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RESEARCH PRODUCT

A Cholestatic Pattern Predicts Liver-Related Events in Patients with Nonalcoholic Fatty Liver Disease

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Background & Aims: Liver test alteration patterns can be categorized as: predominantly hepatocellular(H), with an ALT/ALP ratio>5; predominantly cholestatic pattern(C) with a ratio 55 years(HR2.55,95%C.I.1.17-5.54;p=0.01), platelets<150,000/mmc(HR0.14,95%C.I.0.06-0.32;p<0.001), albumin<4g/L(HR0.62,95%C.I.0.35-1.08;p=0.09), C vs M pattern(HR7.86,95%C.I.1.03-60.1;p=0.04), C vs H pattern(HR12.1,95% C.I.1.61-90.9;p=0.01) and fibrosis F3-F4(HR35.8,95%C.I.4.65-275.2;p<0.001) were independent risk factors for LRE occurrence. C vs M pattern(HR14.3,95%C.I.1.90-105.6;p=0.008) and C vs H pattern(HR15.6,95%C.I. 2.10-115.1;p=0.0068) were confirmed independently associated with LRE occurrence in the validation set. Immunohistochemical analysis found a significant higher prevalence of moderate-high grade ductular metaplasia combined with low grade ductular proliferation in C pattern when compared with biochemical H pattern. Gene expression analysis showed a lower expression of NR1H3, RXRα, VCAM1 in patients with the C pattern. Conclusions: The presence of a cholestatic pattern in patients with NAFLD predicts a higher risk of LRE independently from other features of liver disease. Funding: GS is supported by a Senior Salary Award from Fonds de la Recherche en Sante du Quebec (FRQS) (#296306). Declaration of Interest: GS has acted as speaker for Pfizer, Merck, Novonordisk, Novartis, Gilead, and AbbVie, served as an advisory board member for Merck, Gilead, Pfizer, Allergan, Novonordisk, Intercept and Novartis and has received research funding from Merck and Theratec. All others have nothing to declare. Ethical Approval: Approval was obtained by the Ethical Committee of the University Hospital “Paolo Giaccone” in Palermo.