bubble_chart Overview

Jaundice or cholestasis is a clinical manifestation characterized by the retention of bilirubin in the body, elevated serum bilirubin levels, and the yellow staining of the skin, mucous membranes, and other tissues such as brain tissue. Normally, the total serum bilirubin ranges from 4 to 17 μmol/L, with 80% being unconjugated bilirubin (or indirect bilirubin), approximately 8–13 μmol/L, and the remainder being conjugated bilirubin (or direct bilirubin), about 0–4 μmol/L. When the total serum bilirubin exceeds 17 μmol/L, it is considered hyperbilirubinemia. Generally, if the level is between 17–34 μmol/L, there is no clinically apparent jaundice, known as latent jaundice. If it surpasses 34 μmol/L, yellow discoloration of the skin and mucous membranes becomes visible.

bubble_chart Etiology

1. Normal Bilirubin Metabolism Approximately 80–85% of the bilirubin produced daily in the human body is derived from the breakdown of hemoglobin in aging red blood cells in the blood. The remaining small portion originates from the minor decomposition of immature red blood cells in the bone marrow or non-hemoglobin heme enzymes and cytochromes in other tissues, generating what is termed "shunt bilirubin." In normal individuals, the lifespan of red blood cells in the blood is about 100–120 days, with approximately 1% of red blood cells aging and dying each day. These dead red blood cells are cleared and broken down by phagocytes (primarily in the spleen, liver, and bone marrow). Generally, hemoglobin first releases heme. When heme is degraded in the body, the α-methylene bridge (=CH-) of the porphyrin ring is selectively oxidized and cleaved, converting it into a linear tetrapyrrole compound, releasing CO and iron to form biliverdin. The latter is rapidly reduced to unconjugated bilirubin, a process roughly summarized as follows:

Hemoglobin → globin → heme -CO, -Fe → biliverdin -2H → bilirubin (unconjugated). This process also requires the participation of various enzymes, such as microsomal heme oxygenase (MHO) and soluble biliverdin reductase, both of which require reduced nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. Typically, 1g of hemoglobin releases about 34mg of bilirubin. Under normal circumstances, unconjugated bilirubin can be rapidly cleared from the plasma by hepatocytes. Unconjugated bilirubin is lipid-soluble and binds firmly to plasma albumin in the bloodstream, forming a bilirubin-albumin complex. This complex is relatively stable and cannot pass through semipermeable membranes or cell membranes, nor is it filtered by the glomeruli. When the concentration of organic anions in the blood increases or the pH decreases, unconjugated free bilirubin may form, which can penetrate cell membranes and enter nerve cells rich in phospholipids, leading to kernicterus. In neonatal hyperbilirubinemia, exposure to light (blue or white) can convert unconjugated bilirubin into the E-isomer, which binds to plasma albumin, becomes water-soluble, and lacks neurotoxicity. It can thus be excreted without conjugation, leading to a decrease in unconjugated bilirubin in the blood.

The processes of uptake, conjugation, and excretion of bilirubin in hepatocytes are briefly described below.

(1) Uptake of bilirubin by hepatocytes: On the sinusoidal surface of the hepatocyte membrane, there are specific receptor sites that rapidly take up unconjugated bilirubin from the serum, allowing it to enter the hepatocyte cytoplasm through the microvilli of the hepatocyte membrane. Within hepatocytes, two pigment-binding proteins, known as Y protein and Z protein, specifically bind organic anions, including bilirubin. Experimental evidence shows that Y protein is unique to liver and kidney cells, with higher levels in the liver, and has a stronger affinity for bilirubin, making it the primary protein for bilirubin binding, referred to as the first receptor. Z protein is found in hepatocytes and the mucosal membrane of the distal small intestine, with small amounts also present in tissues such as the heart and brain. It only binds bilirubin when bilirubin levels in the body are excessively high, hence termed the second receptor. During the neonatal period, the liver lacks or has very low levels of Y and Z proteins, which gradually reach normal levels with age. As a result, unconjugated bilirubin in newborns, especially premature infants, cannot be promptly taken up by hepatocytes and converted into conjugated bilirubin, often leading to transient hyperbilirubinemia, known as physiological jaundice of the newborn.

(2) Hepatocyte conjugation of bilirubin: Unconjugated bilirubin binds to receptor proteins and is transported to the smooth endoplasmic reticulum in the cytoplasm. There, under the action of a series of enzymes—primarily various glucuronyl transferases—it catalyzes the transfer of glucuronic acid groups from reduced nicotinamide adenine dinucleotide phosphate (NADPH) molecules to the propionic acid groups of bilirubin, forming bilirubin glucuronide (i.e., conjugated bilirubin). This renders the bilirubin water-soluble, preventing it from crossing cell membranes while allowing it to pass through capillary walls for excretion via bile ducts and kidneys. Any factor that damages hepatocytes can lead to enzyme deficiency, impairing bilirubin conversion.

(3) Transport and excretion of bilirubin by hepatocytes: Hepatocytes transport and excrete the already formed conjugated bilirubin into the bile canaliculi, making it one of the main components of bile. After bile enters the intestines, conjugated bilirubin is converted back into unconjugated bilirubin through the action of bacteria, becoming urobilinogen and stercobilinogen, collectively referred to as urobilinogen. Most urobilinogen is oxidized into stercobilin, giving feces their brown color and excreted with the stool. A portion (10–20%) of urobilinogen is reabsorbed by the intestines and then converted back into conjugated bilirubin by the liver, which is excreted into the bile ducts, forming the enterohepatic circulation. A small portion enters the liver via the portal vein, transmission from one meridian to the next, and then passes through the hepatic vein and inferior vena cava into the systemic circulation, ultimately being excreted by the kidneys.

2. Mechanism of jaundice occurrence Any disruption in the bilirubin metabolism process can lead to jaundice. The mechanisms generally fall into the following categories: (1) Excessive bilirubin production, such as congenital or acquired hemolytic diseases or excessive destruction of immature red blood cells in the bone marrow; (2) Impaired uptake, conjugation, transport, or excretion of bilirubin by hepatocytes, such as liver cell damage, reduced or deficient enzyme activity, or intrahepatic bile stasis; (3) Obstruction of intrahepatic or extrahepatic bile ducts, such as congenital biliary atresia or compression by intrahepatic or extrahepatic tumors.

3. Classification of jaundice There are multiple methods for classifying jaundice. Currently, the most reasonable classification is based on the type of elevated bilirubin in the blood, dividing it into unconjugated hyperbilirubinemia and conjugated hyperbilirubinemia. Clinically, jaundice can also be classified according to its mechanism and the site of pathology, broadly categorized into prehepatic, hepatocellular, and posthepatic types.

(1) Prehepatic jaundice: Excessive production of unconjugated bilirubin may result from congenital or acquired hemolysis or excessive destruction of immature red blood cells in the bone marrow, even without hemolysis in the blood. This type of jaundice occurs because the amount of unconjugated bilirubin increases before entering hepatocytes, far exceeding the liver's clearance capacity (normal liver cells can increase bilirubin clearance up to 7-fold), leading primarily to retention jaundice. Due to hemolysis and anemia, liver function declines, allowing a small amount of conjugated bilirubin (15%) to reflux into the bloodstream.

(2) Hepatocellular jaundice: Jaundice may result from impairment in any one or several steps of bilirubin uptake, conjugation, transport, or excretion by hepatocytes. Hepatocytes may fail to effectively take up unconjugated bilirubin, or uptake may be normal but conjugation impaired due to enzyme deficiency or reduction. In such cases, unconjugated bilirubin increases in the bloodstream. Even if conjugated bilirubin is formed, impaired transport or excretion by hepatocytes will lead to elevated conjugated bilirubin in the blood. Some liver parenchymal diseases involve both mechanisms, resulting in elevated levels of both unconjugated and conjugated bilirubin.

(3) Posthepatic jaundice: Primarily caused by biliary system obstruction. Bilirubin production and conjugation proceed normally, but due to bile duct blockage, conjugated bilirubin cannot be excreted and refluxes into the bloodstream, increasing conjugated bilirubin levels. Prolonged bile stasis (lasting several weeks) can impair hepatocyte function, affecting the conversion of unconjugated bilirubin in hepatocytes, thereby also exhibiting some features of retention jaundice.

bubble_chart Diagnosis

Jaundice can occur in liver diseases or diseases outside the liver, manifesting at different periods after birth, and may be temporary or persistent.

1. Diseases classified as prehepatic jaundice

(1) Hemolytic hyperbilirubinemia: (1) Neonatal hemolytic disease: Hemolysis caused by Rh and ABO blood group incompatibility (details in the chapter on neonatal diseases); (2) Neonatal sepsis: Hemolysis due to infection and toxicity, accompanied by impaired liver function and reduced enzyme activity, which is another cause of jaundice; (3) Hemolysis in newborns caused by water-soluble vitamin K, which is rare but noteworthy; (4) Blood type incompatibility during transfusion; (5) Favism: Severe hemolysis caused by glucose-6-phosphate dehydrogenase deficiency when consuming fava beans; (6) Malignant malaria; (7) Autoimmune hemolytic anemia: Can onset acutely, with cardiac enlargement, heart failure, and severe anemia, leading to delayed development over time or possible gallstones; (8) Snake venom and bee venom can cause severe acute hemolysis; (9) Other hemolytic diseases: Congenital hereditary defects in red blood cell membranes, metabolic enzymes, or hemoglobin, such as hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria, cold hemoglobinuria, thalassemia, etc. These diseases exhibit significant anemia but milder jaundice, as liver cells are not yet damaged and can mostly clear the excess bilirubin.

(2) Non-hemolytic excessive bilirubin production: Such as shunt hyperbilirubinemia, where immature red blood cells in the bone marrow are excessively destroyed without hemolysis in the bloodstream; seen in hematopoietic system disorders like pernicious anemia, thalassemia, and congenital erythropoietic porphyria.

2. Diseases classified as hepatic jaundice

(1) Due to uptake dysfunction: (1) Congenital non-hemolytic unconjugated hyperbilirubinemia (mild Gilbert syndrome), mostly occurring in older children but also in infants or children, presenting with long-term intermittent jaundice but often no obvious symptoms. Phenobarbital can reduce serum bilirubin to normal levels. (2) Neonatal physiological jaundice.

(2) Due to conjugation dysfunction:

1) Congenital enzyme deficiency diseases: (1) Congenital non-hemolytic jaundice prone to kernicterus (Crigler-Najjar syndrome), divided into two types: Type I is recessive inheritance, and Type II is dominant inheritance. Onset in newborns often accompanies kernicterus, with elevated unconjugated bilirubin (especially in Type I) but no hemolysis. The sulfobromophthalein (BSP) test is normal. Phenobarbital can significantly reduce bilirubin levels in Type II but is ineffective for Type I patients. (2) Congenital non-hemolytic jaundice, unconjugated hyperbilirubinemia type (severe Gilbert syndrome), due to impaired uptake of unconjugated bilirubin by liver cells and lack of transferase in liver cell microsomes, leading to impaired bilirubin conjugation and large amounts of unconjugated bilirubin entering the bloodstream. The BSP test is normal.

2) Diseases due to immature enzyme development: Physiological jaundice in newborns and premature infants is the most common non-hemolytic unconjugated hyperbilirubinemia in the neonatal period, with multifactorial causes, possibly due to uptake dysfunction or enzyme deficiency.

3) Diseases due to enzyme inhibition: (1) Temporary familial hyperbilirubinemia (Lucey-Driscoll syndrome). The condition is severe, with onset immediately after birth and a high risk of kernicterus. Unconjugated bilirubin is significantly elevated due to inhibitory substances in the mother’s body. (2) Breastfeeding jaundice: Breastfeeding can prolong neonatal physiological jaundice; stopping breastfeeding normalizes hyperbilirubinemia, possibly due to 3α-20β pregnanediol in breast milk inhibiting hepatic glucuronyltransferase or increased lipoprotein lipase.

(3) Due to transport and excretion dysfunction:

1) Congenital diseases: (1) Congenital non-hemolytic conjugated hyperbilirubinemia type I (Dubin-Johnson syndrome), due to the transport and excretion障碍 of conjugated bilirubin formed in hepatocyte microsomes, which then返流 into the blood circulation. The BSP test is normal at 30 minutes but shows high values after 45 minutes, aiding in differential diagnosis. Phenobarbital may be effective. Jaundice mostly occurs in adolescence but may also be detected in childhood. Hepatocytes have brown pigment deposition, representing a congenital hepatic excretion dysfunction with difficulty in organic anion excretion (including bilirubin, BSP, etc.), only bile salts can be excreted, hence no cutaneous pruritus, and it is a recessive遗传病. (2) Congenital non-hemolytic jaundice, conjugated hyperbilirubinemia type II (Rotor syndrome), similar to Dubin-Johnson syndrome but without pigment deposition in hepatocytes. Some also believe that besides障碍 in hepatocyte transport and excretion of conjugated bilirubin, there is also some障碍 in hepatocyte uptake of unconjugated bilirubin. These two syndromes can be differentiated via liver biopsy. (3) Familial intrahepatic gall fel淤积性 jaundice, mostly seen in childhood or adolescence, and can also occur in the neonatal period. It presents with intermittent发作性 jaundice. The BSP test is normal, serum alkaline phosphatase is elevated, and cholesterol is normal. Patients have severe cutaneous pruritus, malabsorption, and rickets, with the disease cause being a hereditary defect in bile acid metabolism or transport. (4) α1-antitrypsin deficiency can cause gall fel淤积性 jaundice in the neonatal period. It is a congenital遗传性疾病.

2) Acquired diseases: Intrahepatic cholestasis syndrome caused by hepatitis or drugs (such as isoniazid, chlorpromazine, chlorpropamide, methyltestosterone, etc.).

(4) Due to mixed pathogenic factors: Hepatocyte damage leading to impaired uptake, conjugation, transport, and excretion of bilirubin. Seen in: (1) Viral hepatitis; (2) Various infectious or toxic hepatitis; (3) Cholestatic cirrhosis; (4) Hepatocellular carcinoma, which can occur in infants, presenting with severe jaundice, hepatomegaly, irregular and firm liver surface, often accompanied by ascites; (5) Hepatocyte damage caused by toxins, such as mushroom poisoning, cocklebur fruit poisoning, or certain chemical poisonings; (6) Galactosemia, where congenital deficiency of galactokinase leads to galactose accumulation in hepatocytes, impairing function and causing jaundice in neonates; (7) Tyrosinemia and cystic fibrosis of the pancreas may also cause hepatocyte damage and jaundice, but each has distinct clinical manifestations that should be identified; (8) Cytomegalic inclusion disease or other viral infections, such as rubella, herpes simplex, and some enteroviruses, can cause hepatocyte damage and jaundice in infants; (9) Wilson’s disease; leptospirosis, congenital syphilis, and relapsing fever can also damage the liver, leading to impaired liver function and jaundice; toxoplasmosis.

3. Posthepatic jaundice due to congenital malformations, stones, tumors, strictures, inflammation, or Chinese Taxillus Herb worms causing biliary obstruction, mainly including: Congenital biliary atresia; Biliary stones; Biliary ascariasis or clonorchiasis; Primary cholestatic cirrhosis; Congenital choledochal cyst.

bubble_chart Treatment Measures

Except for a few cases of congenital biliary atresia that require surgical intervention, the majority can be treated medically.

1. Chinese Medicinals Traditional Chinese medicine refers to neonatal jaundice as "fetal jaundice," with Virgate Wormwood as the primary treatment. A commonly used formula is the Virgate Wormwood Three-Yellow Decoction (Virgate Wormwood 9g, Skullcap Root 4.5g, Phellodendron Bark 4.5g, Coptis Rhizome 1.5g, Rhubarb Rhizoma 1.5g, Gardenia 3g), which is decocted into a concentrated liquid and administered orally in small, frequent doses once daily. Alternatively, an injection of Virgate Wormwood and Gardenia Yellow diluted with 10% glucose solution can be administered intravenously, gradually reducing jaundice.

2. Phototherapy In the early 1970s, the Shanghai First Maternity and Infant Health Institute collaborated with Fudan University to develop blue light therapy for treating high unconjugated bilirubinemia, achieving results comparable to those abroad. Due to its significant efficacy, simplicity, and minimal side effects, it has been widely adopted. Domestic blue light tubes emit wavelengths of 420–470 nm, close to the peak absorption wavelength of serum bilirubin (460–465 nm). Unconjugated bilirubin undergoes photo-oxidation and isomerization to produce biliverdin and non-toxic, water-soluble dipyrroles, which are less likely to diffuse into the central nervous system and are excreted via bile and urine. White light can also be effective in the absence of blue light tubes, though it is about 5% less effective. In 1983, Vecchi reported that green light with a wavelength of 514.5 μm outperformed white light. In 1984, Shanghai adopted green light, which yielded even better results than blue light.

The effectiveness of phototherapy depends not only on wavelength but also on the skin's exposed surface area and light intensity. Double-sided illumination is faster and more effective than single-sided illumination and reduces the need for repositioning. During treatment, the eyes should be shielded to protect the retina, while the perineum is covered with a small diaper, leaving the rest of the skin exposed as much as possible. Light intensity is influenced by the number of tubes, their arrangement, reflectivity, lifespan, dust accumulation, distance from the skin, and the presence of acrylic barriers. Typically, 5–9 tubes per side are arranged in an arc to ensure uniform distance from the skin, with reflective surfaces and minimal dust accumulation. Blue fluorescent tubes dim faster than white ones, losing 20% brightness after 300 hours, 35% after 900 hours, and 45% after 2,700 hours. Tubes with 20 watts dim faster than those with 40 watts. When a radiometer detects tube power below 300 μW (after approximately 2,500–3,000 hours of use), replacement is necessary. The optimal distance between tubes and skin is 33–50 cm. If light intensity decreases, reducing this distance can maintain an intensity of 200–460 foot-candles. To prevent tube breakage or injury, an acrylic barrier is recommended, though a 5 cm thickness reduces transmittance by about 5%.

The duration of phototherapy depends on the disease cause, jaundice severity, and serum bilirubin levels. Continuous illumination is more effective and simpler than intermittent illumination, though alternating 6-hour intervals between two infants using one phototherapy unit yields similar results. The reduction in bilirubin depends on the disease cause, baseline bilirubin levels before treatment, and postnatal age. Generally, 24 hours of phototherapy reduces bilirubin by about 30%. In some cases of Rh hemolytic disease, early phototherapy within the first day slows bilirubin rise, followed by a gradual decline after 3–4 days, avoiding the need for exchange transfusion. Most cases of high unconjugated bilirubinemia see levels drop below 205 μmol/L (12 mg/dL) after 24 hours of phototherapy, allowing discontinuation. Since skin jaundice fades faster than serum bilirubin in blood vessels, stopping treatment may cause a temporary rebound as bilirubin re-enters the skin from the blood, with gradual resolution over 1–2 days.

During phototherapy, grade I diarrhea with green loose stools, pinpoint-sized red rashes, increased riboflavin breakdown, fever when environmental temperature is too high, and increased insensible water loss may occur. Abnormal liver function, sepsis, and serum conjugated bilirubin levels greater than 68.4 μmol/L (4 mg/dl) accompanied by hyperporphyrinemia can lead to bronze baby syndrome after phototherapy, where the skin and viscera appear bronze-colored, but this resolves spontaneously after stopping the treatment. A sister chromatid exchange test conducted by the Affiliated Hospital of Jinan University Medical College on peripheral blood lymphocytes of 67 neonates with hyperbilirubinemia suggested that prolonged phototherapy may cause DNA injury and potentially lead to long-term side effects. However, a long-term follow-up study by the Guangzhou Red Cross Hospital and others on neonates treated with blue light for hyperbilirubinemia showed no significant differences in physical or intellectual development compared to healthy controls at ages 2.5 to 9 years. Although phototherapy currently has few side effects clinically, appropriate indications should still be followed. If unconjugated bilirubin measured by the Lathe modified method exceeds 205 μmol/L (12 mg/dl) or if neonatal hemolytic disease is confirmed postpartum after prenatal suspicion, phototherapy should not be delayed until bilirubin reaches 205 μmol/L (12 mg/dl). Phototherapy only treats the surface symptom (jaundice) and does not address the root cause, reduce antibodies, or correct anemia. However, for cases requiring exchange transfusion, phototherapy before and after the procedure can reduce the number of transfusions needed and improve efficacy. Green light exposure results in fewer cases of diarrhea, rashes, and riboflavin deficiency. In coastal areas with high humidity, insensible water loss during phototherapy is mild, while inland areas may require a 20–25% increase in fluid intake, with attention to urine output and specific gravity. The temperature of the phototherapy unit should generally be maintained at 30°C to avoid overheating. When increasing ventilation, direct drafts should be avoided.

3. Preventing the reabsorption of intestinal bilirubin Early feeding, timely establishment of intestinal flora, breaking down intestinal bilirubin into urobilinogen, and expelling meconium as soon as possible can reduce intestinal bilirubin and prevent its reabsorption, thereby alleviating the severity of jaundice. Some administer activated charcoal at 0.75g every 4 hours to reduce the intestinal wall's reabsorption of unconjugated bilirubin (enterohepatic circulation), which shows better results when combined with phototherapy.

4. Enzyme induction method Phenobarbital is commonly used to induce the microsomes of liver cells to enhance activity, converting unconjugated bilirubin into conjugated bilirubin. The dose is 4–8mg/kg/day, taken continuously for 4 days or longer, but its effect is relatively slow, taking 3–7 days to show efficacy. Nicethamide (Coramine) can be added at 100mg/kg/day to improve the efficacy of phenobarbital.

5. Exchange transfusion therapy For details, refer to the section on the treatment of neonatal hemolytic disease. Since phototherapy has been widely adopted, the need for exchange transfusions has significantly decreased.

6. Albumin Infusing plasma or albumin can bind free unconjugated bilirubin in the serum to albumin, thereby reducing the chance of unconjugated bilirubin binding to brain cells and lowering the incidence of kernicterus. One hour before an exchange transfusion, administering albumin at 1g/kg per dose, repeated 2–4 times, or using plasma at 25ml once or twice daily, can remove more bilirubin.

7. Adrenocorticosteroids Their main role is to activate liver cell enzyme systems, enhancing the ability of glucuronic acid to bind with bilirubin. Generally, oral prednisone is given at 1–2mg/kg/day. For more severe cases of jaundice, intravenous hydrocortisone at 5–10mg/kg or dexamethasone at 0.4mg/kg/day can be used, with the dose reduced as jaundice subsides until discontinued. Due to the frequent adverse side effects of corticosteroids, they are not routinely administered. With the widespread use of phototherapy, hormone therapy is even less necessary.

8. Tin-protoporphyrin As an inhibitor of heme oxygenase, it prevents the breakdown of hemoglobin, thereby reducing bilirubin formation. This drug has now been synthesized artificially and is expected to be applied clinically in the future.

bubble_chart Prognosis

For low birth weight infants, asphyxiated infants, those with maternal-fetal blood group incompatibility, and other high-risk newborns prone to hyperbilirubinemia, serum bilirubin levels should be monitored early after birth, and phototherapy should be administered when necessary. This is the first critical checkpoint that neonatal department doctors and nurses in maternity hospitals must ensure. For newborns with short hospital stays or early discharge, families should also be informed to seek immediate medical attention if severe or rapidly progressing jaundice occurs. To avoid separating mothers and infants, some countries provide preventive home phototherapy for high-risk infants for 5 to 7 days.

bubble_chart Differentiation

The causes of jaundice vary, and it is difficult to differentiate based solely on clinical manifestations. It is essential to closely combine blood generation and transformation tests, as well as urine and stool-related examinations for accurate judgment. Commonly used reference tests include: serum jaundice index, van den Bergh test, bilirubin quantification, plasma protein quantification, and liver cell enzyme activity-related liver function tests; qualitative or quantitative analysis of urinary bilirubin and urobilinogen; fecal urobilinogen, etc. All types of jaundice exhibit an increase in serum jaundice index and total bilirubin levels. Other laboratory findings are described separately below.

(1) Prehepatic jaundice: Mainly manifests as increased red blood cell destruction and compensatory bone marrow hyperplasia.

1. In the initial stage [first stage] of the disease, serum unconjugated bilirubin increases. If hemolysis continues, the excessive burden on liver cells may lead to damage, and conjugated bilirubin may also increase;
2. The quantity of urobilinogen in the blood also increases due to enhanced intestinal reabsorption of conjugated bilirubin;
3. The van den Bergh test shows an indirect positive reaction;
4. Urinary bilirubin is negative;
5. Both urine and fecal urobilinogen levels increase;
6. Peripheral blood red blood cells and hemoglobin decrease, while reticulocytes increase.

(2) Hepatic jaundice: Two main scenarios can be observed:

1. Type dominated by increased serum unconjugated bilirubin:
   1. Serum primarily shows increased unconjugated bilirubin;
   2. Urobilinogen is undetectable in the blood;
   3. The van den Bergh test shows an indirect positive reaction or minimal delayed direct reaction;
   4. Urinary bilirubin is positive, while urobilinogen is negative or weakly positive;
   5. Fecal urobilinogen is negative or reduced; other liver functions may be normal or slightly abnormal.
2. Type dominated by increased serum conjugated bilirubin:
   1. Serum primarily shows increased conjugated bilirubin;
   2. The van den Bergh test shows a direct positive reaction or dual antagonism;
   3. Hematuria urobilinogen is negative or weakly positive;
   4. Urinary bilirubin increases, while urobilinogen is negative;
   5. Stool color turns grayish-white; other liver function abnormalities may also be detected.

In clinical practice, the most common hepatic jaundice often results from multifaceted damage to liver cell function, leading to more variable laboratory findings or intermediate results between the two types mentioned above.

(3) Posthepatic jaundice: Mainly caused by obstruction of gall fel excretion. Liver cells may be normal in the initial stage [first stage] of the disease, but prolonged conditions can also damage liver cells.

1. In the initial stage [first stage], serum conjugated bilirubin increases, and over time, unconjugated bilirubin may also rise;
2. The van den Bergh test shows a direct rapid or dual antagonism reaction;
3. Urinary bilirubin is strongly positive, while urobilinogen is negative or weakly positive;
4. Fecal urobilinogen is negative;
5. Alkaline phosphatase may increase. To assess the degree of extrahepatic bile duct obstruction, the iodine-labeled rose bengal test can be used (refer to the section on neonatal bile duct atresia).