It is a hereditary genetic condition in which a person has slightly high levels of bilirubin pigment because the liver does not process it properly.
This can give the skin and eyes a slightly yellow color or jaundice.
It is also known as constitutional liver dysfunction and nonhemolytic familial jaundice. The condition is harmless, and patients do not need treatment.
It is believed that between 3 and 7 percent of people have Gilbert’s syndrome, but most do not realize they have it.
Alternative Names of Gilbert’s Syndrome
Icterus intermittent juveniles; Low-grade chronic hyperbilirubinemia; Non-obstructive nonhemolytic family jaundice; Hepatic constitutional dysfunction; Benign bilirubinemia unconjugated; Gilbert’s disease.
Mild jaundice is the only sign that a person has Gilbert’s syndrome.
Many people with Gilbert’s syndrome have no symptoms. About 30 percent discover that they have it by chance through routine tests.
Bilirubin is produced when the body breaks down red blood cells.
In Gilbert’s syndrome, the liver does not process Bilirubin effectively due to an inherited genetic anomaly. This causes it to accumulate in the body.
If a person has too much Bilirubin, they will have jaundice, a yellow tint in the whites of their eyes. The skin can also acquire a yellowish tint if the levels increase more.
Extremely high levels of Bilirubin can cause itching, but this does not occur in Gilbert’s syndrome because bilirubin levels are not as high.
Factors that can cause a slight increase in bilirubin levels and make the symptoms more prominent include:
- Lack of sleep.
- Consumption of alcohol.
Why is Bilirubin high?
These are not necessarily in the order of likelihood.
- Liver problems:
Excess levels of unconjugated Bilirubin can indicate specific liver problems or a high level of decomposition of red blood cells.
While too high levels of conjugated Bilirubin may indicate obstruction of bilirubin excretion to the gallbladder.
- Low excretion of bile:
Bilirubin is excreted in the bile, so if you have lower biliary excretion, Bilirubin may increase.
- Less UGT enzymes:
A group of enzymes in the UGT family (glucuronosyltransferases) reduce Bilirubin, and if it has lower levels of these, it will cause higher Bilirubin.
UGTs usually convert unconjugated Bilirubin into conjugated Bilirubin that can be excreted in the gastrointestinal tract.
In addition to its capacity for xenobiotic detoxification, UGT1A1 plays a vital role in the clearance of Bilirubin.
The reduction in UGT1A1 expression is associated with Gilbert’s syndrome, characterized by mild unconjugated hyperbilirubinemia in the absence of liver disease.
The GG genotype in rs4124874 caused less UGT1A1 and showed a significantly higher frequency in patients with Gilbert’s syndrome (58%) than in healthy volunteers (17%).
- Lowest glucuronidation:
Bilirubin is glucuronidated to be excreted, so low glucuronidation can increase Bilirubin.
- Dysbiosis intestinal:
If you have intestinal dysbiosis, you may have high levels of the enzyme Beta-Glucuronidase, which can decrease glucuronidation.
- Slow flow of the intestine:
Bilirubin levels increase when the intestinal flow (motility) is reduced.
- Baja NRF2:
The UDP-glucuronosyltransferase family (UGT) catalyzes the conjugation of glucuronic acid with drugs, chemicals, and toxins, making them more soluble in water and easily excreted. It has been shown that Nrf2 induces UGT1A1 and UGT1A6.
- Inflammation and oxidative stress:
Oxidative stress and inflammation can also increase Bilirubin by breaking down red blood cells, which turn into Bilirubin (from hemoglobin).
Red blood cells are removed in the spleen as they age or become damaged. This releases hemoglobin, which breaks down into heme. The heme then becomes unconjugated Bilirubin in the spleen. This unconjugated Bilirubin binds to albumin and is sent to the liver.
- Oxygenase heme – 1:
Heme Oxygenase -1 increases Bilirubin by breaking it down, and some people may have higher levels of this enzyme. This produces biliverdin, iron, and carbon monoxide.
Induction of heme oxygenase may be a general response to oxidative stress, and increased levels of Bilirubin could provide an important cellular defense mechanism against oxidative damage.
- Lower CAR (constitutive receptor of Androstane):
CAR regulates the genes that transport bilirubin out of the body and, therefore, controls the amount of Bilirubin, making sure it never becomes high enough to become toxic.
People with high Bilirubin may have lower levels of activation of the constitutive receptor of Androstane.
It has been shown that the constitutive receptor of Androstane induces multiple enzymes, glucuronosyltransferases, and other enzymes that detoxify Bilirubin.
The polymorphism analysis of the UGT1A1 genes revealed that an SNP located within the CAR-responsive region showed a significantly higher frequency in patients with Gilbert’s syndrome (58%) than in healthy volunteers (17%).
- Under Pregnane X Receptor (PXR):
PXR helps detoxify products such as bile and Bilirubin, so if you have Gilbert Syndrome, you may not have enough Pregnane X receptors.
The elimination of bile can help prevent cholestasis.
It has been demonstrated that the Pregnane X receptor induces the expression of multiple key components in the bile and bilirubin elimination pathway, which include UGT1A1, OATP2, GSTA1, and two and MRP2.
According to the pattern of genetic regulation, it has been shown that the activation of PXR in mice prevents experimental hyperbilirubinemia.
- Higher hemoglobin:
Higher hemoglobin levels may also contribute to an increase in Bilirubin.
- Light deficiency:
The blue light breaks the hemoglobin, and if it is not receiving enough light, the Bilirubin will increase. The light allows the excretion of unconjugated Bilirubin in the bile because the light makes it more soluble.
- Superior monocytes in the spleen:
High monocytes in the spleen can increase Bilirubin because they decompose in it.
Bilirubin levels do not reach very high levels with Gilbert’s syndrome, but jaundice can be disturbing.
A person with Gilbert’s syndrome is unlikely to have specific symptoms beyond a bit of yellowing of the eyes.
Some people may experience fatigue and abdominal discomfort, but experts have not established any relationship between higher bilirubin levels and these symptoms.
What increases Bilirubin
Moderate alcohol consumption can increase blood bilirubin levels in non-smokers. The total concentration of Bilirubin in the blood increased significantly after drinking.
Total serum bilirubin increased significantly after drinking from the beginning up to 24 hours in non-smokers (from M = 0.38 to M = 0.51).
Physical training significantly increases bilirubin levels in the blood. However, this effect only occurs with high doses of exercise.
Fasting can increase bilirubin levels due to reduced intestinal mobility.
Short periods of fasting increase the concentration of unconjugated Bilirubin in patients taking Atazanavir.
Before the fasting diet, the average bilirubin concentration was 2.31 mg/dl and 3.84 mg/dl afterward.
- High fat intake:
An increased intake of lipids (fat) intravenously in infants under 28 weeks of age increases free Bilirubin. Higher fat intake leads to more free fatty acids in the blood, increasing Bilirubin in babies.
- Epigalocatequin galato (EGCG):
EGCG increases the secretion of Bilirubin. Therefore, consumption of green tea will increase bilirubin levels.
- Antitubercular drugs:
The use of anti-TB drugs increases bilirubin levels.
Paracetamol (acetaminophen / tylenol) increases bilirubin levels.
Prolonged use of certain antibiotics may cause an increase in bilirubin levels in rats.
- Bacterial overgrowth of the small intestine and abnormal bowel movement:
The downward movement of the intestines and the bacterial overgrowth of the small intestine can increase the levels of unconjugated serum bilirubin and the formation of gallstones.
- Blood and liver diseases:
Excess levels of unconjugated Bilirubin can indicate specific problems with the liver or that there is a high level of decomposition of red blood cells.
While too high levels of conjugated Bilirubin may indicate obstruction of bilirubin excretion to the gallbladder.
Gilbert Syndrome Diet
Experts say there is no need for a change in diet, although alcohol should be avoided, and drinking plenty of water can help prevent dehydration. It is also essential:
- Follow a healthy and balanced diet with lots of fresh fruits and vegetables.
- Eat regularly and do not skip meals.
- Avoid fasting and deficient calorie diets.
A study of one patient suggested that following a specific paleolithic diet, the Paleolithic Ketogenic Diet produced some improvements in bilirubin levels. However, this has not been confirmed by other research.
Gilbert’s syndrome is considered harmless since it usually does not cause any health problems. As a result, no treatment is required.
The symptoms of jaundice can be disturbing, but they are intermittent, there is nothing to worry about, and long-term control is usually not needed.
If symptoms worsen, the person should talk to their doctor so they can rule out any other condition that may have developed.
Gilbert’s syndrome will not harm the liver. In addition to jaundice, there are no known complications.
Management of Gilbert’s syndrome
Gilbert’s syndrome can not be prevented since it is a hereditary disorder.
People with this condition should ensure their doctor knows they have it since extra Bilirubin can interfere with some medications.
The drugs that should be avoided, if possible, are:
- Atazanavir and indinavir are used to treat HIV infection.
- Gemfibrozil, to reduce cholesterol.
- Statins are also used to lower cholesterol when taken with gemfibrozil.
- Irinotecan is used to treat advanced bowel cancer.
- Nilotinib, for the treatment of some blood cancers.
Choosing a healthy lifestyle with healthy foods and plenty of exercise can be helpful.
Exercise can also help control stress, reducing the risk of an outbreak. Alcohol can make the condition worse.
Becoming healthier can significantly reduce bilirubin levels; the tips below can help you achieve it.
Phototherapy reduces high levels of Bilirubin in babies and helps stop jaundice. However, this therapy has side effects, and bilirubin levels can bounce back.
The anthocyanins (pigments) of the plants of Aronia melanocarpa can reduce the concentration of Bilirubin in the blood.
Zinc salts can bind to Bilirubin. In rats, the administration of zinc salt significantly reduces bilirubin levels in the blood. This is due to the inhibition of the enterohepatic circulation of Bilirubin.
- Taurocholic acid:
Taurocholic acid decreases intracellular bilirubin levels in mice.
- Fish oil:
In addition, triglyceride (cholesterol) levels can influence bilirubin levels. Fish oil can reduce cholesterol levels, which in turn lowers bilirubin levels.
Estrogen can reduce bilirubin levels in women. Oral contraceptives, which contain estrogen and progestin, and the use of postmenopausal estrogens lower bilirubin levels.
In rats, aspirin reduces bilirubin levels after surgery.
- El gen UGT1A1:
The UGT1A1 gene and its variants are associated with lower levels of Bilirubin.
Subjects who consumed diets containing vegetables or citrus fruits had significantly lower Bilirubin than subjects who did not eat any vegetables. In individuals with the UGT1A1 genotype, the consumption of vegetables and citrus fruits can reduce bilirubin levels.
- Stem cell therapy:
Human liver stem/progenitor cells derived from adults (ADHLSC) can also reduce bilirubin levels in rats with high levels of Bilirubin.
- Intestinal bacteria:
The microflora of the human intestine can degrade Bilirubin.
In cell cultures, Clostridium perfringens reduce bilirubin dilaurate levels.
Other species that can reduce Bilirubin include Clostridium difficile, Clostridium ramosum, and possibly Bacillus fragilis.
Causes of Gilbert’s syndrome
When the gene passes from parents or parents, a person is born with Gilbert’s syndrome. An individual is more likely to have it if both parents transmit the gene.
The gene causes hyperbilirubinemia or elevated levels of Bilirubin in the blood.
This happens because of the reduced activity of the enzyme glucuronyltransferase, which conjugates or converts Bilirubin into a water-soluble form after it is released from red blood cells at the end of its 120-day lifespan.
When Bilirubin becomes soluble in water, the body excretes it in the bile in the duodenum and finally exits the body in the stool.
A blood test can detect if bilirubin levels are higher than usual.
People with Gilbert syndrome are usually diagnosed in late adolescence or early twenties.
The diagnosis is based on slightly elevated conjugated bilirubin levels in the blood and the appropriate clinical situation.
Genetic tests are usually not necessary.
The diagnosis can be confirmed by administering phenobarbital, which reduces bilirubin levels, and nicotinic acid intravenously, which will increase bilirubin levels.
The elevated level of Bilirubin is usually seen in routine laboratory tests in patients who have no symptoms or when a liver profile is ordered because the patient has jaundice.
If the test results show that water-insoluble bilirubin levels are high, but other tests are standard, Gilbert’s syndrome is the most likely diagnosis.
A doctor may want to perform more tests to ensure the patient does not have another cause of elevated Bilirubin. Some of the other reasons are more serious than others.
Gilbert’s syndrome does not need treatment, but it is essential to make sure that the person does not have another more serious condition.
Other reasons why bilirubin levels may be high
Other causes of elevated Bilirubin include:
Acute inflammation of the liver: could be related to a viral infection, prescription drugs, alcohol, or fatty liver.
Inflammation or infection of the bile duct: This is known as cholangitis, and it can be serious
Obstruction of the bile duct: usually related to gallstones but may be related to the gallbladder or cancer of the bile ducts, or pancreatic cancer.
Hemolytic anemia: bilirubin levels increase when red blood cells are destroyed prematurely.
Cholestasis: bile flow from the liver is interrupted, and the liver’s Bilirubin remains. This can occur with acute or chronic liver inflammation and liver cancer.
Crigler-Najjar syndrome: this hereditary condition affects the specific enzyme responsible for the processing of Bilirubin, which produces an excess of Bilirubin.
Dubin-Johnson syndrome is a hereditary form of chronic jaundice that prevents conjugated Bilirubin from secreting out of the liver cells.
Pseudoarthritis: a harmless form of jaundice in which the yellowish color of the skin results from an excess of beta-carotene, not from a bunch of Bilirubin; Generally eating lots of carrots, squash, or melon.
Tests for these conditions may include:
- An ultrasound of the liver.
- Computed tomography of the abdomen.
- Nuclear medicine examination of the liver and gallbladder.
- Endoscopic examination of the duodenum.
- Magnetic resonance image of the core.
- Fast for 24 hours to see if bilirubin levels increase.
- Genetic test
Home remedies for Gilbert’s Syndrome
Lifestyle and home remedies for Gilbert’s syndrome include:
- Recognize the condition and make sure your doctor knows that you have it, as this can affect which medications are safe to use, including acetaminophen.
- Eat well and exercise regularly to help avoid stress.
- Learn other strategies to reduce stress, such as meditation, reading, or listening to music.
- Avoiding alcohol
Health benefits of the highest levels of Bilirubin
- Higher bilirubin levels are associated with a lower risk of heart disease:
Higher levels of Bilirubin in older people are associated with a lower risk of disabling diseases such as stroke and heart disease.
High bilirubin levels in the blood also reduce the risk of certain heart diseases.
Among individuals with high blood pressure, those with high bilirubin levels were less likely to die of heart disease.
High serum bilirubin can decrease the risk of high blood pressure by functioning as an antioxidant in blood vessels.
- Higher bilirubin levels are associated with a lower risk of type 2 diabetes:
Specific genetic mutations in the UGT1A1 gene, which encode a bilirubin-metabolizing enzyme, are associated with reduced risks of type 2 diabetes in people prone to diabetes on Norfolk Island.
In addition, the study found that the higher the Bilirubin among these people, the less likely they are to develop diabetes.
- Higher bilirubin levels are associated with decreased inflammation in Chronic Obstructive Pulmonary Disease and Migraine:
Chronic obstructive pulmonary disease is an inflammatory disorder associated with oxidative stress. Blood bilirubin has potent antioxidant actions, and higher concentrations can protect against oxidative stress.
In middle-aged smokers, Bilirubin reduces the severity of chronic obstructive pulmonary disease and helps stop its progression.
Patients with migraines with higher CRP, an inflammatory marker, have lower total Bilirubin.
Low serum bilirubin is associated with increased high sensitivity CRP (hs-CRP) in insulin-resistant and type 2 diabetics.
- Higher bilirubin levels reduce mortality rates:
People who had higher levels of Bilirubin had a lower risk of lung cancer and mortality. Low levels of Bilirubin in the blood correlate with an increased risk of lung cancer and death in male smokers.
In comparison with male smokers in the group with the highest bilirubin (> 1mg / dL), those in the group with the lowest Bilirubin (<0.75mg / dL) had an increase of 55% and 66% in the risk of incidence and lung cancer mortality, respectively.
Pathophysiology of Gilbert’s syndrome
Gilbert’s syndrome is a benign familial disorder inherited in an autosomal recessive pattern characterized by intermittent jaundice in the absence of hemolysis or underlying liver disease.
It is recognized that the condition arises from a mutation in the promoter region of the UGT1A1 gene, which results in reduced glucuronyltransferase (UGT) production.
Also called constitutional hepatic dysfunction or familial nonhemolytic jaundice, Gilbert’s syndrome is the mildest form of inherited unconjugated hemolytic hyperbilirubinemia.
The most common hereditary cause of unconjugated hyperbilirubinemia occurs in 3-7% of the world population. By definition, bilirubin levels in Gilbert’s syndrome are less than 6mg / dL, although most patients have levels below 3mg / dL.
Considerable seasonal and daily variations are observed, and in up to a third of patients, bilirubin levels can occasionally be normal.
Gilbert’s syndrome can be precipitated by dehydration, fasting, menstrual periods, or other stress causes, such as an intercurrent illness or vigorous exercise.
Patients may report vague abdominal discomfort and general fatigue without any cause. These episodes usually resolve spontaneously without curative treatment.
As a general rule, Gilbert’s syndrome can be diagnosed with a complete medical history and physical examination and can be confirmed with standard blood tests.
Repeated investigations and invasive procedures are generally not justified in establishing a diagnosis.
Once Gilbert’s syndrome is diagnosed, tranquility is the most critical aspect of the treatment.
In light of the benign and inconsequential nature of the syndrome, medications to treat patients with this condition are not justified in clinical practice.
The activity of glucuronyltransferase in hepatic Bilirubin is steadily reduced to approximately 30% of normal in individuals with Gilbert’s syndrome.
The decrease in bilirubin-UGT activity has been attributed to an expansion of thymine-adenine (TA) repeats in the promoter region of the UGT-1TA gene.
The racial variation in the number of thymine-adenine repeats and a correlation with the enzymatic activity suggest that these polymorphisms contribute to variations in the metabolism of Bilirubin.
A more significant proportion of the bilirubin monoconjugates in the bile reflects a reduced transferase activity.
Fasting, febrile illness, alcohol, or exercise may exacerbate jaundice in patients with Gilbert’s syndrome. Hemolysis and mild jaundice usually occur in stress, starvation, and infection.
Researchers have discovered that Gilbert’s syndrome can coexist with other liver diseases, such as nonalcoholic steatohepatitis.
Therefore, unconjugated hyperbilirubinemia in patients with these other conditions may be due to Gilbert’s syndrome and may not always be attributed to the underlying hepatic disorder.
Mutations of glucuronyltransferase (UGT) in Gilbert’s syndrome
Bilirubin-UGT, which is located mainly in the endoplasmic reticulum of hepatocytes, is responsible for the conjugation of Bilirubin in bilirubin monoglucuronides and diglucuronides.
It is one of several isoforms of glucuronyltransferase enzymes responsible for conjugating a wide range of substrates, including carcinogens, drugs, hormones, and neurotransmitters.
The knowledge of these enzymes has been dramatically improved by characterizing the locus of the UGT1 gene in humans. The gene that expresses bilirubin-UGT has a complex structure located on chromosome 2.
There are five exons, of which exons 2-5, at the 3 ‘end, are constant components of all isoforms of UGT, which encode the uridine diphosphate (UDP) -glucuronic acid binding site.
Exon 1 encodes a unique region within glucuronyltransferase and confers substrate specificity; exon 1a encodes the variable region for bilirubin UGT1A1. Defects in the UGT1A1 enzyme are responsible for Gilbert’s syndrome and Crigler-Najjar syndrome.
The expression of UGT1A1 depends on a promoter region at a 5 ‘position relative to each exon 1 containing a TATA box. Therefore, the altered glucuronidation of Bilirubin may result from mutations in exon 1a, its promoter, or the common exons.
An advance in understanding the genetic basis of Gilbert’s syndrome was achieved in 1995 when anomalies were identified in the promoter’s TATAA region.
The addition of 2 extra bases (TA) to the TATAA region interferes with the binding of the transcription factor IID and results in a reduced expression of bilirubin-UGT1 (30% of normal).
A decrease in bilirubin glucuronidation is observed in the homozygous state, with bile containing an excess of bilirubin monoglucuronide over diglucuronide.
The insertion of a homozygous TA dinucleotide in the TATA regulatory box in the promoter of the UGT 1A1 gene is the most common genetic defect in Gilbert’s syndrome.
In Gilbert’s syndrome, the UGT1A1 * 28 variant reduces the conjugation of Bilirubin by 70% and is associated with the side effects of the irinotecan inhibitor and the protease.
In vivo research on the genotype present in 76% of individuals with Gilbert’s syndrome suggests that the transcription and transcriptional activation of the glucuronidation genes responsible for conjugation and detoxification are directly affected, leading to a lower answer capacity.
Since then, additional mutations have been identified. For example, some healthy Asian patients with Gilbert’s syndrome do not have mutations at the promoter level but are heterozygous for nonsense mutations (Gly71Arg, Tyr486Asp, Pro364Leu) in the coding region.
These individuals also have significantly higher bilirubin levels than patients with the natural allele.
It is unknown whether the reduced activity of bilirubin-UGT results from a reduced number of enzymatic molecules or a qualitative enzyme defect.
To aggravate this uncertainty, other factors (for example, hidden hemolysis or liver transport abnormalities) may be involved in the clinical expression of Gilbert’s syndrome.
For example, many individuals who are homozygous for the TATAA defect do not show unconjugated hyperbilirubinemia, and many patients with reduced levels of bilirubin-UGT, as seen in some granulomatous liver diseases, do not develop hyperbilirubinemia.
Due to the high frequency of mutations in the Gilbert promoter, the heterozygous carriers of the Crigler-Najjar syndromes types 1 and 2 can also carry the long sequence of Gilbert’s TATAA in their normal allele.
These combined defects can lead to severe hyperbilirubinemia and help explain the finding of intermediate levels of hyperbilirubinemia in relatives of patients with Crigler-Najjar syndrome.
Gilbert syndrome can also frequently coexist with conditions associated with unconjugated hyperbilirubinemia, such as thalassemia and glucose-6-phosphate deficiency (G6PD).
Much of the unconjugated hyperbilirubinemia observed could be attributed to the variation in the 1A1 glucuronyltransferase locus.
Origa et al., in a study of 858 patients with transfusion-dependent thalassemia, found that in individuals with a combination of thalassemia and the genotype of Gilbert’s syndrome (TA) 7 / (TA) 7 UGT1A1, the latter affected the prevalence of cholelithiasis and it influenced the age at which the condition arose.
The authors suggested that a biliary ultrasound should be performed in patients with a combination of thalassemia and Gilbert’s syndrome, beginning in childhood.
A Greek study of 198 adult patients with cholelithiasis and 152 controls found evidence of an association between Gilbert’s syndrome and the development of cholelithiasis.
Gilbert’s syndrome’s prevalence varies worldwide, depending on which diagnostic criteria are used (e.g., number of bilirubin determinations, method of analysis, bilirubin levels used for diagnosis, if the patient was fasting).
In molecular genetic studies of polymorphisms in the TATAA promoter region, prevalence estimates can be further complicated, affecting up to 36% of Africans but only 3% of Asians.
Gilbert’s syndrome is diagnosed more commonly in children after puberty than in girls. The apparent sex difference is because the daily production of Bilirubin is lower in women than in men. The male-female ratio for Gilbert’s syndrome varies from 2: 1 to 7: 1.
In Gilbert’s syndrome, there are differences in the mutation of the UGT1A1 gene in certain ethnic groups; The TATAA element in the promoter region is the most common mutation site in the white population.
For example, a strong correlation has been found between the polymorphism UGT1A1 * 28 and hyperbilirubinemia in Romanian patients with Gilbert’s syndrome.
In a study of 292 Romanian patients with Gilbert’s syndrome and 605 healthy homologs, the researchers used amplification of the PCR gene.
They found that the highest frequency polymorphism was UGT1A1 * 28 (7TA), occurring in almost 62% of the entire study group, followed by nearly 37% with the allele UGT1A1 * 1 (6TA), and 0.61% and 0.72%, respectively, with the variants 5TA and 8TA.
Almost 58% of the study cohort had the heterozygous (TA) 6/7 genotype, followed by 32% with the homozygous genotype (TA) 7/7.
Gilbert’s syndrome is a common and benign condition. The bilirubin disposition can be considered within the range of normal biological variation. The syndrome has no harmful associations and an excellent prognosis, and affected people can lead a normal lifestyle.
As additional confirmation of its benign nature, studies have reported excellent results in patients undergoing liver transplantation from donors with Gilbert’s syndrome.
Epidemiological studies have reported an association between Gilbert’s syndrome, hyperbilirubinemia, and a reduced risk of cardiovascular disease.
The exact mechanism for this finding is unclear, but the antioxidant properties of Bilirubin may be contributory along with heme oxygenase.
In addition, the slightly elevated unconjugated Bilirubin seems to be associated with reduced thrombogenesis and inflammation related to platelet activation in patients with Gilbert’s syndrome, which may play a role in protecting these individuals against cardiovascular mortality.
Physicians should be aware that patients with Gilbert syndrome may be at increased risk of developing toxicity from certain medications (e.g., Irinotecan) and protease inhibitors (e.g., Atazanavir, indinavir) that may inhibit the metabolism of the drug. glucuronyltransferase.
A study by Lankisch et al. reported that the risk of severe hyperbilirubinemia with indinavir was associated with genetic variants of the UGT1A3 and UGT1A7 genes and Gilbert’s syndrome (UGT1A1 * 28).
Kweekel et al. reported that patients who were more likely to develop the side effects of irinotecan toxicity, such as neutropenia and life-threatening diarrhea, were more likely to have underlying liver disease and hepatic conjugation disorders or the UGT1A1 genotype * 28.