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Conjugated Hyperbilirubinemia - Causes, Symptoms, Diagnosis, and Treatment

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Conjugated hyperbilirubinemia is an elevation in the levels of conjugated or direct bilirubin. Read the article to know more.

Written by

Dr. Janani R S

Medically reviewed by

Dr. Kaushal Bhavsar

Published At August 17, 2022
Reviewed AtOctober 20, 2022

Introduction:

Conjugated hyperbilirubinemia occurs as a result of an underlying liver disease or condition like biliary obstruction (a block in the bile duct), alcoholic hepatitis (inflammation of the liver due to alcohol consumption), or an autoimmune disease (a disease that occurs when the body’s immune system damages its own the healthy cells or organs). Conjugated bilirubin is a byproduct of heme metabolism. When the levels of the conjugated bilirubin are high than the normal levels, it is called conjugated hyperbilirubinemia.

What Is Conjugated Bilirubin?

Bilirubin is a yellowish pigmented substance that is a result of the normal breakdown of hemoglobin in the red blood cells. During the breakdown of red blood cells, heme is separated from the hemoglobin. Heme is an important substance in the red blood cells that binds with the oxygen present in the lungs and carries it to other parts and tissues. The heme undergoes various processes and is converted to biliverdin (a green pigmented substance).

The biliverdin is further transformed into unconjugated bilirubin by biliverdin reductase (an enzyme present in all tissues which help convert biliverdin to bilirubin). The unconjugated bilirubin is not water-soluble and cannot be removed from the body in this form. It is converted into a water-soluble form called conjugated bilirubin by an enzyme uridine diphosphate (UDP) - glucuronyl transferase (UGT) (UDP-GT). This bilirubin is taken up by the liver and is excreted out of the body in the urine and stools.

What Causes Conjugated Hyperbilirubinemia?

The primary causes of conjugated hyperbilirubinemia are:

  • Metabolic Activity: The defect in any stage of bilirubin production or secretion can lead to high levels of conjugated bilirubin in the blood.

  • Biliary Obstruction: A block in the bile duct that carries bile from the liver and gallbladder to the intestine.

  • Intrahepatic Cholestasis: Cholestasis is the diminished release of bile (a digestive fluid) due to damage to the liver cells. The bile accumulates and causes damage to the liver. This occurs inside the liver, and hence it is called intrahepatic cholestasis.

  • Hepatocellular Injury: Hepatocellular injury is the damage to the liver cells due to viral infections like hepatitis A, B, and E.

Other diseases that cause conjugated hyperbilirubinemia are:

  • Cholelithiasis: It is the presence of stones in the gallbladder.

  • Pancreatitis: Inflammation of the pancreas.

  • Portal Adenopathy: It is the enlarged lymph nodes in the upper part of the abdomen, usually in cases of liver cancer, pancreatic cancer, or lymphoma (cancer of the lymphatic system).

  • Primary Sclerosing Cholangitis: It is a chronic liver disease where the bile ducts are narrowed or blocked, swollen, and scarred.

  • Eosinophilic Granuloma: It is a non-cancerous bone tumor usually affecting children below 10 years of age.

  • Cirrhosis: Cirrhosis is scarring of the healthy liver tissues.

  • Alcoholic Hepatitis: It is inflammation of the liver due to alcohol consumption.

  • Ischemic Hepatopathy: It is a liver damage disease due to reduced oxygen or blood supply to the liver.

  • Drugs and Toxins: Medications like Acetaminophen, when taken for a long time, cause liver damage. Accumulation of toxic or harmful substances which are not removed from the liver due to liver dysfunction also damages liver tissue. These liver damages, in turn, result in dysfunction and reduced bilirubin excretion.

  • Autoimmune Hepatitis: The body’s immune system attacks infectious organisms that enter the body. In an autoimmune condition, the body’s immune system damages and attacks the healthy organs and cells.

  • Sickle Cell Anemia: Sickle cell anemia is a disease that affects oxygen transportation in blood circulation. The red blood cells resemble a sickle, a tool used to cut grass.

  • Budd-Chiari Syndrome: In Budd-Chiari syndrome, the hepatic veins (blood vessels that carry blood from the liver to the heart) are blocked due to a blood clot.

What Are the Symptoms of Conjugated Hyperbilirubinemia?

Symptoms generally depend on the underlying disease, but some common symptoms include,

  • Brown-color urine.

  • Yellowish discoloration of the eyes.

  • Nausea and vomiting.

  • Unintentional weight loss.

  • Feeling weak and tired.

  • Altered mental state.

  • Anorexia (an eating disorder where people eat less to not gain weight).

  • Dyspnea (shortness of breath).

  • Diarrhea.

  • Abdominal pain.

  • Swelling in the legs.

  • Body pain.

  • Chills.

  • Changes in stool appearance.

  • Hematemesis (blood vomiting).

What Are the Tests to Find Conjugated Hyperbilirubinemia?

  • Physical Examination: Physical examination is done to check for yellowish discoloration of the skin and eyes, tenderness or pain in the right upper region above the abdomen, or checking for the presence of a mass in the abdomen.

  • Serum Bilirubin, Total And Direct: A blood test is performed to screen the levels of total bilirubin and direct bilirubin. If the levels are elevated, it suggests cholestasis or hepatocellular injury.

  • Urine Bilirubin: A urine test is performed to detect the presence of bilirubin in the urine. If it tests positive, it suggests underlying liver disease.

  • Ultrasound Abdomen: A high-frequency sound wave is used to capture images of structures inside the body. An ultrasound scan of the abdomen helps to find the liver disease.

  • CT Scan: Computerized tomography (CT) is a series of X-ray images taken from different angles of the body. It provides a detailed image of the structures captured.

  • MRI Scan: Magnetic resonance imaging (MRI) uses a combination of a strong magnetic field and high-frequency radio waves to take a detailed picture of the internal structures in our body. This scan provides a more detailed image of the structure to find out the disease.

  • Endoscopic Retrograde Cholangiopancreatography (ERCP): This technique involves inserting a flexible tube with a light and camera through the mouth into the upper gastrointestinal tract. The upper gastrointestinal tract consists of the food pipe, stomach, and first part of the small intestine called the duodenum. The dye is then injected to view the bile duct, and X-ray images are taken. This procedure is useful in detecting biliary obstruction.

  • Percutaneous Transhepatic Cholangiography (PTC): This procedure uses high-frequency radio waves to capture images of the bile duct to check for bile duct obstruction.

Other diagnostic tests are performed depending on the liver disease like:

  • Complete Blood Count: It is performed to check for anemia (reduced numbers of red blood cells) in hemolysis disease (destruction of red blood cells).

  • Viral Hepatitis, Serologic Studies: A blood test to perform serologic studies to detect viral infection.

How Is Conjugated Hyperbilirubinemia Treated?

  • Treatment depends on the underlying disease or condition that causes it.

  • If the patient is taking any medications that are harmful to the liver, it must be stopped immediately to prevent further liver damage.

  • Treatment involves supportive therapy or curative therapy, depending on the disease; like in viral hepatitis, fluid infusions through veins and monitoring the liver function are done.

What Are the Complications of Conjugated Hyperbilirubinemia?

  • Fat malabsorption (poor fat absorption from the food).

  • Greenish discoloration of the teeth in infants due to long-term hyperbilirubinemia.

  • Infection.

  • Repeated vomiting that is difficult to control.

  • Gallbladder perforation (holes in gallbladder).

  • Thrombosis (blockage in blood vessels due to blood clot).

  • Pain.

What Is the Prognosis of Conjugated Hyperbilirubinemia?

The prognosis depends on the underlying disease or condition. If the underlying condition is a malignancy, then the prognosis will be poor. If the cause is due to infection or non-malignant causes, then the prognosis will be good.

Does Conjugated Hyperbilirubinemia Occur Only in Adults?

No, conjugated hyperbilirubinemia occurs in adults, kids, and infants (babies).

Is Conjugated Hyperbilirubinemia a Disease?

No, conjugated hyperbilirubinemia is not a disease. It is a sign of underlying liver disease or condition.

Conclusion:

Conjugated hyperbilirubinemia occurs as a result of elevated levels of conjugated bilirubin due to a disease or a condition. The common symptoms are jaundice and dark-color urine. Depending on the underlying disease, the symptoms may vary. The methods to find conjugated hyperbilirubinemia depend on the disease suspected, though few tests like total and direct bilirubin tests and urine bilirubin tests reveal conjugated hyperbilirubinemia. The treatment also depends on treating the underlying disease along with immediate stopping of intake of medications like Acetaminophen or other medications that cause liver damage. Though this is an indicator of underlying liver disease, visit the doctor as soon as the signs and symptoms appear. This will enable the doctor to detect and treat the disease early to avoid complications and improve the lifespan of the patient.

Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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