Abstract
Background
There has been an increased interest in the use of noninvasive tests (NITs) to identify advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NALFD). The aim of our study was to define the change in tests’ characteristics (sensitivity and specificity) of different combinations of NITs to detect advanced fibrosis in NAFLD.
Methods
We stratified NITs into first and second tiers and compared two different strategies of combining NITs to screen for advanced fibrosis in patients with NAFLD. One strategy was using NITs in parallel, and the other was using NITs sequentially. Within both of these strategies, there were two ways of interpreting the overall results. The first way was called “the AND rule,” where a positive result required both individual test results to be positive. The second way was called “the OR rule,” where a positive result required only one individual test to be positive. Accuracy of NITs was obtained from the literature search. Combined accuracy and likelihood ratio (LR) were calculated.
Results
Combination testing with parallel and sequential order testing under the AND Rule resulted in overall higher specificity and LR+ then using the NITs alone. Specificity ranged from 0.91 to 0.99, and LR+ from 9.3 to 68.6. The subsequent use of MRE was associated with LR+ between 36 and 69. Sensitivity was higher with parallel and sequential order testing under the OR Rule. LR+ ranged from 1.4 to 7.5, and sensitivity from 0.82 to 0.98.
Conclusion
Screening for advanced fibrosis should be performed sequentially, with positive results confirmed by additional testing. Specificity and LR+ were highest when MRE was employed as the confirmatory test.
Similar content being viewed by others
References
Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital Stat Rep. 2013;61:1–117.
Hoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep. 2012;61:1–5.
Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23:8263–8276.
Younossi ZM, Marchesini G, Pinto-Cortez H, Petta S. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: implications for liver transplantation. Transplantation. 2019;103:22–27.
Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Metaanalytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.
Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study. Gastroenterology. 2018;155:443–457.
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;S0016-5085:30137.
Younossi Z, Stepanova M, Ong JP, et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2019;17:748–755.
Musso G, Gambino R, Cassader M, Pagano G. 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.
Kaswala DH, Lai M, Afdhal NH. Fibrosis assessment in nonalcoholic fatty liver disease (NAFLD) in 2016. Dig Dis Sci. 2016;61:1356–1364. https://doi.org/10.1007/s10620-016-4079-4
Tapper EB, Loomba R. Noninvasive imaging biomarker assessment of liver fibrosis by elastography in NAFLD. Nat Rev Gastroenterol Hepatol. 2018;15:274–282.
Anstee QM, Lawitz EJ, Alkhouri N, et al. Noninvasive tests accurately identify advanced fibrosis due to NASH: baseline data from the STELLAR trials. Hepatology. 2019;70:1521–1530.
McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-inva-sive fibrosis scoring systems can reliably exclude advanced fibrosis inpatients with non-alcoholic fatty liver disease. Gut. 2010;59:1265–1269.
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. Hepatology. 2018;67:328–357.
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–402.
Tapper EB, Challies T, Nasser I, Afdhal NH, Lai M. 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.
Weinstein S, Obuchowski NA, Lieber ML. Clinical evaluation of diagnostic tests. AJR Am J Roentgenol. 2005;184:14–19.
McGee S. Simplifying likelihood ratios. J Gen Int Med. 2002;17:647–650.
Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395.
Xie L, Yui J, Hatori A, et al. Translocator protein (18 kDa), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease. J Hepatol. 2012;57:1076–1082.
Shetty A, Jun Yum J, Saab S. The gastroenterologist’s guide to preventive management of compensated cirrhosis. Gastroenterol Hepatol (N Y). 2019;15:423–430.
Frenette CT, Isaacson AJ, Bargellini I, Saab S, Singal AG. A practical guideline for hepatocellular carcinoma screening in patients at risk. Mayo Clin Proc Innov Qual Outcomes. 2019;3:302–310.
Loomba R, Lim JK, Patton H, El-Serag HB. AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review. Gastroenterology. 2020. https://doi.org/10.1053/j.gastro.2019.12.053. [Epub ahead of print]
Bohula EA, Wiviott SD, McGuire DK, et al. Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med. 2018;379:1107–1117.
Lee Y, Doumouras AG, Yu J, et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17:1040–1060.
Kwak M, Mehaffey JH, Hawkins RB, Hsu A, Schirmer B, Hallowell PT. Bariatric surgery is associated with reduction in non-alcoholic steatohepatitis and hepatocellular carcinoma: a propensity matched analysis. Am J Surg. 2019;S0002-9610:30853. https://doi.org/10.1016/j.amjsurg.2019.09.006.
Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67:829–846.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70:172–193.
Kaplan DE, Serper MA, Mehta R, et al. Effects of hypercholesterolemia and statin exposure on survival in a large national cohort of patients with cirrhosis. Gastroenterology. 2019;156:1693–1706.
Dong Y, Lv Q, Li S, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2017;41:284–295.
Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019;394:2184–2196.
Author information
Authors and Affiliations
Contributions
RK, SS contributed to study concept and design; LL, RK, HMS contributed to acquisition of data; all contributed to analysis and interpretation of data; all contributed to drafting of the manuscript; LL, RK, SS contributed to critical revision of the manuscript for important intellectual content; LL contributed to statistical analysis; N/A contributed to obtained funding; SS contributed to administrative, technical, or material support; study supervision.
Corresponding author
Ethics declarations
Conflict of interest
RK is an employee and owns stock at Gilead Pharmaceuticals. SS is on the speaker bureau and honoraria recipient of AbbVie, Bristol Myers Squibb, Bayer, Eisai, Exelixis, Gilead, Intercept, and Salix. He is also an advisor/consultant for: AbbVie, Bayer, Eisai, Exelixis, Gilead, Intercept, Mallinckrodt, and Salix. APP has no disclosure to report.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Le, L., Kullar, R., Saleh, H.M. et al. Preferred Noninvasive Testing for Nonalcoholic Steatohepatitis. Dig Dis Sci 65, 3719–3725 (2020). https://doi.org/10.1007/s10620-020-06382-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-020-06382-4