(I) Pathogenesis It is currently believed that the genetic or acquired deficiency of bilirubin glucuronosyltransferase activity in the microsomal organelles of hepatocytes affects the normal processing of unconjugated bilirubin binding reactions in hepatocytes, so that the uptake of bilirubin by hepatocytes is also impaired, resulting in a dual defect in the uptake and binding of unconjugated bilirubin by hepatocytes. (ii) Pathogenesis In all patients with liver puncture biopsies, the viability of hepatic bilirubin glucuronosyltransferase was confirmed to be significantly reduced, suggesting that the ability of the liver to remove indirect bilirubin from plasma was reduced, but the concentration of plasma unconjugated bilirubin did not correlate significantly with the degree of reduction in the viability of the enzyme, probably due to the presence of moderate compensatory hemolysis in some patients with Gilbert syndrome. The study of bilirubin transport kinetics suggests that the cause of unconjugated hyperbilirubinemia is not due to excessive production but to a transport defect, and on the other hand, through the abnormal BSP transport that accompanies some patients, also suggests that some patients with this syndrome have a transport defect due to the entry of free bilirubin into the hepatocyte, which is taken up by two low molecular soluble “receptor proteins” (BSP) in the hepatocyte plasma. “receptor proteins” (Y, Z proteins accept) are brought to the endoplasmic reticulum of the sliding surface after entering the hepatocytes and are bound under the action of enzymes, if the amount of Y, Z proteins is insufficient or when the accepting function is poor, it causes transport impairment also affects the uptake and binding of unconjugated bilirubin by hepatocytes, according to the different concentrations of serum bilirubin, the syndrome can be divided into two types, whose pathogenesis The pathogenesis may be different. The pathogenesis of this syndrome may be due to defects in the uptake and transport of unconjugated bilirubin by hepatocytes, such as inadequate soluble protein receptors in the hepatocyte plasma or poor acceptance function, resulting in impaired transport of unconjugated bilirubin in hepatocytes, which affects the uptake of unconjugated bilirubin by hepatocytes. It is also possible that a proportion of mildly ill patients with the same pathogenesis as severely ill patients belong to the same type, i.e. due to an insignificant reduction in glucuronosyltransferase activity, but associated with an inability to measure a very mild reduction in enzyme activity due to the lack of sensitive detection techniques. 2, heavy serum bilirubin greater than 85, 5μmol/L (5mg/dl), often in the neonatal period, jaundice, due to the simultaneous lack of glucuronosyltransferase activity in the particles in the hepatocytes, resulting in poor hepatocyte binding function, resulting in jaundice with increased non-conjugated bilirubinemia. The symptoms of congenital nonhemolytic jaundice are mainly chronic intermittent jaundice since early childhood, which can be insidious; jaundice can persist up to old age, but often gradually decreases with age, serum bilirubin is less than 102,6 μmol/L, usually less than 51,3 μmol/L, with diurnal or seasonal fluctuations, about 1/3 of cases are normal at routine examination, which can be caused by fatigue, emotional Jaundice can be induced or aggravated by fatigue, mood swings, hunger, infection, fever, surgery, alcoholism, and pregnancy. The general condition of the patient is fair and most of them have no obvious conscious symptoms; some of them may be associated with easy fatigue, discomfort in the liver area, dyspepsia, etc. Sometimes patients with Gilbert syndrome may also have mild hemolytic anemia. Except for occasional overt jaundice, there are no abnormal signs, and the liver and spleen are often not enlarged. Depending on the concentration of serum bilirubin, the syndrome can be divided into mild and severe, with mild being more common than severe, with serum bilirubin less than 85l/L; severe with serum bilirubin greater than 85,5μmol/L, often with jaundice in the neonatal period. Because the disease can be confused with a number of diseases with clinical consequences and lead to errors in management, clinical confirmation of the diagnosis is more important, and the following points are highly suggestive of Gilbert syndrome: 1. chronic intermittent or fluctuating mild jaundice, with a trigger for the attack, may have a family history, good general condition, and no obvious symptoms. 2, physical examination, other than mild jaundice, no other abnormal signs, liver and spleen are mostly not large. 3, general liver function (ALT, AST, AKP, bile acids) is normal, only fluctuating elevation of plasma unconjugated bilirubin increased level. 4.No evidence of hemolytic, hepatocellular, or obstructive jaundice. 5, Normal liver histopathology. Gilbert syndrome can be diagnosed if there are no other abnormal laboratory findings after 2 to 3 follow-up visits within 12 to 18 months. Detection of TATAA sequences within the UGT1 promoter or the presence of mutations in the gene can help in the diagnosis. In most cases, the jaundice is mild, with total serum bilirubin ranging from 22.1 to 51.3 μmol/L, with a few cases of 85-102 μmol/L or higher, mainly elevated unconjugated bilirubin in the blood, normal serum bile acids, normal other liver function tests (e.g. ALT, AST and γ-GT), no evidence of hemolysis, normal erythrocyte fragility test, negative urinary bilirubin, normal urinary bilinogen in the feces The amount of urinary bilirubin in the urine was not increased. 1.Good visualization of gallbladder, cholangiography may be abnormal. 2.Phenobarbital test Phenobarbital can induce the activity of hepatic microsomal glucuronosyltransferase, promote the binding of unconjugated bilirubin and glucuronide, and reduce the concentration of plasma unconjugated bilirubin, oral phenobarbital for 2 weeks, 3 times/d, 60mg each time; after taking the drug to determine the concentration of plasma bilirubin, most patients jaundice improved, serum indirect bilirubin significantly decreased, or even can reach normal. If the jaundice is caused by complete deficiency of UGT1, it is not effective. 3, low-calorie diet test 2-3 days to give 1674kJ (400kcal) diet per day, if the plasma indirect bilirubin value increased by more than 100%, or increased by 25, 65μmol/L, there is diagnostic significance, 12-24h after resuming a normal diet, down to the basic level, the sensitivity of low-calorie diet test for this disease is about 80%, the specificity of several 100%, starvation caused by The mechanism of elevated serum bilirubin in patients with Gilbert syndrome may be multifactorial and is related to the following changes caused by starvation: decreased bilirubin ligand and Z protein content in the liver; increased heme catabolism; lipolysis in adipose tissue and increased free fatty acids, causing bilirubin free and released into the circulation; weakened intestinal motility and increased bilirubin enterohepatic circulation. 4.Gilbert syndrome patients were given a tracer dose of radionuclide-labeled indirect bilirubin and the percentage retention in plasma was measured after 24 h. The values of Gilbert syndrome patients were higher than normal. 5. There is no significant change in liver biopsy, occasionally a small amount of steatosis is seen, occasionally there is lipofuscin-like pigmentation around the terminal hepatic vessels, liver puncture to take biopsies for bilirubin glucuronosyltransferase activity measurement, its activity is significantly lower than normal, electron microscopy, can see the coarse endoplasmic reticulum and its protein particles on the hepatocytes are significantly reduced, the smooth endoplasmic reticulum is increased hypertrophy. I. Treatment No specific treatment is usually required, but care should be taken to avoid triggers that lead to increased jaundice. Phenobarbital and other drugs that can induce UGT1 activity: Phenobarbital, Grumet (conductive sleep energy), and clobetine (expectorated ethyl ester) are given orally to patients with this disease, and after 1 week, serum indirect bilirubin will decrease to normal, the mechanism may be accelerated bilirubin outline (due to enzyme induction) and reduced bilirubin conversion rate, but only a temporary effect, phenobarbital 30mg, 3 times/d, can increase Y protein synthesis, which increases the activity of glucuronosyltransferase, while promoting the binding function of hepatocytes to reduce hyperunconjugated bilirubinemia. Tin-protoporphyrin competitively inhibits heme oxygenase and reduces bilirubin production, but its value for this disease remains to be demonstrated. Prognosis Gilbert’s syndrome is a benign disease with benign course and good prognosis.