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

Liang-Jie Tang^{1

2}, Dan-Qin Sun^{3

4}, Sherlot Juan Song^{5

6}, Terry Cheuk-Fung Yip^{5

6}, Grace Lai-Hung Wong^{5

6}, Pei-Wu Zhu⁷, Sui-Dan Chen⁸, Morten Karsdal⁹, Diana Julie Leeming⁹, Pei Jiang¹⁰, Cong Wang¹⁰, Qiang Chen^{2

11}, Christopher D Byrne¹², Giovanni Targher^{13

14}, Mohammed Eslam^{15

16}, Jacob George^{15

16}, Vincent Wai-Sun Wong^{5

6}, Ming-Hua Zheng^{1

17

18}

Affiliations

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.

PMID: 38426611
DOI: 10.1111/liv.15878

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

Liang-Jie Tang et al. Liver Int. 2024 May.

. 2024 May;44(5):1129-1141.

doi: 10.1111/liv.15878. Epub 2024 Mar 1.

Authors

Affiliations

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.

PMID: 38426611
DOI: 10.1111/liv.15878

Abstract

Background: Metabolic 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).

Methods: A 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.

Results: The 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).

Conclusions: The 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.

Keywords: N‐terminal propeptide of type 3 collagen; chronic kidney disease; liver fibrosis; metabolic dysfunction‐associated fatty liver disease; metabolic dysfunction‐associated steatotic liver disease; risk prediction.

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Comment in

PRO-C3, liver fibrosis and CKD: The plot thickens.
Lonardo A. Lonardo A. Liver Int. 2024 May;44(5):1126-1128. doi: 10.1111/liv.15888. Liver Int. 2024. PMID: 38634694 No abstract available.

References

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

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

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