A Dynamic Aspartate‐to‐Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease

The aspartate‐to‐alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver‐relat...

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Vydáno v:Hepatology communications Ročník 5; číslo 6; s. 1021 - 1035
Hlavní autoři: Åberg, Fredrik, Danford, Christopher J., Thiele, Maja, Talbäck, Mats, Rasmussen, Ditlev Nytoft, Jiang, Z. Gordon, Hammar, Niklas, Nasr, Patrik, Ekstedt, Mattias, But, Anna, Puukka, Pauli, Krag, Aleksander, Sundvall, Jouko, Erlund, Iris, Salomaa, Veikko, Stål, Per, Kechagias, Stergios, Hultcrantz, Rolf, Lai, Michelle, Afdhal, Nezam, Jula, Antti, Männistö, Satu, Lundqvist, Annamari, Perola, Markus, Färkkilä, Martti, Hagström, Hannes
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.06.2021
John Wiley and Sons Inc
Wolters Kluwer Health/LWW
Témata:
Adults
Alcohol use
Apolipoproteins
Biopsy
Chronic illnesses
Codes
Fatty liver
Hepatitis
Hospitalization
Hospitals
Laboratories
Liver cancer
Liver cirrhosis
Liver diseases
Medical screening
Mortality
Original
Population
Primary care
RNA polymerase
Womens health
Sweden
Finland
ISSN:2471-254X, 2471-254X
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Shrnutí:The aspartate‐to‐alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver‐related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population‐based health‐examination surveys (FINRISK, 2002‐2012; n = 18,067) with linked registry data for incident liver‐related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver‐related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol‐related liver disease (ALD). The dynamic AAR model predicted liver‐related outcomes both overall (optimism‐corrected C‐statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver‐related outcomes within 10 years. In independent cohorts, the C‐statistic for predicting liver‐related outcomes up to a 10‐year follow‐up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area‐under‐the‐curve (AUC) for detecting prevalent cirrhosis was 0.80‐0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C‐statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.
Bibliografie:Supported by the Mary and Georg Ehrnrooth Foundation (to F.Å.), Medicinska Understödsföreningen Liv och Hälsa (to F.Å.), Finska Läkaresällskapet (to F.Å.), Finnish Foundation for Cardiovascular Research (to V.S.), National Institute of Diabetes, Digestive and Kidney Diseases (K08DK115883 to Z.G.J.), Innovation Fund Denmark (to the University of Southern Denmark), European Union’s Horizon 2020 GALAXY project (grant 668031 to the University of Southern Denmark), Novo Nordisk Foundation to the MicrobLiver Project (NNF15OC0016692 to the University of Southern Denmark), Region of Southern Denmark (postdoctoral stipend to M.T.), Stockholm County Council (K2017‐4579 to P.S.), and Center for Innovative Medicine (grant 20180889 to P.S.).
Potential conflict of interest: Dr. Hammar owns stock in AstraZeneca and consults for Swedish Orphan Biovitrum. Dr. Afdhal advises Echosens. Dr. Ekstedt advises AMRA Medical AB. Dr. Salomaa consults for Novo Nordisk and Sanofi. Dr. Thiele is on the speakers’ bureau for Echosens. The other authors have nothing to report.
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ISSN:2471-254X
2471-254X
DOI:10.1002/hep4.1700