Jaundice is the yellow discoloration seen in the skin and eyes. The yellow discoloration is from a pigment called bilirubin that can be measured in blood. Bilirubin is derived from the oxygen carrying pigment in the red blood cells called hemoglobin. Red cells die, typically around every 80 days in neoborn babies and around 120 days in older children and adults. When the red cells die, they're scavenged in the spleen by specialized cells called reticuloendothelial and the pigment heme. The pigment is then taken up by the liver, tagged by another chemical (conjugated bilirubin) to excrete the bilirubin into bile. Cholestatic jaundice occurs when the excretion of conjugated bilirubin from the liver is impaired.
What causes cholestatic jaundice?
(Getty Images)
Impairment of flow bile from the liver can occur at a microscopic level or due to overt obstruction of the tubes that drain bile from the liver to the intestine, which are called bile ducts. These are uncommon disorders, but improved awareness can lead to earlier diagnosis and better outcomes.
The most common cause of cholestasis is a condition called biliary atresia, which accounts for nearly 50% of causes at this age. In this condition, the bile ducts shrink away early in life, causing bile to build up in the liver, leading to an enlarged liver, progressive scarring of the liver and, eventually, liver failure. Sometimes, nonspecific inflammation of the liver causes impairment of flow of bile, with no clear source of infection to account for it. This condition is called idiopathic neonatal hepatitis, and it typically improves with time.
Sometimes, disorders affecting the excretion of bile acid, a chemical important for digestion and absorption of fat, can cause impaired flow of bile and jaundice. The group of disorders that affects bile acid excretion is called progressive familial intrahepatic cholestasis, or PFIC. In some parts of the world or in certain populations, PFIC can lead to infection of the urinary bladder or tract, as well as sepsis – which can impair bile flow and cause jaundice. Premature babies are also at risk of cholestasis, secondary to impaired bile excretion. Babies and infants who cannot feed for long periods and receive intravenous nutrition are also at risk for cholestasis.
Other genetic disorders other than PFIC can cause cholestasis, too. One of the disorders that is often screened for is alpha 1 anti-trypsin deficiency, or A1AT. Some of the mutations may be associated with retention of the protein (A1AT) in the liver cells, leading to liver damage and cholestasis. Sometimes, a genetic disorder that leads to impaired development of the heart, spine, eye and liver, called Alagille syndrome, has a high chance of causing jaundice. The state screen done on all babies soon after birth may give insight into diagnosis like galactosemia, a disorder that causes impaired bile excretion, secondary to poor metabolism of sugar galactose. There are other causes, but the ones listed above account for 99% of the cases out there. The rest will need input from a specialist like a pediatric gastroenterologist.
When should one think of cholestasis, and what investigation may be required?
If your newborn baby has jaundice, you should seek the help of your pediatrician. If the jaundice persists beyond the first week, your baby's pediatrician will likely check for the conjugated bilirubin. If the fraction is more than 15% of the total, the baby will need close monitoring with serial bilirubin and liver functions, and your child's doctor may seek the help of a gastroenterologist. If the bilirubin is increasing secondary to improper excretion of bile, the baby's stool may start to look pale.
A physical exam by your doctor may reveal jaundice, an enlarged liver and even pale stools. The specialist may order tests to look for the causes detailed above, such as an X-ray of the spine, ultrasound of the heart (ECHO cardiogram), testing for A1AT deficiency or genetic testing that includes PFIC and Alagille syndrome. A special X-ray called a HIDA scan can look at patency of the bile duct by evaluating excretion of an extremely low radionucleotide dye into the intestine. The definitive test for patency of bile duct is an intraoperative cholangiogram, where the surgeon, either laparoscopically or through a small incision on the abdominal wall, injects dye into the bile duct.
What are the treatment options for a baby/infant with cholestatic jaundice?
Patients with cholestasis are often best managed by a pediatric gastroenterologist, in conjunction with a pediatrician. As mentioned above, the important test is an intraoperative cholangiogram, which looks for patency of the bile duct in order to rule out biliary atresia. If the bile duct is not open, a surgery called kasai – done prior to 2 months of age – offers the best outcome to ensure bile flow.
During Kasai surgery (also known as hepatic-portoenterostomy), a piece of bowel is used to connect the liver to the intestine to ensure bile flow. Surgery done after two months is associated with a poor outcome and the need for a liver transplant, and therefore the need for early screening and diagnosis. If the testing or genetic testing comes back positive for PFI, A1AT, alagille syndrome or A1AT deficiency, or if the bile duct is open on testing, Kasai surgery is not required.
Babies and infants with cholestasis often grow poorly, since bile is required for digestion and absorption of fat. Breastfeeding will need supplementation to augment calories, or special formulas that are easy to digest and absorb will need to be started to promote better growth. Fat soluble vitamin deficiency – namely vitamins A, D, E and K – will need to be supplemented more than the daily recommended doses to avoid deficiency. Vitamin K deficiency can be associated with heightened bleeding risk and bruising and will need monitoring. Medication like urosodoexycholic acid may help with bile flow and slow progression of liver disease. Babies and infants with cholestasis can develop excess itching and secondary irritability and may need treatment that includes antihistamines like hydroxyzine or benadryl. Sometimes, in some types of PFICs or alagille syndrome, a special surgery to divert bile can help with itching.
Patients with progressive liver disease, or with excessive itching despite optimal medical and or surgical management, will need to be evaluated for liver transplantation. A timely referral to a liver transplant center is important for optimal outcome and may be coordinated by your pediatrician or gastroenterologist.