Highlights
- •The N-terminal propeptide of type 3 collagen can be used for the staging fibrosis.
- •The ADAPT score has better diagnostic performance for identifying advanced fibrosis.
- •The ADAPT score can be used as new noninvasive tests for diagnosing advanced fibrosis.
Abstract
Background
With metabolic dysfunction-associated fatty liver disease (MAFLD) incidence and prevalence
increasing, it is necessary to identify patients with advanced fibrosis (F3-F4 stages).
We evaluated the performance of new biomarkers and algorithms for diagnosing advanced
fibrosis in an Asian population.
Methods
Data from two Asian cohorts (including 851 biopsy-proven MAFLD [578 from Wenzhou,
273 from Hong Kong]) were studied. The association between N-terminal propeptide of
type 3 collagen (PRO-C3) and the histologic stage of liver fibrosis was analyzed by
multivariable linear regression. The area under the receiver operating characteristic
curve (AUROC) was used to test the diagnostic performance of serum PRO-C3 and the
ADAPT score for advanced fibrosis and compared them to other established non-invasive
tests.
Results
Serum PRO-C3 levels increased progressively across liver fibrosis stages and correlated
with advanced fibrosis (P < 0.001). The ADAPT score had an AUROC of 0.865 (95% confidence
interval 0.829–0.901) for advanced fibrosis; the accuracy, sensitivity and negative
predictive values were 81.4%, 82.2% and 96.1%, respectively. This result was better
compared to that of PRO-C3 alone or other non-invasive fibrosis biomarkers (aspartate
aminotransferase-to-platelet ratio index, Fibrosis-4, BARD, and NAFLD fibrosis score).
In subgroup analyses (including sex, age, diabetes, NAFLD activity score, body mass
index or serum alanine aminotransferase levels), the ADAPT score had good diagnostic
performance.
Conclusion
PRO-C3 and the ADAPT score reliably exclude advanced fibrosis in MAFLD patients and
reduce the need for liver biopsy.
Abbreviations:
ALT (alanine aminotransferase), AST (aspartate aminotransferase), AAR (aspartate aminotransferase to alanine aminotransferase ratio), APRI (aspartate aminotransferase-platelet ratio index), AUROC (area under the receiver operating characteristic curve), BMI (body mass index), CI (95% confidence interval), DCA (decision curve analysis), FIB-4 (fibrosis-4), MAFLD (metabolic dysfunction-associated fatty liver disease), NAFLD (nonalcoholic fatty liver disease), NFS (NAFLD fibrosis score), NPV (negative predictive value), OR (odds ratio), PRO-C3 (N-terminal propeptide of type 3 collagen), PPV (positive predictive value)Keywords
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References
- Estimating global prevalence of metabolic dysfunction-associated fatty liver disease in overweight or obese adults.Clin Gastroenterol Hepatol. 2021; (Online ahead of print)https://doi.org/10.1016/j.cgh.2021.02.030
- The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.Hepatol Int. 2020; 14: 889-919
- From NAFLD to MAFLD: a “redefining” moment for fatty liver disease.Chin Med J (Engl). 2020; 133: 2271-2273
- Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.J Hepatol. 2018; 69: 896-904
- Non-alcoholic fatty liver disease: a growing public health problem in Turkey.Turk J Gastroenterol. 2019; 30: 865-871
- When a new definition overhauls perceptions of MAFLD related cirrhosis care.Hepatobiliary Surg Nutr. 2020; 9: 801-804
- Nonalcoholic fatty liver disease-related cirrhosis is commonly unrecognized and associated with hepatocellular carcinoma.Hepatol Commun. 2017; 1: 53-60
- Change from NAFLD to MAFLD increases the awareness of fatty liver disease in primary care physicians and specialists.J Hepatol. 2021; 74: 1254-1256
- Redefinition of fatty liver disease from NAFLD to MAFLD raised disease awareness: Mexican experience.J Hepatol. 2021; 75: 221-222
- Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population.Liver Int. 2021; 41: 1290-1293
- MAFLD and risk of CKD.Metab Clin Exp. 2021; 115: 154433
- MAFLD identifies patients with significant hepatic fibrosis better than NAFLD.Liver Int. 2020; 40: 3018-3030
- Clinical utility of the MAFLD definition.J Hepatol. 2021; 74: 989-991
- Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study.Hepatology (Baltimore, Md). 2016; 63: 827-838
- Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population.Clin Gastroenterol Hepatol. 2015; 13: 594-601.e1
- 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.e17
- Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.Hepatology (Baltimore, Md). 2003; 37: 1286-1292
- The role of liver fat and insulin resistance as determinants of plasma aminotransferase elevation in nonalcoholic fatty liver disease.Hepatology (Baltimore, Md). 2015; 61: 153-160
- Sampling variability of liver biopsy in nonalcoholic fatty liver disease.Gastroenterology. 2005; 128: 1898-1906
- Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease.Gastroenterology. 2019; 156: 1264-1281.e4
- Non-invasive assessment of non-alcoholic fatty liver disease: clinical prediction rules and blood-based biomarkers.J Hepatol. 2018; 68: 305-315
- A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.Hepatology (Baltimore, Md). 2003; 38: 518-526
- Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C.Liver Int. 2015; 35: 429-437
- ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis.Hepatology (Baltimore, Md). 2019; 69: 1075-1086
- A sequential algorithm combining ADAPT and liver stiffness can stage metabolic-associated fatty liver disease in hospital-based and primary care patients.Am J Gastroenterol. 2021; 116: 984-993
- MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease.Gastroenterology. 2020; 158: 1999-2014.e1
- A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020; 73: 202-209
- EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease.J Hepatol. 2016; 64: 1388-1402
- Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis.Hepatol Res. 2005; 33: 122-127
- Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations.Mod Pathol. 1998; 11: 560-565
- Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology (Baltimore, Md). 2005; 41: 1313-1321
- Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease.Clin Gastroenterol Hepatol. 2009; 7: 1104-1112
- The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.Hepatology (Baltimore, Md). 2007; 45: 846-854
- Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.Hepatology (Baltimore, Md). 2006; 43: 1317-1325
- 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
Article info
Publication history
Published online: December 24, 2021
Accepted:
December 13,
2021
Received:
October 4,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.