Diagnosis of different liver fibrosis characteristics by blood tests in non‐alcoholic fatty liver disease

Aims: Our aim was to develop an accurate, non‐invasive, blood‐test‐based method for identifying the main characteristics of liver fibrosis in non‐alcoholic fatty liver disease (NAFLD). Methods: Fibrosis was staged according to NASH‐CRN and Metavir systems in 226 patients with NAFLD. A fully automated algorithm measured the fractal dimension (FD) and the area of fibrosis (AOF). Independent predictors of diagnostic targets were determined using bootstrap methods. Results: (i) Development. Significant fibrosis defined by NASH‐CRN F≥2 was diagnosed by weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothrombin index [area under the receiver operating characteristic (AUROC)=0.867]; significant fibrosis defined by Metavir F≥2 was diagnosed by weight, age, glycaemia, AST, ALT, ferritin and platelets (FibroMeter AUROC=0.941, P<0.005). AOF was estimated by the combination of hyaluronic acid, glycaemia, AST, ALT, platelets and prothrombin index (_aR²=0.530), while FD was estimated by hyaluronic acid, glycaemia, AST/ALT, weight and platelets (_aR²=0.529). (ii) Evaluation. Although NASH‐CRN was a better system for fibrosis staging, Metavir staging was a better reference for blood test. Thus, the patient rate with predictive values≥90% by tests was 97.3% with Metavir reference vs. 66.5% with NASH‐CRN reference (P<10^?3). FibroMeter showed a significantly higher AUROC than the NAFLD fibrosis score for significant fibrosis, but not for severe fibrosis or cirrhosis, with both staging systems. Relationships between fibrosis lesions were well reflected by blood tests, e.g., the correlation between histological area and FD of fibrosis (r_s=0.971, P<10^?3) was well reflected by the relationship between respective blood tests (r_s=0.852, P<10^?3). Conclusions: Different characteristics of fibrosis in NAFLD can be diagnosed and quantified by blood tests with excellent accuracy.     

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non‐alcoholic fatty liver disease patients

Introduction: Differentiation between steatosis and non‐alcoholic steatohepatitis (NASH) in non‐alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. Patients and methods: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. Results: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86–0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85. Conclusion: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis.     

Ad36 adipogenic adenovirus in human non‐alcoholic fatty liver disease

Aims: Infection with specific pathogens may lead to increased adiposity. The human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis. It seems to improve the metabolic profile, expanding adipose tissue and enhancing insulin sensitivity in animal models. The aim of this study was to investigate whether any association or predictor effect of Ad36 seropositivity is present in non‐alcoholic fatty liver disease (NAFLD), a condition associated with obesity and insulin resistance (IR). Methods: Sixty‐five NAFLD patients and 114 controls were investigated. Ultrasound bright liver score (BLS), body composition, IR evaluated by homeostasis model assessment of insulin resistance index (HOMA or HOMA‐IR) and serum neutralization assay for antibodies to Ad36 were assessed. Results: Ad36‐seropositive patients have a lower risk of bright liver [OR 0.505 (95% confidence interval (CI) 0.265–0.962)]; greater IR leads to a higher risk of bright liver [OR 9.673 (95% CI 4.443–21.058)]. Among NAFLD, Ad36‐seropositive vs. Ad36‐seronegative patients did not show a significant IR difference. Ad36‐seropositive NAFLD patients, with the same levels of HOMA and BLS, had greater body mass index and body fat mass, in comparison with seronegative NAFLD patients. By a multiple linear regression model, BLS was explained by HOMA (β 0.513; P<0.0001), high density lipoprotein cholesterol (β?0.219, P<0.006) and Ad36 seropositivity (β?0.202, P<0.005); Ad36 seropositivity did not explain HOMA in the other multiple logistic regression model. Conclusions: Ad36 seropositivity is not associated with a significant difference of IR in NAFLD patients, but is associated with a greater adiposity. Ad36 seropositivity is associated with a lower occurrence of NAFLD and bright liver, which, conceivably, is not directly mediated by IR.