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増大号 肝疾患 臨床検査でどう迫る? 1章 肝関連検査の見方

肝臓の線維化にかかわる検査

著者: 豊田秀徳1

所属機関: 1大垣市民病院消化器内科

ページ範囲:P.1052 - P.1057

はじめに

 ウイルス肝炎・脂肪性肝疾患に代表されるびまん性肝疾患において,肝線維化は肝硬変および肝細胞癌をはじめとする合併症の発生リスクと密接に関連しており,肝線維化の程度を評価することはびまん性肝疾患診療における最も重要な要素の1つである.従来,肝線維化の有無・程度の評価は肝生検で採取された肝組織の病理学的評価によりなされてきており,現在でも標準的な評価法とされている.

 一方で,肝生検は侵襲的な検査であり一般的に入院が必要なこと,検査に伴う出血のリスクがあること,コストなどの問題点があり,また採取する組織は肝のごく一部であることによるサンプリングエラーの問題,病理所見の観察者間でのvariabilityの問題が以前から指摘されてきた.これらの問題点を踏まえて,昨今ではさまざまな非侵襲的な肝線維化の評価法が提唱されている.非侵襲的な肝線維化の評価は,血液検査によるものと画像検査によるものに大別される.画像検査による肝線維化評価には腹部超音波診断機器を用いた超音波(ultrasound:US)エラストグラフィや磁気共鳴画像(magnetic resonance imaging:MRI)を用いたMRエラストグラフィがあるが,いずれも診断機器を要し,ある程度術者の習熟が必要となる.

 一方,血液検査による肝線維化評価は,採血のみによる評価であり簡便である.現在さまざまな肝線維化の血清マーカーが提唱されているが,最適な血清線維化マーカーや肝線維化評価のカットオフ値はびまん性肝疾患の成因や目的により異なる場合が多いため,その使い分けには注意が必要となる.

 本稿では,肝臓の線維化にかかわる臨床検査について概説し,その特徴,使い分けについて論じたい.

参考文献

1)Laurent TC, et al:Serum hyaluronan as a disease marker. Ann Med 28:241-253,1996
2)Hahn E, et al:Distribution of basement membrane proteins in normal and fibrotic human liver: collagen type IV, laminin, and fibronectin. Gut 21:63-71,1980
3)Murawaki Y, et al:Serum type III procollagen peptide, type IV collagen 7S domain, central triple-helix of type IV collagen and tissue inhibitor of metalloproteinases in patients with chronic viral liver disease: relationship to liver histology. Hepatology 20:780-787,1994
4)Yoneda M, et al:Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage. J Gastroenterol 42:375-381,2007
5)Shima T, et al:A novel rapid immunoassay of serum type IV collagen 7S for the diagnosis of fibrosis stage of nonalcoholic fatty liver diseases. Hepatol Res 51:263-276,2021
6)Ludwig J, et al:Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55:434-438,1980
7)Matsumoto E, et al:Serum type IV collagen concentrations in diabetic patients with microangiopathy as determined by enzyme immunoassay with monoclonal antibodies. Diabetes 39:885-890,1990
8)Ishiba H, et al:Type IV collagen 7S is the most accurate test for identifying advanced fibrosis in NAFLD with type 2 diabetes. Hepatol Commun 5:559-572,2021
9)上野隆登,他:各種肝疾患における血清タイプⅢプロコラーゲンNペプチド,ラミニンの変動と肝免疫組織学的検討.肝臓 30:429-438,1989
10)Keller F, et al:Increased procollagen III production in patients with kidney disease. Nephron 50:332-337,1988
-M2BP: Its role in biological interactions with Kupffer cells. J Gastroenterol Hepatol 32:1387-1393,2017
12)Ishii A, et al:Clinical implications of serum Wisteria floribunda agglutinin-positive Mac-2-binding protein in treatment-naïve chronic hepatitis B. Hepatol Res 47:204-215,2017
-M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C. Aliment Pharmacol Ther 43:114-124,2016
14)Abe M, et al:Association between Wisteria floribunda agglutinin-positive Mac-2 binding protein and the fibrosis stage of non-alcoholic fatty liver disease. J Gastroenterol 50:776-784,2015
15)Nishikawa H, et al:Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level and high-sensitivity C-reactive protein concentration in autoimmune hepatitis. Hepatol Res 46:613-621,2016
16)Umemura T, et al:Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein Level Predicts Liver Fibrosis and Prognosis in Primary Biliary Cirrhosis. Am J Gastroenterol 110:857-864,2015
17)Fujimori N, et al:Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease. World J Gastroenterol 24:1239-1249,2018
18)Honda Y, et al:Autotaxin is a valuable biomarker for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. Hepatol Res 49:1136-1146,2019
19)Feldstein AE, et al:Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 50:1072-1078,2009
20)Chen J, et al:Serum cytokeratin-18 in the diagnosis of non-alcoholic steatohepatitis: A meta-analysis. Hepatol Res 44:854-862,2014
21)Sterling RK, et al:Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317-1325,2006
22)Vallet-Pichard A, et al:FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 46:32-36,2007
23)Kim BK, et al:Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int 30:546-553,2010
24)Shah AG, et al:Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 7:1104-1112,2009
25)Sugiyama A, et al:Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups. BMC Gastroenterol 22:241,2022
26)Kariyama K, et al:Fibrosis-3 index: a new score to predict liver fibrosis in patients with nonalcoholic fatty liver disease without age as a factor. Gastro Hep Adv 1:1108-1113,2022
27)Shiha G, et al:Development and multicenter validation of FIB-6: A novel, machine learning, simple bedside score to rule out liver cirrhosis and compensated advanced chronic liver disease in patients with chronic hepatitis C. Hepatol Res 52:165-175,2022
28)Wai CT, et al:A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38:518-526,2003
29)Xiao G, et al:Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis-4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta-analysis. Hepatology 61:292-302,2015
30)Smith JO, et al:Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C. Aliment Pharmacol Ther 30:557-576,2009
31)Lee J, et al:Prognostic accuracy of FIB-4, NAFLD fibrosis score and APRI for NAFLD-related events: A systematic review. Liver Int 41:261-270,2021
32)Xu XY, et al:The effectiveness of noninvasive biomarkers to predict hepatitis B-related significant fibrosis and cirrhosis: a systematic review and meta-analysis of diagnostic test accuracy. PLoS One 9:e100182,2014
33)Imbert-Bismut F, et al:Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 357:1069-1075,2001
34)Vali Y, et al:FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis. J Clin Med 10:2415,2021
35)Angulo P, et al:The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 45:846-854,2007
36)Mózes FE, et al:Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut 71:1006-1019,2022
37)Glen J, et al:Non-alcoholic fatty liver disease (NAFLD): summary of NICE guidance. BMJ 354:i4428,2016
38)European Association for the Study of the Liver, et al:EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol 75:659-689,2021
39)Inadomi C, et al:Accuracy of the Enhanced Liver Fibrosis test, and combination of the Enhanced Liver Fibrosis and non-invasive tests for the diagnosis of advanced liver fibrosis in patients with non-alcoholic fatty liver disease. Hepatol Res 50:682-692,2020
40)Seko Y, et al:Diagnostic accuracy of enhanced liver fibrosis test for nonalcoholic steatohepatitis-related fibrosis: Multicenter study. Hepatol Res 53:312-321,2023

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出版社:株式会社医学書院

電子版ISSN:1882-1367

印刷版ISSN:0485-1420

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