Level of MFAP4 in ascites independently predicts 1-year transplant-free survival in patients with cirrhosis
Nikolaj Torp,
Mads Israelsen,
Bjørn Madsen,
Philipp Lutz,
Christian Jansen,
Christian Strassburg,
Christian Mortensen,
Anne Wilkens Knudsen,
Grith Lykke Sorensen,
Uffe Holmskov,
Anders Schlosser,
Maja Thiele,
Jonel Trebicka,
Aleksander Krag
Affiliations
Nikolaj Torp
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
Mads Israelsen
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
Bjørn Madsen
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
Philipp Lutz
Department of Internal Medicine I, University of Bonn, Bonn, Germany
Christian Jansen
Department of Internal Medicine I, University of Bonn, Bonn, Germany
Christian Strassburg
Department of Internal Medicine I, University of Bonn, Bonn, Germany
Christian Mortensen
Gastro Unit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
Anne Wilkens Knudsen
Gastro Unit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
Grith Lykke Sorensen
Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
Uffe Holmskov
Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
Anders Schlosser
Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
Maja Thiele
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
Jonel Trebicka
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Internal Medicine I, University Hospital of Frankfurt, Frankfurt, Germany; European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Barcelona, Spain; Institute for Bioengineering of Catalonia, Barcelona, Spain
Aleksander Krag
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Corresponding author. Address: Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Kloevervaenget 10, 5000 Odense C, Denmark.
Background & Aims: Prognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites. Methods: A dual-centre observational study of patients with cirrhosis and ascites recruited consecutively in relation to a paracentesis was carried out. Patients were followed up for 1 year, until death or liver transplantation (LTx). Ascites MFAP4 was tested with the model for end-stage liver disease (MELD-Na), CLIF Consortium Acute Decompensation (CLIF-C AD), and Child-Pugh score in Cox regression models. Results: Ninety-three patients requiring paracentesis were included. Median ascites MFAP4 was 29.7 U/L [22.3–41.3], and MELD-Na was 19 [16–23]. A low MELD-Na score (29.7 U/L) was associated with 1-year transplant-free survival (p = 0.002). In Cox regression, ascites MFAP4 and MELD-Na independently predicted 1-year transplant-free survival (hazard ratio [HR] = 0.97, p = 0.03, and HR = 1.08, p = 0.01, respectively). Ascites MFAP4 and CLIF-C AD also predicted survival independently (HR = 0.96, p = 0.02, and HR = 1.05, p = 0.03, respectively), whereas only ascites MFAP4 did, controlling for the Child-Pugh score (HR = 0.97, p = 0.03, and HR = 1.18, p = 0.16, respectively). For patients with MELD-Na <20, ascites MFAP4 but not ascites protein predicted 1-year transplant-free survival (HR 0.91, p = 0.02, and HR = 0.94, p = 0.17, respectively). Conclusions: Ascites MFAP4 predicts 1-year transplant-free survival in patients with cirrhosis and ascites. In patients with low MELD-Na scores, ascites MFAP4, but not total ascites protein, significantly predicted 1-year transplant-free survival. Lay summary: Patients with cirrhosis who have fluid in the abdomen, ascites, are at an increased risk of death and in need for liver transplantation. Our study identified patients with ascites and a poor prognosis by measuring microfibrillar associated protein 4 (MFAP4), a protein present in the abdominal fluid. Patients with low levels of the MFAP4 protein are at particularly increased risk of death or liver transplantation, suggesting that clinical care should be intensified in this group of patients.
