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. 2017 May 19;15(1):106.
doi: 10.1186/s12967-017-1208-6.

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

Thomas Karlas  1   2 , Lara Weise  3 , Stephanie Kuhn  4 , Felix Krenzien  5 , Matthias Mehdorn  6 , David Petroff  7 , Nicolas Linder  8 , Alexander Schaudinn  8 , Harald Busse  8 , Volker Keim  1 , Johann Pratschke  5 , Johannes Wiegand  1 , Katrin Splith  5 , Moritz Schmelzle  9
Affiliations

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

Thomas Karlas et al. J Transl Med. .

Abstract

Background: The 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.

Methods: Patients 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.

Results: Fifty-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).

Conclusions: Cell-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.

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

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Figures

Fig. 1
Fig. 1
Definition of the patient cohort. NAFLD non-alcoholic fatty liver disease, CAP controlled attenuation parameter, TE transient elastography, MR magnetic resonance
Fig. 2
Fig. 2
Association of cell-free DNA with NAFLD severity. Serum levels of both (a) 90 bp (p = 0.001) and (b) 222 bp (p = 0.009) cfDNA fragments correlate significantly with NAFLD severity (Kruskal–Wallis test and post hoc analysis, Asterisk indicates p values <0.05; double asterisk indicates p values <0.01). cfDNA cell-free DNA, NAFLD non-alcoholic fatty liver disease, ALT alanine aminotransferase, AST aspartate aminotransferase
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