Liver

Labo

The laboratory tests that need to be carried out in order to guide a disease concerning the liver vary according to the clinical impression of the doctor, that is to say the diagnostic direction that he deems appropriate to take.

They vary depending on the suspected disease:
Since the liver has a large reserve of functional cells, i.e. cells parenchymatous, also called hepatocytes, liver damage is clinically visible only relatively late. In fact, it is necessary to destroy a large number of liver cells before clinical signs (symptoms) appear.

On the other hand, the functions of liver cells, which are called hepatocytes , are very complex. They have the role of secreting bile , but also of producing fats ( lipids ) and serum lipoproteins (substances made up of lipids associated with proteins and present in the serum, i.e. the liquid part of the blood).

The liver does not only produce this. It also allows the synthesis of albumin , urea , and coagulation factors, that is to say, proteins playing a key role in blood clotting.

Finally, the liver also plays a role in the functioning and use of cholesterol , the regulation and use of carbohydrates which is called glycogenolysis and finally detoxification, that is to say the "cleaning, a little sweep necessary" of the body because of the penetration, in greater or lesser quantity, of drugs into the body, or other substances which are called exogenous substances, that is to say not produced by the body and coming from outside.

The liver also contains cells capable of clearing particles originating from within the body itself (endogenous toxicity). For this, the body relies on cells produced by the liver. These cells , known as Kupffer cells , are part of the reticuloendothelial system and originate in the bone marrow . These cells have the ability to phagocytize, meaning they capture and then digest foreign particles and neutralize endotoxins . Their role is crucial in immune responses , in other words, the body's defense mechanisms.

In reality, liver function tests — the term used for laboratory tests that provide information about the liver's condition—are primarily used to screen for liver diseases. They also help assess the progression of certain liver diseases and the effectiveness of some treatments. However, they are not very reliable for measuring the severity of liver damage.

Transaminases are enzymes measured within the serum, that is to say, the liquid part of the blood (blood from which the formed elements have been removed: red blood cells, white blood cells and platelets).

There are two types of transaminases:

• The glutamo-oxalo-acetic transaminases, also called aspartate aminotransferase (SGOT or ASAT).
• The glutamopyruvic transaminase or alanine aminotransferase (SGPT or ALAT).

Transaminase levels are significantly elevated when a patient suffers from hepatocellular necrosis , which gastroenterologists call cytolysis , meaning the destruction of liver cells. This occurs during acute hepatitis , following a viral infection, or poisoning by a medication or toxic substance.

The reference values for transaminases are as follows:

• In humans, normal values for ASAT are located between 5 and 30 units per liter. For the ALT, normal values, between 5 and 35 units per liter.
• For women, normal values regarding ASAT are located between 5 and 25 units per liter. For the ALT between 5 and 30 units per liter.

Increased transaminases do not only indicate liver damage, they can also indicate damage to the myocardium (heart muscle) or damage to the muscles in general, that is to say what is usually called skeletal muscles (e.g., limbs). Samples, properly taken for transaminases, must be obtained in dry tubes, and it is necessary to immediately separate the serum from the clot, in order to avoidhemolysis which increases the level of transaminases.
The latter, as far as the liver is concerned, increases in the following diseases:

• L'viral hepatitis acute or chronic.
• L'alcohol poisoning chronic (massive and continuous alcohol absorption).
• L'toxic hepatitis.
• La liver cirrhosis.
• Le liver cancer.
• La cholestasis (obstruction of the passage of bile in the bile ducts).
• Certain parasitic diseases.
• La brucellosis.
• La pancréatite aiguë regarding the pancreas.
• Being overweight.

The amount of transaminases is likely to be high, outside of an illness, in individuals aged over 60: after exercise (especially SGOT), after taking medication in particular:

• Le paracetamol.
• Drugs to combatepilepsy.
• Drugs intended to lower the level of fatty substances in the blood (lipid-lowering agents).
• Anabolic steroids.
• The androgens.
• Antibiotics: macrolides.
• Le clofibrate.
• L'isoniazid,
• La methyldopa.
• Le methotrexate.
• The phenothiazines.
• La morphine.
• The benzodiazepines (like Valium and its derivatives).
• The beta-blockers.
• Oral contraceptives (pill).
• La pyridoxine.
• Some anti coagulants ou antivitamin K.

It should also be noted that a drop in transaminases is likely to occur in the following cases:

• De pregnancy.
• D'hemodialysis repeat.
• Of deficit in pyridoxine.
• Insufficient functioning of the waist.
• End-stage or peracute liver failure.

Alkaline phosphatases are present in particularly high concentrations during extrahepatic cholestasis , i.e., obstruction of the common bile duct, or intrahepatic cholestasis, such as that which occurs in the early stages of primary biliary cirrhosis . Cholestasis can also be caused by medication or result from primary or secondary liver cancer.

Normal (reference) values for alkaline phosphatase are:

• Between 14 and 20 years the normal rate is between 80 and 360 international units per liter.
• In adults, the normal level of alkaline phosphatase is between 40 and 100 units per liter.
• In individuals over 60 years of age, the normal rate is between 50 and 130 units per liter.

It is important to know that storing the serum used for alkaline phosphatase testing in the refrigerator reduces the results by approximately 10%. These tests are usually requested primarily when skeletal (bone) disease is suspected. Therefore, it is necessary to differentiate the bone isoenzyme from that which originates from other organs, mainly the liver, but also the intestines , and, in pregnant women from the 20th week onward, from the placenta . It should be noted that measuring the isoenzyme in amniotic fluid allows for the prenatal diagnosis of cystic fibrosis.

Increased alkaline phosphatase is observed in liver and kidney diseases. gall bladder, in case of extrahepatic cholestasis, that is, in the presence of stones, cancers, etc. Alkaline phosphatases are also increased in the case of intrahepatic cholestasis (cirrhosis, hepatitis), but also in cases of liver cancer and hepatotoxic agents. It is necessary to know that certain medications increase the amount of alkaline phosphatase, in particular anti coagulants, the hypnotics (in theory to promote sleep), the antiepileptic (to treat epilepsy), antidiabetics, L 'allopurinol, the methyldopa, the furosemide, the phenothiazines, the vitamin D, oral contraceptives, antihypertensives and the antimigraine. The meal and the menopause increase the level of alkaline phosphatase by about 15 to 25%. The same is true of age, when it exceeds 60 years.

An increase in 5'-nucleotidase , an enzyme belonging to the phosphatase class , has the same significance as an increase in alkaline phosphatase. However, there is a key difference: it is not related to bone pathology. 5'-nucleotidase levels increase in cases of cholestasis.

Bile acid levels (normal levels are around 5 micromoles per liter) are measured, for example, when a patient presents with pruritus (itching) and/or cholestasis ( when the bile ducts are blocked). When bile acid levels decrease in the bile and intestines, it leads to steatorrhea (fatty stools). This decrease in bile acids also results in malabsorption (ingestion) of fat-soluble vitamins , namely vitamins A , D , and K.

Alanine aminopeptidase is an enzyme whose concentration in blood serum (the liquid part of the blood) is increased in certain liver diseases, particularly intrahepatic and intrahepatic cholestasis. In the first case, it involves difficulty or even an absence of bile flow through the bile ducts located outside the liver ; in the second case, it involves an absence or difficulty of bile flow through the hepatic bile ducts, that is, the bile ducts located inside the liver.

Alpha -fetoprotein is a protein whose serum level is elevated in hepatocellular carcinoma . Measurements sometimes show levels reaching or exceeding 4000 nanograms per milliliter. Alpha-fetoprotein concentrations are also elevated in certain acute viral hepatitis infections known as regenerative hepatitis.

Ammonium should normally be converted into urea , provided that liver function is normal. Ammonium enters the bloodstream via the portal vein . In cases of fulminant hepatitis, poisoning by certain dangerous and liver - toxic substances, and hepatic encephalopathy, a more or less significant increase in blood ammonium levels is observed.

Antibodies are numerous in relation to liver diseases. First, there are antibodies against viral hepatitis, and in particular anti-HA antibodies , which are antibodies directed against the hepatitis A virus antigen.

Must be distinguished :

• An anti-HA antibody of type IgM whose presence reflects a recent or current illness, following the penetration of the virusHepatitis B in the body.
• An anti-HA antibody of the IgG type that is present in the body during chronic infections by the virus ofhepatitis A.

Anti-HBs antibodies are antibodies directed against the HBs antigen. This appears approximately three to seven months after the onset of acute hepatitis B and remains in the body, meaning it persists until the patient's death in the majority of cases.

Anti-HBc antibodies are antibodies directed against what is called the core (central part) of the hepatitis B virus. It is necessary to distinguish between an IgM type anti-HBc antibody, which indicates a current or recent infection with the hepatitis B virus, and an IgG type anti-HBc antibody, which indicates a chronic infection with the virus.

To summarize, a patient who has IgM anti-HBc antibodies in their serum (the liquid part of their blood) indicates that they are developing an infection or have recently had one. A patient with IgG anti-HBc antibodies indicates that they have had a chronic pus infection for a relatively long time.

Anti-HBe antigens indicate that the virus is replicating intensely. The presence of anti-HBe antibodies signifies the cessation of viral replication, linked to the end of the acute phase.

Anti-HC antibodies are antibodies that target a protein belonging to the hepatitis C virus . This type of antibody appears three to six months after the onset of the disease, thus reflecting most cases of chronic hepatitis C.

The hepatitis D antigens and the anti-d antibody , which are difficult to detect, appear during hepatitis D infection in HBsAg carriers. It is necessary to distinguish between an IgM anti-d antibody and an IgG anti-d antibody. The former indicates a current and recent infection, while the latter indicates a previous infection with the hepatitis D virus.

Anti-smooth muscle antibodies are antibodies directed against actin ( a component of muscle) and belong to the IgG class. Anti-smooth muscle antibodies, when present at a titer greater than 1/160, are characteristic of autoimmune chronic active hepatitis . It is important to know that anti-smooth muscle antibodies can also be a characteristic of other diseases besides autoimmune chronic active hepatitis, such as Hodgkin's lymphoma , certain cancers , and infectious diseases.

The antimitochondrial antibodies found in certain primary biliary cirrhoses (in 80 to 90% of cases), in chronic active hepatitis, or in post-necrotic cirrhosis (in 10 to 30% of cases) are not organ-specific antibodies. Furthermore, there is no strong correlation between their quantity, or more precisely their level, and the severity of the disease.

Antinuclear antibodies, which are quite specific to rheumatological diseases such as rheumatoid arthritis among others, can also appear elevated during chronic active hepatitis, mainly in relation to forms not secondary to hepatitis B. Antinuclear antibodies are also present during other autoimmune diseases.

Anti-microsomal antibodies are antibodies that are found in certain autoimmune hepatitis, mainly when these are drug-induced.

Bilirubin is present in blood serum at a concentration of 3 to 10 mg per liter, which corresponds to 5 to 17 micromoles per liter of total bilirubin , which is generally unconjugated. Conjugated bilirubin, on the other hand, is present at a concentration of less than 4 micromoles per liter of blood serum.

When the total bilirubin level exceeds 40 micromoles per liter, jaundice appears.

Conjugated bilirubin, also called direct bilirubin, is increased in the presence of hepatocellular jaundice. This is the case for viral hepatitis, for drug-induced hepatitis, or for cirrhosis. Conjugated bilirubin is also increased in cases of obstruction of the main bile duct, such as in the presence of cancer or a stone.
Unconjugated bilirubin, also called indirect or free bilirubin, is increased in the presence of hemolysis, mainly in hemolytic jaundice, or in certain diseases such as Gilbert's disease.

Total cholesterol and other blood fluids can sometimes indicate liver disease. For example, in cases of acute liver injury, a temporary decrease in alpha-lipoproteins and an increase in triglycerides are observed . In chronic cholestasis, an increase in cholesterol is observed, possibly with the formation of xanthomas (fatty patches on the skin). Cholesterol may also be temporarily elevated, along with an increase in triglycerides, during acute alcoholic hepatitis . Finally, in cases of chronic liver disease, especially when it is at an advanced stage and the patient complains of anorexia (loss of appetite) and malnutrition , the blood cholesterol level (cholesterolemia) is found to be low.

Phospholipids are essential substances for the proper functioning (metabolism) of lipoproteins , which are substances composed of lipids and proteins. A deficiency in lecithin-cholesterol acyltransferase (LCAT) is associated with hypercholesterolemia and hypertriglyceridemia . An increase in phospholipids is sometimes observed in cholestatic hepatitis, type II and III hyperlipidemias, and in familial hypolipidemias.

Gamma -glutamyl transferase ( GGT ) levels are elevated in cholestasis. A parallel increase in alkaline phosphatase is also observed. The GGT level provides a useful indicator of liver function. GGT levels increase in cases of chronic alcohol intoxication.

Serum protein electrophoresis sometimes shows a decrease in albumin, particularly in cases of advanced cirrhosis.

A modest increase in gamma globulins may be observed in acute hepatitis and liver cirrhosis.

There is a very marked increase in gamma globulins in chronic hepatitis, especially in chronic active hepatitis. In autoimmune hepatitis, the increase in gamma globulins is sometimes very significant. In patients with primary biliary cirrhosis, there is an increase in immunoglobulins M.
There is a decrease in alpha 1 globulins, reflecting a deficiency in alpha 1 chymotrypsin, in association with a neonatal hepatitis or a pulmonary emphysema or an cirrhosis.

The Koller test , named after the Swiss scientist Fritz Koller (born in 1906), is a test designed to assess liver function. It involves measuring the prothrombin time (PT) before and after the injection of vitamin K. If a patient has a vitamin K deficiency, this vitamin is administered, and the PT, which was prolonged before the test, returns to normal, provided the liver is healthy. In a patient with liver failure, meaning their liver is not functioning properly, the PT remains elevated after vitamin K administration (the patient's liver cannot utilize the vitamin K). Furthermore, in cases of obstructive jaundice, the administration of vitamin K, which must be intravenous or intramuscular, normalizes the prothrombin level within three days, provided the bile duct obstruction has not caused secondary damage to liver cells. When a persistent decrease in prothrombin levels is observed, this indicates serious damage to the hepatic parenchyma, that is, to the functional cells of the liver.

The BSP, or bromosulfophthalein elimination test , is being phased out. This test was formerly used to detect potential liver cell damage. Its indications are now limited to the diagnosis of Dubin-Johnson syndrome . In this disease, a 45-minute BSP level higher than a 15-minute BSP level is characteristic.

Direct observation of stools , in certain cases, when they are discolored, i.e., acholic (without bile), and of a putty color, can point to a complete obstruction of the bile ducts. Steatorrhea , the presence of fatty substances in the stool due to a lack of bile acid, most often accompanies acholic stools. A patient with more or less discolored excrement is suffering from a more or less complete obstruction of the bile ducts, since bile does not color the stools as it normally would. Furthermore, a positive test for blood (occult blood test) in the stool can suggest hepatic encephalopathy . Testing for parasites in the stool can help identify a possible liver infection (more precisely, infestation) by a parasite.