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PTH-082 Do Serum Markers Of Cell Injury And Death Have Potential To Become Mechanistic Markers In Non-alcoholic Fatty Liver Disease (nafld)?
  1. JI Grove1,
  2. DJ Antoine2,
  3. P Kaye1,
  4. MH Miller3,
  5. JF Dillon3,
  6. ME Allison4,
  7. MW James1,
  8. EA Wilkes1,
  9. AP Jackson1,
  10. IN Guha1,
  11. DP Williams2,
  12. GP Aithal1
  1. 1National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Nottingham, UK
  2. 2Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
  3. 3Biomedical Research Institute, University of Dundee, Dundee, UK
  4. 4National Institute for Health Research Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Abstract

Introduction Degree of hepatocellular injury, necrosis/apoptosis and inflammation may be assessed by the serum markers that reflect the pathogenic process. We investigated the correlation of circulating miR-122, High Mobility Group Box-1 (HMGB1), soluble Fas (sFas) and caspase-cleaved fragment of keratin-18 (CK18) with histological changes in liver biopsy of patients with non-alcoholic fatty liver disease (NAFLD).

Methods Serum analytes were determined in two independent cohorts of patients with NAFLD (derivation cohort n = 165, validation cohort n = 101). Histological parameters were scored using Clinical Research Network system; patients with NAFLD activity scores (NAS) of ≥3 were classified as borderline non-alcoholic steatohepatitis (NASH) and ≥ 5 as definite NASH.

Results There were no significant differences in miR-122, HMGB1, sFas and CK18 M30 levels between those with low (0–2) and high (3–4) stage of fibrosis. Both CK18 M30 as well as CK18 M65 correlated with grades of ballooning (p = 0.003 and p = 0.001) and lobular inflammation (p = 0.006 and p = 0.001). Table 1 summarises the serum levels of all the evaluated markers in subgroups of patients classified as borderline or definite NASH when only patients with low grade fibrosis were included (derivation cohort, n = 145 and validation cohort, n = 90). Importantly, when the cut-off values for CK18 M30 (395 U/L) was used on its own, 57/86 (66%) patients with definite NASH were missed.

Abstract PTH-082 Table 1

Conclusion Biomarkers, UKof cell injury and death in combination have a potential to detect on-going histological activity in NAFLD.

Disclosure of Interest None Declared.

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