Cholesterol Crystals in Hepatocyte Lipid Droplets Are Strongly Associated With Human Nonalcoholic Steatohepatitis.

It is unclear what drives the development of fibrosing nonalcoholic steatohepatitis (NASH). We aimed to determine whether cholesterol crystallization within hepatocyte lipid droplets (LDs) distinguishes patients with fibrosing NASH from patients with isolated hepatic steatosis and to study pathways leading to cholesterol accumulation in hepatocyte LDs Patients with fibrosing NASH (n = 16) were compared to patients with isolated steatosis (n = 14). Almost all patients with fibrosing NASH had free cholesterol staining by filipin (16/16) and cholesterol crystals (15/16) in hepatocyte LDs, mostly in association with the LD membrane, compared to only 3/14 with cholesterol crystals and 3/14 with faint filipin staining in patients with isolated steatosis ( < 0.

The changing faces of cholangitis.

A variety of diseases are included under the umbrella term 'cholangitis', including hepatobiliary diseases with an autoimmune pathogenesis (such as primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-associated sclerosing cholangitis) and disease processes associated with intraductal stones and infectious etiologies (such as ascending bacterial cholangitis, recurrent pyogenic cholangitis, and liver fluke-associated cholangitis). Recent advances in the pathophysiologic bases of these disorders, particularly with respect to the autoimmune variety, are allowing improved diagnosis and prognostication as well as providing the opportunity to refine and re-imagine treatment modalities. The aim of this review is to highlight selected advances in cholangitis research that point to novel insights into the pathophysiology, diagnosis, and treatment of this diverse array of disorders.

Anti-apoptotic phenotypes of cholestan-3β,5α,6β-triol-resistant human cholangiocytes: characteristics contributing to the genesis of cholangiocarcinoma.

The oxysterols cholestan-3β,5α,6β-triol (Triol) and 3-keto-cholest-4-ene (3K4) are increased in Opisthorchis viverrini-associated hamster cholangiocarcinoma and induce DNA damage and apoptosis via a mitochondria-dependent mechanism in MMNK-1 human cholangiocytes. Based on these observations, we hypothesized that chronic exposure of cholangiocytes to these pathogenic oxysterols may allow a growth advantage to a subset of these cells through selection for resistance to apoptosis, thereby contributing to cholangiocarcinogenesis. To test this hypothesis, we cultured MMNK-1 cells long-term in the presence of Triol.

Mechanisms of oxysterol-induced disease: insights from the biliary system.

Oxysterols are oxidized species of cholesterol that are derived from exogenous (e.g. dietary) and endogenous () sources.