MITOCHONDRIAL DNA CIRCULATES IN THE SERUM OF PATIENTS WITH ALCOHOLIC LIVER DISEASE AND REFLECTS ONGOING LIVER INJURY

Background and Aims: Mitochondrial damage-associated molecular patterns(DAMPs) share structural similarity with bacteria and may trigger potent immune response. We have recently demonstrated that mitochondrial DNA is a major component of mitochondrial DAMPs which directly drives liver disease progression. Here, we aimed to investigate circulating mtDNAs and its potential significance as a disease biomarker in patients with alcoholic liver disease (ALD).
Methods: We retrospectively analyzed serum and plasma samples from 43 patients admitted with ALD to Beth Israel Deaconess Medical Centre. Absolute copy number of cell-free mitochondrial DNA was measured using novel inhouse high sensitivity digital droplet polymerase chain reaction assay via amplification of two different mtDNA regions (DL, hND1). The relationship between multiple clinically relevant serum markers and serum and plasma DL and hND1 (as well as their averages) was assessed using linear regression analysis.
Results: The P-values and the correlation coefficients revealed that ALT, ALP, Triglycerides, lipoprotein-Z, lipoprotein-X, and apolipoprotein b were significantly associated with average plasma and serum DL and hND1. Average plasma DL and hND1 correlates better with ALT (r² =0.31, P < 0.001) and ALP (r²=0.29, P < 0.001), while average serum DL and hND1 correlates better with Triglycerides (r² =0.38, P = 0.001), lipoprotein-Z (r² =0.17, P = 0.005), and apolipoprotein b (r² =0.13, P = 0.01) . There was no significant correlation between AST, Z-index and average plasma and serum DL and hND1.
Conclusion: We developed novel ddPCR assay for circulating mtDNA and showed that elevated plasma and serum mtDNA levels correlate with parameters of alcohol-related liver injury and lipid metabolism in patients with AH. mtDNA may be a promising new disease biomarker in patients with alcoholic liver disease, supporting larger, prospective validation studies.