Intrahepatic Cholestatic Syndromes: Pathogenesis, Clinical Features and Management

Abstract

Intrahepatic cholestasis is characterized by a decrease in bile flow in the absence of overt bile duct obstruction, resulting in the accumulation of bile constituents in the liver and blood. Various etiological factors have been incriminated including drugs, total parenteral nutrition, sepsis, pregnancy, graft-versus-host disease and systemic disorders such as sarcoidosis, amyloidosis and Hodgkin’s disease. The pathogenesis of cholestasis is unclear and several mechanisms have been hypothesized, without convincing evidence that any of these play a role in clinical cholestasis. Despite the uncertainty about the pathophysiology of intrahepatic cholestasis, several forms of therapy have been employed. Ursodeoxycholic acid may relieve pruritus and lethargy, and in some cases may modify disease progression. If cholestasis persists, supportive therapy is important to maintain optimal physical and nutritional well-being. In patients with advanced liver disease associated with hepatocellular failure, liver transplantation is the only viable option.

Dietary glycine blunts liver injury after bile duct ligation in rats

“…They include primary sclerosing cholangitis, primary biliary cirrhosis, extrahepatic biliary atresia, idiopathic adulthood ductopenia, idiopathic neonatal hepatitis, Byler's disease, and arteriohepatic dysplasia [1][2][3][4] . Various drugs, total parenteral nutrition, sarcoidosis, chronic liver transplant rejection, and graft-versus-host disease may also cause chronic cholestasis [5][6][7] . Currently the most promising therapy for chronic cholestatic liver diseases is ursodeoxycholic acid [8] , that may delay liver disease progression, but cannot prevent liver injury or fibrosis [9] .…”

Erdosteine treatment attenuates oxidative stress and fibrosis in experimental biliary obstruction

“…On the otherhand various drugs, total parenteral nutrition, chronic liver transplant rejection, and graftversus-host disease can also produce chronic cholestasis [3].…”

Viral gene delivery of superoxide dismutase attenuates experimental cholestasis-induced liver fibrosis in the rat

“…3,4 A number of drugs, sarcoidosis, total parenteral nutrition, chronic liver transplant rejection and graft-versus-host disease can also cause chronic cholestasis. 5 This leads to liver injury and will finally progress to portal fibrosis, cirrhosis and endstage liver disease necessitating liver transplantation. Ursodeoxycholic acid is currently the most promising therapy for chronic cholestatic liver diseases; 6 however, it cannot prevent fibrosis.…”