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1 原 著 , 2014 FIB4 Index FIB4 Index FIB4 Index cut off ,059 FIB4 IndexFIB4 Index 2.67 / FIB4 Index AST ALT FIB4 Index % FIB4 Index 5 FIB4 Index FIB4 Index 4AST AST/ ALT FIB4 Index AST FIB4 Index simple steatosis Sterling 1 AST ALT FIB4 IndexShah 2 high cut off FIB4 Index 1-4 FIB4 Index FIB4 Index FIB4 Index FIB4 Index Tel Fax ( 34 ) Vol.29 No

2 Shah 2 cut off 2.67 FIB4 Index ,059± 47.9± 9.5 9, ± 9.4 2, ±9.2 Sterling 1 FIB4 Index= AST IU/L /10 9 /L ALT IU/L 10 9 /L = 10 4 /mm 3 10 FIB4 Index FIB4 Index FIB4 Index 2.67 FIB4 Index AST ALT FIB4 Index 2.67 SPSS Statics18 IBM SPSS IBM Mann-WhitneyWilcoxon χ 2 p<0.05 1, ,213 1, , ,112 1,200 1,600 1 FIB4 Index 2 12,059 FIB4 Index 2.67 FIB4 Index 2.67 FIB4 Index 11, FIB4 Index Vol.29 No ( 35 )

3 2 n=12,059 FIB4 Index 3 Cut off 2.67 FIB4 Index FIB4 Index 0.99 FIB4 Index 1.91 FIB4 Index FIB4 Index FIB4 Index FIB4 Index FIB4 Index 47.8±9.4 FIB4 Index 58.5±9.8 p<0.001 FIB4 Index FIB4 Index ( 36 ) Vol.29 No

4 4 FIB4 Index cut off 2.67 FIB4 Index 2.67 / 1 FIB4 Index FIB4 Index 2.67 FIB4 Index 2.67 p % % p= % % 2 FIB4 Index FIB4 Index <2.67 FIB4 Index % % % % % % % % p N.S. N.S FIB4 Index 9,373 2,686 FIB4 Index 2 FIB4 Index161FIB4 Index 4AST ALT 4 AST AST/ALT AST/ALT 3 FIB4 Index Vol.29 No ( 37 )

5 3 FIB4 Index 2.67 Index (n = % AST IU/L % ALT IU/L % AST/ALT / μ L % 5 Non Alcoholic Fatty Liver Disease NAFLD Non Alcoholic Steatohepatitis NASH CT 1,7-13 Sterling 1 HIV HCV FIB4 Index Shah 2 NAFLD NAFLD Fibrosis Score ROC high cut off low cut off Yang 3 Sumida 4 FIB4 Index 7FIB4 Index ROC FIB4 Index 6 8 FIB4 Index FIB4 Index 1.3 FIB4 Index98.7 AST ALT FIB4 Index FIB4 IndexFIB4 Index FIB4 Index FIB4 Index FIB4 Index58.5 FIB4 Index FIB4 Index FIB4 Index 5 5 FIB4 Index FIB4 Index FIB4 Index 5 10 FIB4 Index FIB4 Index AST ALT 38 ( 38 ) Vol.29 No

6 AST AST/ALT 0.86 ALT 1.18 AST AST 5 NAFLD AST ALT NASH AST/ALT 14 AST FIB4 Index AST FIB4 Index 15 FIB4 Index FIB4 Index161 3 X CT 16 FIB4 Index FIB4 Index cut off 2.67 cut off FIB4 Index cut off Fujii 17 FIB4 Index BMIHarrison 11 BARD score BMI 18 BMI FIB4 IndexBMI cut off 12,059 9, FIB4 Index FIB4 Index Sterling 1 high cut off 3.25 Sumida 4 NAFLD FIB4 Index Sterling 3.25 Shah cut off cut off 3.25 FIB4 Index FIB4 Index cut off Vol.29 No ( 39 )

7 20 FIB4 Index FIB4 Index AST Sterling RK, Lissen E, Clumeck N, et al: Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006; 43: Shah AG, Lydecker A, Murray K, et al: Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: Yang HR, Kim HR, Kim MJ, et al: Noninvasive parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease. World J Gastroenterol 2012; 18: Sumida Y, Yoneda M, Hyogo H, et al: Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population. BMC Gastroenterol 2012; 12: : 4. NAFLD. NASH NAFLD Poynard T, Bedossa P: Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups. J Viral Hepat 1997; 4: Ratziu V, Giral P, Charlotte F, et al: Liver fibrosis in overweight patients. Gastroenterology 2000; 118: Wai CT, Greenson JK, Fontana RJ, et al: A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003; 38: Angulo P, Hui JM, Marchesini G, et al: The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45: Harrison SA, Oliver D, Arnold HL, et al: Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut 2008; 57: Miyaaki H, Ichikawa T, Nakao K, et al: Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis. Liver Int 2008; 28: Sumida Y, Yoneda M, Hyogo H, et al: A simple clinical scoring system using ferritin, fasting insulin, and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease. J Gastroenterol 2011; 46: NAFLD NASH NAFLD Fujii H, Enomoto M, Fukushima W, et al: Applicability of BARD score to Japanese patients with NAFLD. Gut 2009; 58: NAFLD update Yoneda M, Yoneda M, Mawatari H, et al: Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis 2008; 40: ( 40 ) Vol.29 No

8 Time-dependent Changes in FIB4 Index in Patients with Fatty Liver Disease Nobuyuki Kobayashi 1), Takashi Tsuzuki 1), Tomoko Manzoji 1), Hiroyuki Watabe 1), Miyoko Takezawa 2), Atsushi Tsuchiya 1), Akira Tsuchiya 1) 1) Sagamihara health evaluation and promotion center 2) Department of Gastroenterology, Kitasato University School of Medicine Abstract Objective: To examine the effectiveness of the FIB4 index as an indicator of fibrosis in fatty liver. Methods: In fatty liver patients examined several times, we calculated the FIB4 index for the initial and final examinations. Taking the cutoff point for fibrosis as 2.67, 12,059 individuals in whom the index was less than 2.67 were enrolled as the subjects of this study. The change in the FIB4 index during the period from the initial to the final examination was determined. For subjects in whom the FIB4 index had risen to 2.67 or over at the final examination, we made comparisons by gender as well as by whether the fatty liver was alcoholic or non-alcoholic. We analyzed changes in the factors of the FIB4 calculation formula (age, AST, ALT, platelet counts) as well as those in ultrasonography images. Results: The FIB4 index had risen to 2.67 or above in 161 subjects (1.3%) at the final examination and in these subjects it was significantly higher than at the initial examination. There had been an increase in FIB4 index in 1.1% of subjects followed up for less than 5 years, whereas FIB4 index had increased in 1.6% of those followed up for 5 years or more and the difference between these groups was significant. There were no differences in frequencies of rises in FIB4 index between males and females or between alcoholic and non-alcoholic fatty livers. Regarding the 4 factors of the FIB4 index calculation formula, the biggest change was in AST, with the AST/ALT ratio increasing from 0.86 at the initial examination to 1.18 at the final examination. The only change in ultrasonography images observed was dullness of the hepatic margin in 3 of the 161 subjects. Conclusion: The length of time required for changes in the FIB4 index and the greater change in AST suggest that it could be used as a predictive index of fibrosis. Keywords: FIB4 Index, fatty liver disease, nonalcoholic fatty liver disease (NAFLD), liver fibrosis Vol.29 No ( 41 )

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