What is neonatal persistent cholestatic jaundice? Analysis of the causes of neonatal jaundice

(I) Causes of the disease There are many causes of infantile cholestasis, as shown in Figure 1, which can be mainly divided into three categories: hepatocellular damage, intrahepatic bile duct disease and extrahepatic bile duct disease. Only some of the main causes are described below: 1. Viral hepatitis So far, there has been no report of hepatitis A virus (HAV) causing intrauterine infection in infants through the placenta. my country is a high-incidence area for hepatitis. Most pregnant mothers have hepatitis A IgG antibodies, which give infants passive immunity. Therefore, the chance of hepatitis A in infants under 3 months old is very small. Hepatitis B (HBV) and HBsAg carriers can be transmitted from mother to child during delivery, in utero and after delivery. Delivery infection is the main route, and the mother-to-child infection rate is 20% to 50%. The infection rate is higher for mothers with positive HBeAg, but most infected infants begin to turn positive for HBsAg after 3 months of birth, and a few of them are accompanied by a slight increase in ALT. The HBV intrauterine infection rate is generally reported to be 2.5% to 7.7%, but in recent years, the determination of cord blood lymphocytes and (or) serum HBV DNA has confirmed that the intrauterine infection rate can be as high as 22%. HBV intrauterine infection, except for a few reports of causing fulminant hepatitis, generally manifests as persistent or transient HBsAg positivity, and rarely causes cholestasis symptoms. HBV postpartum infection, the onset of disease is mostly after 3 months. Therefore, cholestasis within 3 months caused by HBV is actually rare, especially for mothers with negative HBsAg. In recent years, it has been confirmed that hepatitis C virus can be transmitted from mother to child, and infants often develop the disease 3 to 12 weeks after birth. 2. Cytomegalovirus inclusion virus (CMV) CMV is the most important pathogen causing cholestasis in my country, generally reported to account for about 25%. In recent years, polymerase chain reaction (PCR) technology has been used to detect CMVDNA in the urine of infants with hepatitis. The positive rate is as high as 67% to 78.3%, while the control of healthy children is only 14.7% to 36.8% (p&0.01). The positive rate of CMVIgG antibodies in pregnant women in my country is as high as 94.6%, but the incidence of cholestasis in infants is far less than that. This is because maternal CMVIgG antibodies can pass through the placenta, which can protect infants to a certain extent. When infants are born, more than 90% of them have no symptoms after intrauterine infection with CMV. Some of those with symptoms have symptoms of cholestasis and have a good prognosis. Postpartum CMV infection often causes respiratory symptoms and rarely causes cholestasis. The diagnosis must be based on the detection of CMV (including CMV antigen or DNA) in the urine or secretions of the sick child, or positive serum CMV IgM. Positive CMVIgG antibodies cannot be diagnosed as CMV infection because it can come from the mother, unless the titer of the double serum increases by 4 times, or the titer is higher than that of the mother at 2 months. 3. Toxoplasmosis The infection rate of the domestic population varies greatly in different regions, with reports ranging from 1.4% to 38.6%, generally & 8%, and significantly higher in rural areas than in cities. Congenital toxoplasmosis infection can cause miscarriage, premature birth and stillbirth; surviving cases may be latently infected or have symptoms, the latter mainly manifested as lesions of the central nervous system and eyes, and some sick children may cause cholestasis. Some people tested serum toxoplasmosis antibodies for 75 cases of cholestasis, with a positive rate of 9.3%, while the normal control group was 2.5%, indicating that toxoplasmosis is one of the pathogens of infant hepatitis. Since drug treatment is effective for this disease, timely diagnosis is very important. Congenital infection diagnosis can be based on positive serum toxoplasmosis IgM antibodies (such as indirect fluorescent antibody test) or detection of toxoplasmosis in body fluids (including its antigen or DNA positive). This disease is effective against sulfonamide, pyrimethamine, spiramycin and clindamycin. 4. Intravenous hypernutrition: 20% to 35% of newborns may develop cholestasis if they are fed intravenously for more than 2 weeks, and 30% to 50% of premature infants. It has been confirmed that it is mainly related to amino acids. After stopping intravenous nutrition for 1 to 4 months, liver function and liver pathological changes can generally be restored. 5. α1-antitrypsin (α1-AT) deficiency α1-AT is a glycoprotein synthesized by the liver and has a strong protease inhibitory effect. The exact mechanism of liver damage caused by deficiency is still unknown. This disease is an autosomal codominant inheritance. According to gene gel electrophoresis, there are at least 24 protein inhibitor (pi) alleles in the population. Normal people are piMM, and children with cholestasis caused by α1-AT deficiency are all piZZ type. Among Westerners, piZZ accounts for about 1/1600 to 2000 live births, of which only 11% to 20% have cholestasis, 7% only have abnormal liver function, and the rest are asymptomatic. In European and American literature, 5% to 18% of cholestasis is caused by α1AT deficiency, and there are a few cases in Japan. In recent population surveys, more than 99% of people in my country are piMM type, and the piZZ gene has not yet been found. 6. Zellweger syndrome is also known as cerebro-hepatorenal syndrome. It is characterized by mental retardation, special facial features (prominent forehead, large anterior fontanelle, far-set eyes, severe hypotonia, and multiple skeletal deformities, such as cartilage calcification and femoral epiphysis detachment. Renal cortical cysts are mostly asymptomatic. This disease is caused by abnormal bile acid metabolism. Most children die within 6 months. Cholesterol in the blood is produced by liver cell metabolism. After combining with glycine and taurine in the cells, it is excreted into the bile capillaries and enters the intestine. After assisting fat absorption, most of it is absorbed in the terminal ileum and enters the portal vein and entero-hepatic circulation and can be reused. Liver cells convert cholesterol into It is a reaction to bile acid and is regulated by the blood bile acid concentration. When bile acid increases, this reaction can be inhibited, and when it decreases, this reaction can be promoted. 2. Pathophysiology and clinical features Cholestasis can cause the following pathophysiological changes and clinical consequences (Figure 2). (1) Substances that are normally excreted through bile are retained or refluxed into the body, increasing their blood concentrations and producing corresponding clinical manifestations. For example, hyperconjugated bilirubinemia causes jaundice; hypercholecidemia can cause skin itching; hypercholesterolemia can cause xanthomas in severe cases. Serum phospholipids and lipoprotein X are both increased. For certain drugs , and the excretion of contrast agents, such as sodium sulfonbromophthalein (BSp) and 131I rose bengal, is also impaired. (2) When bile in the intestine is reduced or absent, and conjugated bilirubin is reduced, the stool becomes light or grayish white; bile acid is reduced, leading to fat and fat-soluble vitamin absorption disorders. Children may suffer from steatorrhea, malnutrition, growth stagnation, and fat-soluble vitamin deficiency. Vitamin A deficiency can cause Bitartrate spots, keratinization of the skin and mucous membranes; D deficiency can cause rickets and tetany; E deficiency can cause neuromuscular degeneration and proximal muscle atrophy; K deficiency can cause Intracranial and gastrointestinal bleeding, prolonged prothrombin time. (3) Hepatocellular damage and/or bile stasis in the bile duct caused by the primary disease can often cause focal necrosis of the liver, giant changes in hepatocellular deformation, hepatosplenomegaly and abnormal liver function, such as elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, 5-nucleotidase and alpha-fetoprotein, and disorders in albumin and coagulation factor synthesis. As the lesion progresses, it can develop into biliary cirrhosis, eventually causing portal hypertension and/or liver failure. However, most children can recover smoothly clinically.