화등이특징적인소견으로관찰된다. 29 앞서언급된문맥압항진성위병증과비교하였을때위체부와위전정부로그발생부위가다르며, 문맥압을감소시키는치료가문맥압항진성위병증을개선시킬수있으나, 위전정부혈관확장증은호전이되지않으므로이두질환은서로다른질환군으로언급되기도한다 위전정부혈관확장증환자의약 30% 가량은간경변증환자에서발생하며 29 간이식이필요한비대상성간경변증환자의약 2.5% 에서위전정부혈관확장증이동반된다고보고된다. 발생기전으로는위전정부의운동성변화, 국소적으로분비되는혈관활성화물질등이관여하는것으로보고되고있으나아직그명확한기전은명확하지않으며, 치료또한내시경을통한플라스마응고소작술같은국소치료법을통하여일차적으로시도할수있으며, 33 이러한치료에반응하지않는경우위전정부절제술이나 estrogen-progesteron과같은호르몬치료등을고려해볼수있다. 30,31,34 결 론 간경변증환자에서는간경변증이없는경우에서와비교하였을때좀더높은출혈의빈도를보이게되는데, 그중상당부분은식도정맥류와위정맥류에서의출혈이주요한요인으로차지하고있다. 정맥류이외의출혈의원인으로는간경변증이없는경우에서와마찬가지로위, 십이지장궤양출혈이주요한부분을차지하고있으며, 그외문맥압항진성위병증, 위전정부혈관확장증등이원인으로차지하고있다. 문맥압항진성위병증이나위전정부혈관확장증등의기전은아직까지분명치않으며치료또한원인에따라다를수있어서이러한상태에대한좀더명확한이해가요구된다. 참고문헌 1. Laine L. Upper gastrointestinal bleeding. Clinical Update American Society of Gastrointestinal Endoscopy 2007; 14: Rockall TA, Logan RF, Devlin HB, Northfield TC. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ 1995;311: Sung JJ, Tsoi KK, Ma TK, Yung MY, Lau JY, Chiu PW. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases. Am J Gastroenterol 2010; 105: Czernichow P, Hochain P, Nousbaum JB, Raymond JM, Rudelli A, Dupas JL, et al. Epidemiology and course of acute upper gastro-intestinal haemorrhage in four French geographical areas. Eur J Gastroenterol Hepatol 2000;12:

6 정우진 문맥압항진성위병증및기타출혈관리 5. Christensen E, Fauerholdt L, Schlichting P, Juhl E, Poulsen H, Tygstrup N. Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone. Gastroenterology 1981; 81: Garden OJ, Motyl H, Gilmour WH, Utley RJ, Carter DC. Prediction of outcome following acute variceal haemorrhage. Br J Surg 1985; 72: Yeomans ND. The ulcer sleuths: The search for the cause of peptic ulcers. J Gastroenterol Hepatology 2011; 26(Suppl.1): Auroux J, Lamarque D, Roudot-Thoraval F, Deforges L, Chaumette MT, Richardet JP, et al. Gastroduodenal ulcer and erosions are related to portal hypertensive gastropathy and recent alcohol intake in cirrhotic patients. Dig Dis Sci 2003; 48: Siringo S, Burroughs AK, Bolondi L, Muia A, Di Febo G, Miglioli M, et al. Peptic ulcer and its course in cirrhosis: an endoscopic and clinical prospective study. J Hepatol 1995;22: Vergara M, Calvet X, Roque M. Helicobacter pylori is a risk factor for peptic ulcer disease in cirrhotic patients. A metaanalysis. Eur J Gastroenterol Hepatol 2002;14: Kim DJ, Kim HY, Kim SJ, Hahn TH, Jang MK, Baik GH, et al. Helicobacter pylori infection and peptic ulcer disease in patients with liver cirrhosis. Korean J Intern Med 2008;23: Jung SW, Lee SW, Hyun JJ, Kim DI, Koo JS, Yim HJ, et al. Efficacy of Helicobacter pylori eradication therapy in chronic liver disease. Dig Liver Dis 2009;41: McCormack TT, Sims J, Eyre-Brook I, Kennedy H, Goepel J, Johnson AG, et al. Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy? Gut 1985;26: Hashizume M, Tanaka K, Inokuchi K. Morphology of gastric microcirculation in cirrhosis. Hepatology 1983;3: Lo GH, Yu HC, Chan YC, Chen WC, Hsu PI, Lin CK, et al. The effects of eradication of Helicobacter pylori on the recurrence of duodenal ulcers in patients with cirrhosis. Gastrointest Endosc 2005;62: Tzathas C, Triantafyllou K, Mallas E, Triantafyllou G, Ladas SD. Effect of Helicobacter pylori eradication and antisecretory maintenance therapy on peptic ulcer recurrence in cirrhotic patients: a prospective, cohort 2-year follow-up study. J Clin Gastroenterol 2008;42: Ripoll C, Garcia-Tsao G. Management of gastropathy and gastric vascular ectasia in portal hypertension. Clin Liver Dis 2010;14: Perini RF, Camara PR, Ferraz JG. Pathogenesis of portal hypertensive gastropathy: translating basic research into clinical practice. Nat Clin Pract Gastroenterol Hepatol 2009;6: Thuluvath PJ, Yoo HY. Portal Hypertensive gastropathy. Am J Gastroenterol 2002;97: Burak KW, Lee SS, Beck PL. Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) syndrome. Gut 2001;49: Primignani M, Carpinelli L, Preatoni P, Battaglia G, Carta A, Prada A, et al. Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC). Gastroenterology 2000;119: de Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol 2000;33: Kim MY, Choi H, Baik SK, Yea CJ, Won CS, Byun JW, et al. Portal hypertensive gastropathy: correlation with portal hypertension and prognosis in cirrhosis. Dig Dis Sci 2010;55: Pérez-Ayuso RM, Piqueé JM, Bosch J, Panés J, González A, Pérez R, et al. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. Lancet 1991;337: Zhou Y, Qiao L, Wu J, Hu H, Xu C. Comparison of the efficacy of octreotide, vasopressin, and omeprazole in the control of acute bleeding in patients with portal hypertensive gastropathy: a controlled study. J Gastroenterol Hepatol 2002;17: Mezawa S, Homma H, Ohta H, Masuko E, Doi T, Miyanishi K, et al. Effect of transjugular intrahepatic portosystemic shunt formation on portal hypertensive gastropathy and gastric circulation. Am J Gastroenterol 2001;96: Zullo A, Hassan C, Morini S. Helicobacter pylori infection in patients with liver cirrhosis: facts and fictions. Dig Liver Dis 2003;35: Takeuchi Y, Kitano S, Bandoh T, Matsumoto T, Baatar D, Kai S. Acceleration of gastric ulcer healing by omeprazole in portal hypertensive rats. Is its action mediated by gastrin release and the stimulation of epithelial proliferation? Eur Surg Res 2003;35:

7 Postgraduate Course Ward EM, Raimondo M, Rosser BG, Wallace MB, Dickson RD. Prevalence and natural history of gastric antral vascular ectasia in patients undergoing orthotopic liver transplantation. J Clin Gastroenterol 2004;38: Selinger CP, Ang YS. Gastric antral vascular ectasia (GAVE): an update on clinical presentation, pathophysiology and treatment. Digestion 2008;77: Sebastian S, O'Morain CA, Buckley MJ. Review article: current therapeutic options for gastric antral vascular ectasia. Aliment Pharmacol Ther 2003;18: Spahr L, Villeneuve JP, Dufresne MP, Tassé D, Bui B, Willems B, et al. Gastric antral vascular ectasia in cirrhotic patients: absence of relation with portal hypertension. Gut 1999;44: Lecleire S, Ben-Soussan E, Antonietti M, Goria O, Riachi G, Lerebours E, et al. Bleeding gastric vascular ectasia treated by argon plasma coagulation: a comparison between patients with and without cirrhosis. Gastrointest Endosc 2008;67: Tran A, Villeneuve JP, Bilodeau M, Willems B, Marleau D, Fenyves D, et al. Treatment of chronic bleeding from gastric antral vascular ectasia (GAVE) with estrogen-progesterone in cirrhotic patients: an open pilot study. Am J Gastroenterol 1999;94:

김범수

김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis