Gilbert's syndrome: symptoms, causes and diagnosis of this liver disease

By Cristiano Antonino On May 15, 2022

Gilbert’s syndrome is a mild and relatively frequent benign liver disease in which the organ fails to properly dispose of bilirubin, a yellowish-orange substance that is produced by the breakdown of red blood cells

Normally, bilirubin is only excreted from the body after undergoing a chemical reaction in the liver, which is responsible for converting the toxic form of the molecule (unconjugated bilirubin) into the harmless form (conjugated bilirubin).

In patients suffering from Gilbert’s syndrome, unconjugated bilirubin accumulates in the blood (unconjugated hyperbilirubinemia), but the blood concentration is variable and only rarely increases to the point of symptoms.

Many patients do not show any symptoms and the diagnosis often occurs by chance, during analyses required for other reasons; occasionally there may be the appearance of a slight yellowish colour of the skin or the whites of the eyes (jaundice and sub-utterus) and possibly non-specific symptoms such as

feeling tired
weakness
abdominal pain

Gilbert syndrome usually does not cause any serious consequences and does not require any treatment

It is caused by a hereditary genetic mutation, so it manifests itself at birth, but is usually not diagnosed for many years.

The syndrome is often diagnosed by chance, for instance when blood tests show that the patient has very high bilirubin.

The most affected are men and it is usually diagnosed during adolescence.

If affected patients experience episodes of hyperbilirubinaemia, these are usually mild and occur when the body is under stress, e.g. when dehydrated, after prolonged fasting, when ill, exercising too intensively or during the menstrual cycle.

Some patients suffering from Gilbert’s syndrome experience abdominal discomfort or fatigue, however, about 30 per cent experience no symptoms at all and the diagnosis is made when routine blood tests indicate an excess of unconjugated bilirubin.

As a matter of interest, it should be noted that Napoleon Bonaparte was also affected.

Causes of Gilbert syndrome

Gilbert syndrome is caused by an abnormality in a gene that is inherited from parents.

The gene controls the expression of an enzyme that is used to break down bilirubin in the liver: if the gene is not functioning properly, an excessive amount of bilirubin accumulates in the blood.

How is bilirubin disposed of?

Bilirubin is a yellowish pigment derived mainly from the breakdown of old red blood cells and only to a small extent (about 20%) from the destruction of proteins circulating in the blood.

The bilirubin thus formed is called indirect (or unconjugated) and, thanks to albumin, is transported in the blood to the liver, where it is conjugated with glucuronic acid (conjugated or direct bilirubin).

This conjugation step is defective in individuals with Gilbert syndrome because the enzyme responsible for it is unable to do its job effectively under certain conditions.

Conjugated bilirubin then leaves the liver and reaches the intestine, mixed with bile. Here it is disposed of along with the faeces. In the healthy patient, only a small amount of bilirubin remains in the blood at this point.

How does the transmission of the gene that causes Gilbert syndrome occur?

The abnormality of the gene that causes the syndrome is quite widespread.

Many people possess a copy of this abnormal gene, but in this case they do not manifest the disorder.

Two copies are normally required for Gilbert’s syndrome to manifest itself, and are therefore inherited from each parent. However, it should be noted that not all individuals with this genetic feature manifest the typical symptoms of the syndrome, a clear sign that other important factors are involved in the genesis of the disorder.

For example, red blood cells may break down too easily, suddenly releasing an excessive amount of bilirubin into the circulation, or there may be problems in the liver in transporting the molecule.

These and other factors could then be influenced by other genes.

Risk factors

The risk of manifesting Gilbert syndrome is increased if both parents are carriers of the modified gene that causes the liver disease

Men are more affected than women
The syndrome is not related to lifestyle, environmental factors or other liver diseases

Triggering factors

Certain disorders and specific situations can increase bilirubin levels, thus favouring the appearance of jaundice and the other symptoms in people with Gilbert syndrome; these include:

Dehydration
fasting or very low-calorie diet
certain common viral illnesses such as flu or colds
stress
excessively intense exercise
menstrual cycle
lack of sleep
surgery

Symptoms of Gilbert syndrome

The characteristic symptom of Gilbert syndrome is the yellowish colour (jaundice) of the normally white part of the eyes and skin, which occurs only occasionally and is caused by slightly higher than normal bilirubin levels in the blood.

Other symptoms that have sometimes been reported by patients affected by the syndrome are:

Fatigue and tiredness
weakness
difficulty concentrating
anxiety
lack of appetite
nausea
abdominal pain
weight loss
itching (without skin rash)

but the scientific literature on these aspects is still unclear on possible causal links.

When to call your doctor

Make a doctor’s appointment if you suffer from jaundice, as this disorder can have several causes and it is therefore necessary to reach a definite diagnosis.

Health hazards associated with Gilbert syndrome

Jaundice

The syndrome is a chronic disease, which therefore accompanies the individual throughout life; however, it does not require any treatment because it poses no health threat and causes neither complications nor an increased risk of liver disease.

The episodes of jaundice and any associated symptoms are generally short-lived and resolve spontaneously, especially if the possible triggering factor (stress, fasting, etc.) disappears.

If the jaundice does not disappear, we advise you to consult your doctor.

Side effects of certain drugs

Deficiency of the enzyme responsible for bilirubin elimination not only causes Gilbert’s syndrome but can also increase the side effects of certain drugs, as it is responsible for their elimination from the body.

In particular, irinotecan, a chemotherapy drug, can reach toxic levels if one suffers from the syndrome, causing severe diarrhoeal episodes.

Some protease inhibitors, used to treat HIV, can cause increased bilirubin levels in patients suffering from the syndrome.

If you suffer from Gilbert syndrome, always consult your doctor before taking a new drug to avoid the risk of side effects.

Gilbert’s syndrome: diagnosis

Although present from birth, Gilbert syndrome is usually not diagnosed until puberty or adulthood because bilirubin production increases during adolescence.

Gilbert syndrome is often diagnosed by chance, following:

blood tests showing very high bilirubin levels
apparently unexplained jaundice

The doctor will examine you and ask if you show the classic symptoms of liver disease, e.g. abdominal pain and darker-than-normal urine.

He or she may recommend blood tests to rule out liver problems that could cause your bilirubin to rise.

The most frequently performed blood tests include:

Bilirubin test
Complete blood count
Liver function tests (transaminases, GGT and others)

When the liver is damaged, it releases specific enzymes into the blood (transaminases) and, at the same time, the levels of proteins produced by the organ begin to decrease significantly.

By measuring the amount of these two parameters in the blood, it is therefore possible to get a fairly accurate picture of liver health: if tests show high bilirubin levels in the blood, but normal liver function, Gilbert syndrome is usually diagnosed.

Only rarely may confirmation through a genetic test be required.

Care and treatment of Gilbert syndrome

No treatment is required for the syndrome; the bilirubin levels in the blood may vary and one may occasionally suffer from jaundice, which, however, disappears spontaneously and without causing any side effects.

Diet and practical remedies

When suffering from Gilbert’s syndrome, there is no reason to change one’s diet and amount of exercise, while the general recommendations on the need to follow a healthy and active lifestyle, eating a varied and balanced diet rich in fruit and vegetables, avoiding overly aggressive weight-loss diets and prolonged periods of fasting remain valid.

Instead, it becomes important to try to avoid all factors that can act as triggers for symptoms, such as dehydration and stress.