Cholestasis - Diagnosis

Laboratory diagnostics of cholestasis

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

The bilirubin content in the blood increases progressively, usually during the first 3 weeks of cholestasis, mainly due to the conjugated fraction. As the severity of cholestasis decreases, the bilirubin level 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.

An increase in the blood alkaline phosphatase content is extremely characteristic. However, when assessing its level in the blood serum, it should be taken into account that it can be increased not only in the case of pathology of the hepatobiliary system. Alkaline phosphatase enters the blood from four sources: the liver, bone tissue, intestines and placenta.

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

• pregnancy (2-3 trimester), mainly due to the enzyme entering the blood from the placenta;
• placental albumin transfusion;
• adolescence - due to rapid bone growth in length

The level of alkaline phosphatase in the blood also increases with bone tissue damage associated with:

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

Increased activity of alkaline phosphatase in the blood serum is also observed in acromegaly (bone alkaline phosphatase), pancreatic adenoma, heart failure (with impaired liver function), ischemic and ulcerative colitis (intestinal alkaline phosphatase), lymphomas and leukemia (due to damage to the liver and bones).

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

5-Nucleotidase is located primarily in bile capillaries, membranes of hepatocyte organelles, and membranes of sinusoids. Compared to alkaline phosphatase, 5-nucleotidase is a more specific enzyme, since its level does not change in bone diseases and normal pregnancy.

Leucine aminopeptidase is a proteolytic enzyme that hydrolyzes amino acids, is present in many tissues, but the largest amount is contained in the liver, in the bile epithelium. Leucine aminopeptidase is considered a characteristic marker of cholestasis syndrome, its level in the blood does not increase in bone diseases, but progressively increases as the pregnancy period increases.

y-Glutamyl transpeptidase (GGTP) is a highly sensitive enzyme that reflects cholestasis. It should be taken into account that this enzyme is contained in the liver, kidneys, and pancreas. Its activity also increases with alcoholic liver damage and liver cancer. GGTP activity does not increase during normal pregnancy.

Increased blood lipid levels are a characteristic sign of cholestasis. The blood contains increased levels of cholesterol, triglycerides (mainly due to the low-density lipoprotein fraction), and phospholipids. It should be taken into account that in extremely severe liver damage, cholesterol synthesis in the liver is impaired and therefore hypercholesterolemia may not occur.

Instrumental diagnostics of cholestasis

• Ultrasound of the liver and biliary tract: the first-line method of examination for cholestasis syndrome, reveals a characteristic sign of biliary tract blockage - expansion of the bile ducts above the site of obstruction to bile outflow (stone or narrowing). If there is a stone or tumor in the area of the common bile duct, its width is above the site of obstruction - more than 6 mm.
• Endoscopic retrograde cholangiochropathy (ERCP): used after detection of duct dilation by ultrasound. The stages of ERCP include fibroduodenoscopy, cannulation of the major duodenal papilla, administration of a contrast agent (verografin) into the bile and pancreatic ducts, followed by radiography. ERCP allows diagnosing tumors and stones of the extra- and intrahepatic bile ducts, primary sclerosing cholangitis, which is characterized by strictures of the intra- and extrahepatic ducts, alternating with areas of normal or slightly dilated ducts.
• Percutaneous transhepatic cholangiography is performed when retrograde filling of the bile ducts is impossible. Using this method, the bile ducts are identified in the direction of the physiological flow of bile and therefore the site of obstruction of the bile ducts can be seen.
• Cholescintigraphy with hemidinoacetic acid labeled with technetium 99Tc: allows localization of the level of damage - intra- or extrahepatic.
• Liver biopsy: can be performed after excluding obstructive extrahepatic cholestasis, as well as after excluding the presence of stones in the hepatic ducts using ultrasound and cholangiografia. Using liver biopsy, it is possible to diagnose various types of hepatitis, cholangitis (in particular, primary sclerosing cholangitis).
• Magnetic resonance cholangiography: has come into use in recent years, its diagnostic value is similar to that of radiocontrast cholangiography.

The greatest differential diagnostic difficulties arise with intrahepatic cholestasis. Of greatest practical importance in this group are acute and chronic hepatitis, occurring with cholestatic syndrome, primary biliary cirrhosis of the liver, primary sclerosing cholangitis, drug-induced cholestasis (diagnosed based on the relationship between the development of cholestasis and taking medications, improvement after discontinuing these drugs).