Background and Aim The recommendation in regard to screening for non‐alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. The aim of this paper was to study the prevalence of NALFD and advanced fibrosis among T2DM patients. Methods This is a cross‐sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥ 263 dB/m, and the liver stiffness measurement was ≥ 9.6 kPa using the M probe or ≥ 9.3 kPa using the XL probe, respectively. Patients with liver stiffness measurement ≥ 8 kPa were referred to the Gastroenterology and Hepatology Clinic for further assessment, including liver biopsy. Results The data of 557 patients were analyzed (mean age 61.4 ± 10.8 years, male 40.6%). The prevalence of NAFLD and advanced fibrosis based on transient elastography was 72.4% and 21.0%, respectively. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR 4.856, 95% confidence interval [CI] 2.749–8.577, P = 0.006), serum triglyceride (OR 1.585, 95% CI 1.056–2.381, P = 0.026), and alanine aminotransferase levels (OR 1.047, 95% CI 1.025–1.070, P < 0.001) while advanced fibrosis was associated with serum high‐density lipoprotein cholesterol (OR 0.355, 95% CI 0.126–0.997, P = 0.049), alanine aminotransferase (OR 1.023, 95% CI 1.009–1.037, P = 0.001), γ‐glutamyltransferase (OR 1.005, 95% CI 1.001–1.008, P = 0.017), and platelet levels (OR 0.995, 95% CI 0.992–0.999, P = 0.010). Seventy‐one patients underwent liver biopsy. The majority had non‐alcoholic steatohepatitis (83.1%) and ≥ F1 fibrosis (87.3%) while advanced fibrosis was seen in 36.6%. Conclusion The prevalence of NAFLD and advanced fibrosis based on transient elastography is high among T2DM patients.

Abbreviations: 95% CI, 95% confidence interval; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUROC, area under the receiver operating characteristic curve; BMI, body mass index; CK18, cytokeratin 18; F, fibrosis stage; FIB-4, fibrosis-4 index; HbA1c, glycated haemoglobin; HOMA, homeostatic model assessment of insulin resistance; MACK-3, combination of hoMa, Ast and CK18; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score; NASH, non-alcoholic steatohepatitis; NFS, NAFLD fibrosis score. Abstract Introduction: MACK-3 (combination of hoMa, Ast and CK18) was reported to be a good biomarker for the diagnosis of fibrotic non-alcoholic steatohepatitis (NASH). However, there is no external validation to date. Aim: To evaluate the accuracy of MACK-3 for the diagnosis of fibrotic NASH. Methodology: Consecutive adult non-alcoholic fatty liver disease (NAFLD) patients who had liver biopsy in a university hospital were included. MACK-3 was calculated using the online calculator using the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18). MACK-3 cut-offs ≤0.134 and ≥0.550 were used to predict absence and presence of fibrotic NASH, respectively. Histopathological examination of liver biopsy specimen was reported according to the NASH Clinical Research Network Scoring System. Results: Data for 196 subjects were analysed. MACK-3 was good for diagnosis of fibrotic NASH (area under receiver-operating characteristics curve [AUROC] 0.80), comparable to the Fibrosis-4 index (FIB4) and the NAFLD fibrosis score (NFS) and superior to the BARD score and CK18. MACK-3 was good for diagnosis of active NASH (AUROC 0.81) and was superior to other blood fibrosis tests. The overall accuracy, percentage of subjects in grey zone, sensitivity, specificity, positive predictive value and negative predictive value of MACK-3 for diagnosis of fibrotic NASH was 79.1%, 46.9%, 100%, 43.8%, 43.1% and 100%, respectively, while for diagnosis of active NASH was 90.0%, 39.3%, 84.2%, 81.4%, 88.9% and 74.5%, respectively. Conclusion: MACK-3 is promising as a non-invasive test for active NASH and fibrotic NASH and may be useful to identify patients who need more aggressive intervention. K E Y W O R D S active NASH, cytokeratin-18, fibrotic NASH, non-invasive test

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