Z Gastroenterol 2020; 58(12): 1233-1240
DOI: 10.1055/a-1291-8483
Übersicht

Leberspezifische Diagnostik bei der nichtalkoholischen Fettlebererkrankung (NAFLD) – wann kann die Leberbiopsie ersetzt werden?

Liver-specific diagnostic for non-alcoholic fatty liver disease (NAFLD) – time to replace liver biopsy?
Schwerpunkt für Metabolische Lebererkrankungen, I. Medizinische Klinik, Universitätsmedizin Mainz, Mainz, Deutschland
,
Schwerpunkt für Metabolische Lebererkrankungen, I. Medizinische Klinik, Universitätsmedizin Mainz, Mainz, Deutschland
› Author Affiliations
Supported by: JMS erhält Forschungsförderung der Europäischen Union Innovative Medicines Initiative 2 (IMI2) (Grant Nummer 777377: LITMUS – Liver Investigation: Testing Biomarker Utility in Steatohepatitis).

Zusammenfassung

Die nichtalkoholische Fettlebererkrankung (NAFLD) ist eine der häufigsten Lebererkrankungen. In Deutschland wird die Prävalenz in der adulten Bevölkerung auf 24 % geschätzt, und die Inzidenz ist ansteigend. Prognostisch ist die Unterscheidung früher und fortgeschrittener Erkrankungsstadien von Bedeutung. Insbesondere das Ausmaß der Vernarbung, die als Leberfibrose bezeichnet wird, beeinflusst Morbidität und Mortalität von Patienten mit NAFLD. Bei Vorliegen einer fortgeschrittener Fibrose und Zirrhose steigen die leberspezifische und die Gesamtmortalität an. Die Leberfibrose entsteht als Konsequenz einer anhaltenden Entzündung des Lebergewebes über die Zeit. Da Entzündung und Fibrose histologische Merkmale der Erkrankung sind, gilt heute als Referenzmethode in der Diagnostik der NAFLD noch die Leberbiopsie. Zunehmend werden nichtinvasive diagnostische Verfahren zum Staging (der Fibrose) und Grading (Aktivität) der Erkrankung entwickelt und validiert. Die aktuelle Übersicht fasst neue Entwicklungen der nichtinvasiven Leberdiagnostik zusammen.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. In Germany, the prevalence in the adult population is estimated at 24 % and the incidence is increasing. Prognostically, the distinction between early and advanced stages of the disease is important. In particular, the extent of scarring considered as liver fibrosis is of prognostic significance. Patients with advanced fibrosis and cirrhosis show increased mortality. Liver fibrosis develops as a consequence of a persistent inflammation of the liver tissue over time. Since inflammation and fibrosis are histological features, liver biopsy is considered the reference method in the diagnosis of NAFLD. More recently, non-invasive diagnostic methods for staging (of fibrosis) and grading (activity) of the disease are being developed and validated. The current review summarizes new developments in non-invasive liver diagnostics.



Publication History

Received: 31 July 2020

Accepted: 09 October 2020

Article published online:
08 December 2020

© 2020. Thieme. All rights reserved.

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  • Literatur

  • 1 Younossi ZM, Koenig AB, Abdelatif D. et al Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73-84 . doi:10.1002/hep.28431
  • 2 Wong RJ, Singal AK. Trends in Liver Disease Etiology Among Adults Awaiting Liver Transplantation in the United States, 2014–2019. JAMA Netw Open 2020; 3: e1920294 . doi:10.1001/jamanetworkopen.2019.20294
  • 3 Roeb E, Steffen HM, Bantel H. et al S2k-Leitlinie nicht alkoholische Fettlebererkrankungen. Z Gastroenterol 2015; 53: 668-723 . doi:10.1055/s-0035-1553193
  • 4 Eslam M, Newsome PN, Sarin SK. et al A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. Journal of Hepatology 2020; DOI: 10.1016/j.jhep.2020.03.039.
  • 5 Diehl AM, Day C. Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis. N Engl J Med 2017; 377: 2063-2072 . doi:10.1056/NEJMra1503519
  • 6 Bedossa P. Current histological classification of NAFLD: strength and limitations. Hepatol Int 2013; 7 (Suppl. 02) 765-770 . doi:10.1007/s12072-013-9446-z
  • 7 Michel M, Kalliga E, Labenz C. et al Ein junger Patient mit Typ-2-Diabetes assoziierter nichtalkoholischer Steatohepatitis, Leberzirrhose und hepatozellulärem Karzinom. Z Gastroenterol 2020; 58: 57-62 . doi:10.1055/a-1062-8788
  • 8 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. Gastroenterology 2015; 149: 389-397.e10 . doi:10.1053/j.gastro.2015.04.043
  • 9 Taylor RS, Taylor RJ, Bayliss S. et al Association Between Fibrosis Stage and Outcomes of Patients with Non-Alcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. Gastroenterology 2020; DOI: 10.1053/j.gastro.2020.01.043.
  • 10 Labenz C, Huber Y, Michel M. et al Impact of NAFLD on the Incidence of Cardiovascular Diseases in a Primary Care Population in Germany. Dig Dis Sci 2019; DOI: 10.1007/s10620-019-05986-9.
  • 11 Labenz C, Huber Y, Michel M. et al Nonalcoholic Fatty Liver Disease Increases the Risk of Anxiety and Depression. Hepatol Commun 2020; DOI: 10.1002/hep4.1541.
  • 12 Huber Y, Labenz C, Michel M. et al The Incidence of cancer in patients living with non-alcoholic fatty liver disease (NAFLD) in Germany. Dtsch Arztebl Int 2020; Accepted Article
  • 13 Kaps L, Labenz C, Galle PR. et al Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease. United European Gastroenterol J 2020; DOI: 10.1177/2050640620944098.
  • 14 Gehrke N, Schattenberg JM. Metabolic inflammation – a role for hepatic inflammatory pathways as driver of comorbidities in non-alcoholic fatty liver disease (NAFLD)?. Gastroenterology 2020; DOI: 10.1053/j.gastro.2020.02.020.
  • 15 Cook N, Geier A, Schmid A. et al Assessing physician preferences on future therapeutic options and diagnostic practices in non-alcoholic steatohepatitis. JHEP Reports 2020; 2: 100081 . doi:10.1016/j.jhepr.2020.100081
  • 16 Davison BA, Harrison SA, Cotter G. et al Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials. Journal of Hepatology 2020; DOI: 10.1016/j.jhep.2020.06.025.
  • 17 Schattenberg JM, Straub BK. On the value and limitations of liver histology in assessing non-alcoholic steatohepatitis. Journal of Hepatology 2020; DOI: 10.1016/j.jhep.2020.07.020.
  • 18 European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388-1402 . doi:10.1016/j.jhep.2015.11.004
  • 19 Kleiner DE, Brunt EM, van Natta M. et al Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321 . doi:10.1002/hep.20701
  • 20 Schattenberg JM, Straub BK. Differenzialdiagnose der Fettlebererkrankung. Gastroenterologe 2020; 69: 896 . doi:10.1007/s11377-020-00416-z
  • 21 Ratziu V, Charlotte F, Heurtier A. et al Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005; 128: 1898-1906 . doi:10.1053/j.gastro.2005.03.084
  • 22 Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001; 344: 495-500 . doi:10.1056/NEJM200102153440706
  • 23 Geier A, Boursier J. Non-invasive diagnosis of patients with ‘at-risk’ NAFLD: only fibrosis counts?. Gut 2020; 69: 1164-1165 . doi:10.1136/gutjnl-2020-320785
  • 24 Hernaez R, Lazo M, Bonekamp S. et al Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011; 54: 1082-1090 . doi:10.1002/hep.24452
  • 25 Petta S, Maida M, Macaluso FS. et al The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease. Hepatology 2015; 62: 1101-1110 . doi:10.1002/hep.27844
  • 26 Tapper EB, Challies T, Nasser I. et al The Performance of Vibration Controlled Transient Elastography in a US Cohort of Patients With Nonalcoholic Fatty Liver Disease. Am J Gastroenterol 2016; 111: 677-684 . doi:10.1038/ajg.2016.49
  • 27 Wong VWS, Vergniol J, Wong GLH. et al Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-462 . doi:10.1002/hep.23312
  • 28 Kennedy P, Wagner M, Castéra L. et al Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions. Radiology 2018; 286: 738-763 . doi:10.1148/radiol.2018170601
  • 29 Sugimoto K, Moriyasu F, Oshiro H. et al The Role of Multiparametric US of the Liver for the Evaluation of Nonalcoholic Steatohepatitis. Radiology 2020; 192665 DOI: 10.1148/radiol.2020192665.
  • 30 Jiang W, Huang S, Teng H. et al Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis. BMJ Open 2018; 8: e021787 . doi:10.1136/bmjopen-2018-021787
  • 31 Palmeri ML, Wang MH, Rouze NC. et al Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. Journal of Hepatology 2011; 55: 666-672 . doi:10.1016/j.jhep.2010.12.019
  • 32 Patel K, Sebastiani G. Limitations of non-invasive tests for assessment of liver fibrosis. JHEP Reports 2020; 2: 100067 . doi:10.1016/j.jhepr.2020.100067
  • 33 Serra-Burriel M, Graupera I, Torán P. et al Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia. J Hepatol 2019; 71: 1141-1151 . doi:10.1016/j.jhep.2019.08.019
  • 34 Ratziu V, Cadranel JF, Serfaty L. et al A survey of patterns of practice and perception of NAFLD in a large sample of practicing gastroenterologists in France. J Hepatol 2012; 57: 376-383 . doi:10.1016/j.jhep.2012.03.019
  • 35 Permutt Z, Le TA, Peterson MR. et al Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease – MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther 2012; 36: 22-29 . doi:10.1111/j.1365-2036.2012.05121.x
  • 36 Roeb E, Geier A. Nichtalkoholische Steatohepatitis (NASH) – aktuelle Behandlungsempfehlungen und zukünftige Entwicklungen. Z Gastroenterol 2019; 57: 508-517 . doi:10.1055/a-0784-8827
  • 37 Bohte AE, van Werven JR, Bipat S. et al The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol 2011; 21: 87-97 . doi:10.1007/s00330-010-1905-5
  • 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: 846-854 . doi:10.1002/hep.21496
  • 39 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: 1317-1325 . doi:10.1002/hep.21178
  • 40 McPherson S, Stewart SF, Henderson E. et al Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut 2010; 59: 1265-1269 . doi:10.1136/gut.2010.216077
  • 41 Younes R, Rosso C, Blanco MJG. et al PS-205-Longitudinal prognostic value of the most common algorithms for fibrosis in non-alcoholic fatty liver disease: An international study in non-cirrhotic, biopsy-proven patients. J Hepatol 2019; 70: e136-e137 . doi:10.1016/S0618-8278(19)30239-7
  • 42 Lazarus JV, Colombo M, Cortez-Pinto H. et al NAFLD – sounding the alarm on a silent epidemic. Nat Rev Gastroenterol Hepatol 2020; 17: 377-379 . doi:10.1038/s41575-020-0315-7
  • 43 Karsdal MA, Daniels SJ, Holm Nielsen S. et al Collagen biology and non-invasive biomarkers of liver fibrosis. Liver International 2020; 40: 736-750 . doi:10.1111/liv.14390
  • 44 Daniels SJ, Leeming DJ, Eslam M. et al ADAPT: An Algorithm Incorporating PRO-C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis. Hepatology 2019; 69: 1075-1086 . doi:10.1002/hep.30163
  • 45 Boyle M, Tiniakos D, Schattenberg JM. et al Performance of the PRO-C3 collagen neo-epitope biomarker in non-alcoholic fatty liver disease. JHEP Reports 2019; 1: 188-198 . doi:10.1016/j.jhepr.2019.06.004
  • 46 Vali Y, Lee J, Boursier J. et al Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis. Journal of Hepatology 2020; DOI: 10.1016/j.jhep.2020.03.036.
  • 47 Verma S, Jensen D, Hart J. et al Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Liver International 2013; 33: 1398-1405 . doi:10.1111/liv.12226
  • 48 Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001; 35: 195-199 . doi:10.1016/S0168-8278(01)00094-0
  • 49 Jun BG, Park WY, Park EJ. et al A prospective comparative assessment of the accuracy of the FibroScan in evaluating liver steatosis. PLoS ONE 2017; 12: e0182784 . doi:10.1371/journal.pone.0182784
  • 50 Eddowes PJ, Sasso M, Allison M. et al Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019; 156: 1717-1730 . doi:10.1053/j.gastro.2019.01.042
  • 51 Byun J, Lee SS, Sung YS. et al CT indices for the diagnosis of hepatic steatosis using non-enhanced CT images: development and validation of diagnostic cut-off values in a large cohort with pathological reference standard. Eur Radiol 2019; 29: 4427-4435 . doi:10.1007/s00330-018-5905-1
  • 52 Younossi ZM, Loomba R, Anstee QM. et al Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology 2018; 68: 349-360 . doi:10.1002/hep.29721
  • 53 Guha IN, Parkes J, Roderick P. et al Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 2008; 47: 455-460 . doi:10.1002/hep.21984
  • 54 Musso G, Gambino R, Cassader M. et al Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011; 43: 617-649 . doi:10.3109/07853890.2010.518623
  • 55 Yoneda M, Fujii H, Sumida Y. et al Platelet count for predicting fibrosis in nonalcoholic fatty liver disease. J Gastroenterol 2011; 46: 1300-1306 . doi:10.1007/s00535-011-0436-4
  • 56 Suzuki A, Lymp J, St SauverJ. et al Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis. Liver Int 2006; 26: 1209-1216 . doi:10.1111/j.1478-3231.2006.01362.x