Noninvasive Assessment of Liver Fibrosis and Its Clinical Significance in Nonalcoholic Fatty Liver Disease

Overview

Journal Hepatol Res

Specialty Gastroenterology

Date 2022 Mar 30

PMID 35352460

Authors

Nobuharu Tamaki

Masayuki Kurosaki

Daniel Q Huang

Rohit Loomba

Affiliations

Soon will be listed here.

Abstract

Liver fibrosis is the most important prognostic factor in patients with nonalcoholic fatty liver disease (NAFLD). Several noninvasive markers for fibrosis, including blood-based markers and imaging based-markers have been developed. Indirect fibrosis markers (e.g., fibrosis-4 index and NAFLD fibrosis score) consist of standard laboratory data and clinical parameters. Given its availability and high negative predictive value for advanced fibrosis, these markers are suitable for screening at primary care. Blood-based fibrogenesis markers (enhanced liver fibrosis and N-terminal propeptide of type 3 collagen), ultrasound-based modalities (vibration-controlled transient elastography, point shear wave elastography [SWE], and two-dimensional SWE), and magnetic resonance elastography have high diagnostic accuracy for liver fibrosis and are suitable for diagnosing liver fibrosis at secondary care centers. Sequential use of these markers can increase diagnostic accuracy and reduce health care costs. Furthermore, combining noninvasive makers may assist in identifying candidates for pharmacological trials and reducing screening failure. Emerging data suggest that these noninvasive markers are associated with liver-related events (hepatocellular carcinoma and decompensation) and mortality. Furthermore, delta change in noninvasive markers over time is also associated with time-course change in fibrosis, liver-related event risk, and mortality risk. However, the association between liver fibrosis and cardiovascular disease (CVD) risk is still controversial. CVD risk may decrease in patients with decompensated liver disease and noninvasive markers may be useful for assessing CVD risk in these patients. Therefore, noninvasive markers may be utilized as measures of fibrosis as well as real-time prognostic tools, in place of liver biopsy.

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References

Chalasani N, Younossi Z, Lavine J, Charlton M, Cusi K, Rinella M . The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017; 67(1):328-357. DOI: 10.1002/hep.29367. View

Niikura T, Imajo K, Ozaki A, Kobayashi T, Iwaki M, Honda Y . Coronary Artery Disease is More Severe in Patients with Non-Alcoholic Steatohepatitis than Fatty Liver. Diagnostics (Basel). 2020; 10(3). PMC: 7151007. DOI: 10.3390/diagnostics10030129. View

Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H . Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography. Gastroenterology. 2015; 150(3):626-637.e7. DOI: 10.1053/j.gastro.2015.11.048. View

Bravo A, Sheth S, Chopra S . Liver biopsy. N Engl J Med. 2001; 344(7):495-500. DOI: 10.1056/NEJM200102153440706. View

Wong G, Chan H, Choi P, Chan A, Lo A, Chim A . Association between anthropometric parameters and measurements of liver stiffness by transient elastography. Clin Gastroenterol Hepatol. 2012; 11(3):295-302.e1-3. DOI: 10.1016/j.cgh.2012.09.025. View

Flint A, Andersen G, Hockings P, Johansson L, Morsing A, Sundby Palle M . Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2021; 54(9):1150-1161. PMC: 9292692. DOI: 10.1111/apt.16608. View

Gantumur D, Harimoto N, Muranushi R, Hoshino K, Batbayar C, Hagiwara K . Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis. Hepatol Res. 2021; 51(10):1058-1063. DOI: 10.1111/hepr.13648. View

Lichtinghagen R, Pietsch D, Bantel H, Manns M, Brand K, Bahr M . The Enhanced Liver Fibrosis (ELF) score: normal values, influence factors and proposed cut-off values. J Hepatol. 2013; 59(2):236-42. DOI: 10.1016/j.jhep.2013.03.016. View

Sharpton S, Tamaki N, Bettencourt R, Madamba E, Jung J, Liu A . Diagnostic accuracy of two-dimensional shear wave elastography and transient elastography in nonalcoholic fatty liver disease. Therap Adv Gastroenterol. 2021; 14:17562848211050436. PMC: 8504217. DOI: 10.1177/17562848211050436. View

10.

Friedrich-Rust M, Hadji-Hosseini H, Kriener S, Herrmann E, Sircar I, Kau A . Transient elastography with a new probe for obese patients for non-invasive staging of non-alcoholic steatohepatitis. Eur Radiol. 2010; 20(10):2390-6. DOI: 10.1007/s00330-010-1820-9. View

11.

Hagstrom H, Nasr P, Ekstedt M, Stal P, Hultcrantz R, Kechagias S . Accuracy of Noninvasive Scoring Systems in Assessing Risk of Death and Liver-Related Endpoints in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2018; 17(6):1148-1156.e4. DOI: 10.1016/j.cgh.2018.11.030. View

12.

Takahashi Y, Kurosaki M, Tamaki N, Yasui Y, Hosokawa T, Tsuchiya K . Non-alcoholic fatty liver disease fibrosis score and FIB-4 scoring system could identify patients at risk of systemic complications. Hepatol Res. 2014; 45(6):667-75. DOI: 10.1111/hepr.12405. View

13.

Castellana M, Donghia R, Guerra V, Procino F, Castellana F, Zupo R . Fibrosis-4 Index vs Nonalcoholic Fatty Liver Disease Fibrosis Score in Identifying Advanced Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease: A Meta-Analysis. Am J Gastroenterol. 2021; 116(9):1833-1841. DOI: 10.14309/ajg.0000000000001337. View

14.

Loomba R, Ratziu V, Harrison S . Expert Panel Review to Compare FDA and EMA Guidance on Drug Development and Endpoints in Nonalcoholic Steatohepatitis. Gastroenterology. 2021; 162(3):680-688. PMC: 9683540. DOI: 10.1053/j.gastro.2021.10.051. View

15.

Yoneda M, Mawatari H, Fujita K, Yonemitsu K, Kato S, Takahashi H . 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. 2007; 42(5):375-81. DOI: 10.1007/s00535-007-2014-3. View

16.

Kleiner D, Brunt E, Van Natta M, Behling C, Contos M, Cummings O . Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41(6):1313-21. DOI: 10.1002/hep.20701. View

17.

Targher G, Byrne C, Lonardo A, Zoppini G, Barbui C . Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016; 65(3):589-600. DOI: 10.1016/j.jhep.2016.05.013. View

18.

Dulai P, Singh S, Patel J, Soni M, Prokop L, Younossi Z . Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017; 65(5):1557-1565. PMC: 5397356. DOI: 10.1002/hep.29085. View

19.

Tapper E, Loomba R . Noninvasive imaging biomarker assessment of liver fibrosis by elastography in NAFLD. Nat Rev Gastroenterol Hepatol. 2018; 15(5):274-282. PMC: 7504909. DOI: 10.1038/nrgastro.2018.10. View

20.

Sheka A, Adeyi O, Thompson J, Hameed B, Crawford P, Ikramuddin S . Nonalcoholic Steatohepatitis: A Review. JAMA. 2020; 323(12):1175-1183. DOI: 10.1001/jama.2020.2298. View