Gilbert's syndrome: what is it, symptoms and treatment, prognosis

What is Gilbert's Syndrome?

Gilbert's syndrome (simple familial cholemia, constitutional hyperbilirubinemia, idiopathic unconjugated hyperbilirubinemia, non-hemolytic familial jaundice) is a benign chronic liver disease, characterized by

• an increase in bilirubin in the blood;
• jaundice.

If the bilirubin in the blood rises slightly, the patient does not develop any symptoms; however if the level of bilirubin in the blood is high, the patient develops a sudden yellowish discoloration of the sclera of the eyes (usually the white part) and skin, a condition known as jaundice.

So jaundice itself is not a disease, it is a sign that something in the body is no longer functioning properly.

Gilbert's syndrome is a hereditary congenital disease and affects about 1-5% of the population of Russia; more common in men, usually no earlier than 15-18 years.

The disease is not serious and does not require special medical treatment.

Bilirubin

Bilirubin is a yellow-orange pigment released into the bloodstream after the destruction of old or damaged red blood cells (red blood cells) and a small portion of serum proteins.

Bilirubin enters the bloodstream associated with albumin and reaches the liver, where it is converted from unconjugated (toxic) form in conjugated (non-toxic) form of bilirubin and after dissolution in water overflows into duodenum along with the bile produced gallbladder.

In the intestine, bilirubin is partially reabsorbed (about 20%) and returns to the liver through the portal vein, and the remaining 80% are converted into urobilinogen by the intestinal bacterial flora and excreted in the feces and in very small quantities from urine.

Causes of Gilbert's syndrome

Gilbert's syndrome is a disease caused by the presence of a genetic mutation in an enzyme called uridine diphosphate glucuronyl transferase (UDPGT).

This enzyme, present in the liver, under normal conditions allows the conversion of bilirubin from a toxic (unconjugated or indirect) form to non-toxic (conjugated or direct) form: in other words, this enzyme allows bilirubin to bind to glucuronic acid, making it water-soluble and facilitates its passage through the bile ducts to enter the intestines with bile, where it performs its main function in the emulsion edible fats.

Due to a genetic mutation in the isoform of the UGT1A enzyme, the amount of uridine diphosphate glucuronyltransferase (UDPGT) decreases, and therefore the ability liver conjugate bilirubin and remove it from the body also decreases: it follows that the toxic amount of bilirubin in the blood increases.

Gilbert's syndrome is a congenital disorder, but although it is already present at the time of birth, the condition does not manifest clinically until the person reaches puberty. In fact, in adolescents, after a change in the hormonal structure, an increased physiological production of bilirubin occurs.

The transmission of this disease is hereditary: the likelihood of infection increases if both parents have a mutated gene for the enzyme and pass it on to their child. In fact, two mutated copies of the gene are required for the clinical manifestation of the disease (autosomal recessive transmission).

It was also noted that 40% of patients with Gilbert's disease have a moderate decrease in mean the life of erythrocytes (in a healthy subject - 120 days), cells containing hemoglobin, from which bilirubin; in other cases, they represent a disturbance in the transport of bilirubin to the liver.

Therefore, it is likely that Gilbert's syndrome is a multifactorial disease, i.e. It has a combination of several reasons that are not yet fully known, and contribute to clinical development disease.

Symptoms of Gilbert's syndrome

Patients often do not know that they are suffering from the disease, because in a third of patients, Gilbert's disease does not cause any symptoms; therefore, the detection of pathology in these cases is completely random, after taking a blood sample according to for other reasons or when examining the level of bilirubin, which shows an increase in the value of indirect bilirubin.

Symptoms, if present, are nonspecific, that is, they are common to a large number of clinical conditions. These are disorders associated with the accumulation of unconjugated bilirubin in the bloodstream, where it irritates various tissues (stomach, skin, brain neurons) and causes:

• digestive disorders;
• abdominal pain;
• widespread itching, no obvious rash;
• tiredness and weakness;
• headache;
• nausea;
• lack of appetite;
• unexplained weight loss;
• general malaise;
• anxiety, nervousness;
• depression;
• distraction of attention.

Jaundice occurs when the bilirubin in the blood exceeds 2.5 mg / dL and is observed almost exclusively in the eyes, in the white part, called the sclera, which tends to acquire a yellowish color: therefore it would be more correct to talk about sub-jaundice. However, this abnormal coloration can often affect the body as well.

Jaundice lasts for a short period of time, tends to resolve spontaneously, and reappears under certain conditions (factors), such as:

• prolonged fasting or unbalanced nutrition;
• stress;
• intense physical activity;
• menstrual cycle;
• alcohol abuse;
• fever;
• infections (flu, cold);
• lack of sleep;
• surgical interventions;
• fortunes dehydration.

Diagnostics

Often the diagnosis is made after the patient seeks a therapist c:

• digestive problems;
• widespread abdominal pain;
• weakness;
• a feeling of general malaise;
• the sudden appearance of yellowness of the skin or sclera of the eyes.

These symptoms are not always present, and it is not uncommon for Gilbert's syndrome to be accidentally discovered after a simple blood test performed as routine screening in an asymptomatic patient.

After collecting the patient's medical history (symptoms, comorbidities, medications taken and prescribed procedures), the doctor asks for a blood test, which in case of illness will show:

• a slight increase in the value of indirect bilirubin (between 1.5 and 6 mg / dl);
• no change in the direct value of bilirubin;
• no changes in other indicators of liver function (ALT, AST, GGT);
• no change in the indicators of protein synthesis (APTT, albuminuria);
• normal blood count.

It would be wise to repeat the blood tests at least a couple of times after 24 hours of fasting: the fasting test is actually spent after a whole day with a reduced calorie intake, allows you to observe a higher increase in only the indirect bilirubin.

An increase in indirect bilirubin and no change in other liver function parameters are typical of Gilbert's syndrome.

In some centers, a genetic test can be done to diagnose the disease (usually, but this is not necessary).

Differential diagnosis

Gilbert's syndrome is not the only one liver diseasewhich can cause jaundice, so if you have jaundice, it is important for your doctor to rule out any other more serious liver disease or biliary tractthat could be causing it, such as:

• acute, chronic and medicinal hepatitis;
• cholelithiasis​;
• cholestasis;
• cirrhosis of the liver;
• liver cancer;
• pancreas cancer;
• obstruction of the biliary tract;
• overproduction of bilirubin (hemolysis, ineffective erythropoiesis),
• other causes of congenital jaundice (Crigler-Nayyar syndrome, Dabin-Johnson syndrome, Rotor syndrome).

In these cases, a blood test will show abnormalities in the functional parameters of the liver; an ultrasound examination of the liver may also be required; and if diagnostic doubts persist, more sophisticated radiological tests may be required.

Prognosis and complications

The prognosis is excellent, Gilbert's syndrome is a benign disease that accompanies the patient throughout his life, but without symptoms or causing only mild and transient disorders.

• Jaundice, if present, is transient and resolves spontaneously without requiring treatment.
• The patient's daily activities and quality of life are not affected.
• People suffering from Gilbert's syndrome are not threatened with life and health, nor do they have a greater risk of developing complications or other liver diseases.
• The disease does not cause liver cirrhosis, hepatitis, or liver tumors.

The only danger to patients may be associated with taking certain medications: deficiency of the enzyme uridine diphosphate glucuronyltransferase (UDFGT) actually not only reduces the ability of the liver conjugate bilirubin, but also remove toxins from the body, i.e. dispose of toxic metabolites present in medications.

This means that patients with Gilbert's disease may be at greater risk of developing or exacerbating side effects from certain medications, such as:

• irinotecan, a chemotherapy drug used to treat colorectal cancer or lung cancer;
• protease inhibitors for the treatment of HIV infection;
• a group of drugs used to lower cholesterol levels.

Taking paracetamol can also cause side effects such as:

• nausea;
• swelling of the skin;
• decrease in blood lymphocytes;
• general malaise.

In fact, paracetamol is broken down by the same enzyme as in Gilbert's syndrome.

Therefore, it is always recommended to consult a doctor before taking any medications.

Treatment for Gilbert's syndrome

To date, there is no drug that can cure Gilbert's syndrome, but this should not bother a patient who in fact does not need specific drug therapy, because of the absolutely benign and harmless course diseases.

The use of phenobarbital to reduce jaundice should not be recommended for aesthetic purposes only, since taking this drug may be burdened with the possible development of side effects. It is best to prevent conditions that trigger episodes of jaundice, such as:

• intense physical activity;
• hunger;
• insomnia;
• thirsty.

Even during pregnancy, treatment of jaundice caused by Gilbert's syndrome is not recommended.

Diet and nutrition

Some dietary advice may be provided by a doctor to improve minor disorders associated with Gilbert's syndrome, as well as in order not to overextend the liver, for example, use in small doses or avoid:

• fatty foods;
• fried food;
• large portions of food at a time;
• alcohol;
• unknown food additives;
• fluorinated water (high in fluoride).

It is necessary to lead a healthy lifestyle, following general recommendations:

• eating several servings of fruits and vegetables a day;
• have a varied and regular diet;
• drink at least 8 glasses of water a day;
• engage in light physical activity;
• remove any source of stress.

Remember: Disease elimination can be stimulated by dietary changes. The complete elimination of animal proteins, simple sugars, alcohol and highly processed foods reduces the accumulation of toxins in the liver. Low doses of vitamin A, niacin, fish oil, or vitamin D are recommended.