Gilbert’s Syndrome

What is Gilbert’s disease?

Gilbert’s Syndrome is a chronic liver condition characterized by a genetically determined persistent increase in the serum levels of indirect bilirubin. It progresses benignly – not leading to cirrhosis or liver cancer. It increases the likelihood of developing cholestasis and gallstone disease, and during exacerbations, noticeably reduces the patient’s quality of life.

About the disease

Gilbert’s Syndrome has other names: non-hemolytic familial jaundice, familial benign hyperbilirubinemia, idiopathic or constitutional unconjugated hyperbilirubinemia, and simple familial cholemia. It is quite common: up to 7-10% of the population of our planet suffer from this condition, with the vast majority being male. Clinically, unconjugated hyperbilirubinemia typically debuts in adolescence or in young people up to the age of 30.
According to some specialists, Gilbert’s Syndrome is not a pathology at all but merely a constitutional peculiarity inherited genetically.

Types
There are two variants of this condition:

“congenital” – symptoms of hyperbilirubinemia first appear unrelated to viral hepatitis;
arising after a person contracts an inflammatory liver disease.
The first variant is more common.

Symptoms

The disease progresses in a wavering manner – its clinical manifestations may vary in degree or may be absent altogether.
The first signs of this condition often appear in males aged 12 to 30. The leading symptom of Gilbert’s syndrome is a yellowish hue of the skin, visible mucous membranes, and sclerae (ranging from subicteric to saturated yellow). Jaundice may appear in isolated areas of the body (e.g., on the feet and/or palms) or diffusely, against a backdrop of overall well-being or as a result of exposure to adverse factors. In most cases, it resolves spontaneously.

Patients may also complain of:
discomfort, heaviness in the right hypochondrium;
heartburn, nausea;
bloating of the intestine;
loss of appetite;
digestive disturbances;
asthenia symptoms (weakness, fatigue, irritability, disrupted sleep, depressed mood);
fatty deposits on the eyelids (xanthelasmas).
A third of patients may not complain of anything – Gilbert’s Syndrome is detected in them entirely by chance during examination for another pathology.

Causes

To understand the causes of Gilbert’s Syndrome, it is worth understanding what bilirubin is and the basic processes of its metabolism in the body. Bilirubin is a bile pigment formed during the breakdown of red blood cells – erythrocytes. In human plasma, it exists in two forms – free, or indirect, and conjugated (bound, direct). Indirect bilirubin is toxic to the human body – high concentrations cause irreparable damage to cells, primarily brain cells. To avoid such a scenario, the body neutralizes indirect bilirubin by binding it to glucuronic acid in the liver, forming direct bilirubin. In this form, the substance enters the bile ducts, from there – into the intestines or through the bloodstream into the kidneys, and is then excreted with feces and urine.
Due to a genetic mutation, the activity of a specific enzyme – UDP-glucuronyltransferase – decreases, and the entire process described above is disrupted, proceeding less actively. As a result, the concentration of indirect bilirubin in the blood increases, and it accumulates in the skin and other tissues.


Factors that trigger the clinical manifestation of Gilbert’s Syndrome include:

  • physical or psychosocial stress;
  • prolonged fasting;
  • dehydration;
  • acute respiratory infections;
  • viral hepatitis;
  • acute or chronic intestinal infections;
  • surgeries;
  • in women – menstrual bleeding;
  • alcohol consumption;
  • the use of certain medications (glucocorticoids, antibiotics, paracetamol).

Diagnosis

The preliminary diagnosis is made by the doctor based on the patient’s complaints, their medical history, and current illness, taking into account the results of the objective examination. During the examination, palpation, and percussion of internal organs, the doctor will pay attention to the yellowing of the skin and mucous membranes, xanthelasmas on the eyelids, hepatomegaly, and splenomegaly. To confirm the diagnosis, the specialist will prescribe further examinations for the patient:
complete blood count (may reveal an increase in hemoglobin levels and/or a decrease in platelet levels);
urinalysis (may show an increase in creatinine concentration);
blood biochemistry (the bilirubin level will be significantly elevated, mainly due to the indirect form, hyperproteinemia (elevated total protein concentration in the blood) may be present; other liver function tests will be within reference ranges);
detection of viral hepatitis markers in the blood;
PCR diagnostics to search for DNA defects;
ultrasound of the abdominal organs and retroperitoneal space (hepatomegaly, splenomegaly, and gallstones may be present);
duodenal probing;
thin-layer chromatography;
in cases of suspected hepatitis, cirrhosis, hepatocellular carcinoma – a puncture biopsy with subsequent microscopic examination of the tissue fragment obtained.
Functional tests sometimes help confirm the diagnosis:
fasting (bilirubin concentration is determined in the blood, then the patient consumes 400 kcal of food per day for two days; after this period, the bilirubin concentration is retested; an increase of 50-100% confirms the diagnosis);
nicotinic acid test (the patient is injected with 40 mg of nicotinic acid into a vein; a sharp increase in bilirubin concentration in the blood after this manipulation confirms the diagnosis);
phenobarbital and rifampicin tests were previously used, but now they are practically not used due to the principles of rational antibiotic therapy and the side effects of these drugs.

Treatment of Gilbert’s Syndrome

This diagnosis itself is not an indication for starting medication. Since the condition is characterized by a fluctuating course, it is important to minimize factors that provoke exacerbations: avoid alcohol abuse, control physical exertion, develop stress resistance, and maintain the immune system.
In terms of diet, patients should avoid fasting, drink enough fluids, and limit the consumption of foods high in hard-to-digest fats such as meat and preservatives.
Adult patients with symptoms of Gilbert’s disease may be prescribed:
cholagogue agents;
medications that improve metabolic processes in hepatocytes;
sorbents;
vitamin complexes;
phototherapy;
blood exchange transfusion.

Prevention

It is not possible to prevent the development of this condition. Couples affected by it may be recommended genetic counseling to assess the likelihood of the disease occurring in offspring.
Reducing the frequency of clinically significant exacerbations can be achieved by minimizing the impact of risk factors on the body.

Rehabilitation

Women and men with Gilbert’s Syndrome are subject to outpatient monitoring by a therapist or gastroenterologist. With a certain periodicity (depending on the specific situation), the doctor conducts a follow-up examination and prescribes a minimum of tests necessary to assess the patient’s current condition.
Since this condition is genetic, it is impossible to cure it, however, correct actions by the patient and the doctor can help control the course of Gilbert’s disease and prevent complications.