Correlation of cell-free DNA plasma concentration with severity of non-alcoholic fatty liver disease

Journal of Translational Medicine

Research

David Petroff¹  Stephanie Kuhn²  Nicolas Linder³  Alexander Schaudinn³  Harald Busse³  Johannes Wiegand⁴  Volker Keim⁴  Thomas Karlas⁵  Moritz Schmelzle⁶  Johann Pratschke⁶  Felix Krenzien⁶  Katrin Splith⁶  Matthias Mehdorn⁷  Lara Weise⁸ 

[1] Clinical Trial Centre, Leipzig University, Leipzig, Germany;Department Environmental Immunology, Helmholtz Centre for Environmental Research GmbH-UFZ, Leipzig, Germany;Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany;Department of Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany;Department of Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany;IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany;Department of Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany;Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany;Medical Faculty, Leipzig University, Leipzig, Germany;

关键词: Controlled attenuation parameter;    Transient elastography;    Cell-free DNA;    MR-spectroscopy;    Non-alcoholic fatty liver disease;    Non-alcoholic steatohepatitis;   

DOI  :  10.1186/s12967-017-1208-6

 received in 2017-01-11, accepted in 2017-05-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe assessment of fibrosis and inflammatory activity is essential to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk for progressive disease. Serum markers and ultrasound-based methods can replace liver biopsy for fibrosis staging, whereas non-invasive characterization of inflammatory activity remains a clinical challenge. Cell-free DNA (cfDNA) is a novel non-invasive biomarker for assessing cellular inflammation and cell death, which has not been evaluated in NAFLD.MethodsPatients and healthy controls from two previous studies were included. NAFLD disease activity and severity were non-invasively characterized by liver stiffness measurement (transient elastography, TE) including steatosis assessment with controlled attenuation parameter (CAP), single-proton magnetic resonance spectroscopy (1H-MRS) for determination of hepatic fat fraction, aminotransferases and serum ferritin. cfDNA levels (90 and 222 bp fragments) were analyzed using quantitative real-time PCR.ResultsFifty-eight NAFLD patients (age 62 ± 11 years, BMI 28.2 ± 3.5 kg/m2) and 13 healthy controls (age 38 ± 12 years, BMI 22.4 ± 2.1 kg/m2) were included. 90 bp cfDNA levels were significantly higher in NAFLD patients compared to healthy controls: 3.7 (1.3–23.1) vs. 2.9 (1.4–4.1) ng/mL (p = 0.014). In the NAFLD cohort, circulating cfDNA correlated significantly with disease activity and severity, especially in patients with elevated liver stiffness (n = 13, 22%) compared to cases with TE values ≤7 kPa: cf90 bp 6.05 (2.41–23.13) vs. 3.16 (1.29–7.31) ng/mL (p < 0.001), and cf222 bp 14.41 (9.27–22.90) vs. 11.32 (6.05–18.28) ng/mL (p = 0.0041).ConclusionsCell-free DNA plasma concentration correlates with established non-invasive markers of NAFLD activity and severity. Therefore, cfDNA should be further evaluated as biomarker for identifying patients at risk for progressive NAFLD.

【 授权许可】

CC BY   
© The Author(s) 2017