What are the characteristics of jaundice caused by cholestatic liver disease in infants? When is surgical treatment required?

Author: Zhong Xuemei, Chief Physician, Children's Hospital, Capital Institute of Pediatrics

Reviewer: Meihua Park, Chief Physician, Peking University Third Hospital

The incidence of infantile cholestatic liver disease varies in different countries and regions due to age and etiology. The incidence in full-term infants is about 1/5000-1/2500, which is not very high, but it is also a relatively common disease in gastroenterology.

Generally speaking, there are three main causes of infantile cholestatic liver disease in my country, namely infection, biliary atresia, and genetic metabolic diseases. It is mainly caused by the obstruction of bile production, secretion, and excretion, which makes it impossible to excrete substances normally excreted from the bile, and they remain in the blood, liver, and extrahepatic tissues, causing a series of symptoms.

Jaundice is the most important manifestation of infantile cholestatic liver disease. How do we distinguish it from physiological jaundice and breast milk jaundice?

Most children may develop jaundice after birth. It is very important to know whether it is physiological jaundice or pathological jaundice.

Physiological jaundice usually appears two or three days after birth, reaches a peak on the fourth or fifth day, and then gradually begins to subside, usually within 7-10 days. It usually does not exceed two weeks for full-term infants and 3-4 weeks for premature infants. In general, the severity of physiological jaundice is not very serious. It is just a slight yellowing of the skin and sclera, usually from the face, gradually to the trunk and limbs, and the palms and soles of the feet are usually not yellow.

Pathological jaundice usually develops early, often within 24 hours after birth. The degree of jaundice is generally severe, and the appearance of the child may be significantly yellow, similar to a golden doll. In addition, the palms and soles of the feet of children with pathological jaundice will also be noticeably yellow. Children with cholestatic liver disease will have persistent jaundice, or after the jaundice subsides normally, it will relapse and gradually worsen. At the same time, the stool color of such children will become lighter, appearing yellow-white, grayish white, or even clay; the urine color will deepen; the bilirubin level will increase significantly, and the increase will be mainly direct bilirubin, accompanied by an increase in transaminase; physical examination may reveal an enlarged liver or a change in texture, and some children may also have an enlarged spleen.

Figure 1 Original copyright image, no permission to reprint

In addition to the need to differentiate from physiological jaundice, there is also a condition called breast milk jaundice. In infants with breast milk jaundice, the jaundice may take longer to subside, specifically, the jaundice in full-term infants does not subside for more than two weeks, and in premature infants for more than three weeks. During the consultation, the doctor will ask in detail about the baby's feeding method, that is, whether it is breastfed or bottle-fed. If the baby is breastfed, the doctor will further observe the baby's reaction, feeding situation, and weight gain. If the jaundice is mild, and the baby's feeding and weight gain are normal, then breast milk jaundice is more likely.

For infantile cholestatic liver disease, etiological treatment is very important. Viral infections require antiviral treatment, bacterial infections require antibiotic treatment, and the general prognosis is relatively good. Cholestasis caused by metabolic diseases is a genetic problem, so early diagnosis is particularly emphasized. Some diseases can be treated through dietary adjustments and can achieve clinical relief. Of course, some inherited metabolic diseases cannot be treated with diet, and the prognosis may be worse. Liver function deteriorates, and liver failure eventually occurs, requiring only liver transplantation. Cholestasis caused by anatomical abnormalities of the hepatobiliary system, such as congenital biliary atresia and congenital common bile duct cyst, requires surgical treatment.

Figure 2 Original copyright image, no permission to reprint

Surgical treatment is mainly applicable to congenital biliary atresia and congenital choledochal cyst. In my country, the incidence of congenital biliary atresia is relatively high. Therefore, for infantile cholestatic liver disease, the first task is to determine whether biliary atresia exists. For congenital biliary atresia, early diagnosis is crucial, because delayed diagnosis may result in missed opportunities for surgery.

Currently, it is recommended to diagnose within 60 days of birth and perform the classic hepaticojejunostomy, also known as the Kasai procedure, as soon as possible. Some children have significant results after undergoing the Kasai procedure. However, some children with congenital biliary atresia do not have a good effect on jaundice reduction after the Kasai procedure, and jaundice persists or cholangitis recurs (the incidence of cholangitis after the Kasai procedure is about one-third). Repeated attacks of cholangitis will lead to a gradual deterioration of liver function and may eventually develop into biliary cirrhosis, at which time liver transplantation should be considered.

If congenital biliary atresia is diagnosed late, that is, discovered only 4 months after birth, the child will often have developed biliary cirrhosis and lose the opportunity for Kasai surgery. As liver function continues to deteriorate, symptoms such as ascites, bleeding, and hypoproteinemia may occur, and liver transplantation is also required at this time.