Hereditary Angioedema Patients Have High Incidence of Fatty Liver Disease, Study Suggests

People with hereditary angioedema appear to have a higher risk of developing non-alcoholic fatty liver disease, even before receiving angioedema medicines that affect liver function, a new study suggests.

Researchers recommend that these patients undergo continuous monitoring to detect and manage fatty liver disease in its early stages.

The study, “Hereditary angioedema may be associated with the development of fatty liver,” was published in The Journal of Allergy and Clinical Immunology: In Practice.

Hereditary angioedema is a rare genetic condition caused by mutations in the genes that hold the instructions to produce one of two proteins, C1 inhibitor protein or coagulation factor XII.

Most treatments for this disease focus on increasing the levels of the missing protein. For example, Danocrine (danazol) is a synthetic steroid that helps raise the amount of C1 inhibitor protein by an unknown mechanism.

However, long-term use of Danocrine is associated with side effects to the liver, so hereditary angioedema patients require tests that assess their liver condition before starting treatment.

These tests, however, have suggested that people with hereditary angioedema have a remarkably higher frequency of non-alcoholic fatty liver disease. This is a condition seen more commonly in overweight or obese people where too much fat builds up in the liver. In extreme cases, it can lead to cirrhosis and liver failure.

A team of researchers in Saudi Arabia evaluated the prevalence of fatty liver in 40 hereditary angioedema patients who had not received Danocrine.

Participants had a median age of 31 years, a median body mass index (BMI) of 25.7, and 60% were women. All patients had a defective C1 inhibitor protein.

The study found that 47.5% of patients had non-alcoholic fatty liver disease, with most cases occurring in patients under 18 or ages 35–44 (26.3% each).

“There is an extremely high prevalence of [non-alcoholic fatty liver disease] in our patients with [hereditary angioedema] compared to about 16.6% in a recent study of the Saudi population,” the researchers stated.

The investigators also noted that the group with hereditary angioedema was overall younger and had a lower BMI than the group in the study of the general population; therefore, it was expected to have an even lower incidence of fatty liver disease.

Other common conditions present in hereditary angioedema patients with fatty liver were dyslipidemia — abnormal amounts of lipids in the blood — and diabetes. These conditions occurred in 26% and 5% of the patients, respectively.

Changes in lifestyle, such as diet and exercise, could help reduce the incidence of fatty liver disease and allow treatment with Danocrine, researchers said. They also recommend that physicians be “cautious in starting medicines like tetracycline or amiodarone in [hereditary angioedema] patients, as it might make their [non-alcoholic fatty liver disease] worse.”

Tests assessing the levels of liver enzymes and a liver ultrasound should be performed in hereditary angioedema patients before starting treatment with Danocrine, and regular screening should be done during the treatment.

“Patients should also be screened for other conditions like obesity, hyperlipidemia, diabetes, metabolic syndrome, and malnutrition,” all risk factors for fatty liver disease, the study stated.