Liver injury laboratory tests mainly show that liver enzymology changes, bilirubin metabolism abnormality, substance synthesis dysfunction and biodegradation function decline, but the biochemical abnormalities and structural changes caused by different diseases are different in nature and degree. Liver injury is mainly characterized by changes in liver enzymology, abnormalities in bilirubin metabolism, dysfunctions in substance synthesis and decreased biodegradation, but the nature and extent of biochemical abnormalities and structural changes caused by different diseases are distinctive. In addition, biliary tract diseases may also cause liver function abnormalities. Liver biochemical tests are commonly used in clinical laboratories, mainly including ALT, AST, total protein, albumin (Alb), globulin, TBil and DBil. In recent years, some new items have been added to the liver biochemical examination, such as ferritin, prealbumin (PA), hyaluronic acid (HA) and so on. Each test index has different clinical significance and can be classified into four categories: markers of hepatocyte injury, markers of bilirubin metabolism, markers of hepatic synthetic function, and liver fibrosis-related serum indexes. By analyzing these markers, the nature and severity of the disease can be determined, providing a basis for diagnosis and treatment. Hepatocyte injury markers Aminotransferases ALT and AST are the most widely used biochemical indicators of hepatocyte injury; ALT is mainly distributed in the cytoplasm of hepatocytes, and AST is mainly distributed in the mitochondria of hepatocytes, with a few distributed in the cytoplasm. When pathogenic factors lead to hepatocyte degeneration and increased cell membrane permeability, ALT is mainly released from the cells; and when hepatocytes are severely damaged and necrotic, AST is released from the mitochondria, leading to a significant increase in serum AST. The AST/ALT ratio decreases when mild hepatitis occurs, and increases when severe hepatitis, cirrhosis and hepatocellular carcinoma occur. Therefore, the determination of serum AST and ALT levels and AST/ALT ratio is beneficial for the diagnosis and identification of liver function abnormalities. Under physiological conditions, serum ALT and AST activities are low, usually below 40 U/L. Under the action of pathogenic factors, hepatocyte degeneration and necrosis can lead to the release of intracellular ALT and AST into the bloodstream and cause elevation of serum aminotransferase activities. Liver disease caused by various pathogenic factors can result in varying degrees of elevation of ALT and AST; therefore, analysis of ALT and AST activities can be used for diagnosis and differentiation of the disease as well as assessment of the severity of the disease. A variety of liver diseases can cause mild to moderate elevations of aminotransferases; therefore, elevations of aminotransferases of less than moderate severity (<300 U/L) are nonspecific. If ALT is sharply elevated (>1000 U/L), it suggests the presence of massive hepatocellular necrosis, which is most commonly associated with acute viral hepatitis, toxic or pharmacologic liver injury, and acute ischemic liver disease. In addition, severe autoimmune hepatitis and hepatomegaly can lead to a dramatic increase in aminotransferases, but accompanied by elevated autoimmune antibodies or abnormal copper metabolism. If the causative factors persist, long-term damage to hepatocytes will cause long-term elevation of aminotransferases. Common diseases include chronic viral hepatitis (hepatitis B and C), alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver injury; rare diseases include autoimmune liver disease, and hepatomegaly, etc. In our country, due to HBV infection, the hepatitis B virus can cause a sharp increase in aminotransferases. In China, due to the high rate of HBV infection, chronic hepatitis B is the main cause of long-term and repeated elevation of aminotransferases, and the elevation of aminotransferases in this group of patients is dominated by ALT, and the ratio of AST to ALT (AST/ALT) is often <1, which makes it easy to make a rapid and definitive diagnosis in combination with virological examination. In patients with alcoholic liver disease, serum aminotransferase levels are usually <400 U/L, and AST is predominantly elevated. In chronic heavy drinkers, AST/ALT>2 suggests the possibility of alcoholic liver disease, and AST/ALT>3 is more diagnostic. In addition, pharmacologic liver injury is also a common cause of liver function abnormalities. Long-term use of anti-tuberculosis drugs such as isoniazid, rifampicin, azole antifungal drugs and antidepressants can cause persistent elevation of serum transaminases, and the liver function rapidly returns to normal after stopping the drugs. In addition to hepatic lesions, other systemic diseases such as hyperthyroidism, infectious diarrhea, anorexia nervosa, Addison’s disease, and myopathies can also cause persistent elevation of serum transaminases. Elevated serum aminotransferases from these diseases tend to be at low to moderate levels, and ALT and AST gradually return to normal when the primary disease is effectively controlled. Table 1 lists the common diseases that cause elevated transaminases. Alkaline phosphatase (ALP) Serum ALP comes mainly from the liver, bones and intestines. Clinical measurement of ALP is mainly used in the differential diagnosis of bone and hepatobiliary system diseases, especially in the differential diagnosis of jaundice. In biliary obstruction, serum ALP is significantly elevated and is proportional to the degree and duration of biliary obstruction, while at this time ALT is not significantly elevated, so the ALT/ALP ratio is small, usually <2; in hepatocellular injury, ALT is significantly elevated, ALP is not elevated or mildly elevated (<3 times the upper limit of normal value), and the ALT/ALP ratio is large, usually >5; while when ALT/ALP is between 2 and 5, it suggests that hepatocellular jaundice is a serious disease, especially in the differential diagnosis of jaundice. -5, it is suggestive of both hepatocellular and biliary tract involvement. Notably, a variety of factors can cause significant elevation of serum ALP in normal subjects. Normal pediatric ALP activity can be 2–5 times that of normal adults. ALP secreted by the small intestine into the blood after a meal (especially a high-fat meal) can generally increase by 30 U/L or more, and can persist for up to 12 h in people with blood group B or O. Pregnancy can also cause ALP to increase, up to 2–3 times the upper limit of normal values. Therefore, these special conditions should be excluded when analyzing ALP elevation. Figure 1 shows the diagnostic flowchart for ALP elevation. γ-Glutamyl transpeptidase (GGT) GGT is mainly distributed in the kidney, liver, pancreas, but the GGT released by the kidney is mainly excreted through the urine; serum GGT is mainly from the liver, and hepatic GGT is mainly distributed in the epithelial cells of the bile ducts and the lumen of the hepatocyte membranes, which will lead to the release of a large amount of GGT into the bloodstream when they are degenerated and necrosis occurs, which will lead to the elevation of serum GGT. Therefore, elevated GGT suggests liver disease, especially biliary tract disease. Extrahepatic cholestasis (caused by gallstones, cholangitis, pancreatic head carcinoma) and hepatocellular carcinoma are characterized by markedly elevated GGT, which can be as high as 5–30 times the upper limit of normal values. In the early stage of obstruction, the GGT/AST ratio is 3–6, and in long-term obstruction, the GGT/AST ratio is often >6. Substantial hepatic diseases, such as acute hepatitis: GGT is usually mildly elevated; fatty liver and cirrhosis in the active stage: GGT is usually mildly elevated; chronic hepatitis and cirrhosis in the inactive stage: GGT can be seen as normal. In addition, serum GGT mainly comes from the liver, so it can be used to assist in determining the source of ALP; elevated ALP and normal GGT indicate that ALP comes from the bone or intestine; if both are elevated, ALP comes from the liver, suggesting the presence of disease in the hepatobiliary system. Bilirubin metabolism markers Bilirubin is produced by the liver and excreted through the biliary tract, the liver has the role of uptake, binding and excretion in bilirubin metabolism. Bilirubin measurements include TBil and DBil, and the difference between the two is indirect bilirubin (IBil). A variety of pathogenic factors can cause elevated serum bilirubin, leading to jaundice. Clinically, jaundice is classified into four categories: (1) hemolytic jaundice; (2) obstructive jaundice; (3) hepatocellular jaundice; and (4) congenital bilirubin metabolism disorder. When intravascular hemolysis or massive rupture of erythrocytes occurs, a large amount of IBil is produced in the body, which exceeds the liver’s uptake and metabolism ability, and IBil in the blood is significantly elevated, resulting in hemolytic jaundice, and at this time, DBil, ALT, AST, and ALP are basically normal; when the bile duct is obstructed due to stones, tumors, or compression by peripheral masses, the DBil secreted by the hepatocytes will be blocked from being discharged and DBil will reflux due to the increase in bile duct pressure, thus resulting in DBil retrograde flow. When the DBil secretion from the liver cells is blocked due to the pressure in the bile duct, DBil will flow backward into the blood due to the increase of pressure in the bile duct, therefore, there is a significant increase of DBil in the blood, but IBil does not increase or increases slightly, and accompanied by the liver enzymology changes, which is called obstructive jaundice. When the hepatocytes are damaged, the liver is unable to completely take up and bind IBil, and DBil is released from the damaged hepatocytes, resulting in elevated DBil and IBil in the blood and a significant increase in transaminases, which leads to hepatocellular jaundice. In addition, Gilbert’s syndrome is characterized by a significant elevation of IBil in the blood due to impaired uptake of IBil by hepatocytes and a deficiency of glucuronosyltransferase in the microsomes of hepatocytes, and Dubin-Jonhson’s syndrome is characterized by an elevation of DBil due to the inability of hepatocytes to excrete DBil into the capillary bile ducts. None of these three bilirubin metabolism disorders cause significant changes in liver enzymology. Accordingly, the type and cause of jaundice can be initially determined. Figure 2 shows a flow chart for the diagnosis of hyperbilirubinemia. Liver synthesis function marker Albumin (Alb) Liver is the only organ that synthesizes Alb, after synthesis, it is needed by the organism, and it is hardly excreted, its half-life in plasma is about 21d, so the level of Alb reflects the anabolic function and reserve function of liver, and it is also an index to assess the severity of cirrhosis and judge the prognosis. the increase of Alb is mainly due to the relative increase of blood concentration. Under the condition of normal diet and normal renal function, the decrease of Alb may be related to liver function abnormality and the decrease of protein synthesizing function of the liver.Some patients have or will have ascites when the Alb is <30g/L, and the prognosis is poor when the Alb is below 25g/L, and very poor when the Alb is 20g/L. It should be pointed out that the Alb is not as high as it should be, because the Alb is not as high as it should be. It should be noted that Alb cannot be used to assess acute liver injury due to its long half-life. Plasma Prothrombin Time (PT) Plasma PT is another indicator for evaluating the synthetic function of the liver, which detects the blood clotting time, and it requires the participation of factors II, V, VII, and IX produced by the liver. When hepatocytes are extensively damaged, the liver's ability to synthesize coagulation factors decreases, resulting in a prolonged PT, which is abnormal if it exceeds 3s; when it exceeds 4--6s, it indicates severe liver injury and a very poor prognosis. PT is superior to Alb in responding to acute injury to liver function, and since only factor VII synthesis is reduced in the early stages of liver disease, PT appears to be prolonged earlier than the activated partial thromboplastin time. PA and serum pseudocholinesterase (PChE), both synthesized by the liver, have half-lives of 1.9 and 10 d=, respectively. Among them, PA, due to its short half-life, can quickly and sensitively reflect hepatocellular damage and liver synthesis function. Studies have shown that the PA abnormality rate in acute hepatitis is 34%, while the Alb abnormality rate is only 17%, so PA can reflect hepatocyte injury more sensitively and can be used as a sensitive indicator to determine acute liver injury. In addition, dynamic monitoring of PA can reflect the improvement or deterioration of hepatic synthetic function in liver failure patients, and the prognosis of those with obvious PA elevation under dynamic observation is good, while the prognosis of those with lowered or insignificant elevation is poor, so the observation of early dynamic change of PA can be used as one of the prognostic indicators of liver failure. Hepatic fibrosis related serum indexes Hyaluronic acid (HA) HA is a kind of aminoglucan distributed in extracellular matrix, which is mainly synthesized by hepatic stellate cells or fibroblasts, and degraded by sinusoidal endothelial cells, and among the many indicators of hepatic fibrosis, the sensitivity of HA is the highest. In acute hepatitis, serum HA is mostly normal, but in chronic hepatitis or cirrhosis, due to the decreased metabolic capacity of the liver, the clearance of HA is reduced, resulting in increased serum HA levels, and its elevated level is positively correlated with the degree of liver inflammation or liver fibrosis. Type IV collagen (C IV) and laminin (LN) C IV and LN are the main components of the basement membrane, and their synthesis increases when liver injury persists, while the liver's ability to degrade them decreases, resulting in capillarization. At the same time, C IV and LN were elevated in serum, and the degree of elevation correlated with the degree of liver fibrosis. Transforming growth factor (TGF)β1 TGFβ1 is the most important hepatic stellate cell activating factor known to date, and is in a state of network balance with other cytokines under normal conditions, working together to maintain the relative stability of the liver's internal environment. In chronic inflammation of the liver, Kupffer cells infiltrate in large numbers and secrete TGFβ1, which further activates the secretion of TGFβ1 by stellate cells and other mesenchymal stromal cells, thus leading to elevated levels of TGFβ1 in the blood circulation, and progressively increasing with the aggravation of hepatic fibrosis. In addition, type III procollagen, platelet-derived growth factor-BB, matrix metalloproteinase-1, matrix metalloproteinase inhibitor-1, and α-macroglobulin are also of diagnostic value for liver fibrosis. The above serum indicators have good specificity, but poor sensitivity, the role of a single indicator to diagnose liver fibrosis is limited, so often combined with a number of indicators to diagnose liver fibrosis. In recent years, a series of non-invasive diagnostic models for liver fibrosis based on various serum indexes have been established both at home and abroad, and the representative ones are FibroTest (whose parameters include α-macroglobulin, serum ApoA1, GGT, bilirubin and intrahepatic bead protein), APRI index (AST-to-platelet ratio index) and Forns index (whose parameters include platelet count, GGT, age and cholesterol). cholesterol), etc. Domestic counterparts also proposed SLFG model (whose parameters include α macroglobulin, age, GGT and HA) and S index (whose parameters include GGT, platelets and Alb) to evaluate liver fibrosis due to chronic HBV infection. These diagnostic models are better able to differentiate between S2 and above liver fibrosis, but have extremely limited diagnostic utility for earlier liver fibrosis. Diagnostic ideas of liver function abnormality (1) history taking, including history of hepatitis virus exposure, alcohol consumption, unclean diet, drugs and toxins, family history, etc.; (2) physical examination, including skin and sclera color, liver size, hepatic tenderness, Murphy's sign, etc.; (3) laboratory examination, including biochemical routines, pathogenicity testing, immunoglobulin classification and quantification and autoantibodies, etc.; (4) imaging examination, including abdominal ultrasound, CCTV, and other tests. (4) Imaging examination, including abdominal ultrasound, CT, magnetic resonance imaging, etc.; (5) Liver puncture biopsy, which is necessary for patients whose etiology is unknown or who need to be evaluated. As there are many causes of liver function abnormalities, including diseases of the liver itself and other systems, it is sometimes difficult to diagnose liver injury, so it is necessary to combine the information from medical history, laboratory tests and imaging to make a clear diagnosis. Summary Liver biochemical examination, including liver enzymology examination, bilirubin metabolism examination, liver synthesis function examination and liver fibrosis serological indexes, etc., can reflect the functional status of the liver in a more comprehensive way, provide important clues for the diagnosis of liver function abnormality, and dynamically monitor the condition of the disease, so it is the most widely used laboratory indexes in clinical application. In addition, the diagnosis of liver function abnormality also requires detailed history taking and comprehensive physical examination, as well as pathogenetic testing and ultrasound, CT and other imaging data and even liver biopsy. Only by combining the information from various aspects can we finally determine the cause of the disease, evaluate the condition and make a clear diagnosis, which in turn will guide the next step of treatment.