The acidic microenvironment in the perisinusoidal space critically determines bile salt-induced activation of hepatic stellate cells.

Cholestatic liver diseases, accompanied by the hepatic accumulation of bile salts, frequently lead to liver fibrosis, while underlying profibrogenic mechanisms remain incompletely understood. Here, we evaluated the role of extracellular pH (pHe) on bile salt entry and hepatic stellate cell (HSC) activation and proliferation. As modulators of intracellular pH (pHi), various proton pump inhibitors (PPI) were tested for their ability to prevent bile salt entry and HSC activation.

Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study.

Background: Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses.

Methods: The observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.

The inhibition of YAP Signaling Prevents Chronic Biliary Fibrosis in the Abcb4 Model by Modulation of Hepatic Stellate Cell and Bile Duct Epithelium Cell Pathophysiology.

Primary sclerosing cholangitis (PSC) represents a chronic liver disease characterized by poor prognosis and lacking causal treatment options. Yes-associated protein (YAP) functions as a critical mediator of fibrogenesis; however, its therapeutic potential in chronic biliary diseases such as PSC remains unestablished. The objective of this study is to elucidate the possible significance of YAP inhibition in biliary fibrosis by examining the pathophysiology of hepatic stellate cells (HSC) and biliary epithelial cells (BEC).

Medical care of patients with Wilson disease in Germany: a multidisciplinary survey among university centers.

Background: Wilson disease (WD) is a rare, hereditary disorder of copper metabolism. Due to its variable symptoms and manifestations, diagnosis remains challenging. Affected patients must obtain lifelong medical treatment, as the disease is fatal if untreated.