RESUMEN
BACKGROUND: There have been no reports of acute-on-chronic liver failure (ACLF) during treatment of chronic hepatitis C (CHC) with direct-acting antivirals (DAAs). CASE SUMMARY: We report a 50-year-old male patient with CHC. The patient sought medical attention from the Department of Infectious Diseases at our hospital due to severe yellowing of the skin and sclera, which developed 3 mo previously and attended two consecutive hospitals without finding the cause of liver damage. It was not until 1 mo ago that he was diagnosed with CHC at our hospital. After discharge, he was treated with DAAs. During treatment, ACLF occurred, and timely measures such as liver protection, enzyme lowering, anti-infective treatment, and suppression of inflammatory storms were implemented to control the condition. CONCLUSION: DAA drugs significantly improve the cure rate of CHC. However, when patients have factors such as autoimmune attack, coinfection, or unclear hepatitis C virus genotype, close monitoring is required during DAA treatment.
RESUMEN
OBJECTIVE: TGF-ß1-induced excessive deposition of extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) process of tubular epithelial cells play critical roles in the progression of renal fibrosis. We are aimed to explore the effects of lysine-specific demethylase 1 (LSD1) in TGF-ß1-treated HK-2 cells and in rats with unilateral ureteral obstruction (UUO), and to investigate the underlying molecular mechanism. METHODS: TGF-ß1-treated HK-2 cells and UUO-treated rats were used to establish the model of renal fibrosis in vitro and in vivo, respectively. Protein expression of LSD1, E-cadherin, a-smooth muscle actin (a-SMA), Vimentin, Jagged-1, Notch-1 and Notch-2 were detected by Western blot. The concentrations of type I collagen (Col-I) and Fibronectin (FN) were measured by ELISA. Transwell assay were used to assess cell invasion. RESULTS: LSD1 was dramatically increased in TGF-ß1-stimulated HK-2 cells. Knockdown of LSD1 decreased the TGF-ß1-induced secretion of Col-I and FN, and suppressed TGF-ß1-induced expression of E-cadherin,α-SMA and Vimentin, while suppressed cell invasion. Consistent with the in vitro data, the severe histopathological damage, collagen deposition and reduced E-cadherin, increased α-SMA induced by UUO was abated by the knockdown of LSD1 in vivo. Moreover, knockdown of LSD1 suppressed TGF-ß1-induced expression of Jagged-1, Notch-1 and Notch-2. Furthermore, we found that inhibition of Notch signaling by a γ-secretase inhibitor RO4929097 almost recapitulated the effects of LSD1 knockdown in TGF-ß1-induced HK-2 cells, and at least in part reversed the effects of LSD1 overexpression on EMT and ECM deposition in HK-2 cells. CONCLUSIONS: Taken together, LSD1 significantly impact on the progression of TGF-ß1-mediated EMT and ECM deposition in HK-2 cells, and it may represent novel target for the prevention strategies of renal fibrosis.