ORIGINAL ARTICLE https://doi.org/.15263/jlmqa.217.39.1.16 FIB-4 Score as a Useful Screening Test for Diagnosing Liver Fibrosis Kwangjin Ahn, Juwon Kim, Yoonjung Kim, Young Uh, and Kap Jun Yoon Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea Corresponding author: Young Uh Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, 2 Ilsan-ro, Wonju 26426, Korea Tel: +82-33-741-1592 Fax: +82-33-731-56 E-mail: u9318@yonsei.ac.kr Background: Liver biopsy is the gold standard for assessing liver fibrosis; however, it has a relatively high risk of resulting in complications. Although a non-invasive method (i.e., transient elastography fibroscan) was introduced, it is expensive and is dependent on the patient s status. Thus, the FIB-4 score, a non-invasive formula, has been used to predict the degree of liver fibrosis. The aim of this study was to evaluate the usefulness of the FIB-4 score in predicting stages of liver fibrosis. Methods: We analysed the age, diagnosis, and liver stiffness of 282 patients by measuring the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as their platelet count. Liver elasticity was evaluated by two classification criteria (Foucher et al. and Mueller et al.). The FIB-4 score was calculated using the formula: age AST/(platelet count ALT 1/2 ). The cut-off value of the FIB-4 score was determined according to the area under the relative operating characteristic curve (AUC) based on liver elasticity. Results: The FIB-4 cut-off values, as determined using two different criteria, have the highest AUC, thereby indicating a robust ability to distinguish between healthy liver tissue and the presence of any liver fibrosis. The FIB-4 score with a cut-off value of 2.7, as determined by Mueller et al., had the highest AUC (.837) and odds ratio (2.741) with a sensitivity of 78.3% and a specificity of 76.5%. Conclusions: An FIB-4 score of 2.7 is a cut-off value that is useful in detecting fibrotic progression in chronic liver disease in our laboratory. Each laboratory should determine an appropriate FIB-4 cut-off value that is relative to the particular characteristics of their patient population. (J Lab Med Qual Assur 217;39:16-22) Key Words: FIB-4 score, Screening, Liver fibrosis pissn: 2384-2458 eissn: 2288-7261 Received July 1, 216, Revision received October 19, 216, Accepted October 27, 216 서론 간경화와간암은간염바이러스감염, 알코올간질환, 혈색소침착증, 자가면역간질환등이치료되지않고만성으로진행될경우발생할수있다 [1]. 만성간질환에서섬유화정도의파악은치료와추적관찰에필수적이다 [2]. 간생검은간섬유화를진단하는표준진단법이지만간의일부만검사하는한계점과침습적시술과정의위험성, 검사자간숙련도차이로인하여실제사용에어려움이있다 [3,4]. 최근개발된간섬유화스캔 (fibroscan) 은간의탄성도를측정하여간섬유화를진단하 는장비로비침습적이고비교적높은정확도를가졌다는장점이있다. 하지만장비의가격과검사비용이비싸며환자가비만이거나좁은갈비사이공간 (intercostal space) 을가졌을경우측정이어렵고복수가있을경우엔측정불가한단점이있다 [5-8]. 다른검사자간측정값이비슷할수록높은값을갖는급내상관계수 (intraclass correlation coefficient) 는검사기구사용시필요한숙련도를평가하는데중요하다. 간섬유화스캔장비의급내상관계수에대한연구에서심한간섬유화환자를측정할땐.98로검사자간높은일치율을보였지만저등급간섬유화환자일경우.6으로매우낮아져측정도구로서 16 Copyright 217 Korean Association of External Quality Assessment Service
한계를보였다 [7]. 미국의보고에따르면새롭게 C형간염바이러스에감염되는빈도는낮아졌지만전체간경화환자가운데만성C형간염에서악화된경우의비율이높아지고있는것으로나타났다 [1]. 이러한만성C형간염환자에서다양한혈액검사수치로계산되는공식들의결과를비교하여간섬유화정도를어떤공식이가장잘반영하는지에관한연구가이루어졌는데이중나이, 아스파르테이트아미노전달효소 (aspartate aminotransferase, AST), 알라닌아미노전달효소 (alanine aminotransferase, ALT), 혈소판수치를이용하여 나이 ( 년 ) AST (U/L)/( 혈소판수 ( 9 /L) (ALT [U/L] 1/2 ) 로계산되는 FIB-4 점수는경한섬유화부터간경화를진단하기까지아주유용한진단도구로나타났다 [2]. 이전많은연구가 FIB- 4 점수는만성C형간염의간경화측정에있어유용하다는연구였지만 [2,9] 최근만성B형간염을제외한만성C형간염과비B 형간염또는비C형간염의간경화진단에도좋은도구임이증명되었다 []. 이번연구는다양한원인에의해간경화가발생한환자들의간섬유화스캔결과와간섬유화진단에유용한 FIB-4 점수를비교하여간경화의발생을선별하는데유용하게사용될수있는지를평가하였다. 재료및방법 1. 자료수집 211년부터 215년까지원주세브란스기독병원에서시행한간섬유화스캔의결과와피검사자의진단명, 혈소판수치, AST, ALT, 나이결과만을코드화하여추출하였고, 해당혈액검사결과는간섬유화스캔을시행한날의전후 1일이내의것으로추출하였다. 추출된 427개의검사결과에서 FIB-4 점수계산에필요한혈액검사가누락된 6개를제외하였고, 간섬유화스캔과 FIB-4 점수사이의통계적상관성을저해할수있는평균에서양쪽 3표준편차를초과하는값 39개를제거하여최종적으로 282개의검사결과를분석에사용하였다 [11]. 진단명은 B형간염바이러스감염, 만성C형바이러스간염, 알코올간질환, 비알코올간질환, 자가면역성간질환, 원인을알수없는경화로분류하였고, 이에해당하지않는경우는기타로분류하였다 (Table 1). 혈소판수치는자동혈액분석장비인 ADVIA212 (Siemens Healthcare Diagnostics, Sacramento, CA, USA) 으로검사하였고, 혈청 AST와 ALT는 modular DPE system (Roche Diagnostics, Basel, Switzerland) 으로측정하였다. 2. 간섬유화스캔간섬유화스캔은 fibroscan (Echosens, Paris, France) 을이용하였으며본기관에서 4년이상측정경험이있는전문가 2인이검사를실시하였다. 환자는등쪽누운자세 (dorsal decubitus position) 에서오른팔을최대외전 (abduction) 시킨자세를유지하고검사자는간의우엽부분의갈비사이공간에서피하 25-65 mm 되는지점의간조직탄성도를측정하였다 [12]. 최근만성C형간염이외에다른원인질환에따른간섬유화정도파악에도간섬유화스캔이유용하다는연구가진행되었지만원인질환별로섬유화등급간결정점 (cut-off value) 을다르게사용해야한다는것에대하여많은논란이있다 [7]. 이번연구처럼다양한원인질환별환자를대상으로간섬유화스캔연구를진행한 Foucher 등 [5] 의결정점과이전본기관의간섬유화스캔에대한연구논문에서피검사자의 81.5% 가알코올성간질환이라는점 [12] 에착안하여알코올성간질환환자를대상으로연구한 Mueller 등 [8] 의결정점을이용하였다. Foucher 등 [5] 의분류체계는 FF1( 정상과경한섬유화군 : <7.2 kpa), F2( 중등도섬유화군 : 7.2-<12.5), F3( 심한섬유화 : 12.5-<17.6) 와 F4( 경화 : 17.6) 의 4등급분류이며, Mueller 등 [8] 의분류는알코올성간질환환자에서 6 kpa 미만은정상 (f), 6-<8 은불명확 (gray zone, f1f2), 8-<12.5는진행성섬유화 (f3), 12.5 이상은경화 (f4) 의 4 단계분류체계이다. 3. 자료분석통계분석은 IBM SPSS Statistics for Windows ver. 2. (IBM Corp., Armonk, NY, USA) 을이용하였다. FIB-4 점수와간섬유화스캔결과값의연관성은 Foucher 등 [5] 과 Mueller 등 [8] 의분류방법에따라상관관계분석을실시하였다. 연속변수는 Kolmogorov-Smirnov test의등분산검정의유의확률이 P>.5이면등분산이가정된 t-test의유의확률을적용하였고, 등분산유의확률이 P.5이면등분산이가정되지않은비모수검정법인 Spearman 상관분석을실시하였으며통계적유의성은 P<.1일때유의한것으로판정하였다. 각분류군간의 FIB-4 점수와의평균치분석은 analysis of variance (ANOVA) 검증을이용하였다. 본연구에서간섬유화스캔을 reference method로사용하였으며 FIB-4 점수의섬유화와경화의단계별진단적예민도와특이도는상대수행능곡선 (relative operating characteristic curve, ROC curve) 으로곡선아래면적 (area under the ROC curve, AUC) 을검정변수값의평균치에따라위양성과진양성의상태변수값을설정하여분석하였다. 교차비 (odds ratio) 는로지스틱회귀분석을이용하였다. www.jlmqa.org J Lab Med Qual Assur 217;39:16-22 17
Table 1. FIB-4 score according to liver stiffness stage Characteristic Patient FIB-4 score Age (yr) Platelet ( 9 /L) AST (U/L) ALT (U/L) Diagnosis Alcoholic liver disease 68 (24.1) 3.28±1.712 51. 152.6 35.6 22.3 Hepatitis B viral liver disease 35 (12.4) 2.76±2.119 47.9 15.6 39.6 39.8 Cirrhosis 23 (8.2) 3.872±1.771 51.3 9.1 36.2 28. Hepatitis C viral liver disease 9 (3.2) 3.531±1.676 62.4 134.3 41.9 39.3 Non-alcoholic liver disease 3 (1.1) 1.83±.713 48.3 28.7 34.3 26.9 Hepatocellular carcinoma 1 (.4) Autoimmune liver disease 1 (.4) Others 142 (5.4) 2.462±1.673 53.5 194.2 38.8 34.9 Foucher s liver stiffness stage Normal or mild fibrosis (FF1) 91 (32.3) 1.68±1.31 52.4 229. 31. 32.4 Moderate fibrosis (F2) 71 (25.2) 2.62±1.656 51. 172.2 4.1 35.8 Severe fibrosis (F3) 33 (11.7) 3.655±1.738 53.1 127.1 42.8 33.5 Cirrhosis (F4) 87 (3.9) 3.963±1.722 52.7 125.4 41.4 28.5 Mueller s liver stiffness stage Normal (f) 2 (36.2) 1.63±1.131 51.8 229.9 31.2 32. Gray zone (f1f2) 35 (12.4) 2.471±1.381 51.1 172.8 42.7 41.3 Advanced fibrosis (f3) 22 (7.8) 3.339±1.854 54.5 138.1 38.4 31.2 Cirrhosis (f4) 123 (43.6) 3.834±1.73 52.5 127.1 42. 29.9 Total 282 (.) Values are presented as number (%) or mean±sd. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. 결과 총 282명의간섬유화스캔과 FIB-4 점수의 Kolmogorov- Smirnov 등분산검정값의유의확률은모두.5 미만이었고, 모두비모수분포를이루고있어 Spearman 상관분석에서의상관계수는.612이었다 (Fig. 1). 알코올간질환환자의간섬유화스캔결과값은 Foucher 등 [5] 과 Mueller 등 [8] 의두분류체계모두에서섬유화가심화될수록 FIB-4 점수도같이증가하였다 (Table 1). ANOVA검사와사후검증을통해두분류모두가장낮은등급과다른모든등급간유의미한차이 () 가있었지만경화와심한섬유화사이엔유의미한차이가없었다 (Foucher 등 [5] 의경우 P=.85, Mueller 등 [8] 의경우 P=.571). Foucher 등 [5] 의기준에서중등도섬유화군은더심한두군과유의미한차이 () 가있었지만 Mueller 등 [8] 기준의불명확등급은진행성섬유화와는유의미한차이가없고 (P=.216) 경화등급만차이가있었다 () (Fig. 2). Foucher 등 [5] 과 Mueller 등 [8] 의두분류에서각각 FF1 FIB-4 score 8 6 4 2 2 Liver stiffness Fig. 1. Both liver stiffness and FIB-4 score are nonparametrically distributed. The Spearman s correlation coefficient is.612 (). 군과 F2-F4 군을분류하는기준과 f 군과 f1-f4 군을나누는기 준에서 AUC, 특이도와교차비가가장큰값을보였다. 하지 만 Foucher 등 [5] 에서경화를기준으로한분류는 AUC 가.8 3 4 5 6 18 J Lab Med Qual Assur 217;39:16-22 www.jlmqa.org
A B P=.1 P=.16 P=.85 P=.46 P=.216 P=.571 8 8 FIB-4 score 6 4 FIB-4 score 6 4 2 2 Normal or mild fibrosis Moderate fibrosis Severe fibrosis Cirrhosis Normal Gray zone Advanced fibrosis Cirrhosis Foucher's liver stiffness stage Mueller's liver stiffness stage Fig. 2. Relationship between FIB-4 score and liver stiffness stages. Crosses at each box plot indicate the FIB-4 score and the interquartile range. An analysis of variance was used for intergroup analysis and each P-value was calculated using multiple comparisons. (A) Foucher s liver stiffness stage. (B) Mueller s liver stiffness stage. The mean value and interquartile ranges, respectively, were as follows: (A) normal or mild fibrosis: 1.61 and.99 2.6; moderate fibrosis: 2.62 and 1.33 3.49; severe fibrosis: 3.66 and 2.6 4.65; cirrhosis: 3.96 and 2.54 5.23; (B) normal: 1.63 and.92 2.5; gray zone: 2.47 and 1.95 3.24; advanced fibrosis: 3.34 and 1.95 4.38; cirrhosis: 3.83 and 2.54 4.95. Table 2. Diagnostic performance of FIB-4 according to liver stiffness stages (N=282) Receiver operating characteristic curve Logistic regression* Liver stiffness stage FIB-4 Odds ratio (95% AUC Sensitivity (%) Specificity (%) P-value cut-off value confidence interval) Foucher s FF1 vs. F2F3F4.821 2.1 75.9 74.7 <.1 2.632 (2. 3.465) FF1F2 vs. F3F4.814 2.54 75.8 72.8 <.1 2.53 (1.694 2.488) FF1F2F3 vs. F4.777 2.82 71.3 7.3 <.1 1.711 (1.451 2.18) Mueller s f vs. f1f2f3f4.837 2.7 78.3 76.5 <.1 2.741 (2.9 3.594) ff1f2 vs. f3f4.831 2.38 78.6 76.6 <.1 2.416 (1.927 3.3) ff1f2f3 vs. f4.88 2.52 75.6 73. <.1 2.12 (1.664 2.432) Abbreviation: AUC, area under the relative operating characteristic curve. *Using the dummy variable method, liver stiffness stages were converted to binary outcomes, which were analysed using a binomial logistic regression model. 보다작았지만 Mueller 등 [8] 의분류에서는모두.8보다높았다. 특히정상 (f) 과섬유화 (f1-f4) 를구분하는 FIB-4 결정점은 2.7이며이때 AUC가.837로제일컸으며교차비도 2.741로가장컸다 (Table 2). 고찰 현재간섬유화진단방법의기준은간생검이지만침습적인검사과정의위험성과판독자에의한결과의가변성으로비교적간단하고비침습적인방법으로간의탄성도를측정하는진단법이개발되었다 [5-8]. 간섬유화스캔은환자의비만정도와 www.jlmqa.org J Lab Med Qual Assur 217;39:16-22 19
복수에영향을많이받는단점이있는데이번연구에선조건에따라자료를추출하여분석하였기에환자의키와체중, 복수여부등의간섭요인에대한정보를조사하지못하였고피검사자식별을하지않은후향적연구의한계점을가지고있다. 위에서언급한바와같이이번연구는의무기록을자세히조사하지못하여자료조사시점이후주치의의의무기록에기록된새로운진단명을정확히알수없어이번연구에서기타진단으로분류된환자가 5.4% 이다. 하지만본기관소화기내과에서 27년부터 211년까지간생검과간섬유화스캔의결과를비교한보고가있었는데이때환자군의 76.2% 가만성간질환의원인이알코올이었으며알코올과 B형, C형간염바이러스와연관된환자는 5.3% 였다 [12]. 그후해당과에서원인질환에따라간경화진단에제한을두지않고간섬유화스캔을실시하였고이러한검사결과를바탕으로데이터를추출한이번연구는실제원인질환이기타로분류된환자의상당수가알코올과연관이있을것으로생각되며이로인해 Foucher 등 [5] 의분류기준보다 Mueller 등 [8] 의기준이이번연구결과에큰영향을미친것으로판단된다. 본연구에서 Mueller 등 [8] 의각기준에따른 FIB-4 점수의 AUC 값들은 Šimundić [13] 의보고를바탕으로판단할때모두좋은진단적도구기준인.8을넘는다. 이전의 Andres- Otero 등 [2] 의간생검을바탕으로중등도간섬유화를진단시 FIB-4 결정점은 1.5이었으며이때 AUC는.882이었고경화를진단할때결정점은 2.63이며 AUC는.964로이전연구들과마찬가지로 FIB-4 점수는섬유화가심해질수록진단에더유용하였다 [5-8]. 하지만이번연구에선오히려섬유화정도가낮을수록 AUC 값이커지며진단적유용성이증가하는것으로나타났다. 섬유화가적더라도간염이나간울혈, 기계적담즙정체가있을경우간섬유화스캔결과가거짓증가를보이는데, 알코올성간질환에서는상기병터들이존재하는경우가많다 [8]. 결국알코올성간질환환자가많음에도간섭요인에대한정보부족으로오히려실제섬유화정도보다심한등급으로진단될환자를배제하지못하여심한섬유화등급에대한 FIB-4 결정점의 AUC가낮은것으로생각된다. 만성간질환의섬유화를예측하기위한비침습적검사로서간섬유화스캔이외에도온혈구계산결과와혈청간기능검사결과를이용한지표들이고안되었다 [14-16]. FIB-4 점수는나이, 혈소판수, AST와 ALT를이용한점수로통상검사를이용하므로쉽게산출할수있고추가검사비용이들지않으나, AST와 ALT검사는 aminotransferase 반응의조효소로 vitamin B6 활성물질인 pyridoxal phosphate를첨가한시약으로검사하는것이권장된다 [17]. 본연구에서측정한 AST와 ALT는 pyridoxal phosphate가첨가되지않은시약으로검사하였는데향후 pyridoxal phosphate 첨가유무에따른 FIB-4 점수의변화를평가할필요가있다. 최근의보고에의하면 C형간염바이러스와비만으로인한비알코올성지방간에서유래하는간경화의비율이증가하는추세에있다 [1]. 하지만많은연구가침습적간생검의높은오진가능성을밝혀냈고 [3,4], 이를해소하고자비침습적방법에대한연구를진행하였다 [2,5-,12]. 이들중싸고빠르고간단하게진단하는 FIB-4의경우경제적한계로값비싼검사가어려운환경에서유용하게쓰일수있을것으로생각된다. 하지만나이가어리고상대적으로정상수치의혈소판을가질경우심한경화가있더라도 FIB-4 점수는낮다. 또한고령이며혈소판이낮게측정될경우섬유화진행이적더라도 FIB-4 점수는높아지게된다. 따라서 FIB-4만으로검사하기보다는간섬유화스캔등다른비침습적검사를동시에진행할경우간생검의빈도를 5%-7% 줄일수있다 [9]. 결론적으로최근국가적으로 C형간염바이러스감염에대한관심이높아지고있는가운데만성간질환으로발전할위험요소를가진환자들의선별검사를통해질병단계에맞는올바른치료가중요해지고있다. 이번연구는간경화로진행가능한간질환환자들을간단한혈액검사를이용하여현재간섬유화를예측하고이를선별할수있는지표를제시한점에서큰의미가있다. Mueller 등 [8] 의연구를바탕으로한결정점의 AUC는모두.8보다높았고, 정상 (f) 과진행하는섬유화상태 (f1-f4) 를구분하는결정점은 2.7이었으며 AUC가.837 로제일높았고민감도와특이도는각각 78.3% 와 76.5% 였다. 따라서간질환이최초진단되고아직만성화가진행되지않았다면이후간단한혈액검사를진행하여 FIB-4 점수가 2.7보다증가한환자를대상으로섬유화파악을위한추가검사를실시한다면적은비용의선별검사를통해질병의심화를놓치지않고시기적절한치료를할수있을것이다. 간섬유화를진단하는 FIB-4 점수의결정점은원인질환에따라차이가있을수있으므로자체적으로각기관의환자특성에따라진단예민도와특이도를설정하기위한연구가필요하다. REFERENCES 1. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 21-213. Gastroenterology 215;149:1471-82. 2. Andres-Otero MJ, De-Blas-Giral I, Puente-Lanzarote 2 J Lab Med Qual Assur 217;39:16-22 www.jlmqa.org
JJ, Serrano-Aullo T, Morandeira MJ, Lorente S, et al. Multiple approaches to assess fourteen non-invasive serum indexes for the diagnosis of liver fibrosis in chronic hepatitis C patients. Clin Biochem 216;49:56-5. 3. Colloredo G, Guido M, Sonzogni A, Leandro G. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 23;39:239-44. 4. Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 22;97:2614-8. 5. Foucher J, Chanteloup E, Vergniol J, Castera L, Le Bail B, Adhoute X, et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 26; 55:43-8. 6. Fraquelli M, Rigamonti C, Casazza G, Conte D, Donato MF, Ronchi G, et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 27;56:968-73. 7. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol 28; 48:835-47. 8. Mueller S, Seitz HK, Rausch V. Non-invasive diagnosis of alcoholic liver disease. World J Gastroenterol 214;2: 14626-41. 9. Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 27;46:32-6.. Okamura Y, Ashida R, Yamamoto Y, Ito T, Sugiura T, Uesaka K. FIB-4 index is a predictor of background liver fibrosis and long-term outcomes after curative resection of hepatocellular carcinoma. Ann Surg Oncol 216;23 (Suppl 4):467-74. 11. Osborne JW, Overbay A. The power of outliers (and why researchers should always check for them). Pract Assess Res Eval 24;9:1-12. 12. Moon KM, Kim G, Baik SK, Choi E, Kim MY, Kim HA, et al. Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis. Clin Mol Hepatol 213;19:389-98. 13. Simundic AM. Measures of diagnostic accuracy: basic definitions. Med Biol Sci 28;22:61-5. 14. Oda K, Uto H, Mawatari S, Ido A. Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: a review of human studies. Clin J Gastroenterol 215;8:1-9. 15. Gorden DL, Myers DS, Ivanova PT, Fahy E, Maurya MR, Gupta S, et al. Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. J Lipid Res 215;56: 722-36. 16. Lombardi R, Pisano G, Fargion S. Role of serum uric acid and ferritin in the development and progression of NAFLD. Int J Mol Sci 216;17:548. 17. Ferard G, Imbert-Bismut F, Messous D, Piton A, Abella A, Burnat P, et al. Influence of pyridoxal phosphate in measuring aminotransferases activities in patients with viral hepatitis. Ann Biol Clin (Paris) 24;62:717-2. www.jlmqa.org J Lab Med Qual Assur 217;39:16-22 21
간섬유화선별진단법으로서의 FIB-4 점수의유용성안광진 김주원 김윤정 어영 윤갑준연세대학교원주의과대학진단검사의학교실 배경 : 간생검이간섬유화의표준진단법이지만침습적방법에따른합병증의위험이상대적으로높다. 비침습적방법으로간섬유화스캔이도입되었으나가격이비싸고환자의신체상태에영향을받는다. 이에 FIB-4 점수는비침습적계산식으로간섬유화정도를예측한다. 본연구는간섬유화단계예측에있어 FIB-4 점수의유용성을평가하고자하였다. 방법 : 나이, 진단명, 간탄성도, 아스파르테이트아미노전달 - 효소 (aspartate aminotransferase, AST), 알라닌아미노전달효소 (alanine aminotransferase, ALT), 혈소판수를코드화하여의무자료를추출하였으며최종적으로 282 명의환자결과를분석하였다. 간탄성도는두연구 (Foucher 등, Mueller 등 ) 의분류기준에따라각각섬유화등급을나누었다. FIB-4 점수는나이 ( 년 ) AST/( 혈소판수 [ 9 /L] (ALT) 1/2 ) 로계산하고간섬유화스캔결과를바탕으로상대수행능곡선 (relative operating characteristic curve, ROC curve) 을그리고곡선아래면적 (area under the ROC curve, AUC) 을이용하여결정점을확인하였다. 결과 : 두분류기준이공통적으로정상과진행된간섬유화를나누는 FIB-4 결정점에서 AUC 가가장컸다. 특히 Mueller 등의기준을바탕으로한 FIB-4 점수가 2.7 일때가장큰 AUC (.837) 와교차비 (2.741) 를보였으며이때의민감도는 78.3%, 특이도는 76.5% 였다. 결론 : 본검사실에서의 FIB-4 점수는결정점을 2.7 로했을때만성간질환의섬유화진행을선별하는데유용하였다. 각검사실에서는환자특성이병원마다다르므로자체적인 FIB-4 결정점을설정하는것이바람직하다. (J Lab Med Qual Assur 217;39:16-22) 교신저자 : 어영우 )26426 강원도원주시일산로 2, 연세대학교원주의과대학진단검사의학교실 Tel: 33)741-1592, Fax: 33)731-56, E-mail: u9318@yonsei.ac.kr 22 J Lab Med Qual Assur 217;39:16-22 www.jlmqa.org