Laboratory tests have the following significance:
(See also the American Gastroenterological Association Medical Position Statement and Technical Review to assess liver function tests in clinical chemistry) Laboratory tests have the following significance: detecting hepatic impairment assessment of the severity of liver injury monitoring the progression of liver disease and the response to treatment refinement the diagnosis Numerous biochemical and secretory tests are called liver function tests. However, of some of these tests is judged not only the liver, they also measure the liver enzymes in the blood stream (eg. B. release of transaminases from injured liver cells or the alkaline phosphatase by cholestasis) are released. Only certain liver function tests detected by the evaluation of hepatobiliary secretion (eg bilirubin.) Or by the synthetic function of the liver (eg prothrombin time [usually expressed as INR, Albumin].) Really the liver function. The most useful laboratory tests in the search for liver diseases are serum transaminases (liver function tests most commonly used), bilirubin and alkaline phosphatase. Certain patterns of biochemical changes can hepatocellular injury of a disturbed bile secretion (cholestasis Usual pattern of laboratory abnormalities) differ. , The measurement of immunoglobulins, antibodies and autoantibodies: test procedures which are useful to detect a viral hepatitis, or an altered immune regulation, the hepatitis serology (serology Acute viral hepatitis overview) are. The following laboratory tests are clearly diagnostically: IgM antibody to hepatitis A virus (anti-HAV) for acute hepatitis A hepatitis B surface antigen (HBsAg) of hepatitis B antibodies to hepatitis C virus (anti-HCV) and HCV RNA of hepatitis C anti-mitochondrial antibody for the presence of primary biliary cirrhosis. Serum ceruloplasmin (reduced) and copper in the urine (increased) for Wilson’s disease serum ?1-antitrypsin for ?1-antitrypsin deficiency ?-fetoprotein for hepatocellular carcinoma Usual pattern of laboratory abnormalities pattern aminotransferase elevations alkaline phosphatase prolongation of prothrombin time Acute necrosis or injury Significantly Frequently Extends present, but in a mild expression, if liver function is severely impaired Chronic hepatocellular disease light to moderate often present, but extended in a mild expression, if liver function is severely impaired cholestasis often present but significantly extended in a mild expression when chronic steatorrhea vitamin K malabsorption caused Can with parenteral (mostly sc) administration of vitamin K can be corrected infiltration Easy Easy to moderate in the Reg el not extended liver failure Depending Depending Extends on the cause of the cause, but often have little if the failure is chronic tests The transaminases alanine aminotransferase in liver damage aminotransferases (ALT) and aspartate aminotransferase (AST) come from damaged liver cells and are therefore sensitive indicators of liver damage. Significantly high values ??(> 500 IU / l; normal ? 40 IU / l), which indicate acute hepatocellular necrosis or injury, resulting in a rule of the following: Acute viral hepatitis toxin or drug-induced hepatitis Ischemic hepatitis or infarction High concentrations are to find a rule for days or viral hepatitis weeks. The level of increase is not necessarily a measure of liver damage. Serial measurements reflect the severity and prognosis resist better than a single measurement. A drop to normal levels indicates a recovery unless it is accompanied by an increase of bilirubin and prothrombin time or INR (which is a fulminant hepatic failure indicates). Fulminant hepatic failure resulting in less liver cells can secrete enzymes. Aminotransferase levels can also enjoy the following be significantly high: Acute exacerbation of autoimmune hepatitis reactivation of chronic hepatitis B Acute Budd-Chiari syndrome Acute fatty liver of pregnancy passage of a gallstone Slight increase (300 to 500 IU / L) persists in chronic liver diseases (eg. B. chronic hepatitis, alcoholic hepatitis) and biliary obstruction, except the passage of a gallstone, which can lead to remarkably high levels temporarily, sometimes in the thousands. Slight increase (<300 IU / l) is non-specific and often observed in diseases such as liver cirrhosis, secondary non-alcohol-related after a viral hepatitis fatty liver (NASH) cholestatic liver diseases liver cancer aminotransferase may be normal in certain liver diseases, as with hemochromatosis methotrexate or amiodarone-induced liver damage chronic hepatitis NASH Increased alanine aminotransferase is low specific for liver damage. Since aspartate aminotransferase found in the heart, skeletal muscle, kidney and pancreas, increased aspartate aminotransferase values ??rhabdomyolysis or the violation of these organs can show. In most liver diseases the ratio of aspartate aminotransferase to alanine aminotransferase is <1. In contrast, in alcoholic liver disease is the ratio> 2 because of alcohol patients a lack of pyridoxal-5′-phosphate prevails; it requires tracking for the synthesis of alanine aminotransferase, but less important for the Syntehese of Aspartataminotransferas. (Contrast, pyridoxine, for a alcohol abuse a defect exists in the majority of patients and which is required for the synthesis of ALT is less essential for the synthesis of the AST.) This lack also explains why the increase of alanine aminotransferase and aspartate aminotransferase in low alcoholic patients is (<300 IU / l) .Laktatdehydrogenase LDH, included in routine analysis is to be found in many other tissues and specific to hepatocellular injury neither sensitive nor. LDH is increased, in particular in ischemic hepatitis and for cancers that infiltrate extensively in the liver. Tests on cholestasis Bilirubin bilirubin, the pigment in the bile, is a degradation product that is released mainly by the natural breakdown of aging erythrocytes of heme. Unconjugated (free) bilirubin is insoluble in water and therefore can not be excreted in the urine; most of unconjugated bilirubin is bound to albumin in plasma. Bilirubin conjugated with glucuronic acid in the liver to form the more water-soluble bilirubin Diglukuronide. Conjugated bilirubin is excreted through the biliary tract into the duodenum, where it Urobilirubinogen (which is reabsorbed in part and excreted back into the bile) and is then converted into an orange urobilin (whose major part will be excreted via the faeces). This bile pigments give the chair its typical color. Hyperbilirubinemia is the result of one or more of the following processes: Increased bilirubin production Decreased liver uptake or conjugation Decreased bile excretion (jaundice) Normally, the total bilirubin in large part unconjugated with values ??of <1.2 mg / dl (<20 .mu.mol / l). Fractionation measures the proportion of conjugated bilirubin (i. E. Directly, because it is directly measured, therefore, so called, without solvent). Fractionation is very useful for the evaluation of neonatal jaundice and elevated bilirubin if other liver function tests are normal, suggesting that no liver dysfunction is the cause. Unconjugated hyperbilirubinemia (proportion of indirect bilirubin> 85%) reflects an increased Bilirubinproduktion (z. B. in hemolysis) or a defective liver uptake or conjugation (z. B. in Gilbert’s syndrome). Such increases of conjugated bilirubin are typically <5 times normal (to <6 mg / dl [<100 .mu.mol / l]), unless it is liver damage before simultaneously. Conjugated hyperbilirubinemia (direct Bilirubinanteil> 50%) is the result of reduced bile formation and excretion (cholestasis). If a high serum bilirubin value with other abnormalities in liver function tests is related, this indicates hepatocellular dysfunction. Serum bilirubin is something not sensitive to liver dysfunction. However, the development of severe hyperbilirubinemia in primary biliary cirrhosis in alcoholic hepatitis and acute liver failure means a poor prognosis. Bilirubinuria reflects the presence of conjugated bilirubin in the urine; Bilirubin spills into the urine, because the levels are significantly increased in the blood, indicating a serious illness. Unconjugated bilirubin can not be excreted in the urine, as it is not water soluble and bound to albumin. A bilirubinuria can at the bedside with a commercially available urine test strip in acute viral hepatitis or other hepatobiliary diseases are detected, even before the onset of jaundice. The diagnostic accuracy of urine samples is limited. The results may be falsely negative, if the urine sample has been stored for a long time, when vitamin C was taken or the urine contains nitrates (eg. B. due to infection of the urogenital tract). Ebeso is also an increase of urobilinogen not specific or sensitiv.Alkalische phosphatase increases this Hepatozytenenzyms indicate cholestasis. Results are not specifically possibly as alkaline phosphatase consists of several isoenzymes and extrahepatic often occurs (eg. As in the placenta, small intestine, leukocytes, kidney and especially bone). The alkaline phosphatase increases to ? 4 times the normal value 1-2 days after initiation of bile duct occlusion, regardless of its location. The values ??may remain elevated for several days, because the half-life of alkaline phosphatase is about seven days after removal of the closure. Increases up to three times the normal value are found in many liver diseases, including hepatitis cirrhosis space-occupying diseases (z. B. carcinoma) Infiltrative diseases (z. B. amyloidosis, sarcoidosis, tuberculosis, metastases, abscesses) syphilitic hepatitis (alkaline phosphatase may be increased disproportionately compared to the small changes in other liver tests) Isolated increases (ie if other liver function tests are normal) may occur Focal liver lesions (z. B. abscess, tumor) partial or intermittent biliary obstruction (z. B. Stein, stenosis, cholangiocarcinoma) syphilitic hepatitis Occasionally infiltrative diseases Isolated increases can be observed in the absence of obvious hepatic or biliary disorder; as in the following: Some cancers with no obvious involvement of the liver (. eg lung cancer, Hodgkin’s lymphoma, renal cell carcinoma) After taking fatty meals (because of an enzyme that is produced in the small intestine) pregnancy (because of an enzyme in the placenta is produced) children and young people who are (chronic because of bone growth) kidney failure still growing (because of an enzyme that is produced in the intestines and bones) levels of ?-glutamyl or 5′-nucleotidase that are more specific to the liver, can hepatic better distinguish them from extrahepatic sources of alkaline phosphatase as the fractionation of alkaline phosphatase, which is technically difficult. Even in otherwise asymptomatic elderly, an increase of alkaline phosphatase is usually from the bones ago stirred (z. B. in Paget’s disease) and does not require any further investigation on Leberschäden.5 ‘-Nucleotidase increases of enzyme levels are just as sensitive as the alkaline phosphatase in the diagnosis of cholestasis and biliary obstruction, but it is more specific and has in most cases to a hepatobiliary disease out. Since the values ??for alkaline phosphatase and 5′-nucleotidase did not always correlate with each other, a value may be normal and the other increases sein.? glutamyl transpeptidase (?-GT), this enzyme increases with hepatobiliary diseases, v. a. in cholestasis, and only moderately correlated with the levels of alkaline phosphatase and 5’-nucleotidase. The values ??do not increase in childhood or during pregnancy in bone disease. However can alcohol and certain drugs (eg. As some anticonvulsants, warfarin) hepatic microsomal enzymes (the cytochrome P-450) stimulate, particularly the increase of GGT and this limited to a certain extent specificity. Testing of liver synthetic function prothrombin time and INR Prothrombin time (PT) is the time in seconds or preferably as a ratio of the measured PT to control PT as INR (n. D. Talk .: International Normalized Ratio) describes (INR tests) indicated become. The INR is more accurate than PT in the monitoring of anticoagulation. PT or INR are valuable parameters to estimate fibrinogen the liver’s ability and synthesize vitamin K-dependent coagulation factors: Factor II (prothrombin), V, VII and X. changes may soon occur because some of the clotting factors a short biological half-life have (z. B. 6 h for factor VII). Pathological values ??indicate a serious disruption of hepatocellular function, a prognostically bad sign for acute liver disorders. In chronic liver disease has an increased or PT INR indicates a progression of liver failure. The PT or INR rises at low hepatocellular damage is not, and is even in existence of cirrhosis often within the normal range. A prolonged PT and INR pathological can also occur on the floor of coagulation disorders such as coagulation or deficiency of vitamin K. A fat malabsorption incl. Cholestasis causes a vitamin K deficiency. In chronic cholestasis a pronounced hepatocellular dysfunction can be excluded if the administration of vitamin K (10 mg sc) to the PT ? 30% within 24 h normalisiert.Serumproteine ??The hepatocytes synthesize the majority of serum proteins, incl. ?- and ? -globulins, albumin and clotting factors (but not the ?-globulins, which are synthesized by B-lymphocytes). Hepatocytes also produce proteins that are useful in the diagnosis of certain diseases: ?1-antitrypsin (absent in ?1-antitrypsin deficiency) ferroxidase (reduced in Wilson’s disease) transferrin (saturated with iron in hemochromatosis) ferritin (greatly increased in hemochromatosis) These proteins are increased in response to damage (eg. as inflammation) from various tissues, so that an increase must be for liver disease not spefzifisch. Serum albumin typically takes in chronic liver diseases from because of the increase in volume of distribution (eg. B. increase in ascites), a reduction of hepatic synthesis or both. Values ??<3 g / dl (<30 g / l) indicate a decreased synthesis toward caused by one of: Advanced cirrhosis (the most common cause) alcohol Chronic inflammation protein deficiency due to malnutrition hypoalbuminemia may also be of an increased loss of albumin through the kidneys (z. B. in nephrotic syndrome), through the intestines (eg. B. Proteinverlustgastroenteropathie) or through the skin (eg. as burns or dermatitis exfoliative) originate. Because albumin has a half-life of about 20 days, it will take weeks until the serum levels rise or fall. Further laboratory tests which reach the intestine (eg. As by uptake of proteins, precipitated urea) ammonia nitrogen compounds, are decomposed by bacteria of the natural intestinal flora, whereby ammonia is released. The ammonia is then picked up and transported to the liver via the portal vein. The healthy liver builds the ammonia coming from the portal vein, easily and converts it to glutamine, which is metabolized by the kidney and excreted in urea. In patients with portosystemic shunts, the diseased liver can not break down the ammonia, which then enters the systemic circulation and possibly contributing to portosystemic (liver) encephalopathy. Elevated ammonia levels are found in hepatic encephalopathy, but the values ??may be erroneously low or high. In advanced liver disease following can raise the levels of ammonia: meals with high-dose proteins Gastrointestinal bleeding hypokalemia metabolic alkalosis certain drugs and toxins (eg alcohol, barbiturates, diuretics, opioids, Valproate.) Hochdosisierte chemotherapy Parenteral Nutrition renal Extreme muscle tension and muscle salicylate intoxication shock Ureterosigmoidostomy infections of the gastrointestinal tract with a urease-producing organism (eg. B. Proteus mirabilis) Because only slightly correlated, the extent of the rise of ammonia value with the severity of hepatic encephalopathy, is the ammonia level determination hilfreich.Serumimmunglobuline limited to monitor therapy In chroni rule liver disorders increase the serum immunoglobulins in general. These increases, however, are not specific and are not BEYOND in their clinical significance. The values ??are slightly elevated in acute hepatitis, moderately in chronic hepatitis and clearly with autoimmune hepatitis. The pattern of immunoglobulin increase adds little information on, although various immunoglobulins are often very high in various diseases: IgM in primary biliary cirrhosis IgA in alcoholic liver disease IgG in autoimmune hepatitis anti-mitochondrial antibody These heterogeneous antibodies are often measured positive with high titers, in> 95% of patients with primary biliary cirrhosis. They can be found occasionally in the following diseases: autoimmune hepatitis drug induced hepatitis other autoimmune diseases such as connective tissue diseases, myasthenia gravis, autoimmune thyroiditis, Addison’s disease and autoimmune hemolytic anemia may be useful anti-mitochondrial antibody in the differential diagnosis of cholestasis because they at extrahepatic biliary obstruction and not vorkommen.Weitere with primary sclerosing cholangitis antibodies Other antibodies can help in the diagnosis of the following: autoimmune hepatitis: antibodies of glattten muscles against actin, antinuclear antibodies against cell nuclei (ANA), which produce a homogenous (diffuse) fluorescence pattern and antibodies against liver, kidney microsomes type 1 (anti-LKM1). Primary biliary cirrhosis: anti-mitochondrial antibody is the key to diagnosis. Primary sclerosing cholangitis: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) can help confirm a suspicion. From an isolated pathology of each of these antibodies are allowed to do any diagnostics and the antibodies are not telling the Pathogenese.? fetoprotein (AFP) AFP, a glycoprotein which normally is in the yolk sac of the embryo and then synthesized by the fetal liver, is the newborn and increased accordingly in the pregnant mother. The AFP level falls during the first year of life quickly and reaches the age of one year adult normal values ??(laboratory dependent <10-20 ng / ml or <10 to 20 mg / l). An increase in the AFP, no matter how small, should give cause to think of a primary hepatocellular carcinoma (HCC). The serum AFP generally correlates with the size of the tumor, with the differentiation and the participation of metastases. Because small tumors produce low levels of AFP, indicate increasing values ??indicate HCC, especially if the tumors have> 3 cm in diameter. AFP also helps prognosis. A small increase of AFT is also found in acute and chronic hepatitis, which probably points to liver regeneration; AFP may occasionally rise up to 500 ng / ml for fulminant hepatitis. High AFP levels, in some other diseases occur (eg. As embryonic teratocarcinoma, hepatoblastoma in children, some liver metastases in the gastrointestinal tract cancer, cholangiocarcinoma some), but are not common and usually they can be clinically and histologically distinguished. Sensitivity, specificity, and peak levels of AFP in patients with HCC vary depending on the population, which reflects the differences in the prevalence of hepatitis and ethnicity. In areas with a relatively low prevalence of hepatitis (z. B. North America, Western Europe), AFP-limit values ??of 20 ng / ml have a sensitivity of 39-64% and a specificity of 76-91%. However, is not produced in all HCC AFP. Thus, AFP is not an ideal screening test, but it plays a role in the diagnosis of hepatocellular carcinoma (HCC). Exceeded the normal value (> 20 ng / ml), particularly if the value increases, leaves a suspect HCC. In patients with cirrhosis of the liver with a mass and a high value (eg. B.> 200 ng / ml), the predictive value is high. The combined use of AFP determination and ultrasound examination is currently offering the best monitoring.