17 In recent years it has become clear that the biology of the biliary epithelial cells, the loss of which is integral to the development of cholestatic disease, is complex. In
contrast to simple models in which the mechanism of injury (be it immune, toxic, or apoptotic) is associated with irreversible loss of the biliary epithelial cells, rather a period of homeostatic proliferation occurs in which the injury and insult triggers an attempt by the body to regenerate the epithelium. The evidence regarding senescence of epithelial cells in the context of cholestatic disease would suggest that it is only when this adaptive response ultimately fails due to exhaustion of proliferative capacity that see more ductopenia occurs, leading to the biological effects of cholestasis.18, 19 It is plausible, therefore, that ATX elevation occurs in the context of cholestasis as part of this homeostatic response. In simple terms, ATX production might represent an element in the body’s attempt to mitigate against biliary epithelial cell injury through up-regulating proliferative capacity. Although
check details this is only a hypothesis, its important implication might be that modulating ATX function with the aim of reducing pruritus might limit the body’s reactive response to cholestasis. The potential effect would be that an ATX-directed therapy might improve cholestatic pruritus at the cost of worsening cholestatic biology. Until we fully understand role, if any, played by ATX in regenerative learn more capacity, and the importance of this process for disease progression, this must remain a concern. “
“Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (HALT-C) trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these
values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C. Patients randomized to no treatment and who had ≥2-year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio, total bilirubin, and albumin) with three categories of change (stable, mild, or severe) over 2 years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome. In all, 470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values.