Research highlights the disease burden of Alagille syndrome in adults

Morgan Faist (Children’s Hospital of Philadelphia, Pennsylvania, USA) explained at AASLD The Liver Meeting in Denver, Colorado, USA, that “long-term outcomes in adults with [Alagille syndrome] remain poorly understood.”

She explained to medwireNews: “Alagille syndrome has historically been regarded as a disease of childhood, [but] now in the age of IBAT [ileal bile acid transporter] inhibitors, we see this population as living much longer, so there is a knowledge gap about what the burden of disease is like for adults with Alagille syndrome.”

To investigate, the researchers, in collaboration with the Alagille Syndrome Alliance, conducted an online cross-sectional survey of adults aged 18 years or older with Alagille syndrome that included disease-specific questions and the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 profile v2.1.

In all, 95 individuals (76.6% women) responded to the survey, 43.4% of whom were 25 years or older and had a bachelor’s degree or higher. The majority (75.6%) were born in North America.

Faist said that most of the survey respondents were students and/or employed (69.1%). She noted that 69.6% required no assistance with their own care, and 26.6% were actively providing care to others.

Among the study participants with the available data, just under a quarter (24.5%) had received a liver transplant, at a median age of 13 years, and 9.8% of patients had received a kidney transplant. Faist pointed out that patients who had received a liver transplant were more likely to also need kidney transplantation than individuals with native livers (26.1 vs 4.3%), which occurred at a median of 22 years after liver transplantation.

Reproductive health was a focus of the survey, and just over half of the women reported pregnancies, at a total of 109. Nearly one third (32.1%) of these ended in miscarriage, which Faist pointed out is “double the rate in the general population,” of 15%. At least one miscarriage was reported by 37.8% of 37 participants, with some patients having “up to four in their lifetime,” she added.

The results also showed that adults with Alagille syndrome scored worse than the general population on seven of eight PROMIS-29 domains, namely physical function, cognitive function, anxiety, depression, fatigue, sleep disturbance, and pain interference. The only exception was the ability to participate in social roles and activities, in which they performed better, Faist said.

She pointed out that a small set of patients with native livers had much higher scores for anxiety and fatigue than those who underwent a liver transplant, which “highlights an area that needs to be researched further.”

Faist concluded that the findings “provide a greater understanding for these patients,” and “bring awareness” to clinicians of the burden of adult Alagille syndrome, which is “not a pediatric disease.” She stressed: “We have adults living with Alagille syndrome, and their manifestations can be different to those children are experiencing, and it is important to appreciate those differences.”