Non-Invasive Assessment of Liver Fibrosis Compared with Liver Biopsy Findings

Abstract

Background: In our country, the high prevalence of chronic liver diseases is influenced by factors such as hepatotoxic viruses, excessive alcohol and drug consumption, and a high incidence of obesity among the population. Although the point at which liver fibrosis becomes irreversible remains unclear, some researchers have suggested, based on clinical studies, that fibrosis may still be reversible in the early stages of cirrhosis. Aim: Therefore, in this study, we aimed to evaluate the degree of liver fibrosis using key markers involved in the pathogenesis of hepatic scarring—MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), and PIIINP (N-terminal propeptide of type III procollagen)—as well as non-invasive serum markers of hepatocyte injury (APRI and FIB-4), and to compare these findings with the results of liver biopsy. Materials and Methods:This analytical case-control study included 50 patients in the State Third Central Hospital. Peripheral blood samples were analyzed for platelet count, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) using a fully automated analyzer, while serum direct markers were measured using ELISA. Non-invasive serum markers (APRI and FIB-4) were calculated using the MD+CALC online system. Liver tissue for histological examination was obtained via biopsy, and the degree of liver fibrosis was assessed according to the METAVIR scoring system. Differences in mean values of quantitative variables between two groups were analyzed using the Mann-Whitney U test was applied. The correlation between METAVIR stages and serum markers was evaluated using Spearman’s correlation. Results: Among the study participants, according to the METAVIR classification, 15 individuals (30%) had no or minimal fibrosis (F0–F1), 26 individuals (52%) had significant fibrosis without cirrhosis (F2–F3), and 9 individuals (18%) had cirrhosis (F4). As the stage of fibrosis increased, the mean levels of AST (r=0.326, p=0.021), ALT (r=0.392, p=0.005), MMP-2 (r=0.393, p=0.005), PIIINP (r=0.472, p=0.001), as well as APRI (r=0.503, p<0.001) and FIB-4 (r=0.482, p<0.001) showed an increasing trend. In contrast, mean platelet count (r=–0.507, p<0.001) and MMP-1 (r=–0.383, p=0.006) decreased with advancing fibrosis stages. Using AUC-ROC analysis to assess the diagnostic performance of both direct and indirect serum markers, the ability to detect significant fibrosis and cirrhosis was estimated as follows: APRI 80%, FIB-4 75%, MMP-1 67.1%, MMP-2 72.2%, and PIIINP 72.3%. Conclusion: In our study, the diagnostic performance of both direct and indirect serum markers for predicting liver fibrosis exceeded 65%. Mean levels of AST, ALT, MMP-2, PIIINP, APRI, and FIB-4 increased with advancing fibrosis stages, whereas mean platelet counts and MMP-1 levels decreased.