Cholestatic liver disease or  primary biliary cirrhosis is an autoimmune liver disease  which leads to a process of progressive destruction of the bile canaliculi (small bile ducts) within the liver.  As a consequence of the destruction of these  ducts,  cholestasis occurs (bile builds up in the liver ) and in time the hepatic tissue is being damaged. This process will lead to hepatic fibrosis and cirrhosis. This disease affects to 1 in 3-4,000 people and it affects women more frequently than men, the sex ratio being around  9:1 (women to men).

The signs and symptoms of cholestatic liver disease are mainly common to all the chronic liver diseases.

Fatigue occurs in about 65% of the patients with cholestatic liver disease and in many cases is the first reported symptom. It exacerbates after meals and it may be associated with sleep abnormalities such as excessive daytime somnolence probably due to the disturbance of the  hypothalamic-pituitary-adrenal axis. Depression and obsessive-compulsive behavior may also be associated to this symptom.

Pruritus (itching) may occur in any liver disease but it occurs more commonly in primary biliary cirrhosis and in sclerosing cholangitis. In
some patients with  cholestatic liver disease the generalized itching may limit normal activities, lead to sleep deprivation, and it may a major impact on the overall quality of life. The pruritus, especially if severe may lead to skin excoriations which may become superinfected. The pathogenesis of pruritus is not well known but it seems to be related to the increased central opioidergic tone.

The patients with cholestatic liver disease will also have a higher risk of acquiring an infection. There have been performed many studies showing that incidence of bacterial infections in these patients is very high, and the incidence of nosocomial bacterial infection (infection acquired while being admitted into a hospital) is much higher than in the general population. It appears that these patientstend to develop many infections determined by gram-negative bacilli especially in the patients who have decreased gastric motility. This change (the decreased gastric motility) will lead to changes in the intestinal flora which will increase the risk of gram-negative bacteremia, through the disruption of the intestinal permeability barrier. Another cause which may predispose to bacterial translocation is gut wall edema, hypoalbuminemia and ascites fluid.

Cachexia and malnutrition are seen in many  patients with primary biliary cirrhosis. There are many factors contributing to the development of this sign: malabsorption of nutrients due to the intestinal edema, diarrhea the decreased bile flow, and the reduced hepatic deposits of  hydrosoluble vitamins. Anorexia results from fatigue and nausea, and the early satiety due to ascites , the decreased gastric emptying, and the psychological discomfort determined by the frequent hospitalizations will lead to a poor food intake. Moreover, the patients with primary biliary cirrhosis have an impaired intermediary metabolism as a result of increased  levels of proinflammatory cytokines and the altered balance of the hormones maintaining the metabolic homeostasis.

Other clinical manifestations of cholestatic liver disease are right upper quadrant discomfort (pain or tenderness -10%), hepatomegaly (increased size of the liver-25%), splenomegaly (spleen larger than normal -9%), hyperpigmentation (25%), xanthomas (cholesterol deposits seen in the palmar creases or above the eyes- 10%), and jaundice (10%).