[Innovations in the medical treatment of gallstones and fatty liver: FABACs (Fatty Acid Bile Acid Conjugates)].
Gallstones and fatty liver are common disorders in the Western world, largely due to dietary and life style factors. Currently, laparoscopic cholecystectomy is the main treatment option for gallbladder stones. Surgery is, however, expensive and may cause morbidity and even mortality. An effective medical treatment would be desirable, especially in patients with mild to moderate symptoms or high surgical risk. Currently, the bile acid UDCA (Ursodeoxycholic acid) is used for oral dissolution treatment and for the prevention of cholelithiasis in selected cases. However, the major limitations of this treatment are its low efficacy, slow action and stone recurrence. Recently, phospholipids rather than bile salts were realized to be the major natural cholesterol solubilizers in bile. They also possess anti-crystallizing activity. The sn-2 fatty acid of the phospholipids molecule was found to be particularly important. This was the background for the development of FABACs (Fatty Acid and Bile Acid Conjugates), which are novel synthetic lipid molecules. These molecules are composed of fatty acids (with chain lengths from C-14 to C-22), that are linked to cholic acid, by an amide bond at position 3. In vitro and in vivo studies (in mice) have shown that FABACs can prevent the formation of cholesterol crystals and dissolve existing ones. C20-FABAC, when given orally, is absorbed and secreted into bile. It was also found to have a series of beneficial effects on cholesterol metabolism. The main treatment for patients with fatty liver consists of lifestyle and diet modifications, which are associated with low compliance. Currently there is no effective medical treatment for this disease. In the FABAC studies on the prevention and dissolution of gallstones in laboratory animals, it was observed that this treatment also prevents the formation of diet induced fatty liver. Further prospective studies found that FABACs indeed prevent/decrease the formation of fatty liver induced by high fat diet. This influence was observed in all the fatty liver parameters (histology as well as chemical analysis), and in different animal strains. Based on these findings, FABACs seem to be good candidates for the medical treatment of hepatobiliary disorders, in particular gallstones and fatty liver disease.
Keizman
Daniel
D
Department of Gastroenterology, the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Goldiner
Ilana
I
Leikin-Frenkel
Alicia
A
Konikoff
Fred M
FM
D001647:Bile Acids and Salts / Q000627:therapeutic use*; D005227:Fatty Acids / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000534:rehabilitation; D042882:Gallstones / Q000188:drug therapy* / Q000534:rehabilitation; D006801:Humans; D008019:Life Style
D001647:Bile Acids and Salts; D005227:Fatty Acids