Infant cholestatic liver disease should first consider these three causes! Cause treatment is the key!

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

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

Infant cholestatic liver disease refers to the disorder of bile production, secretion and excretion due to various reasons in the infancy or neonatal period, which makes the substances excreted from the bile normally, such as bilirubin, bile acid and cholesterol, unable to be excreted from the bile, and remain in the blood, liver tissue and extra-hepatic tissue.

Liver disease and diseases other than the liver may cause cholestatic liver disease.

The first is infectious factors, including viruses, bacteria, and parasites. The most common virus is cytomegalovirus, as well as rubella virus, respiratory enterovirus, adenovirus, herpes simplex virus, etc., which can cause liver damage and lead to cholestasis after infection. Systemic infections caused by bacteria, such as sepsis, septicemia, urinary tract infections, syphilis, etc.; parasitic infections, such as toxoplasmosis, etc., can all lead to cholestasis. Some infections are congenital, that is, they occur in the uterus. Others are intrapartum infections, which are transmitted during the birth canal during the delivery process. In addition, there are cases of postpartum infection. If the mother is infected with cytomegalovirus, the virus may be transmitted to the baby during breastfeeding.

Second, there are congenital anatomical abnormalities of the hepatobiliary system, such as the most common congenital biliary atresia, congenital common bile duct cyst, common bile duct stones, and neonatal sclerosing cholangitis; there are also some hereditary diseases, such as Alagille syndrome and Caroli syndrome, in which abnormal development of the hepatobiliary system causes cholestasis.

Third, genetic metabolic diseases, such as Citrin deficiency, progressive familial intrahepatic cholestasis, tyrosinemia, galactosemia, glycogen storage disease and other metabolic diseases, can lead to cholestasis.

Fourth, premature babies are very light in weight and may need to be given parenteral nutrition, that is, intravenous nutrition. If the infusion of nutrient solution lasts for more than two weeks, it can easily lead to cholestasis.

Fifth, drugs cause liver damage; sixth, diseases other than the liver, such as congenital hypothyroidism and hypopituitarism; seventh, malignant diseases, such as neonatal leukemia and Langerhans cell histiocytosis, can cause cholestasis.

Eighth, after a comprehensive examination, the cause of the disease has not yet been found, which is called idiopathic cholestasis.

In general, in our country, infantile cholestatic liver disease should be paid attention to first. The causes to be considered are infection, biliary atresia, and genetic metabolic diseases. These three factors are more common.

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There are several characteristics of cholestatic liver disease in infants.

First, newborns or infants may have persistent jaundice that does not subside when it should, or reappear after a period of time after the jaundice subsides normally and gradually worsens. Jaundice is the main symptom.

Second, the stool color becomes lighter. Normal infant stool is golden yellow or yellow-green. If the stool color is yellow-white, gray-white, or even clay-colored, be highly alert to cholestasis.

Third, the urine color becomes darker. Urine is particularly easy to stain diapers, and it is not easy to wash off.

Fourth, blood biochemical examinations show a significant increase in bilirubin, mainly direct bilirubin, and transaminase. Physical examinations can reveal an enlarged liver or a change in texture, sometimes accompanied by an enlarged spleen. When bilirubin, bile acid, cholesterol and other substances cannot be excreted normally, they will remain in the liver and cause biliary cirrhosis. Over time, liver function will be damaged, the damage will become more and more serious, and finally liver failure will occur.

Fifth, a small number of children have skin itching, but because they are too young, the symptoms of skin itching may not be very obvious. Slightly older children may have obvious skin scratches and obvious itching. In addition, cholesterol cannot be excreted from the bile, causing an increase in blood cholesterol and the formation of xanthomas under the skin.

The main manifestation of cholestatic liver disease in infants is severe and persistent jaundice. If the jaundice in newborns or young infants persists, parents must attach great importance to it, go to the hospital in time, identify the cause, and diagnose and treat it early.

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Infants with cholestatic liver disease should use some choleretic and hepatoprotective drugs intravenously during the acute and severe stage. Choleretic drugs mainly promote bile secretion and excretion, reduce enterohepatic circulation, reduce the reabsorption and utilization of bile acid, protect liver function, promote liver cell regeneration, etc. After bilirubin and transaminase drop significantly, oral administration can be used. In addition, traditional Chinese medicine can also play an important role in the treatment of cholestatic liver disease, which can reduce jaundice, protect the liver, and resist viruses.

For infant cholestatic liver disease, etiological treatment is very important. Viral infection requires antiviral treatment; bacterial infection requires antibiotic treatment, and antibiotics with relatively high concentrations in bile should be selected.

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 be clinically relieved. For example, children with tyrosinemia should eat milk powder containing low levels of phenylalanine and tyrosine; children with galactosemia should eat special milk powder that does not contain lactose and avoid lactose intake; children with Citrin deficiency should choose milk powder that does not contain lactose and contains high- and medium-chain fatty acids. The treatment effect is better through dietary adjustments. Of course, some genetic metabolic diseases cannot be treated with diet, and the prognosis may be worse. Liver function deteriorates and liver failure occurs, and liver transplantation is the only option.

If it is caused by endocrine diseases, the treatment effect is very good after supplementing thyroid hormone and corresponding hormones.

Cholestasis caused by anatomical abnormalities of the hepatobiliary system, such as congenital biliary atresia and congenital common bile duct cyst, requires surgical treatment. Early diagnosis is crucial for congenital biliary atresia. If misdiagnosed or delayed, the opportunity for surgery may be missed. It is currently recommended to diagnose within 60 days of birth and perform the classic portojejunostomy (Kasai operation) in a timely manner. Some children have better results after this operation. However, if the diagnosis is late, such as after 4 months of birth, the child may have developed biliary cirrhosis and severely damaged liver function, thus losing the opportunity to undergo Kasai operation.