Non-invasive biomarkers for assessment of non-alcoholic fatty liver disease

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Background and Aim : Non-alcoholic fatty liver disease (NAFLD) is a major public health problem afflicting approximately one billion individuals worldwide. Liver biopsy is considered the gold standard for assessment of liver disease severity in patients with NAFLD. It is invasive and is associated with adverse effects, and also has higher inter-observer variability. Liver biopsy is impractical because of large number of individuals who have NAFLD and is not appropriate for screening. Therefore, non-invasive biomarkers to assess disease severity in NAFLD are needed. We use a combined approach of non-invasive imaging modalities and clinical, biochemical, metabolic and lipid biomarkers to grade liver fat and liver fibrosis, to assess presence of NAFLD, and to detect the progressive form of NAFLD, termed non-alcoholic steatohepatitis. Methods: We evaluated 60 patients with presence of metabolic syndrome and suspected NAFLD. Other liver diseases, alcohol consumption ≥ 20 g/day, and use of drugs associated with liver steatosis were excluded. Anthropometric variables (weight, BMI, waist circumference), liver function tests, full blood count, serum lipids, fasting glucose, abdominal ultrasonography, liver transient elastography (TE) with fibroscan M probe (XL probe only in 5%) and CAP (controlled attenuation parameter) were assessed. The cut-off values for CAP and TE were defined as previously published. Indirect markers for fibrosis and steatosis were calculated. Results: The mean age was 59 years, 59% female. 72% patients had diagnosis of diabetes mellitus (DM). The median weight was 90.3 kg, median BMI 32 kg/m² and median waist circumference – 112.8 cm. According to the Hepatic Steatosis Index, 4% of the patients were without NAFLD (HSI below 30) and 92% showed HSI higher than 36. Abdominal ultrasonography findings of hepatic steatosis were: 6% with no evidence of steatosis, 15% with grade I, 26% with grade II, and 53 % with grade III. The share of patients with CAP value under 215 db/m was 6% (suggestive steatosis under 33%), with CAP value between 217 db/m and 252 db/m – 10% (steatosis 34%-66%), with CAP value between 253 db/m and 296 db/m – 25% (steatosis over 67%), and 58% of patients had CAP value over 297 db/m. A FIB-4 index below 1.3 was found in 70% of patients. Respectively, 22% had FIB-4 index between 1.3 and 2.67. The share of patients with significant fibrosis with higher FIB-4 was 7.5%. TE values ≥ 7.9 kPa were identified in 34% of patients. Conclusion: A combined approach of non-invasive biomarkers is better recommended for the diagnosis and grading of liver steatosis and for the detection of progressive forms of NAFLD.