The Role of Signal Transducer and Activator of Transcription 5 and Transforming Growth Factor-β1 in Hepatic Fibrosis Induced by Chronic Hepatitis C Virus Infection in Egyptian Patients

Objective: To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC). Subjects and Methods: Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age-and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-beta(1), alpha-smooth muscle actin (alpha-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve. Results: Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 +/- 5.62 vs. 14.73 +/- 6.52, p <= 0.001); on the contrary, TGF-beta(1), alpha-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p <= 0.01 and 0.001, respectively). TGF-beta(1) and a-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-beta(1): 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p <= 0.04; mean a-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p <= 0.05). STAT5 had a significant negative correlation with TGF-beta(1) (p <= 0.001), while no correlation was detected with a-SMA (p <= 0.8). Conclusions: STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-beta(1) but not through the activation of hepatic stellate cells. (C) 2018 The Author(s) Published by S. Karger AG, Basel.