非酒精性脂肪性肝病相关肝纤维化及其组织学量化分析

汪艳; 侯金林

doi:10.3969/j.issn.1001-5256.2017.12.008

非酒精性脂肪性肝病相关肝纤维化及其组织学量化分析

DOI: 10.3969/j.issn.1001-5256.2017.12.008

汪艳,
侯金林

1. 器官衰竭防治国家重点实验室广东省肝纤维化工程技术研究中心南方医科大学肝病研究所
2. 南方医科大学南方医院感染内科暨肝病中心

基金项目:

国家自然科学基金(81670522)；广州市科技计划项目(201607020019)；

详细信息

中图分类号: R575
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- 被引次数: 29
出版历程
- 出版日期: 2017-12-20

Hepatic fibrosis in nonalcoholic fatty liver disease and its quantitative assessment

Research funding:

摘要

摘要: 非酒精性脂肪性肝病(NAFLD)正逐渐成为慢性肝病肝纤维化发生的首要原因。组织学肝纤维化可能是目前对NAFLD预后进行判断的最重要独立影响因素。NAFLD相关肝纤维化在肝病进展中具有与其"代谢性"病生机制紧密相关的特征:其发生发展与肥胖、代谢综合征相关危险因素、年长等主要因素显著相关;其组织学分布、变化特征以及与其他组织学特征的关联性也不同于其他主要肝病。在已有组织学评价标准的基础上,准确量化分析NAFLD相关肝纤维化对于疾病分层、疗效观察以及新型诊疗工具研发可能具有研究和应用价值。
- 非酒精性脂肪性肝病 /
- 肝硬化 /
- 组织学
Abstract: Nonalcoholic fatty liver disease ( NAFLD) is becoming a primary etiology underlying the chronic liver injury-related fibrogenesis among general population. Histologic fibrosis has been demonstrated as the most important independent predictor for the major outcomes of NAFLD patients. NAFLD-related fibrosis has distinct characteristics through the disease course, which is largely attributed to its " metabolic" pathophysiology: The progression of fibrosis is correlated to the factors including obesity, metabolic syndrome components, aging, etc.;and the patterns of histologic distribution and evolution as well as the association with the other histological features are remarkably different from those of the other chronic liver diseases. Based on the criteria of current standard histology, accurate quantitative assessment of NAFLD fibrosis could be relevant in terms of research and utilization to stratifying the disease risk, monitoring the therapeutic response, as well as to facilitating the development of new diagnostic tools.
- nonalcoholic fatty liver disease /
- liver cirrhosis /
- histology

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参考文献(58)

[1]WHO.Obesity and overweight:fact sheet[C/OL].2016.http:/www.who.int/mediacentre/factsheets/fs311/en/.

[2] YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al.Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J].Hepatology, 2016, 64 (1) :73-84.

[3]DYSON J, JAQUES B, CHATTOPADYHAY D, et al.Hepatocellular cancer:the impact of obesity, type 2 diabetes and a multidisciplinary team[J].J Hepatol, 2014, 60 (1) :110-117.

[4]WONG RJ, AGUILAR M, CHEUNG R, et al.Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States[J].Gastroenterology, 2015, 148 (3) :547-555.

[5]KABBANY MN, CONJEEVARAM SELVAKUMAR PK, WATT K, et al.Prevalence of nonalcoholic steatohepatitis-associated cirrhosis in the United States:an analysis of national health and nutrition examination survey data[J].Am J Gastroenterol, 2017, 112 (4) :581-587.

[6]ESTES C, RAZAVI H, LOOMBA R, et al.Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease[J].Hepatology, 2017.[Epub ahead of print]

[7]HAAS JT, FRANCQUE S, STAELS B.Pathophysiology and mechanisms of nonalcoholic fatty liver disease[J].Annu Rev Physiol, 2016, 78:181-205.

[8]ADAMS LA, ANSTEE QM, TILG H, et al.Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases[J].Gut, 2017, 66 (6) :1138-1153.

[9]SANYAL AJ, FRIEDMAN SL, MCCULLOUGH AJ, et al.Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis:findings and recommendations from an American Association for the Study of Liver Diseases-U.S.Food and Drug Administration Joint Workshop[J].Hepatology, 2015, 61 (4) :1392-1405.

[10] European Association for the Study of the Liver.EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease[J].J Hepatol, 2016, 64 (6) :1388-1402.

[11] CHALASANI N, YOUNOSSI Z, LAVINE JE, et al.The diagnosis and management of nonalcoholic fatty liver disease:practice guidance from the American Association for the Study of Liver Diseases[J].Hepatology, 2017.[Epub ahead of print]

[12]LOOMBA R, SANYAL AJ.The global NAFLD epidemic[J].Nat Rev Gastroenterol Hepatol, 2013, 10 (11) :686-690.

[13]KLEINER DE, BRUNT EM, van NATTA M, et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease[J].Hepatology, 2005, 41 (6) :1313-1321.

[14]WILLIAMS CD, STENGEL J, ASIKE MI, et al.Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy:a prospective study[J].Gastroenterology, 2011, 140 (1) :124-131.

[15]ADAMS LA, LYMP JF, ST SAUVER J, et al.The natural history of nonalcoholic fatty liver disease:a population-based cohort study[J].Gastroenterology, 2005, 129 (1) :113-121.

[16]KLEINER D, BRUNT EM, BELT P, et al.Diagnostic pattern and disease activity are related to disease progression and regression in nonalcoholic fatty liver disease[J].Hepatology, 2016, 64 (S1) .

[17]MCPHERSON S, HARDY T, HENDERSON E, et al.Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies:implications for prognosis and clinical management[J].J Hepatol, 2015, 62 (5) :1148-1155.

[18]EKSTEDT M, HAGSTROM H, NASR P, et al.Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up[J].Hepatology, 2015, 61 (5) :1547-1554.

[19]SINGH S, ALLEN AM, WANG Z, et al.Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis:a systematic review and meta-analysis of paired-biopsy studies[J].Clin Gastroenterol Hepatol, 2015, 13 (4) :643-54.

[20]WONG VW, WONG GL, CHOI PC, et al.Disease progression of non-alcoholic fatty liver disease:a prospective study with paired liver biopsies at 3 years[J].Gut, 2010, 59 (7) :969-974.

[21]SANYAL AJ, BANAS C, SARGEANT C, et al.Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C[J].Hepatology, 2006, 43 (4) :682-689.

[22]BHALA N, ANGULO P, van DER POORTEN D, et al.The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis:an international collaborative study[J].Hepatology, 2011, 54 (4) :1208-1216.

[23]KAWAMURA Y, ARASE Y, IKEDA K, et al.Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma[J].Am J Gastroenterol, 2012, 107 (2) :253-261.

[24]ASCHA MS, HANOUNEH IA, LOPEZ R, et al.The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis[J].Hepatology, 2010, 51 (6) :1972-1978.

[25]YATSUJI S, HASHIMOTO E, TOBARI M, et al.Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C[J].J Gastroenterol Hepatol, 2009, 24 (2) :248-254.

[26]MOHAMAD B, SHAH V, ONYSHCHENKO M, et al.Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis[J].Hepatol Int, 2016, 10 (4) :632-639.

[27]ANGULO P, KLEINER DE, DAM-LARSEN S, et al.Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease[J].Gastroenterology, 2015, 149 (2) :389-397, e10.

[28]HAGSTROM H, NASR P, EKSTEDT M, et al.Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD[J].J Hepatol, 2017.[Epub ahead of print]

[29] DULAI PS, SINGH S, PATEL J, et al.Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease:Systematic review and meta-analysis[J].Hepatology, 2017, 65 (5) :1557-1565.

[30]ADAMS LA, SANDERSON S, LINDOR KD, et al.The histological course of nonalcoholic fatty liver disease:a longitudinal study of103 patients with sequential liver biopsies[J].J Hepatol, 2005, 42 (1) :132-138.

[31]PAIS R, CHARLOTTE F, FEDCHUK L, et al.A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver[J].J Hepatol, 2013, 59 (3) :550-556.

[32]SHIGEFUKU R, TAKAHASHI H, NAKANO H, et al.Correlations of hepatic hemodynamics, liver function, and fibrosis markers in nonalcoholic fatty liver disease:comparison with chronic hepatitis related to hepatitis C virus[J].Int J Mol Sci, 2016, 17 (9) :1545.

[33]STINE JG, SHAH NL, ARGO CK, et al.Increased risk of portal vein thrombosis in patients with cirrhosis due to nonalcoholic steatohepatitis[J].Liver Transpl, 2015, 21 (8) :1016-1021.

[34]KIM D, KIM WR, KIM HJ, et al.Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States[J].Hepatology, 2013, 57 (4) :1357-1365.

[35]BRIL F, BARB D, PORTILLO-SANCHEZ P, et al.Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease[J].Hepatology, 2017, 65 (4) :1132-1144.

[36]European Association for Study of Liver;Asociacion Latinoamericana para el Estudio del Higado.EASL-ALEH Clinical Practice Guidelines:non-invasive tests for evaluation of liver disease severity and prognosis[J].J Hepatol, 2015, 63 (1) :237-264.

[37]CASSINOTTO C, BOURSIER J, de LEDINGHEN V, et al.Liver stiffness in nonalcoholic fatty liver disease:A comparison of supersonic shear imaging, Fibro Scan, and ARFI with liver biopsy[J].Hepatology, 2016, 63 (6) :1817-1827.

[38]PETTA S, MAIDA M, MACALUSO FS, et al.The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease[J].Hepatology, 2015, 62 (4) :1101-1110.

[39]JOO SK, KIM W, KIM D, et al.Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease[J].Liver Int, 2017.[Epub ahead of print]

[40]BRUNT EM.Nonalcoholic fatty liver disease:pros and cons of histologic systems of evaluation[J].Int J Mol Sci, 2016, 17 (1) .Pii:E97.

[41]BRAVO AA, SHETH SG, CHOPRA S.Liver biopsy[J].N Engl JMed, 2001, 344 (7) :495-500.

[42]RATZIU V, CHARLOTTE F, HEURTIER A, et al.Sampling variability of liver biopsy in nonalcoholic fatty liver disease[J].Gastroenterology, 2005, 128 (7) :1898-906.

[43]GOLDSTEIN NS, HASTAH F, GALAN MV, et al.Fibrosis heterogeneity in nonalcoholic steatohepatitis and hepatitis C virus needle core biopsy specimens[J].Am J Clin Pathol, 2005, 123 (3) :382-387.

[44]SAAB S, PHAN J, JIMENEZ MA, et al.Endoscopic ultrasound liver biopsies accurately predict the presence of fibrosis in patients with fatty liver[J].Clin Gastroenterol Hepatol, 2017, 15 (9) :1477-1478.

[45]BEDOSSA P, CONSORTIUM FP.Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease[J].Hepatology, 2014, 60 (2) :565-575.

[46]BRUNT EM, JANNEY CG, di BISCEGLIE AM, et al.Nonalcoholic steatohepatitis:a proposal for grading and staging the histological lesions[J].Am J Gastroenterol, 1999, 94 (9) :2467-2474.

[47]MATTEONI CA, YOUNOSSI ZM, GRAMLICH T, et al.Nonalcoholic fatty liver disease:a spectrum of clinical and pathological severity[J].Gastroenterology, 1999, 116 (6) :1413-1419.

[48]PAVLIDES M, BIRKS J, FRYER E, et al.Interobserver variability in histologic evaluation of liver fibrosis using categorical and quantitative scores[J].Am J Clin Pathol, 2017, 147 (4) :364-369.

[49]GERMANI G, HYTIROGLOU P, FOTIADU A, et al.Assessment of fibrosis and cirrhosis in liver biopsies:an update[J].Semin Liver Dis, 2011, 31 (1) :82-90.

[50]ZIOL M, KETTANEH A, GANNE-CARRIE N, et al.Relationships between fibrosis amounts assessed by morphometry and liver stiffness measurements in chronic hepatitis or steatohepatitis[J].Eur J Gastroenterol Hepatol, 2009, 21 (11) :1261-1268.

[51]WANG Y, HOU JL.Fibrosis assessment:impact on current management of chronic liver disease and application of quantitative invasive tools[J].Hepatol Int, 2016, 10 (3) :448-461.

[52]ASSELAH T, MARCELLIN P, BEDOSSA P.Improving performance of liver biopsy in fibrosis assessment[J].J Hepatol, 2014, 61 (2) :193-195.

[53]PATEL K, BEDOSSA P, CASTERA L.Diagnosis of liver fibrosis:present and future[J].Semin Liver Dis, 2015, 35 (2) :166-183.

[54]BEDOSSA P, PATEL K.Biopsy and noninvasive methods to assess progression of nonalcoholic fatty liver disease[J].Gastroenterology, 2016, 150 (8) :1811-1822.

[55]SHIHA G, IBRAHIM A, HELMY A, et al.Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis:a 2016update[J].Hepatol Int, 2017, 11 (1) :1-30.

[56]XU S, WANG Y, TAI DC, et al.q Fibrosis:a fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients[J].JHepatol, 2014, 61 (2) :260-269.

[57]WANG Y, HUANG W, LI R, et al.Systematic quantitation of histologic patterns shows accuracy in reflecting cirrhotic remodeling[J].JGastroenterol Hepatol, 2017, 32 (9) :1631-1639.

[58]WANG Y, VINCENT R, YANG J, et al.Dual-photon microscopy-based quantitation of fibrosis-related parameters (q-FP) to model disease progression in steatohepatitis[J].Hepatology, 2017, 65 (6) :1891-1903.

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