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16 September 2023

Hepatic Lysosomal Enzyme Activity in Primary Biliary Cholangitis

Background: Lysosomal enzymes are implicated in autophagy and senescence. Hepatic lysosomal enzymes have not been studied in Primary Biliary Cholangitis (PBC). We therefore quantified the activities of lysosomal hydrolases in liver tissue of PBC patients. Methods: We compared enzyme activities in liver tissue from PBC patients with normal livers. Alcoholic liver disease and chronic viral disease served as disease controls. Results: Cathepsin B1 was significantly increased in early PBC (225.1 ± 18.06 mean ± SD, p < 0.0001) and reduced in later stages (66.5 ± 9.7, p = 0.004, controls 130.4 ± 14.9). It was reduced in patients with extensive fibrosis such as alcoholic and viral cirrhosis (p < 0.01 and p = 0.004 respectively) but not in chronic hepatitis. Cathepsin D was increased in early PBC (39 × 103 ± 4.8 SD, p < 0.0001) and less so in later stages (20.1 × 103 ± 3.9, p = 0.05, controls 14.1 × 103 ± 2.9). It was also increased in the presence of histological necro-inflammation in hepatitis. Treatment with ursodeoxycholate (UDCA) restored the abnormal values of enzymes in PBC. Lipid hydrolases mostly paralleled the changes of Cathepsins. Sequential measurements in serum of patients with acute alcoholic hepatitis showed that cathepsin B1 gradually decreases, and esterases increase as aminotransferases improve. Conclusions: The increased activity of lysosomal enzymes in early PBC are possibly on line with increased senescence. Treatment with UDCA restores abnormal values. In chronic liver disease, Cathepsin B1 reduction is associated with fibrosis and increased cathepsin D with necro-inflammation. Abnormalities of lysosomal enzymes indicate impairment of the final stage of autophagy in chronic liver disease.

Keywords: Acid lipase; Cathepsin; Chronic liver disease; Esterase; Lysosomal enzyme


21 March 2023

Established Hepatic Stellate Cell Lines in Hepatology Research

Hepatic stellate cells comprise a minor cell population in the liver that plays a key role in the pathogenesis of hepatic fibrosis. In chronic liver damage, they undergo a transition from a quiescent to a highly proliferative phenotype with the capacity to synthesize large quantities of extracellular matrix compounds such as collagens. Because of their pivotal role in liver disease pathogenesis, this hepatic cell population has become into the focus of liver research for many years. However, the isolation of these cells is time consuming and requires trained laboratory personnel. In addition, working with primary cells requires the following of ethical and legal standards that need to be approved by the respective authorities. Therefore, continuous growing hepatic stellate cells have become very popular in research laboratories because they are widely available, easy to handle, allow a continuous supply of materials, and further allow reduction of lab animal use in biomedical research. This communication provides some general information about immortalized hepatic stellate cell lines from mouse, rats and humans.

Keywords: Cell culture; Cell lines; Hepatic stellate cells; Myofibroblasts; Liver; Fibrosis; In vitro; Translational research