无创肝纤维化诊断研究现状与前景
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摘要
肝纤维化是许多慢性肝病进展为肝硬化、肝癌的共同病理过程,肝穿刺活组织检查作为准确度最高的确诊手段因各种弊端而不能成为常规检查方法。介绍了临床上较为实用的血清学与影像学方法,并分析了其各自的优缺点及研究现状。认为经过专家学者们的不断探索,无创诊断方法的地位日益凸显,在不久的将来有望取代肝活组织检查,成为确诊肝纤维化的有效手段。
Liver fibrosis is a common pathological process in the progression of various chronic liver diseases to liver cirrhosis and liver cancer,and liver biopsy with the highest accuracy in diagnosis cannot be used as a routine examination due to several drawbacks. This article introduces several serological and imaging methods used in clinical practice and analyzes their advantages/disadvantages and the current status of research. It is believed that thanks to the efforts of experts and scholars,noninvasive diagnostic methods have become more and more important and may replace liver biopsy and become an effective method for the diagnosis of liver fibrosis in the near future.
Liver fibrosis is a common pathological process in the progression of various chronic liver diseases to liver cirrhosis and liver cancer,and liver biopsy with the highest accuracy in diagnosis cannot be used as a routine examination due to several drawbacks. This article introduces several serological and imaging methods used in clinical practice and analyzes their advantages/disadvantages and the current status of research. It is believed that thanks to the efforts of experts and scholars,noninvasive diagnostic methods have become more and more important and may replace liver biopsy and become an effective method for the diagnosis of liver fibrosis in the near future.
引文
[1]ASRANI SK,LARSON JJ,YAWN B,et al.Underestimation of liver-related mortality in the United States[J].Gastroenterology,2013,145(2):375-382.
[2]PISCAGLIA F,MARINELLI S,BOTA S,et al.The role of ultrasound elstographic techniquesin chronic liver disease:Current status and future perspectives[J].Eur J Radiol,2013,83(6):450-455.
[3]TANG N,ZHANG Y,LIU Z,et al.Correlation analysis between four serum biomarks of liver fobrosis and liver function in infants with cholestasis[J].Biomed Rep,2016,5(1):107-112.
[4]QI X,LI H,CHEN J,et al.Serum liver fibrosis markers for predicting the presence of gastroesophageal varices in liver cirrhosis:A retrospective cross-sectional study[J].Gastroenterol Res Pract,2015,2015:274534.
[5]ZHANG XD,LI WJ,GAO YN,et al.Diagnosis value of serum laminin and hyaluronic acid in liver fibrosis[J].China Med Herald,2017,14(23):111-113,121.(in Chinese)张新弟,李卫娟,高娅妮,等.血清层粘连蛋白、透明质酸诊断肝纤维化的价值[J].中国医药导报,2017,14(23):111-113,121.
[6]QI XS,LIU X,ZHANG Y,et al.Serum liver fibrosis markers in the prognosis of liver cirrhosis:A prospective observational study[J].Med Sci Monit,2016,22:2720-2730.
[7]WAI CT,GREENSON JK,FONTANA RJ,et al.A simple noninvasive index can predict both significant fibrosis ancirrhosis in patients with chronic hepatitis C[J].Hepatology,2003,38(2):518-526.
[8]WU FX,GAO BH,NIU CY,et al.Value of aspartate aminotransferase-to-platelet ratio index in diagnosis and prediction of liver fibrosis degree in patients with chronic hepatitis B[J].J Clin Hepatol,2017,33(8):1483-1486.(in Chinese)吴方雄,高保华,牛春燕,等.APRI评分对慢性乙型肝炎肝纤维化程度的诊断及预测价值[J].临床肝胆病杂志,2017,33(8):1483-1486.
[9]STERLING RK,LISSEN E,CLUMECK N,et al.Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection[J].Hepatology,2006,43(6):1317-1325.
[10]MA XH,ZHANG X,YOU Y,et al.Diagnostic value of APRIcombined with FIB-4 for significant liver fibrosis in patients with chronic hepatitis B[J].Chin J Gastroenterol,2017,22(9):544-547.(in Chinese)马晓辉,张新,游云,等.APRI、FIB-4联合对慢性乙型肝炎患者显著肝纤维化的诊断价值[J].胃肠病学,2017,22(9):544-547.
[11]ZHU MY,ZOU X,LI Q,et al.A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis Bvirous infection[J].J Viral Hepat,2017,24(7):589-598.
[12]Chinese Society of Hepatology and Chinese Society of Infectious Disease,Chinese Medical Association.The guideline of prevention and trement for chronic hepatitis B:A 2015 update[J].J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
[13]FORNS X,AMPURDANES S,LLOVET JM,et al.Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model[J].Hepatology,2002,36(4 pt 1):986-992.
[14]CALES P,OBERTI F,MICHALAK S,et al.A novel panel of blood markers to assess the degree of liver fibrosis[J].Hepatology,2005,42(6):1373-1381.
[15]CHINDAMO MC,BOURSIER J,LUIZ RR,et al.Fibrosis assessment using fibrometer combined to first generation tests in hepatitis C[J].World J Hepatol,2017,9(6):310-317.
[16]LEMOINE M,SHIMAKAWA Y,NAYAGAM S,et al.The gamma-glutamyl transpeptidase to platelet ratio(GPR)predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa[J].Gut,2016,65(8):1369-1376.
[17]HU QG,WANG YQ,GAO YF,et al.The noninvasive diagnostic value of PLT/GGT ratio liver fibrosis in the patients with chronic hepatitis B virous infection[J].Acta Univ Med Anhui,2017,52(10):1568-1571.(in Chinese)胡庆刚,王殷秋,郜玉峰,等.PLT/GGT比值对慢性HBV感染者肝纤维化的无创诊断价值[J].安徽医科大学学报,2017,52(10):1568-1571.
[18]HUANG CM,YANG Z,NIE YQ,et al.Value of gamma-glutamyl transpeptidas-to-platelet ratio in predicting liver fibrosis stage in chronic hepatitis B patients in Guangdong,China[J].J Clin Hepatol,2018,34(6):1204-1208.(in Chinese)黄春明,杨湛,聂玉强,等.GGT/PLT比值对广东地区慢性乙型肝炎患者肝纤维化分期的预测价值[J].临床肝胆病杂志,2018,34(6):1204-1208.
[19]GHAFOORY S,VARSHNEY R,ROBISON T,et al.Platelet TGF-β1 deficiency decreases liver fibrosis in a mouse model of liver injury[J].Blood Advances,2018,2(5):470-480.
[20]XU AJ,XUE JY,YU SY,et al.The correlation of serm TGF-β1 content with liver fibrosis and Th1/Th2 immune levels in patients with chronic hepatitis B[J].J Hanan Med Coll,2018,24(2):195-197.(in Chinese)徐爱静,薛建亚,余思雨,等.慢性乙肝患者血清TGF-β1含量检测及与肝纤维化、Th1/Th2免疫水平的相关关系[J].海南医学院学报,2018,24(2):195-197.
[21]LIM JK,FLAMM SL,SINGH S,et al.American Gastroenterological Association Institute guideline on the role of elastography in the evaluation of liver fibrosis[J].Gastroenterology,2017,152(6):1536-1543.
[22]RAGAZZO TG,PARANAGUA-VEZOZZO D,LIMA FR,et al.Accuracy of transient elastography-fibrosis,acoustic radiation force impulse(ARFI)imaging,the enhanced liver fibrosis(ELF)test,APRI,and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C[J].Clinics,2017,72(9):516-525.
[23]OU XJ,WANG XM,WU XN,et al.Comparison of FibroTouch and FibroScan for the assessment of fibrosis in chronic hepatitis B patients[J].Chin J Hepatol,2015,23(2):103-106.(in Chinese)欧晓娟,王晓明,吴晓宁,等.FibroTouch与FibroScan在慢性乙型肝炎患者肝纤维化评估中的比较[J].中华肝脏病杂志,2015,23(2):103-106.
[24]HERRMANN E,de LEDINGHEN V,CASSINOTTO C,et al.Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography:An individual patient databased meta-analysis[J].Hepatology,2018,67(1):260-272.
[25]PAUL SB,DAS P,MAHANTA M,et al.Assessment of liver fibrosis in chronic hepatitis:Comparison of shear wave elastography and transient elastography[J].Abdom Radiol(NY),2017,42(12):2864-2873.
[26]MOUSTAFA EF,MAKHLOUF N,HASSANY SM,et al.Noninvasive assessment of liver fibrosis in patients with hepatic C:Shear wave elastography and colour Doppler velocity profile technique versus liver biopsy[J].Arab J Gastroenterol,2017,18(1):6-12.
[27]XIAO G,ZHU S,XIAO X,et al.Comparison of laboratory tests,ultrasound,or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease:Ameta-analysis[J].Hepatology,2017,66(5):1486-1501.
[28]SCHMILLEVITCH J,CHAMMAS MC,PUGLIESE V,et al.Acoustic radiation force impulse(ARFI)elastography compared with biopsy for evaluating hepatic fibrosis after liver transplantation:A cross-sectional diagnostic study[J].Sao Paulo Med J,2016,134(6):513-518.
[29]MOIL K,ARAI H,ABE T,et al.Spleen stiffness correlates with the presence of ascites but not esophageal varices in chronic hepatitis C patients[J].Biomed Res Int,2013,2013:857862.
[30]WANG M,LIU TT,WANG XM,et al.Comparison of acoustic radiation force impulse and transient electrography for the diagnosis of fibrosis in patients with non-alcoholic fatty liver disease[J].J Clin Exp Med,2018,17(2):124-128.(in Chinese)王民,刘婷婷,王晓明,等.评价声辐射力脉冲成像诊断非酒精性脂肪性肝病纤维化的效能[J].临床和实验医学杂志,2018,17(2):124-128.
[31]PFEIFER L,ZOPF S,SIEBLER J,et al.Prospective evaluation of acoustic radiation force impulse(ARFI)elastography and highfrequency B-mode ultrasound in compensated patients for the diagnosis of liver fibrosis/cirrhosis in comparison to mini-laparoscopic biopsy[J].Ultraschall Med,2015,36(6):581-589.
[32]SHIHA G,SEIF S,ELDESOKY A,et al.A simple bedside blood test(Fibrofast;FIB-5)is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C[J].Hepatol Int,2017,11(3):286-291.
[33]TOSON EA,SHINA GE,EL-MEZAYEN HA,et al.Noninvasive estimation of liver fibrosis in biopsy-proven hepatitis C virus-infected patients:Angiogenic fibrogenic link[J].Eur JGastroenterol Hepatol,2017,29(2):199-207.
[34]AHMED HASSAN E,SHARAF EL-DIN ABD EL-REHIM A,AHMED SAYED ZE,et al.VAP score as a novel non-invasive liver fibrosis model in patients with chronic hepatitis C[J].Hepatol Res,2017,47(13):1408-1416.
[2]PISCAGLIA F,MARINELLI S,BOTA S,et al.The role of ultrasound elstographic techniquesin chronic liver disease:Current status and future perspectives[J].Eur J Radiol,2013,83(6):450-455.
[3]TANG N,ZHANG Y,LIU Z,et al.Correlation analysis between four serum biomarks of liver fobrosis and liver function in infants with cholestasis[J].Biomed Rep,2016,5(1):107-112.
[4]QI X,LI H,CHEN J,et al.Serum liver fibrosis markers for predicting the presence of gastroesophageal varices in liver cirrhosis:A retrospective cross-sectional study[J].Gastroenterol Res Pract,2015,2015:274534.
[5]ZHANG XD,LI WJ,GAO YN,et al.Diagnosis value of serum laminin and hyaluronic acid in liver fibrosis[J].China Med Herald,2017,14(23):111-113,121.(in Chinese)张新弟,李卫娟,高娅妮,等.血清层粘连蛋白、透明质酸诊断肝纤维化的价值[J].中国医药导报,2017,14(23):111-113,121.
[6]QI XS,LIU X,ZHANG Y,et al.Serum liver fibrosis markers in the prognosis of liver cirrhosis:A prospective observational study[J].Med Sci Monit,2016,22:2720-2730.
[7]WAI CT,GREENSON JK,FONTANA RJ,et al.A simple noninvasive index can predict both significant fibrosis ancirrhosis in patients with chronic hepatitis C[J].Hepatology,2003,38(2):518-526.
[8]WU FX,GAO BH,NIU CY,et al.Value of aspartate aminotransferase-to-platelet ratio index in diagnosis and prediction of liver fibrosis degree in patients with chronic hepatitis B[J].J Clin Hepatol,2017,33(8):1483-1486.(in Chinese)吴方雄,高保华,牛春燕,等.APRI评分对慢性乙型肝炎肝纤维化程度的诊断及预测价值[J].临床肝胆病杂志,2017,33(8):1483-1486.
[9]STERLING RK,LISSEN E,CLUMECK N,et al.Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection[J].Hepatology,2006,43(6):1317-1325.
[10]MA XH,ZHANG X,YOU Y,et al.Diagnostic value of APRIcombined with FIB-4 for significant liver fibrosis in patients with chronic hepatitis B[J].Chin J Gastroenterol,2017,22(9):544-547.(in Chinese)马晓辉,张新,游云,等.APRI、FIB-4联合对慢性乙型肝炎患者显著肝纤维化的诊断价值[J].胃肠病学,2017,22(9):544-547.
[11]ZHU MY,ZOU X,LI Q,et al.A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis Bvirous infection[J].J Viral Hepat,2017,24(7):589-598.
[12]Chinese Society of Hepatology and Chinese Society of Infectious Disease,Chinese Medical Association.The guideline of prevention and trement for chronic hepatitis B:A 2015 update[J].J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
[13]FORNS X,AMPURDANES S,LLOVET JM,et al.Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model[J].Hepatology,2002,36(4 pt 1):986-992.
[14]CALES P,OBERTI F,MICHALAK S,et al.A novel panel of blood markers to assess the degree of liver fibrosis[J].Hepatology,2005,42(6):1373-1381.
[15]CHINDAMO MC,BOURSIER J,LUIZ RR,et al.Fibrosis assessment using fibrometer combined to first generation tests in hepatitis C[J].World J Hepatol,2017,9(6):310-317.
[16]LEMOINE M,SHIMAKAWA Y,NAYAGAM S,et al.The gamma-glutamyl transpeptidase to platelet ratio(GPR)predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa[J].Gut,2016,65(8):1369-1376.
[17]HU QG,WANG YQ,GAO YF,et al.The noninvasive diagnostic value of PLT/GGT ratio liver fibrosis in the patients with chronic hepatitis B virous infection[J].Acta Univ Med Anhui,2017,52(10):1568-1571.(in Chinese)胡庆刚,王殷秋,郜玉峰,等.PLT/GGT比值对慢性HBV感染者肝纤维化的无创诊断价值[J].安徽医科大学学报,2017,52(10):1568-1571.
[18]HUANG CM,YANG Z,NIE YQ,et al.Value of gamma-glutamyl transpeptidas-to-platelet ratio in predicting liver fibrosis stage in chronic hepatitis B patients in Guangdong,China[J].J Clin Hepatol,2018,34(6):1204-1208.(in Chinese)黄春明,杨湛,聂玉强,等.GGT/PLT比值对广东地区慢性乙型肝炎患者肝纤维化分期的预测价值[J].临床肝胆病杂志,2018,34(6):1204-1208.
[19]GHAFOORY S,VARSHNEY R,ROBISON T,et al.Platelet TGF-β1 deficiency decreases liver fibrosis in a mouse model of liver injury[J].Blood Advances,2018,2(5):470-480.
[20]XU AJ,XUE JY,YU SY,et al.The correlation of serm TGF-β1 content with liver fibrosis and Th1/Th2 immune levels in patients with chronic hepatitis B[J].J Hanan Med Coll,2018,24(2):195-197.(in Chinese)徐爱静,薛建亚,余思雨,等.慢性乙肝患者血清TGF-β1含量检测及与肝纤维化、Th1/Th2免疫水平的相关关系[J].海南医学院学报,2018,24(2):195-197.
[21]LIM JK,FLAMM SL,SINGH S,et al.American Gastroenterological Association Institute guideline on the role of elastography in the evaluation of liver fibrosis[J].Gastroenterology,2017,152(6):1536-1543.
[22]RAGAZZO TG,PARANAGUA-VEZOZZO D,LIMA FR,et al.Accuracy of transient elastography-fibrosis,acoustic radiation force impulse(ARFI)imaging,the enhanced liver fibrosis(ELF)test,APRI,and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C[J].Clinics,2017,72(9):516-525.
[23]OU XJ,WANG XM,WU XN,et al.Comparison of FibroTouch and FibroScan for the assessment of fibrosis in chronic hepatitis B patients[J].Chin J Hepatol,2015,23(2):103-106.(in Chinese)欧晓娟,王晓明,吴晓宁,等.FibroTouch与FibroScan在慢性乙型肝炎患者肝纤维化评估中的比较[J].中华肝脏病杂志,2015,23(2):103-106.
[24]HERRMANN E,de LEDINGHEN V,CASSINOTTO C,et al.Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography:An individual patient databased meta-analysis[J].Hepatology,2018,67(1):260-272.
[25]PAUL SB,DAS P,MAHANTA M,et al.Assessment of liver fibrosis in chronic hepatitis:Comparison of shear wave elastography and transient elastography[J].Abdom Radiol(NY),2017,42(12):2864-2873.
[26]MOUSTAFA EF,MAKHLOUF N,HASSANY SM,et al.Noninvasive assessment of liver fibrosis in patients with hepatic C:Shear wave elastography and colour Doppler velocity profile technique versus liver biopsy[J].Arab J Gastroenterol,2017,18(1):6-12.
[27]XIAO G,ZHU S,XIAO X,et al.Comparison of laboratory tests,ultrasound,or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease:Ameta-analysis[J].Hepatology,2017,66(5):1486-1501.
[28]SCHMILLEVITCH J,CHAMMAS MC,PUGLIESE V,et al.Acoustic radiation force impulse(ARFI)elastography compared with biopsy for evaluating hepatic fibrosis after liver transplantation:A cross-sectional diagnostic study[J].Sao Paulo Med J,2016,134(6):513-518.
[29]MOIL K,ARAI H,ABE T,et al.Spleen stiffness correlates with the presence of ascites but not esophageal varices in chronic hepatitis C patients[J].Biomed Res Int,2013,2013:857862.
[30]WANG M,LIU TT,WANG XM,et al.Comparison of acoustic radiation force impulse and transient electrography for the diagnosis of fibrosis in patients with non-alcoholic fatty liver disease[J].J Clin Exp Med,2018,17(2):124-128.(in Chinese)王民,刘婷婷,王晓明,等.评价声辐射力脉冲成像诊断非酒精性脂肪性肝病纤维化的效能[J].临床和实验医学杂志,2018,17(2):124-128.
[31]PFEIFER L,ZOPF S,SIEBLER J,et al.Prospective evaluation of acoustic radiation force impulse(ARFI)elastography and highfrequency B-mode ultrasound in compensated patients for the diagnosis of liver fibrosis/cirrhosis in comparison to mini-laparoscopic biopsy[J].Ultraschall Med,2015,36(6):581-589.
[32]SHIHA G,SEIF S,ELDESOKY A,et al.A simple bedside blood test(Fibrofast;FIB-5)is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C[J].Hepatol Int,2017,11(3):286-291.
[33]TOSON EA,SHINA GE,EL-MEZAYEN HA,et al.Noninvasive estimation of liver fibrosis in biopsy-proven hepatitis C virus-infected patients:Angiogenic fibrogenic link[J].Eur JGastroenterol Hepatol,2017,29(2):199-207.
[34]AHMED HASSAN E,SHARAF EL-DIN ABD EL-REHIM A,AHMED SAYED ZE,et al.VAP score as a novel non-invasive liver fibrosis model in patients with chronic hepatitis C[J].Hepatol Res,2017,47(13):1408-1416.