Role of SERPINB3 like serological and molecular biomarker into NASH development and progression

Background: NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) are emerging conditions that sequentially affect hepatocyte metabolism. Fibroblast Growth Factor 21 (FGF21) is produced by the liver and has autocrine and paracrine actions on liver energy metabolism while serpinB3 (SCCA) is produced by damaged liver cells and is considered a marker of progression to cirrhosis and hepatocellular carcinoma. Aim of the study: A first aim of this study is to investigate expression profile of FGF21 and its receptor/coreceptor in liver biopsies of patients with NAFLD and NASH. A second aim is to assess whether circulating concentration of SCCA-IgM is increased in patients with NASH compared to patients with pure fatty liver. Materials and methods: Expression of FGF21 and its receptor was measured by real-time PCR in liver biopsies of 42 patients with NAFLD/NASH and 16 matched controls. Moreover in a separate group of patients with NAFLD (n = 39) and NASH (n = 45) serum concentration of SCCA-IgM was measured. Results: A significant lower expression of FGF21 (53±3.1 u.a. vs 27.2±1 u.a., p < 0.05), FGF21-R1 (4.7±0.2 u.a. vs 2.7±0.1 u.a., p < 0.02) and its coreceptor-klotho (107.6±6.4 u.a. vs 64.0±1 u.a., p < 0,03) was found in patients with NAFLD/NASH. SCCA-IgM serum concentration was significantly increased in patients with NASH compared with those with NAFLD (9.2±1.8 vs 31.0±7.2 u.a./mL, p = 0.007). Conclusions: Downregulation of FGF21, FGF21-R1 and-klotho suggests that both low hormonal levels and its membrane receptor and coreceptor might contribute to detrimental metabolic effect in hepatocytes of NAFLD/NASH patients. Moreover higher circulating levels of SCCA-IgM in patients with NASH compared to those with pure fatty liver suggest that this protein might represent a possible marker of hepatic damage before the progression to cirrhosis and hepatocellular carcinoma.