What is Gilbert Syndrome?
Gilbert syndrome is a genetic condition affecting how your liver processes a substance called bilirubin. Bilirubin is a yellow substance our body produces when it replaces old red blood cells. Usually, the liver processes bilirubin, which then passes through your digestive system and out of your body. However, in Gilbert Syndrome, the liver doesn’t process bilirubin efficiently, leading to high levels in the blood. This is called unconjugated hyperbilirubinemia, and it often results in bouts of jaundice, which is a yellowing of the skin and eyes.
It’s key to note that Gilbert syndrome isn’t harmful, and typically, doesn’t require treatment. But it’s crucial to differentiate it from other conditions that can also lead to unconjugated hyperbilirubinemia. This includes diseases that impact either the process of bilirubin uptake, the combination or conjugation of bilirubin, and overproduction of bilirubin in general.
Consider other liver-related conditions too, like Crigler-Najjar syndrome, which has significant unconjugated hyperbilirubinemia. Other diseases can cause blood cells to break down rapidly, increasing bilirubin production, and thereby also causing high levels of unconjugated bilirubin. Conditions that can lead to this situation include genetic disorders of red blood cells, infections, reaction to medication or toxins, and some types of anemia.
Most people with Gilbert syndrome don’t show any symptoms related to liver disease, but some factors can trigger a higher bilirubin level. These can include fasting, illness, menstruation, and dehydration.
It’s also important to consider that other liver disorders, both acute and chronic, can cause both unconjugated and conjugated hyperbilirubinemia, meaning both processed and unprocessed bilirubin levels are high. When the liver is impacted by a disease, the proportion of processed or conjugated bilirubin goes up. That’s why when doctors see patients with high bilirubin levels and jaundice, they also consider conditions like viral, metabolic, or autoimmune liver disorders.
Before diagnosing Gilbert syndrome, doctors will conduct a detailed examination, run targeted lab tests, rule out other conditions related to unconjugated hyperbilirubinemia, and consider if other liver diseases could cause the symptoms. Once Gilbert syndrome is diagnosed, the main approach to treatment is regular monitoring as the condition doesn’t usually cause harmful effects. Lastly, keep in mind that people with Gilbert syndrome generally have an excellent prognosis, meaning they are expected to live a normal and healthy life.
What Causes Gilbert Syndrome?
Gilbert syndrome is a condition that can cause increased levels of a substance called bilirubin (known as unconjugated hyperbilirubinemia) and yellowing of the skin and eyes (jaundice). Certain situations can make these symptoms more likely, like not eating enough, experiencing reactions that break down red blood cells faster than usual (hemolytic reactions), having an illness with a fever, menstruating, and intense physical activity.
A person’s bilirubin levels can dramatically increase if they reduce their daily food intake down to 400 calories, often within 48 hours. Interestingly, a similar rise in bilirubin can also occur even when a person receives enough daily calories as long as they’re not consuming sufficient fats. Luckily, eating a regular diet usually returns the bilirubin levels back to normal within 12 to 24 hours.
Several possible explanations exist as to why diet changes can cause a rise in bilirubin levels in people with Gilbert syndrome. Theories include an increased recycling of bilirubin in the liver and gut, a decrease in bilirubin binding due to a decrease in a substance known as UDP-glucuronic acid, and the release of bilirubin from fat cells.
Risk Factors and Frequency for Gilbert Syndrome
Gilbert syndrome is a condition that affects between 4% and 16% of the population. It typically shows up during early adolescence, and is more common in males. This could be because males have different hormone levels and produce more bilirubin. The condition often gets diagnosed around puberty because of changes in hemoglobin and hormone levels. Additionally, about 30% of white and black individuals carry a variant promoter related to the syndrome; however, this is less common in individuals from Japan.
- Gilbert syndrome affects 4% to 16% of people.
- Symptoms usually appear during early adolescence.
- The syndrome is more commonly found in males.
- The condition is often diagnosed around puberty.
- About 30% of whites and blacks have a genetic variant linked to Gilbert syndrome; this is less common in Japanese individuals.
- People with Gilbert syndrome and a deficiency in glucose-6-phosphatase may experience prolonged neonatal jaundice.
Signs and Symptoms of Gilbert Syndrome
Gilbert syndrome is a condition that usually develops during adolescence and tends to affect males more than females. Except for mild yellowing of the skin and eyes (jaundice), individuals with this condition do not usually show symptoms related to liver disease. However, they might have symptoms related to possible triggers. An interesting point to note is that people with Gilbert syndrome have a higher chance of developing gallstones. There can also be an overproduction of bilirubin, a yellow pigment, due to underlying blood cell destruction, which may lead to an increase in unconjugated bilirubin, a form of bilirubin that’s not attached to another substance.
Physicians need to consider other diseases related to the liver, based both on the medical history of the patient and physical examination. Certain behaviours like heavy consumption of alcohol, drug use, risky sexual behaviour, tattoos, body piercing, blood transfusions could suggest the risk for conditions like hepatitis B or C or even liver cancer.
- Heavy alcohol consumption
- Recreational drug use
- Blood transfusions
- Body piercing
- Engaging in unsafe sexual practices
- Immunoglobulin injections
- Tattoos or other skin modifications
A history of conditions like diabetes, high blood pressure, abnormal blood lipid levels, and obesity could be indicators for non-alcoholic fatty liver disease. This disease is increasingly becoming one of the most common liver diseases in the US. Also, any family history of autoimmune diseases might hint towards conditions like primary biliary cholangitis, primary sclerosing cholangitis, or autoimmune hepatitis. One thing to note is that patients with Gilbert syndrome do not show signs of extreme liver dysfunction like variceal bleeding, fluid buildup in the abdomen, hepatic encephalopathy, or certain syndromes and conditions linked to portal hypertension.
Testing for Gilbert Syndrome
Gilbert syndrome is a condition that leads to higher levels of a substance known as unconjugated bilirubin in your blood. Typically, this level is below 4 mg/dL. However, this level can change depending on certain factors. Importantly, people with this syndrome generally show normal results on various blood tests. These tests include complete blood count, reticulocyte count (measuring young red blood cells), lactate dehydrogenase (a type of enzyme), and a peripheral smear (examining your blood under a microscope).
Also, two other important substances, aminotransferases and alkaline phosphatase, are typically normal as well.
Usually, imaging tests of the liver or the bile ducts are not necessary unless your doctor suspects another condition other than Gilbert syndrome. Similarly, a liver biopsy (a procedure that involves taking a small sample of the liver for testing) is rarely done. Tests like fasting for 48 hours or following a low-calorie diet are also not typically needed. If Gilbert syndrome is difficult to diagnose, doctors might consider genetic testing. This involves assessing the activity of a gene called UGT1A1, and looking for changes in this gene.
Before diagnosing Gilbert syndrome, other liver diseases that can lead to high bilirubin levels should be considered. If there is a suspicion of viral hepatitis (a liver disease caused by viruses), tests should be done for hepatitis A, B, and C. If there’s a possibility of autoimmune hepatitis (a disease where the body’s own immune system attacks the liver), certain tests including liver biopsy may be necessary. People who might have primary biliary cholangitis (a condition that slowly destroys the bile ducts in the liver) would also have to undergo certain tests, possibly including a liver biopsy.
If the doctor suspects Wilson disease (a rare disorder that causes too much copper to accumulate in the body), they might consider tests for a protein called ceruloplasmin, as well as tests for copper levels in blood and urine, liver biopsy, and a specific eye examination for detecting excessive copper accumulation.
Finally, if alpha-1-antitrypsin deficiency (a disease that raises your risk for lung and liver disease) is a possibility, it might be necessary to measure the alpha-1-antitrypsin level and conduct genetic testing.
Treatment Options for Gilbert Syndrome
People with Gilbert syndrome typically don’t need any specific treatment. It’s also suggested to avoid any unneeded medical tests. However, managing triggers that could cause an increase in the substance called unconjugated bilirubin might be beneficial.
If a person with Gilbert syndrome experiences a high level of bilirubin along with abnormalities in other liver-related substances (aminotransferases and alkaline phosphatase), further testing may be needed. This could involve checking for diseases that may harm the liver, such as viral, metabolic, autoimmune, or ones caused by certain medicines.
In cases where the symptoms or liver enzyme levels suggest a different health problem, the doctor may recommend getting an imaging test for the liver and bile ducts. The bile ducts are tubes that carry bile—a substance produced by the liver that helps with digestion—from the liver to the gallbladder and the small intestine.
Patient with signs of severe liver disease—like bleeding from enlarged veins in the esophagus (variceal bleeding), fluid build-up in the abdomen (ascites), or a decline in brain function resulting from liver disease (hepatic encephalopathy)—should go and see a specialist such as a gastroenterologist or a hepatologist. These specialists would then conduct additional tests and treatments, and might even consider assessing the patient for a potential liver transplant.
What else can Gilbert Syndrome be?
Hyperbilirubinemia is a medical term that refers to having excessive levels of bilirubin, a yellow compound, in your blood. Importantly, there are two types: Unconjugated and Conjugated Hyperbilirubinemia.
Unconjugated Hyperbilirubinemia can be caused by various conditions:
- Increased production of bilirubin, which could be due to breaking down a lot of red blood cells, resorbing hematoma, dyserythropoiesis, or Wilson Disease.
- Impaired liver’s ability to absorb bilirubin, caused by such conditions as heart ailments, portosystemic shunts, Gilbert syndrome, or certain medications.
- Problems in joining bilirubin with another substance in the liver (impaired bilirubin conjugation), which could occur with Gilbert syndrome, Crigler-Najjar syndrome types I and II, or advanced liver disease.
On the other hand, Conjugated Hyperbilirubinemia might occur due to:
- Defects in moving organic anions in the liver’s ducts, like in Dubin-Johnson syndrome.
- Disturbance in reabsorbing associated bilirubin from liver cells, as seen in Rotor syndrome.
- Cholestasis outside the liver, which could be due to choledocholithiasis, malignancy in the pancreaticobiliary region, primary sclerosing cholangitis, pancreatitis, or parasite infection.
- Cholestasis inside the liver, likely from viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, primary biliary cholangitis, effects of certain drugs and toxins, sepsis, infiltrative diseases, parenteral nutrition, sickle cell disease, pregnancy, or end-stage liver disease.
What to expect with Gilbert Syndrome
People with Gilbert syndrome can expect a great outcome, similar to the general health expectations of the overall population. Gilbert syndrome is a common, harmless liver condition where the liver doesn’t properly process bilirubin – a yellow-brown substance produced by the liver and excreted in the bile. The condition might even have some benefits due to slightly increased bilirubin levels. This could include a lower occurrence of atherosclerosis, a condition where the arteries become clogged with fatty substances, endometrial cancer (a cancer that happens in the lining of the uterus), Hodgkin lymphoma (a type of lymphoma, which is cancer of the lymph nodes), and mortality related to cancer.
Possible Complications When Diagnosed with Gilbert Syndrome
Gilbert syndrome is a harmless genetic disorder that affects how the body processes a substance called bilirubin. Despite impacting the liver, it doesn’t increase the risk of serious liver diseases or liver-related death. As it is a genetic disorder, it’s important to inform patients and their family members about its inherited nature and its typically benign course. This is to avoid unnecessary medical tests.
However, if there are signs indicating either an acute (short-term) or chronic (long-term) liver disease based on the patient’s symptoms or lab results, a more in-depth check-up should take place. This analysis should test for other potential causes of liver diseases, such as viral infections, metabolic discrepancies, or autoimmune disorders.
Preventing Gilbert Syndrome
People with Gilbert syndrome should know about certain factors that can potentially cause their bilirubin level to go up. This includes fasting too long, illness, menstruation, physical exertion that’s too intense, particular types of reactions in your body related to red blood cells, and not drinking enough water. Staying clear from these triggers can help you feel less worried about abnormal bilirubin levels.
Patients as well as their families should understand that Gilbert syndrome is not dangerous, how it is passed on in families, and that it does not require any treatment. They should also be reassured that people with Gilbert syndrome can lead healthy lives with an excellent prognosis.
