Congenital biliary atresia

Introduction to congenital biliary atresia Biliary atresia (BA) is a rare and serious jaundice disease in the neonatal period, but it is a major problem requiring surgical treatment of neonatal obstructive jaundice. Biliary atresia is not a rare disease, at least half of the cases of neonatal long-term obstructive jaundice, the incidence rate is about 1:8000 ~ 1:14000 surviving babies, but the regional and ethnic differences, the case reported in Asia is Many, the incidence of the Eastern nation is 4 to 5 times higher, and the ratio of men to women is 1:2. basic knowledge The proportion of illness: 0.0035% Susceptible population: newborn Mode of infection: non-infectious Complications: portal hypertension

Congenital biliary atresia

Viral infection (50%):

There is no clear conclusion on the cause. Pathological examination revealed inflammatory changes in the liver tissue, inflammatory cell infiltration around the hilar and bile duct, microscopic pus or localized necrosis in the hepatic lobule, granulation tissue formation in the bile duct occlusion, and contrast pathology of extrahepatic biliary atresia and neonatal hepatitis. The study found that the liver tissue lesions were similar, only to a different extent. Extrahepatic biliary atresia was mainly characterized by bile duct thrombosis and inflammatory lesions, while infant hepatitis hepatocyte necrosis was more prominent. Therefore, it is now considered that biliary atresia may be associated with infants. Acquired diseases similar to the pathological process of hepatitis.

Biliary atresia seen after birth is the terminal stage and outcome of the inflammatory process. Inflammation damage causes scarring and occlusion of the bile duct fibers, and the cause of inflammation is mainly viral infection, such as hepatitis B virus, cytomegalovirus, etc., may also be rubella. Virus, hepatitis A virus or herpes virus.

Congenital factors (20%):

Some scholars have suggested that abnormalities in the confluence of pancreaticobiliary ducts may also be congenital factors in the occurrence of biliary atresia. Early thought that the disease is a congenital biliary dysplasia, and is related to the developmental dysfunction or disorder of the bile duct system during the 4th to 10th week of embryonic period. However, biliary atresia has not been found in the anatomy of the biliary system of a large number of abortions or premature infants. There is more evidence to support the formation of the disease. Some of the sick children have normal yellow stools at birth, and grayish white stools and jaundice appear only a few weeks later. It also suggests that these patients have biliary obstruction after birth.

Although the cause of this disease is many, the end result is obstruction of bile excretion pathway and obstructive jaundice. Recent studies have shown that the development of intrahepatic and extrabiliary tracts is two sources, which can explain that the biliary atresia can be smooth under the gallbladder. The situation of occlusion caused by lumenal fibrosis above the hepatic bile duct.

Pathogenesis:

The disease is due to biliary obstruction, cholestasis, damage to the liver parenchyma, early liver can be slightly enlarged, can develop into severe biliary cirrhosis after a few months, the liver is obviously swollen, the texture becomes hard, showing brownish green It is fine-grained or nodular, and the network can be seen as a network-like gray-white connective tissue hyperplasia. Under the microscope, the hepatic lobule is separated and deformed by the fibrous tissue of the hyperplasia, the size is different, the shape is different, and the central vein is biased or unclear. The hepatic cell line is disordered, the hepatic sinusoids are dilated or narrowed, the hepatocytes have bile deposition, and are uniformly yellow-stained, fine-grained or coarse-grained. In all cases, hepatocyte vacuolar degeneration, hepatocyte swelling, hepatocyte proliferation And Kupffer cell mobilization, intrahepatic pathological changes can be expressed as bile retention 2 to 3 months after birth, cirrhosis, 5 to 6 months of birth, most of the interlobular bile duct destruction disappeared, small bile ducts are not arranged neatly, Stenosis or atresia, the neonatal bile duct is significantly reduced, the bile duct is rarely seen in the portal area, the intrahepatic bile duct of the extrahepatic bile duct is open, and the extrahepatic part or complete atresia, due to the site of obstruction and The pathological changes of biliary atresia are also different. The biliary tract of the atresia is histologically consistent with inflammatory changes. The connective tissue with a little cell infiltration consists of the inner surface covering the granulation tissue. Many round cell infiltration and phagocytosis can be seen in the granulation tissue. The tissue cells of the pigment, but the common bile duct has no pathological changes, the histological structure is normal, and the inner lining is cylindrical epithelium. Some scholars have found that more than 2/3 of the patients with bile duct atresia have giant hepatocytes. Similar to neonatal giant cell hepatitis, it is considered that these two diseases are closely related.

Hitch listed 8 indicators according to changes in liver tissue structure: 1 hepatic lobular structure changes; 2 hepatocyte cytoplasmic swelling; 3 portal area inflammation; 4 bile fluid stasis; 5 fibrosis; 6 bile duct hyperplasia; 7 giant cell transformation; Hematopoiesis. The latter five indicators are significant for differences in bile duct atresia and neonatal hepatitis.

Electron microscopy showed that there were many different types of electron dense material (EDM) in the liver cells, and there were also EDM in the cytoplasm of Kupffer. Some cell membranes were damaged near the capillary tube. The cell gap is irregularly enlarged, and the microvilli are not abnormal. Compared with biliary atresia, the EDM of the liver tissue of neonatal hepatitis patients is less, the number of capillary bile ducts is slightly less, the diameter of the tube is slightly smaller, and no damage is observed. There are more fluff. At present, scholars have different interpretations of biliary atresia and need to be further studied.

Congenital biliary atresia prevention

Biliary atresia does not require surgical treatment, only 1% survive to 4 years old, but it takes a lot of determination to undergo surgery, which has far-reaching effects on infants and families. Early development is delayed, and hospitalization is repeated in the first year. Complex problems such as reoperation.

Surgery will undoubtedly prolong survival, reporting a 3-year survival rate of 35 to 65%. The basis for long-term survival is:

1 surgery 10 to 12 weeks after birth;

2 There is a large bile duct (>150m) in the hilar region;

3The blood bilirubin concentration was <8.8mg/dl 3 months after operation. In recent years, Kasai reported that 221 cases were performed in 22 years. So far, there are 92 cases of survival, 79 cases of jaundice disappeared, and 26 cases of 10 years old and older, the oldest Among the 29-year-old, long-term survivors, 2/3 cases had no clinical problems, and 1/3 of cases had portal hypertension and liver dysfunction.

For many years, Kasai surgery has been applied as a first-stage treatment step for biliary atresia. After the baby develops and grows, liver transplantation is performed to achieve a permanent cure.

Congenital biliary atresia Complications , portal hypertension, jaundice

Biliary atresia first causes liver changes, liver function is impaired, and late stage due to cirrhosis, portal hypertension complicated with esophageal varices, rupture, bleeding, many children with umbilical hernia or inguinal hernia.

Postoperative complications often threaten life, the most common is postoperative cholangitis, the incidence rate is 50%, or even up to 100%, the most likely pathogenesis is ascending infection, but sepsis is rare, liver tissue culture at the time of attack Rarely get bacterial growth, some scholars believe that this is the result of hepatic portal anastomosis, blocking the extrahepatic lymphatic outflow, resulting in easy infection and intrahepatic cholangitis, unfortunately each episode aggravates liver damage, thus accelerating biliary cirrhosis The process is more likely to occur in the first year after surgery, and then gradually decrease, 4 to 5 times to 2 to 3 times per year. The application of aminoglycoside antibiotics for 10 to 14 days can be antipyretic and biliary recovery, often in the first During the year, prophylactic combined antibiotics and choleretic drugs, another important complication is the proliferation of fibrous tissue at the anastomotic site. As a result, bile stops, and the hope of re-operation to restore bile circulation is 25%. In addition, intrahepatic fibrosis continues to develop, and the result is Cirrhosis, some cases progress to portal hypertension, hypersplenism and esophageal varices.

Congenital biliary atresia symptoms Common symptoms varicose veins intrahepatic cholestatic liver splenomegaly ascites diarrhea biliary cirrhosis portal hypertension vitamin D deficiency skin dry biliary obstruction

Gradual jaundice, scleral yellow staining is the earliest sign. Astragalus may appear shortly after birth or within 1 month, and after physiological jaundice subsided for 1 to 2 weeks, it should gradually subside, but progressively aggravated, with With the increase of jaundice, the stool is lightened from normal yellow to white terracotta, sometimes from white terracotta to pale yellow. This is because the blood bile pigment concentration is too high. The biliary pigment penetrates into the intestine through the intestinal wall, causing fecal coloration and urine. The color deepens like a dark brown.

Nutritional development in the first 3 months, no significant change in height and weight, slow development after 3 months, poor nutrition, apathetic, anemia, biliary obstruction after 5-6 months, fat malabsorption, fat-soluble vitamin deficiency The whole body state deteriorates rapidly, vitamin A deficiency causes dry eyes, nail deformity, dry skin lacks elasticity; vitamin D deficiency causes vitamin D deficiency, convulsions; vitamin K deficiency, decreased serum thrombin, subcutaneous congestion and nosebleed; Easy to combine upper respiratory tract infections and diarrhea.

Physical examination showed abdominal distension, enlarged liver, smooth surface, hard texture, rounded edges; advanced intrahepatic cholestatic, hepatic fibrosis, biliary cirrhosis, splenomegaly, abdominal varicose veins and ascites and other portal hypertension symptoms, Finally, leading to liver failure, hepatic encephalopathy is often the direct cause of death of this disease, such as the inability to reconstruct the biliary tract, the general survival period is 1 year.

The main symptoms of biliary atresia are persistent jaundice, terracotta feces, tea-like urine and hepatosplenomegaly. In the advanced stage, biliary cirrhosis, ascites, abdominal varicose veins and severe coagulopathy may occur. Individual children due to intrahepatic The formation of "vasodilating substances" causes the pulmonary circulation and the systemic circulation to be short-circuited, and the cyanosis and clubbing appear.

The early diagnosis of bile duct atresia is still very difficult. The diagnostic methods used are various in form and have different methods. Comprehensive analysis is needed in combination with clinical and laboratory tests, supplemented by radionuclide examination, cholangiography and liver biopsy. Advocate early surgical exploration.

Examination of congenital biliary atresia

There are many experimental methods, but the specificity is poor. When the biliary atresia occurs, the serum total bilirubin is increased, and the proportion of bilirubin in one minute is also increased accordingly. The abnormally high value of sputum phosphatase has reference value for diagnosis. The high peak of -glutamyltransferase is higher than 300IU/L, which is persistently high or rapidly increasing. The higher the level of 5' nucleotidase in bile duct hyperplasia, the higher the value is >25IU/L, the red blood cells pass Hydrogen hemolytic hemolysis test method is more complicated. If hemolysis is more than 80%, it is positive, and the high alpha-fetoprotein peak value is lower than 40g/ml. The results of other routine liver function tests have no discriminative significance.

For the pathogenesis of jaundice, the color change of feces, and the physical examination of the abdomen should be traced and analyzed, and the following examinations are considered to have certain diagnostic value.

(1) Dynamic observation of serum bilirubin

Serum bilirubin is measured weekly. If the bilirubin level curve decreases with the course of the disease, it may be hepatitis. If it continues to rise, it suggests biliary atresia, but severe hepatitis with extrahepatic biliary obstruction may also be persistent. Ascending, at this time it is difficult to identify.

(2) Ultrasound imaging examination

If the gallbladder is not seen or there is a small gallbladder (less than 1.5cm), it is suspected to be biliary atresia. If there is a normal gallbladder, it supports hepatitis. If the distribution pattern of intrahepatic bile duct can be seen, it can help the diagnosis.

(3) 99mTc-diethyl iminodiacetic acid (DIDA) excretion test

In recent years, it has replaced the 131 iodine-labeled rose red excretion test, which has a higher rate of hepatocyte extraction (48% to 56%). It is superior to other items and can diagnose partial biliary obstruction due to structural abnormalities, such as choledochal cyst or Extrahepatic bile duct stenosis, when complete obstruction occurs, scanning can not be seen in the intestinal development, can be used as a differential identification of severe intrahepatic cholestasis, in the early stage of biliary atresia, liver cells function well, liver shadow appears in 5 minutes, but no biliary development Even after 24 hours, no intestinal development was observed. When the neonatal hepatitis was used, although the function of the liver cells was poor, the extrahepatic biliary tract was unobstructed, and the intestinal tract was developed.

(4) Quantitative determination of lipoprotein-X (Lp-x)

Lipoprotein-X is a low-density lipoprotein that is elevated in biliary obstruction. All cases of biliary atresia have been elevated, and have been positive at very young age. Neonatal hepatitis cases are negative early, but with Age-growth can also be converted to positive. If the birth has been more than 4 weeks and Lp-X is negative, biliary atresia can be excluded; if >500mg/dl, the possibility of biliary atresia is high, and cholestyramine 4g/day can also be taken. 2 to 3 weeks, compared with the indicators before and after medication, if the content decreases, it supports the diagnosis of neonatal hepatitis syndrome. If it continues to rise, there may be biliary atresia.

(5) Quantitative determination of bile acid

Recently used in blood paper tablets serum total bile acid quantitative method, serum total bile acid at the time of biliary atresia is 107 ~ 294mol / L, generally considered to be 100mol / L are spleen, the same age without jaundice control group is only 5 ~ 33mol / L, the average is 18mol/L, so it has diagnostic value. Urinary bile acid is also an early screening method. The average urinary bile acid is 19.93±7.53mol/L in biliary atresia, while the control group is 1.60±0.16mol/L. 10 times larger than normal children.

(6) cholangiography

ERCP has been used in early differential diagnosis, and angiography has found that biliary atresia has the following conditions:

1 only pancreatic duct development;

2 Sometimes the pancreaticobiliary duct abnormality can be found, the pancreatic duct and the bile duct can be developed, but the intrahepatic bile duct is not developed, suggesting intrahepatic atresia.

Neonatal hepatitis syndrome has the following signs: 1 the pancreatic duct is normal; 2 common bile duct development, but fine.

(7) Histopathological examination of liver puncture

It is generally recommended for liver biopsy, or percutaneous transhepatic angiography and biopsy. Neonatal hepatitis is characterized by irregular lobular structure, hepatocyte necrosis, giant cell changes and portal inflammation. The main manifestations of biliary atresia are bile ducts. Obvious hyperplasia and bile embolism, fibrosis around the portal vein, but some specimens can also see multinucleated giant cells. Therefore, liver biopsy can sometimes cause difficulty in diagnosis or even error, and 10 to 15% of cases cannot be diagnosed correctly.

In short, at 1 month after birth, once the biliary atresia is highly suspected, a variety of differential diagnosis methods should be performed, such as clinical, laboratory, ultrasound, radiology and tissue sectioning. Surgical exploration should also be considered. If the diagnosis is still unknown for 2 months, the right upper quadrant incision should be performed. The liver tissue specimen and cholangiography can be obtained through minimal operation. If the gallbladder is found, the normal bile is puncture, indicating that the proximal bile duct system is not occluded. Contrast imaging to determine the distal bile duct system, if the extrahepatic bile duct is not closed, then a biopsy or biopsy is taken, taken from two liver lobe for diagnosis, and if the small gallbladder has white bile, it should still be tested for cholangiography. Because of neonatal hepatitis with severe intrahepatic cholestasis or lack of intrahepatic bile duct, the gallbladder can be seen in the contracture. If the angiography shows the extrahepatic bile duct and dysplasia, but the patency, the biopsy will end the operation, if the gallbladder is locked. Or absent, the liver gate area tissue is dissected for hepatic portal anastomosis.

In typical cases of biliary atresia, infants are born in full-term. They are often regarded as normal infants by parents and doctors 1 to 2 weeks after birth. Most of them are abnormal, and the color of stool is normal. The jaundice is gradually 2 to 3 weeks after birth. It was revealed that in some cases, jaundice appeared in the first few days after birth, when it was misdiagnosed as physiological jaundice, the stool became brownish yellow, yellowish, beige, and later became bile-free clay-like grayish white, but in the later stages of the disease, even Slightly yellowish, this is due to the increased concentration of bile pigment in the blood and other organs, and a small amount of bile pigment enters the intestine through the intestinal mucosa and is mixed with feces. The urine color is darker, the diaper is dyed yellow, and after the appearance of jaundice, usually Does not fade, and deepens, the skin becomes golden yellow or even brown, scratches due to itching, sometimes lipomarous fibroids, but not common, in some cases, clubbing may occur, or accompanied by purpura, liver Swelling, hard texture, spleen rarely in the early stage, such as sputum and swollen spleen in the first few weeks, may be the cause of the liver, with the development of the disease caused by portal hypertension.

In the early stage of the disease, the baby's general condition is good, but there are different degrees of malnutrition, length and weight. The mother often describes the baby's excitement and anxiety. This excitement may be related to the increase of serum bile acid. Fat-soluble vitamin deficiency, vitamin D deficiency can be associated with rickets and broad bones, due to changes in hemodynamics, partial arteriovenous short-circuit and peripheral vascular resistance are reduced, high-level hearts can be heard in the precordial region and lung fields Noise.

Diagnosis and diagnosis of congenital biliary atresia

Can be diagnosed based on clinical symptoms and laboratory tests.

Differential diagnosis

1. Neonatal hepatitis: This disease is the most difficult to distinguish from neonatal hepatitis. Some scholars believe that biliary atresia and neonatal hepatitis may be different pathological changes of the same disease. About 20% of neonatal hepatitis has complete biliary obstruction stage, obstruction The performance of jaundice is very similar to biliary atresia, but most of the extrahepatic biliary tract of these children is normal, rarely seen splenomegaly, after general treatment, most 4 to 5 months later, biliary tract clearing, jaundice gradually subsides, can naturally heal Therefore, through long-term clinical observation, a differential diagnosis can be made. If congenital biliary atresia can perform biliary reconstruction within 2 months, good bile drainage effect can be obtained; more than 3 months of liver has been caused by biliary cirrhosis Irreversible damage, even if the surgery, the effect is not good, so early differential diagnosis is very important.

(1) Clinical identification points: more male infants than female infants, and more biliary atresia than male infants; hepatitis jaundice is less fluctuating, jaundice persists in biliary atresia; yellow soft stool in hepatitis, biliary atresia The color appears earlier and lasts longer; when the biliary atresia is heavier than hepatitis, the texture is hard, often accompanied by splenomegaly.

(2) Laboratory identification:

1 serum bilirubin: children with hepatitis gradually decreased with the course of the disease, biliary atresia continued to rise.

2 alkaline phosphatase: neonatal hepatitis rarely exceeds 40U, decreases with the improvement of hepatitis; biliary atresia continues to increase.

3 activation of serum leucotranspeptidase: only 23% of cases of neonatal hepatitis exceed 500U.

4 Determination of serum 5'-nucleotidase: biliary atresia increased the concentration of this enzyme; neonatal hepatitis patients generally do not exceed 25 U / L.

5 serum bile acid determination: biliary atresia is significantly higher than neonatal hepatitis serum bile acid, dynamic observation is more meaningful.

6 serum alpha-fetoprotein determination: hepatocyte proliferation, neonatal alpha-fetoprotein synthesis, increased concentration in neonatal hepatitis, if the peak is greater than 40ng / dl can be diagnosed as neonatal hepatitis, biliary atresia is mainly bile duct epithelial hyperplasia, no hepatocyte proliferation Therefore, the serum alpha-fetoprotein is negative, rarely positive, and the average is low, the difference between the two is obvious.

(3) Auxiliary inspection:

1 Determination of bilirubin in the duodenal drainage: Duodenal fluid without bilirubin, 90% of congenital biliary atresia, help early diagnosis of congenital biliary atresia.

2131I-RB excretion test and 99mTc-PL scan: normal 131I-RB after intravenous injection, for liver polyhedral cells and excreted through the bile to the intestine, not absorbed by the intestine, biliary atresia in children with red rose in the liver Entering the intestine, therefore, the content of 131I in the feces can be determined to understand the biliary obstruction. Generally, the content of 131I in the feces is measured after injecting the vein for 2 hours at 2UC/kg, and 90% of the biliary atresia 131I is less than 5% with the fecal excretion. Almost all children with hepatitis are more than 10%. 99mTc-PL scan also helps to identify biliary atresia and neonatal hepatitis.

3 Liver biopsy: neonatal hepatitis is mainly caused by hepatic parenchymal cell lesions, while biliary atresia is mainly caused by bile duct system and portal vein lesions. Although there are no characteristic changes in pathological changes of biliary atresia and neonatal hepatitis, only the severity is different. However, in the area of the portal area, there is a significant difference between the bile and the lobes in the lobular area within the unit area.

Type 4B ultrasound: Intrahepatic bile duct, common bile duct, gallbladder is a normal image in neonatal hepatitis, but the extrahepatic biliary tract of biliary atresia cannot be detected, the gallbladder is small or not developed, and the liver is accompanied by splenomegaly.

5 percutaneous transhepatic cholangiography (PTC): This test can not only be used to identify biliary atresia and neonatal hepatitis, and children with biliary atresia can perform PTC examination before surgery to understand the lesions of the intrahepatic and extrahepatic biliary tract, determine the obstruction site, This determines the procedure.

2. Neonatal hemolysis: This disease is similar to biliary atresia in the early stage. There are jaundice, hepatosplenomegaly, etc., but the child has severe anemia. The peripheral blood is like a lot of nuclear red blood cells. As the sick child grows up, the blood picture returns to normal.

3. Neonatal lactating jaundice: the disease is caused by the inhibition of the activity of glucuronyl transferase by certain substances in breast milk. Generally, the jaundice is aggravated 4 to 7 days after birth, the deepest in 2 to 3 weeks, and the blood bilirubin is up to 15 ~ 25mg / dl, 2 to 4 days after stopping the milk, hyperbilirubinemia quickly subsided, the disease is clinically no hepatosplenomegaly and gray stool.

4. Congenital choledochal cyst: the disease is jaundice, abdominal mass, grayish white stool, but jaundice is intermittent, B-ultrasound can be found in liquid level lumps.

In addition, the tumor near the extrahepatic biliary tract or the lymph node at the lower end of the common bile duct can compress the biliary tract to cause obstructive jaundice; congenital duodenal atresia, annular pancreas and congenital hypertrophic pyloric stenosis can also cause obstructive jaundice. It should also be differentiated from jaundice caused by infectious jaundice and abnormal enzyme metabolism.

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