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Case Details

A 26-year-old female at 32 weeks of gestation presented to the clinic with complaints of generalized itching. Patient reported no rash or skin changes. She denied any change in detergent, soaps, or perfumes. She denied nausea and vomiting .There was no history of any drug intake or previous allergies. There was no fever or any other medical illness.

On physical examination, there were no rashes apparent on her skin and only some excoriations were there from itching. 

Laboratory investigations revealed slightly elevated serum transaminases and bilirubin levels, Alkaline phosphatase levels were much higher than normal.

What is the patient’s likely diagnosis?

What is the cause of the patient’s generalized itching?

Case discussion

The patient is most probably having intrahepatic cholestasis ofpregnancy.

Generalized pruritus in pregnancy and a characteristic enzyme profile; it’s a typical picture of intrahepatic cholestasis of pregnancy. High alkaline phosphatase is a marker of cholestasis. (It is also high late in normal pregnancy due to the influx of placental alkaline phosphatase, But in cholestasis the level may be 4 times the normal reference range). Slightly high transaminases differentiate it from viral hepatitis in which very high levels are found and the high levels (In the present case) are due to bile salts induced toxic damage to the liver cells.Bilirubin is high due to intrahepatic obstruction as a result of cholestasis.  This is conjugated type. Increased serum bile salts and accumulation of bile salts in the dermis of the skin are responsible for generalized itching.

Intrahepatic cholestasis of pregnancy (ICP) is a benign disorder that occurs in the second or third trimester and resolves spontaneously after delivery. Cholestasis of pregnancy is a condition in which the normal flow of bile from the gallbladder is impeded, leading to accumulation of bile salts in the body. 

Basic concept of Bile Salts

Bile salt molecules secreted by the gallbladder are essential for the emulsification and absorption of fats. They are the salt forms of bile acids, which are the major product of cholesterol catabolism in the liver.

There are two primary bile acids formed in the liver from cholesterol: cholic acid and Chenodeoxycholic acid. The formation of bile acids prevents cholesterol accumulation in organs;  since the body cannot break down the steroid ring of cholesterol. Bile acids are conjugated with Glycine or taurine in the liver prior to secretion, forming glyco- or tauro conjugates. 

Bacterial enzymes present in the intestine produce the secondary bilesalts, deoxycholate and lithocholate, by reducing the primary bile salts. Bile salts perform important functions and are recycled by the body.In the gut, the glycine or taurine moieties are removed from the bile salts.They are reabsorbed in the small intestine along with  the secondary bile acids and returned to the liver for reuse via the portal vein.The body produces 400 mg of bile salts per day from cholesterol; this represents the fate of half of the cholesterol used daily in metabolism (800 mg). Between 20 to 30 g of bile salts secreted from the liver in to the duodenum per day,  less than 0.5 g per day of bile salts are lost through excretion.


Figure- showing enterohepatic recirculation of bile salts

Intrahepatic cholestasis of pregnancy is a syndrome of unknown etiology characterized by a 100-fold increase in maternal and fetal blood bile salt levels. Bile salts are produced in both the fetal and maternal liver. The fetus transfers the bile salts across the placenta for disposal. When the function of the maternal gallbladder is slowed, bile salts can accumulate in the liver and bloodstream, ultimately resulting in the classical pruritus symptoms. It is believed that pregnancy-related hormones may slow bile salt excretion from the gallbladder.

It is speculated that the hormones such as estrogen and progesterone, which are elevated in pregnancy, cause a slowing of the gallbladder function, leading to this disorder. The incidence of intrahepatic cholestasis of pregnancy is highest during the third trimester, when estrogen levels peak.


 Generalized pruritus is the main symptom of intrahepatic cholestasis of pregnancy. The itching may be more intense over the palms and soles but can extend to the trunk, extremities,eyelids, and, in rare cases, the oral cavity. The pruritus is worse at night.Jaundice is uncommon (10-25%); when it occurs, jaundice follows the onset of pruritus.


 The serum bilirubin levelis usually lower than 6 times the upper limit of reference range and is usually conjugated. Fever is rare. Steatorrhea may be present, which may lead to deficiency of fat-soluble vitamins, especially vitamin K. Aminotransferases levels are less than 1000 U/L, which distinguishes intrahepatic cholestasis (IHC) from viral hepatitis. Alkaline phosphatase is 4 times higher than the reference range (44-147 U/L). Interestingly, gamma-glutamyltranspeptidase levels are within the reference range or only mildly elevated.Liver biopsy is rarely needed for diagnosis but reveals cholestasis with minimal hepatocellular necrosis.


Medical treatment is directed at relieving maternal symptoms and improving fetal outcome. Pruritus can be controlled with antihistaminics, and ursodeoxycholic acid.

More severe cases may require bile salt binders such as Cholestyramine or corticosteroids. Fetal outcome is improved with early diagnosis and prompt treatment.

The most successful therapy for cholestasis of pregnancy has been ursodeoxycholic acid.Ursodeoxycholic acid is a naturally occurring bile acid, which, when administered, relieves both pruritus and liver function abnormalities.Experimental evidence suggests that it protects hepatocytes from bile acid-induced cytotoxicity and improves hepatobiliaryexcretion. Additionally, it decreases bile salt transfer to the fetus and improves the secretory function of placental trophoblastic cells. Ursodeoxycholicacid is recycled through the enterohepatic circulation.

Cholestyramine is another treatment option for cholestasis of pregnancy. It is an oral medication that binds bile salts in the intestine and promotes their excretion in the feces. As this drug is not absorbed, it most likely has little effect on the fetus. Effects on the fetus are still under evaluation. However, Cholestyramine can interfere with the absorption of fat soluble vitamins, such as vitamins A, D, E, and K. In rare cases, drug-induced vitamin K deficiency is believed to contribute to hemorrhages during childbirth.

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