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What is cholestasis?

Bile, an aqueous fluid produced by the cells of the liver, is stored mainly in the gallbladder and dumped into the duodenum (first part of the small intestine) through a conduit called the main bile duct. It contains mainly bile acids which facilitate the digestion of lipids.

Cholestasis is a decrease or discontinuation of biliary secretion , which is responsible for a lack of transport of bile acids from the liver to the intestine and an increase in the concentration of bile acids and blood in the tissues.

There are two types of cholestasis:

– intrahepatic cholestasis  : the cause of stopping the flow of bile is located inside the liver. The causes are related to liver cell function abnormalities: viral hepatitis, drug hepatitis, alcoholic hepatitis , liver cancer , hepatic metastases, cirrhosis , abscess and hydatid cyst, primary biliary cirrhosis, hepatic granulomatosis.

– extrahepatic cholestasis  : in this case, the cause of stopping the flow of bile is located outside the liver. The causes are dominated by: adenocarcinoma of the head of the pancreas , lithiasis (ie calculus) of the main bile duct , cholangiocarcinoma (cancer of the bile ducts), primary sclerosing cholangitis (inflammatory and fibrosis of the intra and extrahepatic bile ducts).

Symptoms of cholestasis

Clinical signs of cholestasis are dominated by jaundice (yellow skin and integument) associated with dark urine , discolored stools, and pruritus (itching).

In case of extra-hepatic cholestasis, hepatomegaly (enlargement of the liver detected by palpation of the abdomen), a large gallbladder and fever may be demonstrated by the physician during the clinical examination.

Depending on the cause of cholestasis, other nonspecific clinical signs may be found (eg, weight loss in case of cancer).

The biological analyzes of the blood reveal:

an increase in alkaline phosphatase which is the key element in the diagnosis of cholestasis.

an increase in gamma-glutamyl transpeptidase (gGT). This increase is nonspecific for cholestasis and can be observed in all hepatic and biliary disorders (alcoholism for example)

-an increase in conjugated bilirubin , responsible for jaundice

signs of deficiency in vitamins A, D, E, K

a reduction in the prothrombin (PT) level linked to a decrease in factor V (coagulation protein) in case of hepatocellular insufficiency

To find out the cause of cholestasis, abdominal ultrasonography is the first – line examination, showing dilatation of the bile ducts in cases of extrahepatic cholestasis. In case of intrahepatic cholestasis, the abdominal ultrasound does not find any dilation of the bile ducts.

In second intention, the doctor may be required to prescribe other radiological examinations:

– a cholangiopancreatography (radiography of the bile ducts after use of a contrast medium)

– an abdominal scan

-a MRI (Magnetic Resonance Imaging Nuclear) biliary

-an echo-endoscopy

In the absence of abnormality of the bile ducts demonstrated by the ultrasound, other examinations are practiced to highlight the cause of the cholestase:

-Specialized blood tests (search for anti-mitochondrial antibodies and antinuclear antibodies) may be indicative of primary biliary cirrhosis.

a search for viruses responsible for hepatitis can be carried out

If these different tests failed to identify a specific cause, a liver biopsy may be necessary.

Special case: pregnancy cholestasis.

-It occurs most often during the third trimester of pregnancy and constitutes a danger for the fetus.

-The mechanism is linked to an accumulation of bile acids in the maternal blood; these excess bile acids can cross the placenta and accumulate in the bloodstream of the fetus.

-Less than 1% of pregnancies are affected by pregnancy cholestasis

-The risk of pregnancy cholestasis is increased in case of twin pregnancy, personal or family history of cholestasis

-It manifests as pruritus (severe itching) preferentially in the palms of the hands and soles of the feet, but the whole body may be concerned. In the absence of medical management, jaundice may appear

-The diagnosis is confirmed by blood tests showing an increase in bile acids

-The risk, not important for the mother, can be serious for the fetus: fetal suffering and risk of premature delivery

-Usodeoxycholic acid treatment reduces the increase of bile acids and pruritus

-After delivery, pruritus gradually disappears and liver function returns to normal

-Surveillance is necessary during a possible future pregnancy.

Medical treatment of cholestasis

The treatment is above all that of the cause .

The treatment of cholestasis may require the use of surgery which aims to restore the flow of bile to the duodenum.

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