Biochemical tests for hepatobiliary disease
GOT, GPT both increased very high compared to normal, but the increase of GPT was higher than that of GOT, increased early before jaundice, in the first week of jaundice
The liver is an organ with many important functions such as metabolizing protid, glucid, and lipid substances; is a place to produce proteins (albumin, fibrinogen) for blood; conjugated bilirubin plays a role in detoxification in the liver... To evaluate liver function, many tests can be done. Currently, people usually do some of the following tests.
Tests to evaluate liver function
The GOT enzyme, serum GPT
GOT and GPT are two amino-exchange enzymes (transaminases), found in many body tissues. Among the amino-exchange enzymes, GOT and GPT have the highest activity and have many clinical applications. GOT is abundant in cardiomyocytes, GPT is abundant in liver parenchymal cells.
GOT (glutamat Oxaloacetat Transaminase, or AST (Aspartat transaminase), GPT (Glutamat pyruvat transaminase), or ALT(Alanin transaminase).
They catalyze the following amine exchange reactions:
Aspartate + α-ketoglutarate <= (GOT) => Glutamate + Oxaloacetate
Alanine + α-cetoglutarate <= GPT => Glutamate + Pyruvate
Determination of GOT, GPT activities allows to assess the extent of damage (destruction) of liver parenchyma cells.
Acute viral hepatitis:
GOT, GPT both increased very high compared to normal (maybe > 1000U/l), but the increased level of GPT was higher than that of GOT, increased early before jaundice, in the first week of jaundice (increased prolongation in the first week of jaundice). progressive chronic hepatitis).
GOT, GPT activities increased more than 10 times, which indicates that liver parenchymal cells are strongly damaged. An increase in GOT >10 times normally indicates acute damage to the liver parenchyma cells. Lesser increases may occur with other forms of liver injury.
GOT, GPT increased the highest in the first 2 weeks and then gradually decreased after 7-8 weeks.
GOT, GPT both increase but mainly increase GPT, can increase 100 times compared to normal. Especially very high in acute alcohol poisoning with delirium, carbon tetrachloride poisoning (CCl4), morphine or toxic chemical poisoning... Levels of LDH are higher than other enzymes: LDH > GOT > GPT.
GOT/GPT ratio > 1, with GOT increased about 7-8 times higher than normal, is common in people with liver disease and alcoholic hepatitis.
Chronic hepatitis, alcoholic cirrhosis, and other causes:
GOT increased from 2 to 5 times, GPT increased less, GOT increased more than GPT.
Acute biliary obstruction due to stones causing liver damage:
GOT, GPT can increase up to 10 times, if stones do not cause liver damage, GOT, GPT will not increase.
Obstructive jaundice, GOT, GPT increased slightly, the level increased insignificantly associated with alkaline phosphatase increased more than 3 times compared to normal. GOT, GPT increase slowly steadily to very high (maybe more than 2000 U/l), then suddenly decrease within 12 - 72 hours is considered as acute biliary tract obstruction.
GOT is also elevated in acute myocardial infarction and in myopathy, but GPT is normal.
GPT is more specific in liver diseases.
A very high increase in GOT, up to 1000 U/l, then gradually decreases to 50% within 3 days, falling below 100 U/l within 1 week suggests liver shock with necrosis of liver parenchymal cells. For example cirrhosis, arrhythmia, sepsis.
In addition, GOT and GPT increased slightly in some cases with treatment such as oral contraceptives, anticoagulants.
Previously, the GOT and GPT activities were determined by the Reitman, Frankel method, which was improved by Severa, which was expressed as Amol of pyruvic acid formed in 1 hour under the catalysis of the enzyme present in 1 ml of serum.
Normal: GOT = 1,5µmol acid pyruvic/1ml/1h. GPT = 1,3µmol acid pyruvic/1ml/1h.
In clinical practice, people often use De Ritis index (GOT/GPT) to look at the change of GOT, GPT and diagnose and predict liver diseases.
Currently, the determination of GOT, GPT by kit and semi-automatic or automatic machines has been greatly shortened (3-5 minutes). GOT, GPT activity determined (according to the recommendations of IFCC - International Federation of Clinical Chemistry) based on the following reactions:
α- cetoglutarat + Aspatat <= (GOT) => Glutamat + Oxaloacetat
Oxaloacetat + NADH + H + <= (MDH) => Malat + NAD +.
MDH is malate dehydrogenase, measuring the decrease in NADH at 340 nm, from which enzyme activity is calculated.
Because different manufacturers have different reagent kits and machines, the results of GOT and GPT activities (at 37oC) are different but they are almost similar. For example, GOT, GPT activities at 37OC have values as shown in the table below.
Total bilirubin, serum direct bilirubin
Bilirubin is a degradation product of hemoglobin in the endothelial reticulum of tissues such as the liver, spleen, and bone marrow.
Serum total bilirubin, consisting of indirect bilirubin (70%) and direct bilirubin (30%), can be written as:
Total Bilirubin (<17.1 µmol/l) = Indirect Bilirubin (<12 µmol/l) + Direct Bilirubin (< 5.1 µmol/l).
Indirect bilirubin is toxic, insoluble in water, it binds to albumin, or α1-globulin, which is the transport form of bilirubin in the blood. Direct bilirubin is also called conjugated bilirubin (conjugated with glucuronic acid), it gives a rapid Diazo reaction, is water-soluble, and crosses the glomerular membrane.
High levels of bilirubin in the blood will enter the tissues and cause jaundice.
Test for total bilirubin, direct bilirubin is significant in the differential diagnosis of some jaundice. Total bilirubin increased more than 2 times above normal (> 42.75 µmol/l) causing clinical jaundice.
Jaundice due to biliary obstruction:
Plasma alkaline phosphatase is the best standard for evaluating biliary obstruction. If it increases more than 5 times normal, then it indicates biliary tract obstruction.
Direct bilirubin is very high in the blood, total bilirubin is also increased, there is bilirubinuria.
Jaundice due to biliary obstruction is seen in bile duct obstruction due to stones, pancreatic head tumors, worms in the bile duct. In extrahepatic biliary obstruction, bilirubin may gradually rise to levels of 513 - 684 µmol/l (30 - 40 mg/dl).
Elevated serum bilirubin and alkaline phosphatase (ALP) may be seen in hemolysis. In contrast, normal plasma bilirubin but elevated ALP suggests intrahepatic biliary obstruction, metabolic disease, or infiltrative liver disease. Disturbance of liver metabolism causes an increase in plasma ALP 1.5-3 times higher than normal.
Jaundice due to hemolysis (hemolysis):
In hemolysis, plasma total bilirubin is rarely increased more than 5 times the normal, unless associated with liver disease.
In clinical practice, the ratio of direct bilirubin to total bilirubin can be used to differentiate:
<20% occurs in hemolytic states.
20-40% more intrahepatic disease than extrahepatic biliary obstruction.
40 - 60% occur in both intra and extrahepatic cells.
>50% of the obstruction is external to the liver than to the intrahepatic disease.
Indirect bilirubin increased very high in the blood, total bilirubin increased sometimes 30-40 times, even up to 80 times higher than normal. Bilirubinuria is negative (with urobilinogen).
Hemolytic jaundice is seen in neonatal hemolytic jaundice (physiological jaundice), malignant malaria, venomous snakebites (cobra) due to the presence of an excessively high concentration of phospholipase A enzyme in snake venom that converts lecithin into lysolecithin. is a substance that reduces the durability of membranes, especially the red blood cell membranes, causing hemolysis, causing metabolic disorders, severe and possibly fatal.
Jaundice due to liver damage:
In acute viral hepatitis (typical infectious hepatitis) bilirubin rises early and appears in the urine before jaundice; There is urobilinogen.
Because liver damage reduces the conversion of bilirubin to bilirubin LH (TT), total bilirubin is elevated in the blood but direct bilirubin is decreased.
In liver failure, severe cirrhosis, bilirubin LH decreases due to decreased liver function, reduces the conjugation of bilirubin with glucuronic acid to form conjugated bilirubin in the liver.
In liver cancer, serum total bilirubin is very high, possibly 10 to 20 times higher than normal (171-342 mol/l).
Quantification of total protein, plasma albumin
Plasma protein = 60 - 80 g/l, in which albumin = 38 - 54 g/l, globulin = 26 - 42 g/l. One can use electrophoresis to analyze and quantify plasma protein components.
Quantitative tests of total protein, plasma albumin are meaningful to evaluate the synthesis function of the liver.
Severe liver failure, cirrhosis reduces albumin synthesis, thereby reducing plasma protein, reducing osmotic pressure affecting the exchange of water and salt between plasma and intercellular fluid.
For accurate results, it is necessary to test serology without hemolysis, because if hemolysis is high, GOT, elevated bilirubin will give false results, for example, GOT can be up to 10 times higher than normal.
You can refer to the enzyme activity values in children and young men and women according to the table.
Table: Normal values GOT, GPT in children's serum (According to Jacques Wallach MD, 1994).
Blood ammonia (NH3) test
Normally, ammonia is generated from metabolism, along with CO2, ATP synthesizes urea in the liver, urea is carried in the blood through the kidneys and excreted in the urine.
Normal: NH3 blood concentration = 6 - 30 μmol/l. Elevated blood NH3 is seen in some liver diseases such as:
The NH3 test in arterial blood is more accurate than venous blood because it accurately reflects the concentration of NH3 in the blood taken to toxic organs and tissues, especially to the nervous system (brain).
Common enzyme tests to evaluate liver function
GPT (Glutamat pyruvat transaminase)
Evaluation of liver parenchymal cell damage.
GGT (Gamma-glutamyl transferase)
GGT is a cell membrane enzyme, abundant in the kidneys, pancreas, liver, spleen, and small intestine. GGT activity in renal tubules is 12 times greater than in the pancreas, 25 times greater in the liver, and is present in plasma.
Valuable for evaluation of hepatic cholestasis because it is very sensitive to cholestasis.
Transport of amino acids across cell membranes (it takes 3 ATP to transport 1 amino acid with high intensity, especially glutamic acid and cysteine).
Currently, many studies have proven that GGT together with GOT, GPT also has the effect of early diagnosis, monitoring and treatment of hepatobiliary diseases, assessing the extent of damage to liver parenchyma cells.
GGT is elevated in hepatobiliary disease, the level of increase is higher than that of GOT, GPT. In advanced chronic hepatitis, GGT is elevated, GOT and GPT are also increased, but the increase of GGT is higher than with GOT, GPT.
In hepatitis, cirrhosis caused by alcohol intoxication, GPT, and alkaline phosphatase are very high and are an indicator of liver parenchymal cell damage and alcohol intoxication.
GGT/ALP ratio >5, is common in people with alcoholic liver disease. Elevated, stand-alone GGT is a sensitive test, commonly used to check for alcohol intoxication.
CHE (Cholinesterase) serum
Assessment of the liver's synthetic function.
Cholinesterase (CHE) catalyzes the hydrolysis of acetylcholine to produce choline and acetic acid according to the following reaction:
In liver diseases (such as liver failure, cirrhosis) CHE activity is much lower than normal.
In addition to evaluating the synthesis of liver function, CHE changes have also been observed in several other diseases such as:
CHE is elevated in some neurological diseases (eg, depression,
Strongly reduced in acute and chronic poisoning of nerve agents such as Tabun, Sarin, Soman (military chemical poison) ...
If the activities of 3 enzymes GPT, GGT and CHE are normal, it can be confirmed that over 98% do not have liver disease.
If an enzyme in the 3 enzymes above is not normal, do the following 3 enzyme tests: GOT, GLDH, ALP.
G O T
Assessment of damage in mitochondria of liver parenchyma cells. Elevated in advanced chronic hepatitis, chemical intoxication.
GLDH (Glutamate dehydrogenase)
It is a highly active enzyme that catalyzes the direct deamination-oxidation reaction of glutamic acid to form NH3 and α-cetoglutarate.
GLDH is localized to the mitochondria of liver parenchymal cells.
The results of GLDH activity assess the severity of damage and destruction of liver parenchyma cells.
ALP (Alkaline phosphatase)
Evaluation of the degree of cholestasis in the liver. In cholestasis, ALP is higher than normal.
ALP activity < 280 U/l (37OC).
Also, do some other tests
Total bilirubin, direct plasma.
10 urine indicators.
Quantification of ammonia and fibrinogen.
Quantification of HBsAg, anti-HBV, anti-HCV...
Some liver diseases and biochemical tests
Acute viral hepatitis:
Viral hepatitis is a common infectious disease, often with severe consequences, including liver cancer.
Biochemical tests to be done include:
GOT, GPT plasma increase rapidly, GPT increases early before jaundice, the increase can be up to 2000-3000 U/l.
GOT, GPT decreases rapidly within a few days after the appearance of jaundice and returns to normal about 2 - 5 weeks later. In hepatitis associated with infection (leukocytosis), elevated GOT and GPT are usually < 200 U/l, peak at 2-3 weeks from the onset of the disease, and return to normal at week 5.
GGT also increased, sometimes higher than GPT. That said, GGT is important for the early diagnosis of liver and biliary diseases.
In acute viral hepatitis, GPT > GOT > LDH activity.
ALP and GGT were slightly elevated, reflecting mild hepatic cholestasis.
CHE decreased from week 2 to week 4.
Bilirubin increases: in the stage of acute jaundice, direct bilirubin increases, accounting for 50 -
70% (normally 25 - 30%), then indirect bilirubin increases
Serum iron is increased.
Plasma protein electrophoresis, the results vary as follows:
α1, α2- globulin increased in the first stage, then gradually decreased. . β-globulin increases persistently.
γ-globulin increases frequently.
After 1-2 weeks of treatment, GOT and GPT return to normal, GGT returns to normal at the slowest, but when GGT returns to normal, it will indicate that the liver parenchymal cells have stabilized - that is suggestive GGT test also has prognostic significance, treatment of viral hepatitis.
After the jaundice phase of acute viral hepatitis, if treated well, it will move to the remission phase. This is the beginning of the recovery phase. Symptoms of this stage are:
Bilirubinuria gradually decreased and disappeared while plasma bilirubin remained high compared to normal.
Urine urobilinogen is increased.
Serum bilirubin is increased.
If monitoring and treatment are not good, acute viral hepatitis easily turns to chronic hepatitis.
An increase in GGT in combination with MCV (mean erythrocyte volume) > 100 or an increase alone has a diagnostic value for alcoholic hepatitis.
GOT is increased (<300U/l), but GPT is normal or slightly elevated. GOT, GPT tests have higher specificity but lower sensitivity than GGT. GOT/GPT ratio >1 combined with increased GOT (<300U/l) indicates that about 90% of patients have alcoholic liver disease. This distinguishes it from viral hepatitis where GOT and GPT are uniformly elevated.
In acute alcoholic hepatitis, GGT often increases rapidly, the level of GGT > GOT. GGT is abnormally variable in alcoholic hepatitis, even in people with a history of normal liver disease.
Alkaline phosphatase, plasma bilirubin may be normal or slightly elevated but not of diagnostic value. However, if bilirubin continues to rise during 1 week of treatment, the diagnosis should be reconsidered.
In chronic hepatitis, 5 - 10% of the causes are due to acute hepatitis B virus infection. In general, acute viral hepatitis B can be divided into 3 stages:
The acute phase of hepatitis:
Usually lasts 1 - 6 months with symptoms:
GOT, GPT increased more than 10 times compared to normal.
Bilirubin is normal or slightly elevated. Chronic hepatitis:
Liver enzymes increased by more than 50% lasting for more than 6 months, possibly up to 1 year or more. Most cases of the untreated disease will lead to cirrhosis and liver failure.
GOT and GPT activities increased 2-10 times compared to normal levels.
The patient is stable, healthy, and symptom-free.
GOT, plasma GPT decreased to normal or decreased to the low limit.
Stable chronic hepatitis:
The enzymes commonly quantified to monitor chronic hepatitis are GOT, GPT, GGT and CHE. Enzyme tests show the progression and extent of liver parenchymal cell damage.
GOT, GPT, and GGT were moderately increased (because of mild damage to the liver parenchyma).
ALP, GLDH, and CHE are at normal values.
Total bilirubin increased slightly, possibly greater than 17.1 μmol/l.
If you do not drink alcohol, beer and light work, the disease has a good prognosis.
Chronic (active) hepatitis:
GOT and GPT increased slightly; GGT and GLDH increased sharply, reflecting severe damage to liver parenchyma cells.
CHE and coagulation enzymes are reduced.
Blood bilirubin increased.
If treatment is not good, chronic hepatitis can easily turn into cirrhosis; the prognosis is worse.
Bilirubin is often elevated, can persist for many years, mainly by increasing free bilirubin (except in cases of cirrhosis due to biliary obstruction, conjugated bilirubin is increased). Fluctuations in the level of bilirubin reflect the functional state of the liver. Elevated bilirubin levels are seen in post-necrotic cirrhosis.
GOT activity is elevated (≤ 300 u/l) in 65-75% of cirrhotic patients. GPT increased, the increase was lower (< 200 u/l) in 50% of patients. The degree of change in GOT and GPT reflects the destruction of liver parenchyma cells.
ALP is increased in 40-50% of patients.
Normal or slightly decreased plasma protein. Plasma albumin may be normal in the presence of mild hepatocellular damage. A decrease in plasma albumin reflects the progression of ascites or bleeding.
Total plasma cholesterol was normal or slightly decreased. Lowering cholesterol esters reflects decreased liver function due to more destruction of liver parenchyma cells.
Bilirubinuria increased, urobilinogen normal or increased.
Serum uric acid is usually elevated.
Electrolyte balance and acid-base balance reflect disturbances in different combinations at one time such as malnutrition, dehydration, hemorrhage, metabolic acidosis, respiratory acidosis.
GOT, GPT increase can be up to 4-5 times normal, the level of increase GOT > GPT.
GLDH increased slightly.
ALP, bilirubin may be normal.
In the above tests, pay attention to GGT and GLDH tests because they reflect the degree of alcohol intoxication and the degree of liver cell damage.
Cirrhosis after hepatitis:
Prognosis is worse than alcoholic cirrhosis. Biochemical tests typically show the following results:
GOT and GPT increase, GPT increase > GOT.
GGT increased, the increase was less than alcoholic cirrhosis. + ALP increases.
There may be jaundice due to hyperbilirubinemia.
The sharp increase in GLDH reflects the strong destruction of liver parenchyma cells.
Urinary galactose test: positive.
Bilirubin may be reduced in some cases of hepatitis or cirrhosis.
For cirrhosis after hepatitis, it is necessary to check and monitor the enzymes ALP, GLDH, LDH, GGT every 6 months. If the disease progresses badly, it is necessary to check once every 3-4 months.
There are two types of biliary cirrhosis: primary biliary cirrhosis and secondary biliary cirrhosis.
Primary biliary cirrhosis:
The clinical symptoms of cholestasis are typical of long duration (possibly lasting several years) associated with elevated IgM antibodies. People rely on antibodies (of IgM) to distinguish primary biliary cirrhosis from secondary cirrhosis.
Bilirubin is normal in the early stages of cholestasis but is elevated in 60% of patients over the course of the disease and is a definitive diagnostic marker.
Direct bilirubin elevation: 80% of patients had elevations higher than 85.5 μmol/l (5mg/dl) and 20% of patients had elevations higher than 171 μmol/l (>10 mg/dl).
Indirect bilirubin is normal or slightly elevated.
Plasma ALP is markedly increased in 50% of cases, the increase is > 5 times higher than normal.
ALP, GGT increased very strongly, reflecting cholestasis in the liver.
GLDH, GOT, GPT high increase
5'-nucleotidase, GGT increased in parallel with ALP. (5'-nucleotidase normal: 2-15 U/l); In addition, it is increased in intrahepatic and extrahepatic biliary tract obstruction, increased in hepatitis, mainly in cases of intrahepatic cholestasis.
CHE decreases in late stages of the disease.
Cholesterol is markedly increased.
Secondary biliary cirrhosis:
Secondary biliary cirrhosis is associated with cholangitis and cholestasis, with biochemical tests usually showing the following results:
GOT, GPT, GLDH increased higher than normal.
ALP, GGT increased.
CHE is slightly reduced and may be normal.
Direct bilirubin is elevated, total blood bilirubin is increased.
Alkaline phosphatase increased.
Total cholesterol increased.
Positive urinary bilirubin decreased urobilinogen, decreased stercobilinogen.