Original articleResearch correspondenceSerum Activity of Macrophage-Derived Adenosine Deaminase 2 Is Associated With Liver Fibrosis in Nonalcoholic Fatty Liver Disease
Section snippets
Methods
We measured the rate of 3 tandem enzyme activities in extracellular ADP metabolism in the serum of 100 biopsy-proven NAFLD patients and studied their cross-sectional association to liver fibrosis (Figure 1A). These patients were selected from a previously described prospective NAFLD registry to approximate an equal distribution of fibrosis stages.5 Blood samples were collected at the index visit. Liver biopsies performed within 3 months of enrollment were reviewed by a hepatobiliary pathologist
Results
Among 100 patients in the study, 41 were female, 89 were diagnosed with nonalcoholic steatohepatitis (NASH), 57 had stages 2 to 4 fibrosis, and 12 had cirrhosis. Among the 3 enzymatic steps, the rate of conversion from adenosine to inosine via ADA was significantly higher among patients with stages 2 to 4 fibrosis compared with patients with stages 0 to 1 fibrosis (18.7 ± 6.9 vs 14.8 ± 5.0 U/L, respectively), whereas the rates of conversion from ADP to AMP and AMP to adenosine were not
Discussion
This study showed a positive cross-sectional association between the circulating activity of ADA2, a macrophage-derived deaminase, and liver fibrosis in NAFLD. The emerging association between ADA2 deficiency and vasculitis suggests a potential mechanistic link underscoring this association, in which ADA2 modulates macrophage phenotype and impacts fibrogenesis.
ADA2 expression was observed in both infiltrative and resident macrophages in the liver. Defects in ADA2 have been linked to impaired
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Conflicts of interest The authors disclose no conflicts.
Funding Supported in part by a Clinical Research Award from the American College of Gastroenterology and the Alan Hofmann Clinical and Translational Research Award from the American Association for the Study of Liver Diseases (Z.G.J.), and National Institutes of Health grants P01HL107152 and R21CA164970 (S.C.R.) and K23DK083439 (M.L.).