Congenital non-hemolytic jaundice

　　One, Etiology

　　Currently, most people believe that the insufficient activity of bilirubin glucuronosyltransferase in the microsomal organs of hereditary or acquired liver cells affects the normal course of the binding reaction of unconjugated bilirubin within the liver cells, thereby causing liver cells to have difficulty in absorbing bilirubin, and thus leading to a double defect in the uptake and binding function of unconjugated bilirubin by liver cells.

　　Two, Pathogenesis

　　In all the liver biopsy tissue specimens of patients, it has been confirmed that the activity value of bilirubin glucuronosyltransferase in the liver is significantly reduced, indicating that the liver's ability to clear indirect bilirubin from plasma is decreased, but there is no significant relationship between the concentration of unconjugated bilirubin in plasma and the degree of reduction in enzyme activity. This may be due to the fact that some patients with Gilbert's syndrome also have a mild compensatory hemolysis; the study of bilirubin transport dynamics suggests that the cause of unconjugated hyperbilirubinemia is not due to excessive production, but due to transport defects. On the other hand, the presence of BSP transport abnormalities in some patients also suggests that some patients with this syndrome have transport function defects. Since free bilirubin enters the liver cells and is transported to the smooth endoplasmic reticulum by two low molecular weight soluble 'receptor proteins' (Y, Z proteins) within the cytoplasm of liver cells, where it is combined under the action of enzymes. If the amount of Y, Z proteins is insufficient or the acceptance function is poor, it will cause transport disorders and also affect the uptake and binding of unconjugated bilirubin by liver cells. According to the concentration of serum bilirubin, this syndrome can be divided into two types, and the pathogenesis may be different.

　　1. Mild type

　　The severe type is more common, with serum bilirubin levels below 85.5mol/L and normal urobilinogen in the feces. The pathogenesis may be a defect in the process of liver cells taking up and transporting non-conjugated bilirubin. If there is insufficient solubility protein receptor in the cytoplasm of liver cells or if its acceptance function is poor, it causes a transport barrier of non-conjugated bilirubin in liver cells, affecting the poor uptake of non-conjugated bilirubin by liver cells. However, it is also possible that some mild patients have the same pathogenesis as severe patients, belonging to the same type, i.e., due to a slight decrease in the activity of glucuronyltransferase, but due to the lack of sensitive detection technology, it is related to the inability to detect a slight decrease in enzyme activity.

　　2. Severe type

　　Serum bilirubin levels greater than 85.5mol/L (5mg/dl) often appear in the neonatal period. Due to insufficient activity of the intracellular glucuronyltransferase in liver cells, the binding function of liver cells is poor, causing increased non-conjugated bilirubinemia and jaundice.

　　Mild hemolytic anemia may be present.

　　The prognosis of this disease is related to the nature of jaundice, the strength of the physique, and factors such as treatment and nursing. Although Yang jaundice, Yin jaundice, and acute jaundice have different properties and varying degrees of severity, they can transform into each other under certain conditions. Yang jaundice can transform into acute jaundice if the patient's physique is weak and the pathogen is severe, with the jaundice deepening rapidly and symptoms of severe heat and toxicity appearing. Yang jaundice can also transform into Yin jaundice due to injury to the spleen Yang and the transformation of dampness from cold. Yin jaundice can develop into Yang jaundice if it is heavily affected by damp-heat. Acute jaundice can lead to Yang Qi failure in the liver and kidneys if heat and toxicity are severe, or if there is significant bleeding. Yin jaundice can transform into mass or distension if it does not improve after long-term treatment.

　　In general, the prognosis of Yang jaundice is good, while acute jaundice affects the heart and blood, leading to poor prognosis. As for Yin jaundice, if the Yang Qi gradually recovers and jaundice diminishes, the prognosis is better; if Yin jaundice does not improve after long-term treatment, it can transform into a severe condition such as distension due to heat and injury to Yin and blood, leading to poor prognosis. Acute jaundice has a high mortality rate, and if signs of Yang Qi failure in the liver and kidneys appear, the prognosis is extremely poor.

　　The main manifestation is chronic intermittent jaundice starting from childhood, which can be latent; jaundice can persist into old age, but it often gradually diminishes with age, with serum bilirubin levels below 102.6μmol/L, generally less than 51.3μmol/L, showing diurnal or seasonal fluctuations. Approximately 1/3 of cases are normal during routine examinations. Jaundice can be induced or exacerbated by fatigue, emotional fluctuations, hunger, infection, fever, surgery, alcoholism, or pregnancy.

　　1. Timely premarital physical examination and prenatal diagnosis are also very critical. Such as ultrasound monitoring, karyotype examination, etc.

　　2. It is not advisable to drink alcohol, smoke, fatigue, or take medication before pregnancy. During pregnancy, it should be avoided to catch a cold, be exposed to direct sunlight, high temperatures, and stay away from chemical harmful substances.

　　3. Timely bilirubin, blood routine, and ultrasound monitoring for children after delivery.

　　1. Good gallbladder imaging

　　Gallbladder imaging may show no abnormalities.

　　2. Phenobarbital test

　　Phenobarbital can induce the activity of liver microsomal glucuronyltransferase, promote the binding of unconjugated bilirubin with glucuronic acid, and reduce the concentration of unconjugated bilirubin in plasma. After taking phenobarbital orally for 2 weeks, 3 times a day, 60mg each time, the concentration of plasma bilirubin is measured. Most patients show improvement in jaundice, and the serum indirect bilirubin concentration decreases significantly, even reaching normal levels; it is ineffective for jaundice caused by complete absence of UGT1.

　　3. Low-calorie diet test

　　2-3 days of daily 1674kJ (400kcal) diet, if the plasma indirect bilirubin level increases by more than 100%, or by 25.65μmol/L, it has diagnostic significance. After 12-24 hours of returning to normal diet, it decreases to the baseline level. The sensitivity of the low-calorie diet test for this disease is about 80%, and the specificity is almost 100%. The mechanism by which hunger causes an increase in serum bilirubin in Gilbert's syndrome patients may be multifactorial and related to the following changes caused by hunger: decreased content of bilirubin ligands and Z proteins in the liver; increased hemoglobin catabolism; lipolysis in adipose tissue, increased free fatty acids, leading to the liberation of bilirubin and its release into the circulation; weakened intestinal peristalsis, increased enterohepatic circulation of bilirubin.

　　4. Test for Gilbert's syndrome

　　The patient is administered a trace amount of radioactive isotope-labeled indirect bilirubin, and the percentage retained in the plasma 24 hours later is measured. The value in Gilbert's syndrome patients is higher than that in normal people.

　　5. Liver biopsy

　　No significant changes, occasionally a small amount of fatty change can be seen, and occasionally there is a deposition of lipofuscin-like pigment around the terminal hepatic blood vessels. Liver biopsy to obtain living tissue for the determination of bilirubin glucose醛酸transferase activity shows that the activity is significantly lower than that of normal people. Electron microscopy examination shows that the rough endoplasmic reticulum and the protein particles on it in the liver cells are significantly reduced, while the smooth endoplasmic reticulum increases in size and hypertrophy.

　　1. Drink more vegetable juice

　　Regularly drinking beet juice (made from the root and top), carrot juice (containing beta-carotene), and asparagus juice. Mixing fresh kale and carrots into a vegetable juice blend is very effective. Grape juice, cherry juice, and all dark-colored juices, including black currant juice, are excellent nutritious juices. Fresh apple juice is also beneficial. The best time to drink juice is in the morning, while vegetable juice is best consumed in the afternoon. Only drink mineral water or distilled water.

　　2. Eat more onions and garlic

　　Onions and garlic are excellent health foods. Eating ten raw almonds a day, which are rich in laetrile and also an antitumor agent. You can eat more sprouts, such as radish sprouts, soybean sprouts, and it is best to eat them raw, or just blanch them with boiling water.

　　3. Eat more raw radish

　　Many people know that at present, a drug called 'interferon' is often used in hospitals. It is a glycoprotein produced by the body's own white blood cells, which has the function of inhibiting the rapid division of cancer cells in the body. However, the interferon produced in the human body is very little, so scientists have developed drugs such as 'interferon inducers' to stimulate and induce the human body to produce more interferon.

　　In daily diet, there are also some foods that can induce interferon, among which the best is radish. Studies have shown that active components of interferon-inducing agents, such as double-stranded ribonucleic acid, can have a significant inhibitory effect on cancer cells of esophageal cancer, stomach cancer, nasopharyngeal cancer, and cervical cancer. However, since this active component is not heat-resistant, it will be destroyed during cooking, so eating radish raw is beneficial for cancer prevention.

　　1. Treatment

　　Generally, no special treatment is needed. However, it is important to avoid triggers that may worsen jaundice.

　　Phenobarbital and other drugs that can induce UGT1 activity: Patients with this disease are given oral phenobarbital, griseofulvin (dormition), and clofibrate (lipolytic ethyl ester), and after one week, the serum indirect bilirubin will decrease to normal. The mechanism may be the acceleration of bilirubin clearance (due to enzyme induction) and the reduction of bilirubin conversion rate, but it has only a temporary effect. Phenobarbital 30mg, three times a day, can increase the synthesis of Y protein, increase the activity of glucuronyltransferase, and promote the binding function of liver cells to reduce hyperbilirubinemia.

　　Tin-protoporphyrin can competitively inhibit heme oxygenase, reduce bilirubin production, but its value for this disease is yet to be proven.

　　2. Prognosis

　　Gilbert's syndrome is a benign disease with a benign course and a good prognosis.