UGT1A1: Gilbert syndrome and the cancer medicine irinotecan

Bilirubin is a yellow by-product of old red blood cells. The liver has to make it water-soluble before it can leave the body in bile, and the UGT1A1 enzyme does that by a process called glucuronidation. MedlinePlus Genetics describes the enzyme as converting toxic unconjugated bilirubin into a non-toxic form.

Because the same enzyme also processes certain medicines, its activity affects both bilirubin levels and drug handling. The two are connected only through the shared enzyme; having a slightly raised bilirubin does not mean you have a medicine problem, and having no jaundice does not exclude one.

The NHS says Gilbert syndrome is common and may cause mild jaundice that comes and goes. It results from an inherited alteration affecting the liver's handling of bilirubin. The NHS lists triggers for an episode as over-exercising, lack of sleep, alcohol and dehydration, and says the condition does not cause liver damage, does not usually cause serious health problems and does not shorten life. There is a slightly increased chance of gallstones.

Diagnosis is usually made from blood tests including liver function tests, and a genetic test can confirm it. MedlinePlus Genetics names the common UGT1A1*28 variant, a two-letter insertion in the promoter region that lowers production, and the G71R change that is common in people of Asian ancestry.

Irinotecan is a chemotherapy medicine used in several cancers including bowel cancer. Cancer Research UK lists its common effects: infection risk through a fall in white cells, anaemia, loss of appetite, nausea, hair loss, mouth sores, fatigue and diarrhoea. Its active breakdown product is cleared via UGT1A1, so when enzyme activity is low the active product can persist longer.

The FDA table of pharmacogenetic associations lists UGT1A1 under irinotecan and indicates that dose adjustment or other changes may be considered in certain metaboliser types. The Cancer Research UK page retrieved for this guide does not mention Gilbert syndrome or UGT1A1, so it is reasonable to ask the oncology team directly whether the information applies to you.

• Tell your oncology team if you have been diagnosed with Gilbert syndrome or have had unexplained raised bilirubin.

• Ask whether UGT1A1 testing is part of your service's pathway and how a result would change the plan.

• Ask for the advice-line number and the diarrhoea plan before the first cycle.

Cancer Research UK says diarrhoea during irinotecan can be life-threatening and that people should contact the treatment centre at the first signs. Some teams provide anti-diarrhoea medicine to take home with instructions. The page also describes an acute cholinergic syndrome, with diarrhoea, sweating, stomach cramps, extra saliva and watery eyes.

Contact the advice line straight away for a temperature of 37.5 degrees Celsius or above, or below 36 degrees, since a fall in white cells can make infection dangerous. If you cannot reach anyone and feel seriously unwell, NHS 111 or 999 are the urgent routes.

The NHS advises people with Gilbert syndrome to check with a healthcare professional when starting new medicines, and gives statins as an example where closer monitoring may be sensible. Most medicines are used normally, and a pharmacist can usually advise quickly.

The practical self-care points are to stay hydrated, keep regular sleep, moderate alcohol, avoid crash dieting and long fasts, and mention the diagnosis when attending clinics or having surgery. A new, deeper jaundice, dark urine with pale stools or abdominal pain is not typical Gilbert syndrome and needs medical assessment.

Crigler-Najjar syndrome arises when both gene copies are altered. In type 1 the enzyme is absent, and in type 2 it retains less than 20 per cent of normal function, according to MedlinePlus Genetics. Both can lead to severe unconjugated hyperbilirubinaemia, jaundice and, in the worst cases, brain damage from bilirubin build-up called kernicterus. These are specialist conditions identified in infancy or childhood and are not the same as Gilbert syndrome.