The liver is a vital organ involved in numerous metabolic processes such as cholesterol and bile acid metabolism, biliary lipid secretion, and bile formation. Cholesterol balance across the liver has a crucial effect on influencing plasma total and LDL cholesterol levels and biliary cholesterol concentrations. Cholesterol and bile acid biosyntheses are primarily modulated by negative feedback regulatory mechanisms through the sterol regulatory element-binding protein isoform 2 (SREBP-2) and the farnesoid X receptor (FXR) pathways, respectively. The conversion of cholesterol to bile acids in the liver can balance the fecal excretion of bile acids, which is an important route for the removal of cholesterol from the body. Bile formation begins in the bile canaliculi, and maintenance of the enterohepatic circulation of bile acids results in a continuous secretion of bile. Hepatic secretion of biliary lipids is determined mainly by a group of ATP-binding cassette (ABC) transporters that are located on the canalicular membrane of hepatocytes, which are regulated by various nuclear receptors. Bile acids promote bile flow by their osmotic effects. Also, they are essential for the intestinal absorption of cholesterol, fatty acids, and fat-soluble vitamins and play an important role in aiding the digestion of dietary fat. Bile acids function as signaling molecules and anti-inflammatory agents to regulate lipid, glucose, and energy metabolism by rapidly activating nuclear receptors and cell signaling pathways. This eBook summarizes the progress in the molecular and cellular mechanisms of cholesterol and bile acid metabolism and the physical-chemistry of biliary lipids, with emphasis on biliary lipid metabolism that is regulated by nuclear receptors in the hepatobiliary system.

Gallstone disease is one of the most prevalent digestive diseases, resulting in a considerable amount of financial and social burden in the USA. Approximately 20 million Americans have gallstones. Because gallstone disease is a common clinical problem, basic and clinical studies on this disease continue to advance at a rapid pace, and a book focusing on basic science, current diagnosis and management of gallstones will greatly help practicing gastroenterologists, gastroenterological endoscopists, physicians and surgeons to understand the etiology of this disease and the availability of effective medical therapies. In this book, recognised medical experts discuss recent advances in the epidemiology, pathophysiology, pathogenesis, genetics and diagnosis, as well as endoscopic, medical and surgical therapies of gallstone disease. This compilation on gallstone disease was written by fifty authors from eight countries (Canada, China, Germany, Italy, Japan, the Netherlands, the United Kingdom, and the USA). There are thirty chapters in this book. Chapters One and Two discuss the epidemiology and natural history of cholesterol and pigment gallstone disease. Chapters Three through Six summarise recent progress in the pathogenesis of gallstone disease from a physical-chemical and pathophysiological perspective. Chapter Seven elucidates the roles of the immune system and the microbiome on the pathogenesis of cholesterol gallstones. Chapters Eight and Nine review the roles of nuclear receptors and the enterohepatic circulation of bile acids in cholesterol gallstone diseases. Chapters Ten through Twelve discuss the discovery of Lith genes and more fundamental knowledge concerning the genetic determinants and the molecular mechanisms underlying the critical role of Lith genes in gallstone formation in mice and humans. Chapter Thirteen discusses gallstones in pregnancy and explains why gallstone prevalence is higher in women than in men. Chapters Fourteen through Eighteen discuss the effects of diet, insulin resistance, obesity, diabetes, and nonalcoholic fatty liver disease on the formation of cholesterol gallstones. Chapter Nineteen provides diagnostic flow charts for biliary lithiasis. In Chapter Twenty, important non-invasive imaging findings of common gallbladder pathology are reviewed, and current strategies for the optimal use of imaging in the evaluation of patients with suspected gallbladder disease is discussed. Chapter Twenty-One evaluates current pharmacological therapy in cholesterol gallstones. Chapter Twenty-Two describes laparoscopic cholecystectomy. Chapters Twenty-Three through Twenty-Six discuss surgical treatment and endoscopic management of common bile duct stones and hepatolithiasis. Chapter Twenty-Seven reviews recent progress on the endoscopic treatment of bile duct stones with endoscopic papillary large balloon dilation. Chapter Twenty-Eight addresses surgical treatment of gallstones and their complications. Chapter Twenty-Nine discusses treatment of intrahepatic duct stones from a Western perspective. Chapter Thirty describes the history and incidence rate of Mirizzi syndrome, and summarises recent progress in its classification, diagnosis, and management. The articles in this book provide a state-of-the-art review of the current knowledge on the lithogenesis and the management of gallstone disease, as well as promote future epidemiological investigation, basic and translational research, and clinical studies on this prevalent biliary disorder worldwide.