Serum PRO‐C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort

Author:

Tang Liang‐Jie12,Sun Dan‐Qin34,Song Sherlot Juan56,Yip Terry Cheuk‐Fung56,Wong Grace Lai‐Hung56ORCID,Zhu Pei‐Wu7,Chen Sui‐Dan8,Karsdal Morten9ORCID,Leeming Diana Julie9ORCID,Jiang Pei10,Wang Cong10,Chen Qiang211,Byrne Christopher D.12,Targher Giovanni1314ORCID,Eslam Mohammed1516ORCID,George Jacob1516,Wong Vincent Wai‐Sun56ORCID,Zheng Ming‐Hua11718ORCID

Affiliation:

1. MAFLD Research Center, Department of Hepatology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China

2. Cancer Center, Faculty of Health Sciences University of Macau Taipa Macau SAR China

3. Department of Nephrology Jiangnan University Medical Center Wuxi China

4. Affiliated Wuxi Clinical College of Nantong University Wuxi China

5. Department of Medicine and Therapeutics The Chinese University of Hong Kong Hong Kong China

6. State Key Laboratory of Digestive Disease The Chinese University of Hong Kong Hong Kong China

7. Department of Laboratory Medicine the First Affiliated Hospital of Wenzhou Medical University Wenzhou China

8. Department of Pathology the First Affiliated Hospital of Wenzhou Medical University Wenzhou China

9. Nordic Bioscience Biomarkers and Research A/S Herlev Denmark

10. Fosun Diagnostics (Shanghai) Co., Ltd Shanghai China

11. MOE Frontier Science Centre for Precision Oncology University of Macau Taipa Macau SAR China

12. Southampton National Institute for Health and Care Research, Biomedical Research Centre University of Southampton and University Hospital Southampton Southampton UK

13. Department of Medicine University of Verona Verona Italy

14. IRCCS Sacro Cuore Don Calabria Hospital Negrar di Valpolicella Italy

15. Storr Liver Centre Westmead Institute for Medical Research, Westmead Hospital Westmead New South Wales Australia

16. University of Sydney Sydney New South Wales Australia

17. Institute of Hepatology Wenzhou Medical University Wenzhou China

18. Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province Wenzhou China

Abstract

AbstractBackgroundMetabolic dysfunction‐associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N‐terminal propeptide of collagen type 3 (PRO‐C3) is a biomarker of advanced fibrosis in MAFLD and PRO‐C3 may be involved in renal fibrosis. We aimed to use PRO‐C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD–CKD).MethodsA derivation and independent validation cohort of 750 and 129 Asian patients with biopsy‐confirmed MAFLD were included. Serum PRO‐C3 concentration was measured and regression analyses were performed to examine associations with MAFLD–CKD. A derivative algorithm for MAFLD–CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis.ResultsThe study included two Asian cohorts (n = 180 with MAFLD–CKD; mean‐eGFR: 94.93 mL/min/1.73 m2; median‐urinary albumin‐to‐creatinine ratio: 6.58 mg/mmol). PRO‐C3 was associated with the severity of MAFLD‐CKD and independently associated with MAFLD–CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08–1.23, p < .001). A new non‐invasive score (termed PERIOD) including PRO‐C3 efficiently predicted MAFLD‐CKD (AUROC = .842, 95% CI: .805–.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691–.893) with similar results in all patient subgroups. In the MAFLD–CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO‐C3‐based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836–.964).ConclusionsThe PERIOD score is helpful for accurately predicting the risk of MAFLD–CKD. PRO‐C3 can also be used to assess liver fibrosis in people with MAFLD–CKD.

Funder

National Natural Science Foundation of China

Chinese University of Hong Kong

Publisher

Wiley

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