Piero Portincasa

Therapy of gallstone disease: What it was, what it is, what it will be

Cholesterol gallstone disease is a common clinical condition influenced by genetic factors, increasing age, female gender, and metabolic factors. Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones, new perspectives regarding medical therapy of cholelithiasis are currently under discussion, also taking into account the pathogenesis of gallstones, the natural history of the disease and the analysis of the overall costs of therapy. A careful selection of patients may lead to successful non-surgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones. The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations, suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis, might be proposed as additional approaches for treating cholesterol gallstones. In this review we discuss old, recent and future perspectives on medical treatment of cholesterol cholelithiasis.

Simvastatin increases AQP2 urinary excretion in hypercholesterolemic patients: A pleiotropic effect of interest for patients with impaired AQP2 trafficking

We previously reported that statins improve the symptoms of X‐linked nephrogenic diabetes insipidus (X‐NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of statins on AQP2 trafficking and kidney‐concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24‐hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine‐concentrating defects caused by defective AQP2 plasma membrane trafficking, like X‐NDI.

Biliary proteins and their redox status changes in gallstone patients

Background  Proteins might act as pronucleating agents of cholesterol crystallization in bile. However, little is known about the redox status of biliary proteins in humans and their interaction with crystallization of biliary cholesterol.