대한내과학회지 : 제 74 권제 5 호 2008 종설 (Review) FibroScan 을이용한간탄력도검사 연세대학교의과대학내과학교실, 간경변증임상연구센터 한광협 김승업 Liver stiffness measurement using FibroScan KwangHyub Han, M.D. and Seung Up Kim, M.D. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Liver Cirrhosis Clinical Research Center, Seoul, Korea Progressive liver fibrosis is a similar feature of all chronic liver diseases and eventually develops liver cirrhosis. The prognosis and treatment plans of chronic liver diseases depend strongly on the degree of liver fibrosis. These facts raise clinical interests in quantifying liver fibrosis. Although liver biopsy has been the gold standard for assessment of liver fibrosis, it has some technical limitations and risks. Accordingly, an increasing need for alternative noninvasive method to quantify liver fibrosis has been a major challenge that has stimulated search for new noninvasive methods. Such methods for diagnosing liver fibrosis have progressed significantly over the last few years notably with the appearance of several serological markers which have been reported to predict the presence of significant fibrosis or cirrhosis in patients with chronic liver disease with considerable accuracy. However, complicated calculation, cost problems, and influences of extrahepatic conditions make it less accessible to clinicians. Recently, liver stiffness measurement using FibroScan is emerging as a new diagnostic method for liver fibrosis. It is totally noninvasive and reproducible and gives an immediate result without intra and interobserver variability. Its clinical use in comparison with liver biopsy and several available serologic markers is now intensively being investigated. Here, we review the currently available data on FibroScan. (Korean J Med 74:463471, 2008) Key Words : Liver fibrosis; Liver cirrhosis; Liver stiffness; Fibroscan; Transient elastography 서론만성간염에서간세포염증및괴사가지속되면간섬유화가발생하고간섬유화가더욱진행되면결국간경변증으로이행한다 1). 임상적으로만성간질환에서간경변증으로진행을막는것이치료의중요한목표이며, 이는간암을비롯한간경변증의합병증으로인한사망을감소시키므로만성간질환의진행과정에서간섬유화를평가하고간경변증을진단하는것은예후및치료방침의결정에중요한역할을한 다 24). 지금까지만성간질환의진행은주로혈액검사와초음파검사등으로확인했지만간섬유화가심하지않은경우에는이러한검사들도간섬유화의예측력에있어한계를보이고있다. 간조직생검은간섬유화와간경변증을직접적으로검사하는것으로최종적진단방법으로서의역할을했다. 하지만간조직생검은침습적인검사로시술과관련된합병증이발생할수있다 5, 6). 시술후의통증은비교적흔하며검사와관련된사망도보고되었다. 이러한문제점들로간조직 *The authors equally contributed to this work. 463
The Korean Journal of Medicine : Vol. 74, No. 5, 2008 생검을시행하려는의사나시행받는환자들에게거부감이있으며특히반복적인검사가필요할경우에는더욱간조직생검이어렵게된다. 일부간섬유화를가지고있는환자에서혈소판의저하나응고장애가동반되어있어간조직생검이금기가되는경우도있다. 이외에도검사자간또는검사자내의간조직생검결과의다양성이문제가되기도한다. 간조직생검에서충분한간조직이얻어지지않으면진단이어려운경우도있으며충분한간조직이얻어졌다하더라도간실질의전체를대변하지못할가능성은여전히남아있다. 이러한침습적인문제점으로비침습적으로간섬유화를예측하는많은모델들이개발되어왔다 79). 혈청표지자를이용한것으로간섬유화의과정에서혈청에서증가하는물질들을이용하는직접적인방법이있으며, aspartate aminotransferase (AST), alanine aminotransferase (ALT), 나이, 혈소판수등을이용하는간접적인방법이있으나복잡한수식, 비용적인문제, 그리고간외적인영향에따라서수치가변할수있는점들이여전히문제점으로지적되고있다. 최근 FibroScan 을이용한간탄력도검사가간섬유화를비침습적으로예측할수있다는많은연구결과가보고되고있다. 저자들은색인단어 FibroScan, Transient elastography, Liver stiffness 를이용하여 Medline 을검색하고현재까지보고된연구결과를분석하여간탄력도검사의임상적유용성과한계점을알아보았다. 간탄력도검사 1. 원리간탄력도검사의원리는간의단단함 (stiffness) 과간섬유화 (fibrosis) 가연관성을가지고있고간의탄력도 (elasticity) 는간의단단함과역시상관관계를가지고있다는것을이용하는것으로결과적으로간의탄력도와간섬유화는깊은상관관계를가지고있어간의탄력도측정으로간섬유화를예측할수있다는것이다 10). 간의단단함을측정하기위하여간의조직병리상태에좌우되는탄력도를이용하고압력의단위인 kilopascal (kpa) 로표현된다. 간탄력도검사기기의탐촉자는자체적으로저진동수의탄력파를만들고이렇게만들어진탄력파는늑골사이피부표면을통과하여간으로전파되고변환기 (transducer) 를통하여방출하고되돌아온초음파의이동속도를측정한다. 이동속도가빠를수록간이더단단함을시사하며간접적으로간섬유화가상대적으로진행했음을알 수있다. 간탄력도검사의장점은통증이없고비침습적이며, 쉽고빠른검사가가능하며, 약 5분만에즉시결과를얻을수있고, 재현성이높으며, 타장기의영향이없이직접간실질의탄력도를측정하고, 총간실질의약 1/500을대표한다 10). 2. 검사방법검사는식사후적어도 2시간이후에시행한다. 환자의오른팔을머리뒤로들어올리고누운상태에서간위치의우측늑간의피부표면에수직으로탐촉자를위치한다. 검사자는화면상간내혈관구조를피하여적절한 ( 약 6 cm 이상두께 ) 병소를향하여탐촉자의버튼을누른다. 측정하는간의용적은 3 cm 2 이상이다. 반복적으로최소한 10회이상반복측정하고환자가불안한증상을보이면무호흡상태에서측정할수있다. 탄력파의속도가숫자로표기된다. 10회이상측정하여자동적으로계산된중앙값과오차를기록한다. 3. 간염바이러스에의한만성간질환환자에서의간섬유화의진단간탄력도검사는만성 C형간염에서처음시행되었고최근만성 B형간염에도적용되기시작하였다. Ziol 등 11) 은 251명의만성 C형간염환자들을대상으로간탄력도를측정하여 Metavir 간섬유단계와비교하였다. 이연구에서간탄력도는간조직생검의섬유화정도와의미있는상관관계를보였다. The area of receiver operating characteristic curve (AUROC) 는 F2 이상 (significnat fibrosis) 에서 0.79, F3 이상 (advanced fibrosis) 에서 0.91, F4(cirrhosis) 에서는 0.97로간섬유화를예측하였으며각각의기준값은각각 8.8 kpa, 9.6 kpa, 14.6 kpa로보고하였다. Foucher 등 12) 은 711명의만성간질환환자들 (C형 398명, B형 43명을포함 ) 을대상으로분석을하였으며역시간탄력도와간섬유화는높은상관관계를보였다 (r=0.73). AUROC 는 F2 이상에서 0.80, F3 이상에서 0.90, F4에서는 0.96이었다. GanneCarrie 등 13) 은 1,007명의만성간질환환자들을연구하였고이연구에서 F4에대한 AUROC는 0.95였으며기준값은 14.6 kps로정하여양성예측도 74%, 음성예측도 94% 의결과를보고하였다. 저자들도국내에서처음으로 228명의만성 B형간염환자들을분석한결과를보고하였다. 간탄력도수치는비활동성보유자평균값이 7.0 kpa, 만성간염 8.3 kpa, 대상성간경변증 15.9 kpa, 비대상성간경변증 31.8 kpa, 간세포암종 45.1 kpa로 464
KwangHyub Han, et al : Liver stiffness measurement using FibroScan 보고하여간질환의진행에따라간탄력도검사의의미있는차이를확인하였다 14). 지금까지의연구결과들의섬유화정도에따른 AUROC 및기준값을표로정리하였다 ( 표 1). 4. 인체면역결핍바이러스 (Human immunodeficiency virus, HIV) 와간염바이러스에의한복합감염으로인한만성간질환환자에서의간탄력도검사의유용성 De Lédinghen 등 15) 은 HIV와 C형간염바이러스에동시감염된만성간질환환자 72명을대상으로간탄력도검사와간섬유화단계와의높은상관관계를보고하였다 (Kendall tb=0.48; p<0.0001). 이연구에서간섬유화를간접적으로예측하는표지자인 AST/ALT ratio, aspartate aminotransferase to platelet ratio index (APRI) 등의 AUROC보다의미있게높았다. Vergara 등 16) 도 HIV와 C형간염바이러스에동시감염된 169명의만성간질환환자를대상으로간탄력도검사의간섬유화예측의정확성을보고하였다. Barreiro 등 17) 은 HIV와 C형간염바이러스에동시감염된환자 283명의간탄력도를분석하였고간섬유화를예측하는인자로제3형 C 형간염바이러스, 나이, ALT 증가여부등을보고하였다. Castellares 등 18) 은 2,168명의 HIV에환자에서 12kPa을넘는경우간경변증으로정의하여간경변증의유병률, 원인및치료성과에대한후향적연구를보고하였다. Maida 등 19) 은 HIV와 C형간염바이러스가동시에감염되었으나지속적으로 AST, ALT가정상소견을보이는환자에서도 8.9% 에서는 HCVRNA가양성인것을확인하였고, 간탄력도검사를시행하였을경우 F3 이상인경우가 25% 에서관찰되어추적관찰의중요성에대해서보고하기도하였다. 5. 혈청표지자와의비교간탄력도검사는이전의혈청학적인간섬유화예측모델과비교되어예측력을평가받고있으며대부분의연구에서간탄력도의간섬유화예측력이동등하거나우월한것으로보고되고있다. Colleta 등 20) 은 40명의정상간기능을보이는만성 C형간염환자들을대상으로간탄력도검사와직접적인혈청학적표지자중하나인 FibroTest의정확도를비교하여 FibroTest보다간섬유화의예측능력이우수함을보고하였다. Castera 등 21) 도간탄력도검사와 FibroTest 및 APRI의간섬유화예측력을만성 C형간염환자 183명을대상으로분석하였고, 특히간탄력도검사와 FibroTest 를복합하였을경우예측력이가장높아지는것을확인하였다. Coco 등 22) 도 F2 이상에서간탄력도검사와 APRI, Forns index, FibroTest를비교하였고, F4에대해서는간탄력도검사와 APRI, hyaluronic acid, FibroTest를비교하여간탄력도검사의높은간섬유화예측력을보고하였다. 이처럼단독검사의간섬유화예측력의정확성을비교할뿐만아니라최근에는간탄력도검사와다른혈청학적검사들을복합함으로써간섬유화예측력을높이려는시도가활발히이루어지고있다. Castera 등 23) 은 FibroTest 와간탄력도검사또는 APRI 와복합을함으로서 C형간염바이러스에의한만성간질환에서간섬유화의예측력을분석하였고이러한결과를통해 F2 이상에서는약 50~70%, F4에서는 75% 의환자에서간섬유화를진단하기위한간조직생검을피할수있었다고보고하였다. 간탄력도검사와 FibroTest 또는혈청학적간섬유화예측모델의복합검사는정상 ALT를보이는만성 C형간염환자에서나비활동성 B형간염보균자를대상으로연구되기도하였다 2427). 하지만간탄력도검사와 FibroTest 의결과가불일치하는경우가있으며이의원인을밝히기위한연구도추가로진행되고있다 28, 29). 6. 만성간질환환자의추적관찰에있어서간탄력도검사의유용성간섬유화가진행되어간경변증이발생하게되면정맥류, 복수, 간세포암종등의합병증이발생하게된다. 이러한합병증이발생하게되면수명이단축되는결과를보여이러한합병증을조기에예측하는것은임상적으로큰의미를가진다. Foucher 등 12) 이간경변증의합병증을예측할수있는기준값을제시하였다. F23의식도정맥류를 90% 이상의음성예측도를가지고확인할수있는 27.5 kpa, Child Pugh 분류 B 또는 C를예측하는 37.5 kpa, 복수발생의과거력을유무를확인하는 49.1 kpa, 간세포암종의존재를확인하는 53.7 kpa, 그리고식도정맥류출혈을예측하는 62.7 kpa이그예이다. 그이후에도식도정맥류의존재를예측할수있는기준값들이제시되었다. Kazemi 등 30) 이 165명의간경변증을가진환자들을분석하여간탄력도검사가식도정맥류의존재여부와밀접한관계를보인다는것을보고하였다. 저자들은간세포암종의존재및향후 1~2년기간동안간세포암종발생의예측에도간탄력도검사가도움이된다는보고를하였다 31, 32). 그외에도 4 cm 이하의단일간세포암종을가지고있는환자들에서간탄력도를측정하여간세포암종이없는간경변환자에서보다의미있게간탄력 465
대한내과학회지 : 제 74 권제 5 호통권제 573 호 2008 도가높은것을확인하여간세포암종발생의위험인자로서의간탄력도검사의유용성이보고되기도하였다 33). 간정맥압력차 (hepatic venous pressure gradient, HVPG) 또는식도정맥류의존재여부를이용하여간탄력도와문맥압항진증과의관계를분석한연구들도있다. Vizzutti 등 34) 은간탄력도검사와간정맥압력차를 C형만성간염환자를대상으로비교하였고높은상관관계가있음을확인하였다 (r=0.81). 간정맥압력차가 10 mmhg일경우기준값은민감도 97% 음성예측도 92% 를보이는 13.6 kpa로결정되었고 12 mmhg 에서는민감도 94%, 음성예측도 91% 를보이는 17.6 kpa로결정되었다. 이연구에서식도정맥류의크기와간탄력도와상관관계는밝히지못하였다. 하지만 Kazemi 등 30) 은식도정맥류의크기와간탄력도검사사이에의미있는상관관계를보고하여결과해석에주의가필요하다. 이외에도 C형간염바이러스에의한간질환으로간이식을받은경우재발의예측하는데간탄력도검사가도움이된다는일부보고가있으며 3537), 간세포암종으로근치적간절제술을시행하는환자들에게서수술전시행한간탄력도검 사와 Indocyanine green retention rate at 15 minitus (ICG R15) 검사의수술후간기능저하예측력을비교하여간탄력도검사의유용성을저자들이보고하였다 38). 7. 기타원인에의한간섬유화를진단하는간탄력도검사의유용성 Corpechot 등 39) 은 51명의담즙성간경변증 (primary biliary cirrhosis, PBC) 와 21명의경화성담관염 (primary sclerosing cholangitis, PSC) 환자를대상으로간탄력도검사의결과를 Metavir 간섬유단계와비교하였다. Pares 등 40) 은 150명의경화성담관염환자들의간탄력도검사결과를 Ludwig 간섬유단계와비교하였고높은상관관계를보고하였다 (r=0.57, p<0.001). GómezDominguez 등 41) 도담즙성간경변증에서간섬유화와간탄력도와의높은상관관계와 UDCA 등을사용한후추적관찰에있어서유용성을보고하기도하였다. 비알코올성지방간염 (nonalcoholic steatohepatitis: NASH) 에대해서도간탄력도검사의유용성이일부보고되었다 42, 43). Table 1. Diagnostic performance for hepatic fibrosis and cirrhosis by transient elastography Ziol 11) Foucher 12) GanneCarrie 13) Kim 14) Colletta 20) Castera 21) Coco 22) No. of study patient 251 711 1007 228 40 183 228 Etiology HCV HBV Alcohol Other 251 (100) 398 (56.0) 43 (6.0) 89 (12.5) 181 (25.5) 493 (50.0) 122 (12.1) 75 (7.5) 317 (31.5) 228 (100) 40 (100) 183 (100) 149 (65.4) 79 (34.6) AUROC F 2 F 3 F=4 0.79 0.91 0.97 0.80 0.90 0.96 0.95 0.72 0.92 0.97 0.83 0.90 0.95 0.932 0.957 Optimal Cutoff F 2 F 3 F=4 8.8 9.6 14.6 7.2 12.5 17.6 14.6 8.74 7.1 9.5 12.5 8.3 14.0 Diagnostic index (F=4) Sensitivity Specificity PPV NPV 86 96 78 97 77 97 91 92 79 95 74 96 87 91 77 95 78.3 98.2 97.8 81.6 HCV, hepatitis C virus; HBV, hepatitis B virus; AUROC, area under receiver operating characteristic curve; PPV, positive predictive values; NPV, negative predictive value 466
한광협외 1 인 : FibroScan 을이용한간탄력도검사 그외에도 A형혈우병과 C형간염을동시에가지고있어간조직생검이어려운경우 44), 크론병이나건선환자에서 methotrexate 를사용하고있는경우간섬유화를예측함에있어간탄력도검사의유용성이보고되기도하였다 45, 46). 8. 한계점간탄력도검사의정확성이떨거지거나불가능한경우는일반적으로복수가있거나늑골사이간격이좁은경우를들수있다 10). 복수가있는경우는탄력파가간실질에도달하지못하여측정이어렵고늑골사이간격이좁으면탐촉자의위치설정이어렵기때문이다. 이러한한계점이외에도최근간탄력도검사에영향을미칠수있는요인에대한많은연구가있었다. Foucher 등 47) 은높은체질량지수 (> 28 kg/m 2 ) 를보이는환자에서간탄력도검사의실패가능성이 4.5% 로체질량지수가낮은환자에서보다비교적높다는결과를보고하였다. Kettaneh 등 48) 은체질량지수뿐만아니라나이에따라서도간탄력도검사의성공률이달라질수있다고보고하였다. 이외에도 Coco 등 22) 이 B와 C형간염바이러스에의한만성간질환환자에서간수치가상승하였을때간탄력도검사가영향을받을수있다고보고하였다. 이후 Sagir 등 49) 은급성간손상이있는경우에간경변증을진단하는데간탄력도검사는유용하지못하다고하였고, Arena 등 50) 도간염바이러스에의한급성간손상이있는경우 AST, ALT 수치에따라서간탄력도수치가변동함을보고하여간손상에의한간조직괴사를동반한간조직의병리학적인변화가간탄력도수치를변동시킬수있음을확인하였다. AST, ALT 이외에도총빌리루빈수치에의해간탄력도가영향을받는것을보고한연구도있다 51). 본저자들도급성간염환자들을대상으로입원당시와간기능검사가정상화되었을때간탄력도검사를시행하였고간탄력도검사결과에영향을미치는인자에대해회귀분석을시행하여 AST, ALT 보다총빌리루빈수치의변화가간탄력도의변화가가장상관관계가있는것을확인하였다 (p=0.530, 0.933 vs. 0.001). 9. 향후연구지금까지간탄력도검사의유용성에대한대부분의보고들은주로단면적인방법으로간섬유화를진단하는데초점이맞춰져있었다. 하지만앞으로는질병의악화를추적하거나항바이러스약물에의한간섬유화의호전을관찰하는등추적관찰의도구로서의검증이추가적으로필요하다 5255). 외국의보고에따르면 C형간염바이러스에의한만성간질환의경우는간탄력도검사의간섬유화의예측력이상당히높은것으로보고되었지만아직 B형간염바이러스에의한만성간질환의경우에는 C형에서보다는다소예측력이떨어지는것으로알려져있으며이는 B형간염바이러스에의한간경변증의경우에는간섬유화가 C형에서보다주로대결절형으로발현된다는것으로일부설명하고있지만간섬유화의조직학적특징과간탄력도검사의상관관계에대한연구가간탄력도검사의예측력을높이는데도움을줄것이다. 본저자들도 B형간염바이러스에의한만성간질환환자에서간경변증의예측력을높이기위해 age platelet index (API) 와간탄력도검사의결과를복합적으로해석하는것을보고하였지만 56), 지금까지알려진직접, 간접혈청학적표지자들을간탄력도검사와적절히조합하여간섬유화의예측력을높이기위한연구가더욱진행되어야할것이다. 또한우리나라는 HIV와간염바이러스의복합감염일경우 B형간염바이러스에의한것이많은부분을차지하고있지만이부분에대한연구가없어이에대한분석이요구된다. 간이식후간염바이러스에의한재발을예측하는것에대해서도 C형간염바이러스에대해서는외국에서일부연구가되어있지만이역시 B형간염바이러스에의한간이식후재발에대해서는연구가없다 3537). 최근증상이없고정상간기능을보이는일반인을대상으로검진목적으로서의간탄력도검사의유용성에대한연구도진행되고있으며일부에서의미있는간섬유화의유병률을보고하기도하였지만의료비용을고려한추가연구가필요하다 57, 58). 일부보고에따르면간탄력도검사수치가검사위치에따라서차이를보이는경향이있어간섬유화를가장정확히예측할수있는측정위치에대한연구도필요하다 59, 60). 만성간질환환자나급성간염에이환된환자에게서간기능악화가간탄력도검사수치에영향을준다는보고들이발표되고있고간기능이정상화되었을때간탄력도수치가정상으로회복되지않는일부환자들이있다는것에대해서도보고되었지만그러한환자들에게서언제다시간탄력도검사를진행하는것이실제의간섬유화를정확히예측하는가에대한연구도아직없는실정이다 49, 50). 늑골간격이좁은소아에서는간탄력도검사가어려웠지만최근새로개발된탐촉자를이용하여소아에서그유용성도보고되고있다 61. 최근자기공명영상을이용한 magnetic resonance elastography(mre), 초음파에간탄력도검사의탐촉자를추가장착하여실시간으로초음파 467
The Korean Journal of Medicine : Vol. 74, No. 5, 2008 를시행하면서간탄력도를검사하는것 (Real time elastography) 도시도되고있다 6265). 하지만 MRE에대해서는비용효과면과간탄력도검사와의비교연구가선행되어야하겠다. 지금까지국내에보고된간탄력도검사에대한연구는본저자들이발표한것을포함하여 2개의연구이외에는없다 14, 66). 따라서국내의환자들에게간탄력도검사를적용하기위해서는국내의활발한연구가필요하다. 결 만성간질환환자에서중증섬유화나간경변증으로의진행을예측하기는쉽지않으며간조직생검은침습적방법으로시술과관련된합병증이발생할수있다. 간탄력도검사는비침습적으로간탄력도를측정하여간섬유화를평가할수있다. 하지만간탄력도검사에대한연구들은주로 C형간염바이러스에의한만성간질환환자에서간섬유화의예측에대한유용성에대한것이어서우리나라처럼 B형간염바이러스에의한만성간질환환자유병률이높은곳에서는그연구결과들은바로적용하기는어려운실정이다. B형간염바이러스에대한간탄력도검사의유용성에대해서더많은연구가이루어지고간탄력도검사결과에영향을미치는요인에대해더많은연구가진행되어간탄력도검사의간섬유화예측력이검증된다면만성간질환환자의진단, 치료반응평가등임상적으로많은도움이될것이다. 중심단어 : 간섬유화 ; 간경변증 ; 간탄력도 ; FibroScan; 순간탄성측정법 론 REFERENCES 1) Poynard T, Mathurin P, Lai CL, Guyader D, Poupon R, Tainturier MH, Myers RP, Muntenau M, Ratziu V, Manns M, Vogel A, Capron F, Chedid A, Bedossa P; PANFIBROSIS Group. A comparison of fibrosis progression in chronic liver diseases. J Hepatol 38:257 265, 2003 2) Wright TL. Introduction to chronic hepatitis B infection. Am J Gastroenterol 101(Suppl. 1):S1 6, 2006 3) Consensus Statement. EASL international consensus conference on hepatitis C. J Hepatol 30:956 961, 1999 4) Strader DB, Wright T, Thomas DL, Seeff LB. AASLD practice guidelines. Diagnosis, management and treatment of hepatitis C. Hepatology 39:1147 1171, 2004 5) Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biospy: a multicentre retrospective study on 68,276 biopsies. J Hepatol 2:165 173, 1986 6) McGill DB, Rakela J, Zinsmeister AR, Ott BJ. A 21year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 99:1396 1400, 1990 7) Pradat P, Alberti A, Poynard T, Esteban JI, Weiland O, Marcellin P, Badalamenti S, Trépo C. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology 36:973 977, 2002 8) Kim BK, Kim SA, Park YN, Cheong JY, Kim HS, Park JY, Cho SW, Han KH, Chon CY, Moon YM, Ahn SH. Noninvasive models to predict liver cirrhosis in patients with chronic hepatitis B. Liver Int. 27:969 976, 2007 9) Rosenberg WM, Voelker M, Thiel R, Becka M, Burt A, Schuppan D, Hubscher S, Roskams T, Pinzani M, Arthur MJ; European Liver Fibrosis Group. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 127:1704 1713, 2004 10) Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 29:1705 1713, 2003 11) Ziol M, HandraLuca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 41:48 54, 2005 12) Foucher J, Chanteloup E, Vergniol J, Castera L, Le Bail B, Adhoute X, Bertet J, Couzigou P, de Lédinghen V. Diagnosis of cirrhosis by transient elastography (FibroScan): A prospective study. Gut 55:403 408, 2006 13) GanneCarrie N, Ziol M, de Lédinghen V, Douvin C, Marcellin P, Castera L, Dhumeaux D, Trinchet JC, Beaugrand M. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 44:1511 1517, 2006 14) Kim HS, Kim JK, Park YN, Myung SM, Pang MS, Yoon KT, Lee KH, Paik YH, LEE KS, Ahn SH, Chon CY, Moon YM, Han KH. Noninvasive assessment of liver fibrosis by measuring the liver stiffness and biochemical markers in chronic hepatitis B patients. Korean J Med 72:459 469, 2007 15) de Lédinghen V, Douvin C, Kettaneh A, Ziol M, Roulot D, Marcellin P, Dhumeaux D, Beaugrand M. Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C viruscoinfected patients. J Acquir Immune Defic Syndr 41:175 179, 2006 16) Vergara S, Macías J, Rivero A, GutiérrezValencia A, GonzálezSerrano M, Merino D, Ríos MJ, GarcíaGarcía JA, Camacho A, LópezCortés L, Ruiz J, de la Torre J, Viciana P, Pineda JA; Grupo para el Estudio de las Hepatitis Viricas 468
KwangHyub Han, et al : Liver stiffness measurement using FibroScan de la SAEI. The use of transient elastometry for assessing liver fibrosis in patients with HIV and hepatitis C virus coinfection. Clin Infect Dis 45:969 974, 2007 17) Barreiro P, MartínCarbonero L, Núñez M, Rivas P, Morente A, Simarro N, Labarga P, GonzálezLahoz J, Soriano V. Predictors of liver fibrosis in HIVinfected patients with chronic hepatitis C virus (HCV) infection: assessment using transient elastometry and the role of HCV genotype 3. Clin Infect Dis 42:1032 1039, 2006 18) Castellares C, Barreiro P, MartínCarbonero L, Labarga P, Vispo ME, Casado R, Galindo L, GarcíaGascó P, GarcíaSamaniego J, Soriano V. Liver cirrhosis in HIVinfected patients: prevalence, aetiology and clinical outcome. J Viral Hepat 15:165 172, 2008 19) Maida I, Soriano V, Barreiro P, Rivas P, Labarga P, Núñez M. Liver fibrosis stage and HCV genotype distribution in HIVHCV coinfected patients with persistently normal transaminases. AIDS Res Hum Retroviruses 23:801 804, 2007 20) Colletta C, Smirne C, Fabris C, Toniutto P, Rapetti R, Minisini R, Pirisi M. Value of two noninvasive methods to detect progression of fibrosis among HCV carriers with normal aminotransferases. Hepatology 42:838 845, 2005 21) Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, de Lédinghen V. Prospective comparison of transient elastography, FibroTest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 128:343 350, 2005 22) Coco B, Oliveri F, Maina AM, Ciccorossi P, Sacco R, Colombatto P, Bonino F, Brunetto MR. Transient elastography. A new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat 14:360 369, 2007 23) Castera L, Sebastiani G, Le Bail B, de Lédinghen V, Couzigou P, Alberti A. Prospective comparison of two algorithms combining noninvasive tests for staging of fibrosis in chronic hepatitis C (abstract). Hepatology 46:320A, 2007 24) Castera L, Foucher J, Bertet J, Couzigou P, de Lédinghen V. FibroScan and FibroTest to assess liver fibrosis in HCV with normal aminotransferases. Hepatology 43:373 374, 2006 25) MorenoOtero R, TraperoMarugan M, Mendoza J. Liver fibrosis assessment by transient elastography in hepatitis C patients with normal alanine aminotransferase. Gut 55:1055 1056, 2006 26) Castera L, Foucher J, Bernard PH, Bertet J, Couzigou P, de Le dinghen V. Transient elastography (FibroScan) and Fibro Test to assess liver fibrosis in inactive hepatitis B carriers: a prospective controlled study (abstract). Hepatology 44:489A, 2006 27) Chan HLY, G.L.H. Wong GLH, Wong VWS, Choi PCL, Chan AWH, Chum RHL, Chan HKW, Lau KKK, Sung JJY. Transient elastography (FibroScan) can detect advanced liver fibrosis best patients with normal alanine transaminase (abstract). EASL 2008 28) Poynard T, Ingiliz P, Munteanu M, Lebray P, Morra R, Messous D, ImbertBismut F, Benhamou Y, Ratziu V. Concordance between FibroTest (FT) and FibroScan (FS): a new noninvasive methodology to improving accuracy in a world without a gold standard (abstract). Hepatology 44: 189A, 2007 29) Castera L, Le Bail B, Foucher J, Bertet J, Darriet M, Couzigou P, de Lédinghen V. Prospective analysis of discordance between FibroScan and FibroTest when used in combination as firstline assessment of liver fibrosis in chronic hepatitis C (abstract). Hepatology 42:440A, 2005 30) Kazemi F, Kettaneh A, N'Kontchou G, Pinto E, GanneCarrie N, Trinchet JC, Beaugrand M. Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices. J Hepatol 45:230 235, 2006 31) Ahn SH, Kim SU, Kim DY, Kim JK, Yang HJ, Paik YH, Lee KS, Kim BS, Chon CY, Moon YM, Han KH. The usefulness of measuring liver stiffness in predicting the development hepatocellular carcinoma (abstract). Hepatology 46:782A, 2007 32) Ahn SH, Kim SU, Han KH, Lee JH, Yang HJ, Kim DY, Paik YH, Lee KS, Kim BS, Chon CY, Moon YM. Can liver stiffness predict the presence hepatocellular carcinoma? (abstract). Hepatology 46:800A, 2007 33) Nahon P, Kettaneh A, Lemoine M, Seror O, Grando V, Barget N, Bourcier V, Nkontchou G, Trinchet JC, Beaugrand M, GanneCarrie N. Liver stiffness measurement by FibroScan in cirrhotic patients with small hepatocellular carcinoma (HCC): Retrospective study comparing 50 cases with 197 compensated ChildPugh A cirrhotic patients without HCC (abstract). Hepatology 44:513A, 2006 34) Vizzutti F, Arena U, Romanelli RG, Rega L, Foschi M, Colagrande S, Petrarca A, Moscarella S, Belli G, Zignego AL, Marra F, Laffi G, Pinzani M. Liver stiffness measurement predicts severe portal hypertension in patients with HCVrelated cirrhosis. Hepatology 45:1290 1297, 2007 35) Rigamonti C, Donato MF, Fraquelli M, Agnelli F, Ronchi G, Casazza G, Rossi G, Colombo M. Transient elastography predicts fibrosis progression in patients with recurrent hepatitis c after liver transplantation (in printing). Gut 2008 36) Harada N, Soejima Y, Taketomi A, Yoshizumi T, Ikegami T, Yamashita Y, Itoh S, Kuroda Y, Maehara Y. Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation. Transplantation 85:69 74, 2008 37) Carrión JA, Navasa M, Bosch J, Bruguera M, Gilabert R, Forns X. Transient elastography for diagnosis of advanced 469
대한내과학회지 : 제 74 권제 5 호통권제 573 호 2008 fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation. Liver Transpl 12:1791 1798, 2006 38) Kim SU, Ahn SH, Park JY, Kim DY, Chon CY, Choi JS, Kim KS, Han KH. Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan ) before curative resection of hepatocellular carcinoma: A pilot study (abstract). EASL 2008 39) Corpechot C, El Naggar A, PoujolRobert A, Ziol M, Wendum D, Chazouilleres O. Inte re^t de l e lastographie he patique impulsionnelle pour l e valuation de la fibrose he patique au cours des maladies cholestatiques chroniques (abstract). Gastroenterol Clin Biol 29:906, 2005 40) Pares A, Caballeria L, Lazaro E, GarciaCriado A, Navasa M, Gilabert R. Transient elastography: a new and useful noninvasive method for assessing liver damage progression in primary biliary cirrhosis (abstract). Hepatology 42(S1):A464, 2005 41) GomezDominguez E, Jime nezridruejo1 JM, Monteagudo JAM, GarciaBuey L, Bienvenido A, MorenoOtero1 R. Efficacy of liver stiffness measurement (FibroScan ) for the follow up of patients with primary biliary cirrhosis (abstract). Hepatology 44:633A, 2007 42) Yoneda M, Fujita K, Inamori M, Nakajima A, Tamano M, Hiraishi H. Transient elastography in patients with nonalcoholic fatty liver disease (NAFLD). Gut 56:1330 1331, 2007 43) Fukuzawa Y, Kizawa S, Ohashi T, Matsumoto E, Sato K, Ayada M, Hotta N, Okumura A, Ishikawa T, Kakumu S. Efficacy of noninvasive hepatic fibrosis quantificatedevaluation by liver elasticity measurement in nonalcoholic steatohepatitis (NASH) comparison of ultrasonic transient elastography and histopathological diagnosis (abstract). Hepatology 44:649A, 2007 44) Grunhage F, Oldenburg J, Goldmann G, Vidovic N, Wasmuth JC, Spengler U, Sauerbruch T, Lammert F. Transient elastography (FibroScan ) in patients with chronic hepatitis C virus infection and haemophilia A (abstract). Hepatology 46:719A, 2007 45) Laharie D, Chabrun E, Schaeverbeke T, Hubiche T, Doutre MS, Longy M, Pellegrin JL, Foucher J, Castera L, Salaun F, Villars S, Zerbib F, de Ledinghen V. Usefulness of FibroScan for the follow up of patients treated with methotrexate (abstract). Hepatology 46:807A, 2007 46) Berends MA, Snoek J, de Jong EM, Van Krieken JH, de Knegt RJ, van Oijen MG, van de Kerkhof PC, Drenth JP. Biochemical and biophysical assessment of MTXinduced liver fibrosis in psoriasis patients: Fibrotest predicts the presence and FibroScan predicts the absence of significant liver fibrosis. Liver Int 27:639 645, 2007 47) Foucher J, Castera L, Bernard PH, Adhoute X, Laharie D, Bertet J, Couzigou P, de Lédinghen V. Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations. Eur J Gastroenterol Hepatol 18:411 412, 2006 48) Kettaneh A, Marcellin P, Douvin C, Poupon R, Ziol M, Beaugrand M, de Lédinghen V. Features associated with success rate and performance of FibroScan measurements for the diagnosis of cirrhosis in HCV patients: A prospective study of 935 patients. J Hepatol 46:628 634, 2007 49) Sagir A, Erhardt A, Schmitt M, Häussinger D. Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology 47:592 595, 2008 50) Arena U, Vizzutti F, Corti G, Ambu S, Stasi C, Bresci S, Moscarella S, Boddi V, Petrarca A, Laffi G, Marra F, Pinzani M. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 47:380 384, 2008 51) Seo YS, Suh SJ, Kwon YD, Park S, Keum B, Park BJ, Kim YS, Jeen YT, Chun HJ, Kim CD, Ryu HS, Um SH. The result of liver stiffness measurement is influenced by the serum bilirubin level (abstract). Hepatology 46:837A, 2007 52) de Lédinghen V, Castera L, Foucher J, Tournan R, Bernard PH, Moisset G, Xavier M, Bertet J. Evaluation of fibrosis evolution using noninvasive methods according to sustained virological response in HCV patients: a pilot prospective controlled study (abstract). Hepatology 44:337A, 2006 53) Hezode C, Castera L, Rosa I, Roulot D, Leroy V, BouvierAlias M, RoudotThoraval F, Douvin C1, Mallat A, Pawlotsky JM. Dynamics of liver stiffness during peginterferon alpharibavirin treatment in patients with chronic hepatitis C (abstract). Hepatology 46:366A, 2007 54) Takeda T, Yasuda T, Nakayama Y, Nakaya M, Kimura M, Yamashita M, Sawada A, Abo K, Takeda S, Sakaguchi H, Shiomi S, Asai H, Seki S. Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C. World J Gastroenterol 12:7768 7773, 2006 55) Colletta C, Smirne C, Fabris C, Foscolo AM, Toniutto P, Rapetti R, Minisini R, Sala L, Fangazio S, Pirisi M. Regression of fibrosis among longterm responders to antiviral treatment for chronic viral hepatitis (abstract). Hepatology 46:300A, 2007 56) Kim SU. Ahn SH, Park JY, Kang W, Kim DY, Park YN, Chon CY, Han KH. Liver stiffness measurement in combination with noninvasive markers for the improved diagnosis of Bviral liver cirrhosis (in printing). J Clin Gastroenterol 2008 57) Roulot D, Czernichow S, Costes JL, Le Clésiau H, Beaugrand M. Is liver stiffness measurement an appropriate screening method to detect liver fibrosis in the general population? 470
한광협외 1 인 : FibroScan 을이용한간탄력도검사 (abstract). EASL 2008 58) Klemmensen B, Riis T, Skamling M, Pedersen C, Christensen PB. Outreach screening of drug users with FibroScan identifies a high proportion of severe fibrosis nor preciously recognized (abstract). EASL 2008 59) Konate A, Boursier J, Re aud S, Quemener E, Fouchard Hubert I, Oberti F, Cale`s P. Liver stiffness measurement by transient elastography: predictive factors of accuracy, success and reproducibility (abstract). Hepatology 46:452A, 2006 60) Abergel A, Bonny C, Randl K, Nicolas C, Roszyk L, Noirfalise C, Massoulier S, Chanteranne B, Sapin V, Bommelaer G. FibroScan measures according to intercostal space: validity and concordance (abstract). EASL 2008 61) de Lédinghen V, Le Bail B, Rebouissoux L, Fournier C, Foucher J, Miette V, Castéra L, Sandrin L, Merrouche W, Lavrand F, Lamireau T. Liver stiffness measurement in children using FibroScan:feasibility study and comparison with Fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy. Pediatr Gastroenterol Nutr 45:443 450, 2007 62) Huwart L, Sempoux C, Salameh N, Jamart J, Annet L, Sinkus R, Peeters F, ter Beek LC, Horsmans Y, Van Beers BE. Liver fibrosis: noninvasive assessment with MR elastography versus aspartate aminotransferasetoplatelet ratio index. Radiology 245:458 466, 2007 63) Yin M, Talwalkar JA, Glaser KJ, Manduca A, Grimm RC, Rossman PJ, Fidler JL, Ehman RL. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol 5:1207 1213, 2007 64) FriedrichRust M, Ong MF, Herrmann E, Dries V, Samaras P, Zeuzem S, Sarrazin C. Realtime elastography for noninvasive assessment of liver fibrosis in chronic viral hepatitis. AJR Am J Roentgenol 188:758 764, 2007 65) Lewin M, PoujolRobert A, Boëlle PY, Wendum D, Lasnier E, Viallon M, Guéchot J, Hoeffel C, Arrivé L, Tubiana JM, Poupon R. Diffusionweighted magnetic resonance imaging for the assessment of fibrosis in chronic hepatitis C. Hepatology 46:658 665, 2007 66) Kang JK, Cheong JY, Cho SW, Cho JH, Park JS, Kim YB, Kim DJ, Hwang SG, Yang JM, Park NY. Liver stiffness measurement for the diagnosis of hepatic fibrosis in patients with chronic viral hepatitis. Korean J Hepatol 13:521 529, 2007 471