Cholestasis: diagnosis

Laboratory diagnostics of cholestasis

The syndrome of cholestasis is characterized by an increase in the blood content of all components of bile.

The content of bilirubin in the blood progressively increases usually during the first 3 weeks of cholestasis, mainly due to the conjugated fraction. With a decrease in the severity of cholestasis, the level of bilirubin in the blood begins to decrease quite slowly due to the fact that during the existence of cholestasis, bilialbumin (bilirubin bound to albumin) is formed in the blood.

Extremely characteristic increase in the blood alkaline phosphatase. However, when evaluating its serum level, it should be borne in mind that it can be increased not only in the pathology of the hepatobiliary system. Alkaline phosphatase enters the blood from four sources: the liver, bone tissue, intestine and placenta.

An increase in the level of alkaline phosphatase in the blood is possible under the following physiological conditions:

• pregnancy (2-3 trimester), mainly due to the introduction of the enzyme into the blood from the placenta;
• transfusion of placental albumin;
• teenage period - due to the rapid growth of bones in length

The level of alkaline phosphatase in the blood also increases when the bone tissue is damaged, associated with:

• Paget's disease;
• rickets;
• renal-tubular osteomalacia;
• chronic renal insufficiency;
• hyperparathyroidism;
• osteosarcoma;
• metastases of malignant tumors in the bone;
• myeloma;
• fractures of bones;
• aseptic bone necrosis.

An increase in the activity of alkaline phosphatase in the serum is also observed with acromegaly (bone alkaline phosphatase), pancreatic adenoma, heart failure (with liver dysfunction), ischemic and ulcerative colitis (intestinal alkaline phosphatase), with lymphomas and leukemias (due to liver damage and bones).

It is important to know that increasing the activity of alkaline phosphatase in the blood is a highly sensitive test not only for cholestasis, but also for granulomatous diseases of the liver: sarcoidosis, tuberculosis, as well as abscesses and liver tumors.

5-Nucleotidase is located predominantly in the bile capillaries, membranes of the hepatocyte organelles and membranes of sinusoids. In comparison with alkaline phosphatase, 5-nucleotidase is a more specific enzyme, since its level in diseases of bones and normal pregnancy does not change.

Leucinaminopeptidase is a proteolytic enzyme that hydrolyzes amino acids, is found in many tissues, but the greatest amount is contained in the liver, in the biliary epithelium. Leucinaminopeptidase is considered a characteristic marker of cholestasis syndrome, its level in the blood does not increase with bone diseases, but it progressively increases as the gestation period increases.

y-Glutamyltranspeptidase (GGTP) is a highly sensitive enzyme that reflects cholestasis. It should be borne in mind that this enzyme is found in the liver, kidneys, pancreas. His activity is also increased with alcoholic liver damage, liver cancer. The activity of GGTP during normal pregnancy does not increase. 

The increase in lipid levels in the blood is a characteristic sign of cholestasis. The blood increases the cholesterol, triglycerides (mainly due to the fraction of low-density lipoproteins), phospholipids. It should be borne in mind that with extremely severe liver damage the synthesis of cholesterol in the liver is disturbed and therefore hypercholesterolemia may not be present.

Instrumental diagnostics of cholestasis

• Ultrasound of the liver and bile ducts: the primary method of investigation in the syndrome of cholestasis, reveals a characteristic sign of blockade of the biliary tract - the expansion of the bile ducts over the obstruction site for the outflow of bile (stone or constriction). If there is a stone or tumor in the region of the common bile duct, its width is above the obstacle - more than 6 mm.
• Endoscopic retrograde cholangiopathy (ERCH): it is used after detection of the expansion of the ducts with ultrasound. The stages of ERGH include fibroduodenoscopy, cannulation of the large duodenal papilla, the introduction of a contrast agent (veroprography) into biliary and pancreatic passages followed by radiography. ERCG allows to diagnose tumors and stones of extra- and intrahepatic biliary tracts, primary sclerosing cholangitis, which is characterized by strictures of intra- and extrahepatic passages, alternating with sections of normal or somewhat enlarged ducts.
• Percutaneous transhepatic cholangiography is performed if retrograde filling of the bile ducts is impossible. When this method is used, the bile ducts are revealed in the direction of the physiological current of the bile and, therefore, one can see the place of obstruction of the biliary tract.
• Cholescintigraphy with hemidinoacetic acid, labeled with technetium 99Tc: allows localizing the level of lesion-inside-or extrahepatic.
• Puncture liver biopsy: can be performed after exclusion of extrusive extrahepatic cholestasis, as well as excluding the presence of stones in the hepatic ducts by ultrasound and cholangiophage. With the help of liver biopsy, it is possible to diagnose various variants of hepatitis, cholangitis (in particular, primary sclerosing cholangitis).
• Magnetoresonant cholangiography: has been used in recent years, its diagnostic value is similar to radiocontrast cholangiography.

The greatest differential diagnostic difficulties occur with intrahepatic cholestasis. The most important practical value in this group are acute and chronic hepatitis, which occur with cholestatic syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, drug cholestasis (diagnosed on the basis of the association of development of cholestasis with medication, improvement after withdrawal of these drugs).