Jaundice in Adults (Hyperbilirubinemia)

Picture of Jaundice of the Face and Eyes Courtesy of the CDC

• Jaundice is a yellowish discoloration of the skin, mucous membranes, and the white of the eyes caused by elevated levels of the chemical bilirubin in the blood (hyperbilirubinemia). The term jaundice is derived from the French word jaune, which means yellow. Jaundice is not a disease per se, but rather a visible sign of an underlying disease process.
• Jaundice is typically seen when the level of bilirubin in the blood exceeds 2.5-3 mg/dL (milligrams per deciliter).
• Jaundice in adults can be caused by a variety of medical conditions, some of which are serious and potentially life-threatening.
• Any adult who develops jaundice needs to undergo a comprehensive medical evaluation in order to determine its cause.
• Neonatal jaundice, a condition seen in newborns, is most often a benign condition that improves without serious after effects).

As already mentioned, jaundice is not a disease, but rather a visible sign of an underlying disease process. Individuals with jaundice will have a yellow discoloration of the skin to varying degrees, and may also exhibit yellowing of the mucous membranes and of the white of the eyes. However, depending on the underlying cause of jaundice, individuals may experience different symptoms. Some individuals may have very few if any, symptoms at all, while others may experience more severe and pronounced symptoms. Individuals with jaundice may experience any of the following signs and symptoms.

• Pale-colored stools
• Dark-colored urine
• Skin itching
• Nausea and vomiting
• Rectal bleeding
• Diarrhea
• Fever and chills
• Weakness
• Weight loss
• Loss of appetite
• Confusion
• Abdominal pain
• Headache
• Swelling of the legs
• Swelling and distension of the abdomen due to the accumulation of fluid (ascites)

The risk factors for developing jaundice vary based on the underlying cause.

• Certain people with hereditary conditions (for example, thalassemia or hereditary spherocytosis) are at an increased risk of developing jaundice from hemolysis.
• People who consume alcohol heavily are at an increased risk of developing alcoholic hepatitis, pancreatitis, and cirrhosis leading to jaundice.
• People who are at an increased risk of exposure to the different types of viral hepatitis (for example, hepatitis B and hepatitis C) are at risk of developing jaundice at the time of infection or subsequently, if liver disease occurs or if liver cancer develops later.
• Other risk factors include:
  • Eating raw shellfish
  • Drug injections of other substances
  • Tattooing
  • Birth between 1945 and 1965
  • Being an unvaccinated (for hepatitis)
  • Healthcare professionals
  • Participating in high-risk sexual activity

Picture of the liver and where it is located in the abdomen.

Jaundice in adults is caused by various medical conditions that affect the normal metabolism or excretion of bilirubin. Bilirubin is mostly formed from the daily breakdown and destruction of red blood cells in the bloodstream, which release hemoglobin as they rupture. The heme portion of this hemoglobin molecule is then converted into bilirubin, which is transported in the bloodstream to the liver for further metabolism and excretion. In the liver, the bilirubin is conjugated with glucuronic acid (made more water-soluble), and is excreted into the gallbladder (where it is stored) and then eventually passed into the intestines. In the intestines, a portion of the bilirubin is excreted in the feces, while some are metabolized by the intestinal bacteria to urobilinogen and excreted in the urine.

Jaundice occurs if there is a dysfunction of the normal metabolism and/or excretion of bilirubin. This disruption in the metabolism or excretion of bilirubin can occur at various stages, and it is, therefore, useful to classify the different causes of jaundice based on where the dysfunction occurs. The causes of jaundice are generally classified as pre-hepatic (the problem arises before secretion to the liver), hepatic (the problem arises within the liver), and post-hepatic (the problem arises after bilirubin is excreted from the liver).

What causes pre-hepatic (liver) jaundice?

Jaundice caused during the pre-hepatic phase is due to the excessive destruction (hemolysis) of red blood cells from various conditions. This rapid increase in bilirubin levels in the bloodstream overwhelms the liver's capability to properly metabolize the bilirubin, and consequently the levels of unconjugated bilirubin increase. Conditions which can lead to an increase in the hemolysis of red blood cells include:

• Malaria,
• Sickle cell disease,
• Hereditary spherocytosis,
• Thalassemia,
• Glucose-6-phosphate dehydrogenase deficiency (G6PD),
• Drugs or other toxins, and
• Autoimmune disorders.

Jaundice caused during the hepatic phase can arise from abnormalities in the metabolism and/or excretion of bilirubin. This can lead to an increase in both unconjugated and/or conjugated bilirubin levels. Conditions with a hepatic cause of jaundice include:

• Acute or chronic hepatitis (commonly viral [Hepatitis A, B, C, D, E] or alcohol-related)
• Cirrhosis (caused by various conditions including alcohol toxicity)
• Drugs or other toxins
• Crigler-Najjar syndrome
• Autoimmune disorders
• Gilbert's syndrome
• Liver cancer

Jaundice from a post-hepatic cause arises from a disruption (an obstruction) in the normal drainage and excretion of conjugated bilirubin in the form of bile from the liver into the intestine. This leads to increased levels of conjugated bilirubin in the bloodstream. Conditions that can cause post-hepatic jaundice include

• Gallstones,
• Cancer (pancreatic cancer, gallbladder cancer, and bile duct cancer),
• Strictures of the bile ducts,
• Cholangitis,
• Pancreatitis, and
• Parasites (for example, liver flukes).

The presence of jaundice requires a comprehensive medical evaluation to determine the cause. Initially, your healthcare professional will take a detailed history of your illness and perform a physical exam, which can sometimes determine the cause of jaundice. Initial blood testing will also be undertaken, with special attention being given to your:

• Liver blood tests
• Complete blood count (CBC)
• Electrolyte pane
• Lipase levels 

Blood testing for exposure to hepatitis may also be ordered. Additional blood testing may be ordered based on the initial results. A urinalysis will likely also be ordered.

Depending on the results of initial blood tests, further studies may be needed to help diagnose the underlying disease process. In certain cases, imaging studies will need to be obtained in order to evaluate for any abnormalities of the liver, gallbladder, and pancreas. These imaging studies may include:

• Abdominal ultrasound
• Computerized tomography (CT) scan
• Magnetic resonance imaging (MRI)
• Cholescintigraphy (HIDA scan)

Occasionally, people will need further invasive testing to determine the cause of jaundice. Procedures that may be ordered include endoscopic retrograde cholangiopancreatography (ERCP) or a liver biopsy.

The treatment for jaundice depends entirely on the underlying cause. Once a diagnosis has been established, the appropriate course of treatment can then be initiated. Certain patients will require hospitalization, whereas others may be managed as outpatients at home.

• In certain individuals with jaundice, the treatment will consist of supportive care and can be managed at home. For example, most cases of mild viral hepatitis can be managed at home with watchful waiting and close monitoring by your doctor (expectant management). Novel medications for hepatitis C now can offer a cure for this condition.
• Alcohol cessation is necessary for patients with cirrhosis, alcoholic hepatitis, or acute pancreatitis secondary to alcohol use.
• Jaundice caused by drugs/medications/toxins requires discontinuation of the offending agent. In cases of intentional or unintentional acetaminophen (Tylenol) overdose, the antidote N-acetylcysteine (Mucomyst) may be required.
• Various medications may be used to treat the conditions leading to jaundice, such as steroids in the treatment of some autoimmune disorders. Certain patients with cirrhosis, for example, may require treatment with diuretics and lactulose.
• Antibiotics may be required for infectious causes of jaundice, or for the complications associated with certain conditions leading to jaundice (for example, cholangitis).
• Blood transfusions may be required in individuals with anemia from hemolysis or as a result of bleeding.
• Individuals with cancer leading to jaundice will require consultation with an oncologist, and the treatment will vary depending on the type and extent (staging) of cancer.
• Surgery and various invasive procedures may be required for certain patients with jaundice. For example, certain patients with gallstones may require surgery. Other individuals with liver failure/cirrhosis may require a liver transplant.

The type of complication and the severity of complications vary with the underlying cause leading to jaundice. Certain individuals will not suffer any long-term after effects and will have a full recovery, while for others the appearance of jaundice will be the first indication of a life-threatening condition. A few of the potential complications include:

• Electrolyte abnormalities
• Anemia
• Bleeding
• Infection/sepsis
• Chronic hepatitis
• Cancer
• Liver failure
• Kidney failure
• Hepatic encephalopathy (brain dysfunction)
• Death

The prognosis for individuals with jaundice depends on the underlying cause of the condition. There are certain conditions that carry an excellent prognosis with individuals making a full recovery. However, more serious causes of jaundice can sometimes be fatal despite medical or surgical intervention. The development and severity of complications will also determine an individual's prognosis, as well a patient's underlying health and comorbidities (presence of other diseases). Therefore, a case-by-case assessment by your health care professional is necessary in order to determine a more accurate prognosis.

Certain conditions leading to jaundice can be prevented, whereas others may be less preventable. However, there are certain measures that can be taken in order to decrease the risk of developing jaundice.

• Take medications as instructed in order to prevent potential liver damage or unintentional overdose. Individuals with certain medical conditions (for example, G6PD deficiency or cirrhosis) should avoid certain medications altogether. Discuss medications with your health care professional.
• Avoid high-risk behaviors such as unprotected intercourse or intravenous drug use, and implement universal precautions when working with blood products and needles. This can decrease your risk of developing hepatitis B or hepatitis C.
• Consider being vaccinated against hepatitis A and hepatitis B. There is currently no available vaccine against hepatitis C.
• Avoid potentially contaminated food products or unsanitary water, as this may decrease your risk of developing hepatitis A.
• When traveling to areas where malaria is endemic, take the recommended precautions and prophylactic medications in order to prevent the development of malaria.
• Consume alcohol responsibly and only in moderation. This can prevent alcoholic hepatitis, alcoholic cirrhosis, and pancreatitis, among other conditions. Certain individuals will need to avoid alcohol altogether.
• Avoid smoking, as it is a risk factor for the development of pancreatic cancer, as well as many other malignancies.