Congenital biliary atresia in neonates
Introduction
Introduction to congenital biliary atresia in neonates Congenital biliary atresia (congenital biliary atresia) is one of the main causes of obstructive jaundice in neonatal period. It is not uncommon. The incidence rate is higher in Japan and China than in Europe and America. The cause is still unclear. The clinical symptoms of this disease (jaundice, gray stool) are often From 1 week to several weeks after birth, some children have a normal color after birth, until the full moon is gradually whitened. Therefore, biliary atresia is considered to be formed after birth, not congenital disease. basic knowledge The proportion of the disease: the incidence rate of newborn babies is 0.05% Susceptible people: children Mode of infection: non-infectious Complications: cirrhosis, gastrointestinal bleeding, anemia
Cause
Neonatal congenital biliary atresia
(1) Causes of the disease
The cause of biliary atresia is more complicated, and it is still not very clear. There are congenital biliary dysplasia, viral infection, abnormal pancreaticobiliary duct flow, and bile acid metabolism disorder.
1. Congenital dysplasia: This disease was previously considered to be a congenital biliary dysplasia. However, in recent years, pathological and clinical studies have concluded that this theory is not completely reliable. Clinically common congenital malformations, such as anal atresia, intestinal atresia , esophageal atresia, etc., often accompanied by other malformations, and biliary atresia is rarely accompanied by malformations; in the fetal autopsy, no biliary atresia has been found, the clinical symptoms of this disease sometimes begin to appear several weeks after birth, or After the physiological jaundice subsided, the jaundice was reproduced. When the biliary atresia was performed, the hilar part was explored. Even in the so-called "inoperable type", small stalk-like biliary tract remnants were observed, and the bile duct lumen was observed in the tissue section. Biliary epithelium, residual bile pigment and inflammatory cell infiltration, etc., further indicate that biliary atresia is not a congenital malformation, but a disease that occurs before and after birth.
2. Infectious factors: Some people have proposed biliary atresia, neonatal hepatitis and choledochal cyst are caused by viral infection, belonging to the same lesion, but the lesions are different. After liver and biliary infection, the liver is giant cell, bile duct epithelium. Damage, resulting in obstruction of the lumen, formation of biliary atresia or choledochal cyst, inflammation can also be caused by bile duct fibrosis and progressive bile duct occlusion, there are more reports of cytomegalovirus infection and biliary atresia, choledochal cyst The incidence is closely related.
3. Congenital pancreatic duct and bile duct confluence abnormality: Pancreatic duct and bile duct confluence abnormality refers to congenital malformation in which the pancreatic duct and bile duct do not meet in the duodenal wall during embryonic period, and it is not only congenital choledochal cyst, Biliary duct stones, pancreatic stones, pancreatitis, biliary tract cancer, and one of the important causes of pancreatic cancer have also been reported to cause abnormal biliary obstruction.
(two) pathogenesis
It is divided into two types: intrahepatic type and extrahepatic type. The former has few cases and has not been reported in China. The extrahepatic type is divided into 6 types. The type I, II and III are usually called "non-satisfiable", or the surgical effect is not Ideal type, accounting for 80% to 90%, treatment is poor, the prognosis is very poor; and IV, V, VI is called anastomotic type, accounting for 10% to 20%, type 6 biliary atresia, I and II are considered to be biliary development Poor, inflammation damages the bile duct epithelium, fibrotic changes, the lumen gradually narrows, but not completely locked, such as the lesions gradually improve, there is the possibility of recovery, if the inflammation continues to develop, the entire biliary tract is completely locked, the third type is true The biliary atresia, the external biliary tract is seriously affected, the epithelium is completely damaged, and all the structures are fibrotic. Because the bile duct disappears completely, there is no cavity with a cavity in the liver, duodenal ligament and hepatic hilum. A small amount of mucosal tissue can be seen, and anastomosis can not be performed. The IV, V, and VI types are biliary tract interruptions, that is, the extrahepatic biliary tract is finally blindly closed, and the bile is connected to the liver in the blind pocket, so an anastomosis operation can be performed. Children's liver is bile Sexual cirrhosis, intrahepatic bile duct hyperplasia, severe bile duct in the tube, sometimes small bile duct burst, bile flooding into pieces, liver cells and capillary bile ducts are also severely cholestatic, hepatocytes can have giant cell changes, portal vein fibers Chemical.
Prevention
Neonatal congenital biliary atresia prevention
At present, the cause is still unclear, there are no precise preventive measures, and preventive measures should be carried out from pre-pregnancy to prenatal:
Pre-marital medical examination plays an active role in preventing birth defects. The size of the effect depends on the examination items and contents, including serological examination (such as hepatitis B virus, treponema pallidum, HIV) and reproductive system examination (such as screening for cervical inflammation). General medical examinations (such as blood pressure, electrocardiogram) and asking about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
Pregnant women should avoid harmful factors as far as possible, including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, toxic and harmful heavy metals, etc. In the process of antenatal care during pregnancy, systematic screening of birth defects is required, including Regular ultrasound examination, serological screening, etc., if necessary, a chromosome examination.
Once an abnormal result occurs, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether there is sequelae after birth, whether it can be treated, how to prognose, etc., and take practical measures for diagnosis and treatment.
Complication
Neonatal congenital biliary atresia complications Complications, cirrhosis, gastrointestinal bleeding, anemia
Can be complicated by cirrhosis, portal hypertension, gastrointestinal bleeding, hepatic coma, sepsis, etc.; to children with growth disorders, nutritional deficiencies, anemia and so on.
Symptom
Neonatal congenital biliary atresia symptoms Common symptoms Astragalus bilirubin increased biliary atresia gray-white stool liver enlargement urinary yellow-like tea skin ecchymosis mobile voiced portal hypertension high pressure ascites
1. Astragalus: Astragalus is the first symptom. It usually begins to appear gradually 1 to 2 weeks after birth. A few cases will not start until 3 to 4 weeks, but there are cases of jaundice in the first week. After the appearance of jaundice, it is usually Does not fade, and deepens, the skin becomes golden yellow or even brown, mucous membrane, sclera also significantly yellow, and even the tears and saliva are yellow.
2. Changes in fecal color: Most children in the first few days after birth have no abnormal performance, the color of stool is normal, and the feces become yellowish in the same period of jaundice, gradually becoming yellowish white, or turning into clay-like gray, but in the course of disease In progress, sometimes it can be changed to yellow-white. It is reported that 15% of children with biliary atresia have white stools 1 month after birth, and in the late stage, due to the increased concentration of bile pigment in blood and other organs, a small amount of bile pigment can After the gut gland is discharged into the intestine, some stools are pale yellow.
3. Urine color change: The color of urine becomes darker with the increase of jaundice, like black tea, and the diaper is dyed yellow.
4. Itchy skin: The skin may have scratches due to itching.
5. Liver enlargement: Abdominal abdomen bulging, liver enlargement is significant, can be 1 to 2 times larger than normal, especially the right lobe of the liver, the lower edge can exceed the umbilical cord to reach the right armpit, the longer the course of disease (4 to 5 months) Or longer, the liver is larger, the margin is very clear, the liver is hard at the time of percussion, the spleen is swollen in almost all cases, the edge is several centimeters at or below the cost of the costal margin, the abdominal wall vein is exposed, very advanced cases, abdominal cavity There can be a certain amount of ascites in the body, so that the percussion has a mobile dullness.
6. Systemic conditions: The nutritional development of sick children generally does not change much within 3 to 4 months. Good milk, no nausea, vomiting and other gastrointestinal symptoms, body length, weight and normal baby are no different, occasionally children with mental fatigue The movements and reactions are slightly retarded compared with healthy infants; those with a course of 5 to 6 months may have a good appearance, but the physical development has begun to slow down and the spirits are wilting. Some cases have been shown due to the decrease of serum prothrombin. Bleeding tendency, skin ecchymosis, nosebleed, etc., all kinds of fat-soluble vitamin deficiency can be manifested; when vitamin A is deficient, it occurs in eye diseases and epithelial keratin changes in other parts of the body; vitamin D deficiency can be associated with rickets or other The sequelae, most of the children with biliary atresia are around 1 year old, and die due to cirrhosis, portal hypertension, and hepatic coma.
Examine
Neonatal congenital biliary atresia
1. Determination of serum bilirubin: serum bilirubin increased, especially direct bilirubin increased significantly, serum bilirubin reached 85 ~ 340mol / L (5 ~ 20m / dl), dynamic observation can continue to increase.
2. Determination of liver function: Zinc sulfate turbidity test (ZnTT) and thymol turbidity test (TTT) were positive for 3 months after birth, and the cephalin flocculation test was later than ZnTT and TTT. Most of ALT and AST showed mild or moderate elevation, rarely exceeding 500U. Lactate dehydrogenase and leucine aminopurine were mostly normal or slightly elevated. Alkaline phosphatase was born after 3 months. Cases are elevated, generally above 20U (Golden), and more than 40U (Gold) is diagnostic, and increases with the increase of age.
3. Urine bilirubin, urinary biliary original measurement: fecal urinary bilirubin and fecal bilirubin negative reaction, urine does not contain urinary bilirubin and bilirubin, late part of serum bilirubin can penetrate into the intestinal lumen through the intestinal wall And produce a small amount of urinary biliary and fecal biliary, oxidized to urinary bilirubin and bilirubin.
4. Serum 5-nucleotidase assay: 5-nucleotidase activity was significantly increased, biliary atresia was higher than the upper limit of normal 15U, 33.33% was higher than 50U, and neonatal hepatitis was lower than 50U This result is consistent with histopathological changes, that is, biliary atresia is serious, and there is significant difference between it and neonatal hepatitis. The 5-nucleotidase can be determined to help the early diagnosis of biliary atresia.
5. Determination of serum bile acid: The serum bile acid is significantly increased in children with biliary atresia, and dynamic observation is helpful for differential diagnosis of neonatal hepatitis.
6. Determination of serum alpha-fetoprotein (AFP): AFP is produced by normal fetal liver. It disappears naturally after 1 month of birth. The biliary atresia is mainly bile duct epithelial hyperplasia, no hepatocyte proliferation, no AFP synthesis, negative qualitative test, even Positive, the average value is very low, hepatocyte proliferation in neonatal hepatitis, AFP synthesis increased, blood AFP increased, by radioimmunoassay, continuous quantitative determination, peak greater than 4mg / dl can be diagnosed as neonatal hepatitis.
7. Plasma low-density lipoprotein (LP-x) test: LP-x is a normal low-specific gravity lipoprotein in the serum of patients with obstructive jaundice. In the biliary atresia, bile stagnates in the liver, and serum LP-x is obvious. Increase.
8. Red blood cell hydrogen peroxide hemolytic enzyme test: fat-soluble vitamin E deficiency in biliary obstruction, erythrocyte membrane lack of vitamin E, loss of vitamin E oxidation, can not prevent H2O2 induced hemolysis, if the hemolysis rate increases, indirectly prove vitamin E deficiency, indicating the degree of obstruction, normal baby hemolysis <20%, if hemolysis is more than 80%, it is positive.
9. Determination of bilirubin in duodenal drainage fluid: The principle of this method is that bile can not enter the digestive tract in children with biliary atresia, duodenal juice does not contain bile pigment, and neonatal duodenal drainage with metal head is used. Tube, through the nasal cavity (or oral cavity) inserted into the stomach, exhausted gastric juice, placed in the right lateral position, the hip is slightly padded, infused with 20ml of water to stimulate gastric peristalsis, continue to intubate under the X-ray screen, make metal The head enters the second segment of the duodenum, and the duodenal juice is drawn. After the first tube is exhausted (the bile is filled into the test tube), 33% magnesium sulfate is injected from the drainage tube by 2 to 5 ml/kg, and then 10 is extracted every 15 minutes. The duodenal juice was filled into "A", "B", "C" tubes, pH value, white blood cells and bilirubin, and Li Suisheng reported 19 cases of duodenal juice without bilirubin. 18 cases were diagnosed as Biliary atresia, 11 cases of duodenal juice containing bilirubin were diagnosed as biliary atresia, 2 cases of severe jaundice, and serum bilirubin is too high, from the intestinal wall into the intestinal lumen, this method can be A 90% diagnosis rate is helpful for early diagnosis of biliary atresia.
10. B-type ultrasound: more than the extrahepatic biliary tract can not be explored, the gallbladder is not obvious or significantly reduced, dynamic observation of changes before and after gallbladder feeding, more helpful for diagnosis.
11. Hepatobiliary dynamic examination
(1) 131I-labeled rose red excretion test: more than 90% of biliary atresia 131I excretion with feces is below 5%, and neonatal hepatitis is almost all above 10%.
(2) 99mTc hepatobiliary imaging: There were reports of 26 cases of biliary atresia in 24 cases of hepatobiliary examination, all of the extrahepatic biliary tract and intestinal tract did not have radioactive 99mTc, diagnosed as biliary atresia, no case of missed diagnosis.
12. Liver puncture examination Percutaneous liver biopsy due to the improvement of puncture needle and operation technology, few complications such as bleeding and bile leakage, can effectively diagnose the disease, the diagnosis rate is 60% to 92%.
13. Percutaneous transhepatic cholangiography (FTC): PTC examination is not affected by the degree of jaundice and extrahepatic biliary drainage. Successful angiography can clearly show complete intrahepatic and extrabiliary images, as well as neonatal and infants. The anatomical features of the bile duct, the success rate of PTC is lower than that of older children.
(1) The purpose of PTC examination before surgery: The purpose of PTC examination before biliary atresia is:
1 Identification of neonatal hepatitis and biliary atresia.
2 understand the structure of the intrahepatic bile duct.
3 determine the type of biliary atresia.
4 to provide a basis for the choice of surgical methods.
(2) The purpose of doing PTC after surgery: The purpose of doing PTC after surgery is:
1 Know whether the anastomosis is narrow or not.
2 Estimated prognosis.
3 options for reoperation.
PTC is safer and easier to operate, but it is still traumatic, and can be complicated by biliary leakage peritonitis, intra-abdominal hemorrhage, high fever and pneumothorax. It is reported that the incidence of the first two complications is 1% to 2%, which should be strict. Master the indications.
14. Laparoscopy: After artificial pneumoperitoneum under anesthesia, a laparoscope is inserted through a small incision in the abdominal wall to observe the abdominal organs and tissues. When examining the upper abdomen, the stomach tube should be placed to absorb the stomach contents, and laparoscopic identification of the newborn Hepatitis and biliary atresia have a certain significance. The color, size and morphological structure of the liver can be observed. If the gallbladder or gallbladder is not found, it can be diagnosed as biliary atresia. If the gallbladder has not been seen, a fine needle can be used for cholangiography. Alternatively, a fine needle or a thin plastic tube can be inserted into the gallbladder cavity through the abdominal wall liver and gallbladder bed to observe the biliary tract. If the angiography shows that the extrahepatic bile duct is open and the contrast agent is injected into the duodenum, the liver can be excluded. External biliary atresia, liver biopsy can also be taken under laparoscopy.
15. Retrograde pancreatic duct via fiberoptic endoscopy, cholangiography (ERCP) This test can not only diagnose biliary atresia, biliary dysplasia and neonatal hepatitis (ie, biliary atresia should be considered in patients with biliary tract dysplasia). It can display the shape and movement of the pancreatic duct, and provide imaging features for the presence or absence of pancreatic duct and bile duct confluence.
Diagnosis
Diagnosis and diagnosis of congenital biliary atresia in neonates
diagnosis
The main symptoms of biliary atresia are persistent jaundice, grayish white feces, jaundice, abdominal augmentation, hepatosplenomegaly, elevated serum bilirubin, total bilirubin, direct bilirubin, elevated alkaline phosphatase, ALT light Increased degree, urinary bilirubin positive, fecal bilirubin negative, according to which diagnosis can be made, B-mode ultrasound abdominal examination, liver nucleus dynamic examination and duodenal fluid bilirubin examination, can determine the pathological type of biliary atresia It shows the shape and function of the biliary tract and is differentiated from hepatitis.
Differential diagnosis
1. Neonatal hepatitis: The identification of this disease and neonatal hepatitis is the most difficult. About 20% of neonatal hepatitis in the process of disease development, complete biliary obstruction, obstructive jaundice, in addition to jaundice, can also be There is deep urine, grayish white feces, and it looks like biliary atresia. However, most of these patients have normal extrahepatic bile ducts, rarely splenomegaly. 80% of them can be cured by general treatment. Most newborns have hepatitis for 4 to 5 months. After the biliary effusion is excreted, the jaundice gradually declines, so a long-term clinical observation can make a differential diagnosis, but the biliary atresia within 2 months after birth, if you can receive biliary reconstruction surgery, you can generally get good bile. Drainage effect, and more than 2 months of surgery, biliary cirrhosis often caused irreversible liver damage, although the biliary tract can be reconstructed, but the prognosis is poor, the main points of clinical identification of biliary atresia and neonatal hepatitis:
(1) Gender: There are more male infants than female infants, and more biliary atresia than male infants.
(2) Astragalus: Hepatitis is generally mild, jaundice has fluctuating changes, jaundice with biliary atresia is persistently aggravated, and there is no intermittent period.
(3) Feces: Hepatitis is yellow soft stool, and biliary atresia occurs earlier in white clay and lasts for a long time.
(4) Signs: Hepatitis is not as big as biliary atresia. The liver of biliary atresia is often more than 4cm below the rib. It is tough and has a dull edge, often accompanied by splenomegaly.
(5) Course of disease: In the first half of life, neonatal hepatitis can gradually improve and heal, while biliary atresia has less than one year of survival.
2. Neonatal hemolysis: The main cause in China is ABO blood group incompatibility, but Rh blood group incompatibility is rare. The early manifestation of this disease is similar to biliary atresia, with jaundice, hepatosplenomegaly, etc., but it is characterized by at birth, baby The skin is golden yellow, with significant anemia, muscle tension relaxation and nervous system symptoms. Nuclear jaundice can be life-threatening. The peripheral blood picture is examined with a large number of nucleated red blood cells. As the sick child grows up, the blood picture is more self-returning or returns to normal after transfusion. The jaundice is gradually reduced and the color of the stool is normal.
3. Breast milk jaundice: Generally, jaundice is obviously aggravated 4 to 7 days after birth, jaundice is gradually reduced in 2 to 3 weeks, and the low level is maintained for 3 to 12 weeks. After stopping for 2 to 4 days of breastfeeding, hyperbilirubinemia rapidly subsides. After 6 to 9 days after the termination of breastfeeding, jaundice disappeared. The disease is clinically free of hepatosplenomegaly and grayish white feces.
4. Congenital choledochal dilatation: This disease can also occur in the neonatal period of jaundice, mostly cyst type, often with abdominal distension or upper abdominal mass for treatment, B-mode ultrasound can show cystic dilatation of the common bile duct, when the cyst is small It is not easy to be timely and clinically misdiagnosed as biliary atresia.
5. Lymph node enlargement at the lower end of the common bile duct and jaundice caused by upper intestinal obstruction: the mass near the extrahepatic bile duct or the lymph node enlargement at the lower end of the common bile duct can inhibit the biliary tract and obstructive jaundice. In these cases, the common bile duct and gallbladder All have mild expansion, can be confirmed by B-mode ultrasound, in addition, congenital duodenal atresia, annular pancreas and congenital hypertrophic pyloric stenosis and other cases can also be complicated by jaundice, such diseases in addition to jaundice, clinically It is not difficult to identify the performance of the primary disease.
In addition to the above-mentioned jaundice, it should also be differentiated from jaundice caused by infectious jaundice and abnormal enzyme metabolism.
