Cholestasis has numerous causes, including infections, metabolic problems, genetic defects, and blockages.
The most common symptoms are jaundice and dark urine.
The diagnosis is made by blood tests, and then other blood tests, imaging tests, and sometimes liver biopsy are done to determine the specific cause.
Treatment depends on the cause.
Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells that carries oxygen) is broken down as part of the normal process of recycling old or damaged red blood cells. Bilirubin is carried in the bloodstream to the liver and processed so that it can be excreted out of the liver as part of bile (the digestive fluid produced by the liver). Bilirubin processing in the liver involves attaching it to another chemical substance in a process called conjugation.
Bile is transported through the bile ducts into the beginning of the small intestine (duodenum). If bilirubin cannot be processed and excreted by the liver and bile ducts quickly enough, it builds up in the blood (hyperbilirubinemia Jaundice in the Newborn Jaundice is a yellow color to the skin and/or eyes caused by an increase in bilirubin in the bloodstream. Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells... read more ). The excess bilirubin settles in the skin, the whites of the eyes, and other tissues, causing them to turn yellow (jaundice Jaundice in the Newborn Jaundice is a yellow color to the skin and/or eyes caused by an increase in bilirubin in the bloodstream. Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells... read more ).
In cholestasis, the liver cells process bilirubin properly, but the excretion of bile is impaired at some point between the liver cells and the duodenum. This results in an increase in conjugated bilirubin in the blood and a decrease in bile delivered to the small intestine.
Another effect of bile not being excreted normally into the small intestine is that digestion is impaired. Bile is important for digestion because it helps the body absorb fats and the fat-soluble vitamins Overview of Vitamins Vitamins are a vital part of a healthy diet. The recommended dietary allowance (RDA)—the amount most healthy people need each day to remain healthy—has been determined for most vitamins. A safe... read more A, D, E, and K. When there is not enough bile in the intestine, fat absorption is impaired, which can lead to vitamin deficiency, inadequate nutrition, and a failure to grow and gain weight.
Cholestasis in the newborn can be caused by
Biliary atresia Biliary Atresia Biliary atresia is a birth defect in which the bile ducts progressively narrow and become blocked after birth, preventing bile from reaching the intestine. This defect causes bile to collect... read more is a blockage of the bile ducts that starts in the fetus near the end of the pregnancy or in the first several weeks of life. It is more common among full-term infants than premature infants. Affected infants typically develop jaundice in the first several weeks of life.
Biliary cysts or bile duct cysts are enlargements of parts of the bile ducts. These rare cysts are typically caused by a birth defect in the area where the bile duct and the pancreatic duct meet (see figure View of the Liver View of the Liver Cholestasis is a reduction of bile formation or bile flow. As a result, bilirubin backs up into the bloodstream (hyperbilirubinemia), leading to a yellow to yellow-green discoloration of the... read more ). Biliary cysts are more common among infants who have polycystic kidney disease Polycystic Kidney Disease(PKD) Polycystic kidney disease is a hereditary disorder in which many fluid-filled sacs (cysts) form in both kidneys. The kidneys grow larger but have less functioning tissue. Polycystic kidney disease... read more (PKD). PKD is an inherited disorder that causes cysts to form in the kidneys.
Infections can lead to cholestasis in the newborn. Some infecting organisms are
Viruses: Including cytomegalovirus Cytomegalovirus (CMV) Infection Cytomegalovirus infection is a common herpesvirus infection with a wide range of symptoms: from no symptoms to fever and fatigue (resembling infectious mononucleosis) to severe symptoms involving... read more , herpes simplex virus Herpes Simplex Virus (HSV) Infections Herpes simplex virus infection causes recurring episodes of small, painful, fluid-filled blisters on the skin, mouth, lips (cold sores), eyes, or genitals. This very contagious viral infection... read more , and rubella Rubella Rubella is a contagious viral infection that typically causes mild symptoms, such as joint pain and a rash, but can cause severe birth defects if the mother becomes infected with rubella during... read more
Bacteria: Most often urinary tract infection Urinary Tract Infection (UTI) in Children A urinary tract infection is a bacterial infection of the urinary bladder (cystitis), the kidneys (pyelonephritis), or both. Urinary tract infections are caused by bacteria. Infants and younger... read more and/or blood stream infection (sepsis Sepsis and Septic Shock Sepsis is a serious bodywide response to bacteremia or another infection plus malfunction or failure of an essential system in the body. Septic shock is life-threatening low blood pressure ... read more ) caused by Escherichia coli Escherichia coli Infections Escherichia coli (E. coli) are a group of gram-negative bacteria that normally reside in the intestine of healthy people, but some strains can cause infection in the digestive tract, urinary... read more or group B streptococcus Streptococcal Infections Streptococcal infections are caused by any one of several species of Streptococcus. These gram-positive, sphere-shaped (coccal) bacteria (see figure How Bacteria Shape Up) cause many disorders... read more
Gestational alloimmune liver disease is a disorder that begins before birth. In this disease, antibodies from the mother cross the placenta and attack the fetus's liver.
Metabolic disorders Overview of Hereditary Metabolic Disorders Hereditary metabolic disorders are inherited genetic conditions that cause metabolism problems. Heredity is the passing of genes from one generation to the next. Children inherit their parents'... read more that cause cholestasis are numerous and include alpha-1 antitrypsin deficiency Alpha-1 Antitrypsin Deficiency Alpha-1 antitrypsin deficiency is a hereditary disorder in which a lack or low level of the enzyme alpha-1 antitrypsin damages the lungs and liver. Alpha-1 antitrypsin deficiency is caused by... read more , galactosemia Galactosemia Galactosemia (a high blood level of galactose) is a carbohydrate metabolism disorder that is caused by a lack of one of the enzymes necessary for metabolizing galactose, a sugar that is part... read more , tyrosinemia Tyrosinemia Tyrosinemia is a disorder of amino acid metabolism that is caused by a lack of the enzyme needed to metabolize tyrosine. The most common form of this disorder mostly affects the liver and the... read more , bile acid defects, and fatty acid oxidation disorders Fatty Acid Oxidation Disorders Fatty acid oxidation disorders are lipid metabolism disorders that are caused by a lack or deficiency of the enzymes needed to break down fats, resulting in delayed mental and physical development... read more . These disorders occur when the newborn is missing an enzyme that is needed to break down a certain substance, allowing toxic substances to accumulate and damage the liver.
Genetic defects, such as Alagille syndrome and cystic fibrosis Cystic Fibrosis (CF) Cystic fibrosis is a hereditary disease that causes certain glands to produce abnormally thick secretions, resulting in tissue and organ damage, especially in the lungs and the digestive tract... read more , may cause cholestasis in the newborn. Genetic defects and other gene mutations can disrupt normal bile production and removal, which causes cholestasis.
Toxic causes include the use of intravenous feeding Intravenous Feeding Intravenous feeding is used when the digestive tract cannot adequately absorb nutrients, as occurs in severe malabsorption disorders. It is also used when the digestive tract must be temporarily... read more (parenteral nutrition) in extremely premature newborns or in infants who have short bowel syndrome Short Bowel Syndrome Short bowel syndrome is a disorder causing diarrhea and poor absorption of nutrients (malabsorption), which often occurs after surgical removal of a large portion of the small intestine. This... read more . In recent years, centers have begun using a different type of fat in the intravenous formulation Formulas Intravenous feeding is used when the digestive tract cannot adequately absorb nutrients, as occurs in severe malabsorption disorders. It is also used when the digestive tract must be temporarily... read more , which appears to have reduced the risk of cholestasis.
Neonatal hepatitis syndrome is the term used to describe inflammation in the newborn's liver for which there is no identified cause. This diagnosis is being made less frequently due to advances in tests that can determine an exact cause.
Symptoms of cholestasis typically develop during the first 2 weeks of a newborn's life. Infants with cholestasis have jaundice and often have dark urine, light-colored stools, and/or an enlarged liver. Bilirubin in the skin can cause itching, which makes infants irritable. Because infants with cholestasis may not properly absorb fats and vitamins, they may not grow well.
Other problems, such as abdominal swelling caused by fluid in the abdomen (ascites Ascites Ascites is the accumulation of protein-containing (ascitic) fluid within the abdomen. Many disorders can cause ascites, but the most common is high blood pressure in the veins that bring blood... read more ) and bleeding in the upper digestive tract caused by enlarged veins in the esophagus (esophageal varices Esophageal Varices Esophageal varices are enlarged veins in the esophagus, which can cause major bleeding. Esophageal varices are caused by high blood pressure in blood vessels in and around the liver (portal... read more ), may develop as liver disease progresses.
Almost all newborns have higher bilirubin levels in their blood (hyperbilirubinemia) during the first week of life than they do later on. This normal jaundice (physiologic jaundice) resolves over a week or two, and the bilirubin level returns to normal. For infants who remain jaundiced at 2 weeks of age, doctors check to see if the elevated bilirubin is conjugated or unconjugated. A high level of conjugated bilirubin indicates liver dysfunction and possible cholestasis. A high level of unconjugated bilirubin is not caused by liver dysfunction. If that test indicates cholestasis is present, infants have additional blood tests to determine if the liver is inflamed or not functioning normally (see Liver Blood Tests Liver Blood Tests Liver tests are blood tests that represent a noninvasive way to screen for the presence of liver disease (for example, hepatitis in donated blood) and to measure the severity and progress of... read more ). Doctors do other tests to determine the cause of cholestasis.
Doctors do ultrasonography Ultrasonography Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography... read more of the abdomen to assess the size of the liver and view the gallbladder and major bile duct. In another type of imaging test called cholescintigraphy Radionuclide (Radioisotope) Scanning Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography... read more (hepatobiliary scintigraphy or scan), doctors inject a radioactive substance into the infant's vein. They then follow the movement of the radioactive substance as it is secreted from the liver and passes into the gallbladder and through the bile ducts into the duodenum.
If doctors cannot diagnose the cause, they remove a sample of the infant's liver for further evaluation (biopsy Biopsy of the Liver Doctors can obtain a sample of liver tissue during exploratory surgery, but more often they obtain a sample by inserting a hollow needle through the person's skin and into the liver. This type... read more ). The biopsy may be done with or without operative cholangiography Operative Cholangiography Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography... read more , which involves the injection of a substance that can be seen on x-rays directly into the gallbladder to better determine if the bile ducts are normal.
Prognosis varies greatly. Depending on the cause, infants may recover completely or develop liver failure Liver Failure Liver failure is severe deterioration in liver function. Liver failure is caused by a disorder or substance that damages the liver. Most people have jaundice (yellow skin and eyes), feel tired... read more or cirrhosis of the liver Cirrhosis of the Liver Cirrhosis is the widespread distortion of the liver's internal structure that occurs when a large amount of normal liver tissue is permanently replaced with nonfunctioning scar tissue. The scar... read more (scarring of the liver).
Biliary atresia Biliary Atresia Biliary atresia is a birth defect in which the bile ducts progressively narrow and become blocked after birth, preventing bile from reaching the intestine. This defect causes bile to collect... read more can result in progressively worsening liver disease even if it is appropriately diagnosed and treated. Infants who are not treated frequently die of liver failure by 1 year of age.
Cholestasis caused by intravenous nutrition will correct itself if the intravenous nutrition is stopped before the infant develops severe liver disease. If intravenous nutrition cannot be stopped, then a different formulation containing fish oil can be used to relieve the cholestasis.
Gestational alloimmune liver disease that is not treated early typically has a poor prognosis.
Infants who have biliary atresia are treated with a surgical procedure called portoenterostomy (Kasai procedure). Ideally, this procedure should be done in the first 1 to 2 months of life. During this procedure, a part of the small intestine is attached to an area of the liver so that bile can drain into the small intestine. Infants who do not respond well to this procedure ultimately require a liver transplant Liver Transplantation Liver transplantation is the surgical removal of a healthy liver or sometimes a part of a liver from a living person and then its transfer into a person whose liver no longer functions. (See... read more .
Some metabolic diseases such as galactosemia can be treated. Galactosemia is treated Treatment Galactosemia (a high blood level of galactose) is a carbohydrate metabolism disorder that is caused by a lack of one of the enzymes necessary for metabolizing galactose, a sugar that is part... read more by eliminating milk and milk products (which contain the sugar galactose) from the infant's diet. Typically, infants are given a soy formula.
Infants who have gestational alloimmune liver disease may be treated with immune globulin (antibodies obtained from the blood of people with a normal immune system) given by vein or by withdrawing a large amount of the infant's blood and replacing it with transfused blood (exchange transfusion).
It is important to promote good nutrition and give supplements for any deficiencies in vitamins A, D, E, and K. Infants with cholestasis typically do not absorb fat well, so using formulas that contain specialized fat (medium-chain triglycerides) improves their fat absorption and growth. Some infants are not able to drink enough formula to achieve normal growth and may need a concentrated formula that contains more calories per ounce.
Infants who do not have biliary atresia may be given ursodeoxycholic acid to increase bile flow and improve their liver disease.