Diagnostics of progression of liver fibrosis in patients with non-alcoholic steatohepatitis combined with obesity and chronic calculous cholecystitis

The aim of the work is to investigate the diagnostic value of laboratory blood biomarkers – alanine aminotransferase, aspartate aminotransferase, oxyproline and prothrombin time in comparison with morphological indicators for diagnosis of the degree of liver fibrosis in patients with comorbid course of non-alcoholic steatohepatitis (NASH) combined with obesity and chronic calculous cholecystitis. The data of 22 patients with NASH combined with obesity and chronic calculous cholecystitis was analyzed by laboratory and morphological indicators. There were 6 (27.2%) men and 16 (72.8%) women among the patients. Liver biopsy was performed intra-operatively on performing surgical treatment of calculus cholecystitis. METAVIR and Е. Brunt criteria were used in the histological diagnosis of NASH, as well as for determination of the stage of liver fibrosis (LF). Hepatic tissue fibrogenesis was assessed by serum values of total (OPT), free (OPF) and protein-bound (OPB) oxyproline, activity of indirect fibrosis markers – alanine ami­notransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio and prothrombin time (РТТ). As a mathematical tool for modeling, stepwise discriminant analysis was used. Fibrosis of the first stage (F1) was observed in 5 (22.7%) patients, the second stage of fibrosis (F2) – in 7 (31.8%), F3 stage of fibrosis - in 10 (45.5%) patients. Analysis of the morphological study of liver biopsy samples in examined patients with NASH indicates that established histological changes combine the signs of fatty and protein degeneration of hepatocytes, inflammation and necrosis in the lobules. Among the indicators included in the mathematical model the highest diagnostic significance can be attributed to the AST / ALT ratio (F = 9.03; p = 0.003) and the level of OPF (F = 5.67; p = 0.016), whereas OPB level has the lowest value (F = 2.94; p = 0.086). Evaluation of the accuracy of the method for determining of the LF phase based on the proposed algorithm showed that the frequency of correct detecting of F1 and F2 stages of LF was 100%, for the F3 stage - 90% (1 case attributed to the F2 stage). In general, the accuracy of the method was 95.5% (95% CI 86.8-100%), sensitivity – 90.0% (95% CI 71.4-100%), specificity – 100% (95% CI 92,5 – 100%), validity - 90.0%. Evaluation of the stage of LF in patients with NASH combined with obesity and chronic calculous cholecystitis, which was determined using discriminant functions calculated from laboratory data (OPT, OPF, OPB, ALT, AST / ALT ratio and PTT), is very much in line with the corresponding results of histopathological studies of liver biopsy samples.