Rare liver diseases strain families’ finances, quality of life: Study
Diagnostic delays, lack of access challenge rural families, per study in China
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Rare genetic liver conditions like progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome pose a substantial financial and quality-of-life burden on families, a study in China found.
The burden is compounded by delayed diagnosis, elevated out-of-pocket expenses, and limited access to specialized care, particularly for families living in rural and underserved areas, and “underscore the need for improved diagnostic accuracy, early intervention, more coordinated rare disease care networks and enhanced psychosocial and financial support policies for this vulnerable population,” the researchers wrote.
The study, “The disease burden and health-related quality of life in Chinese children with genetic cholestatic liver diseases: a cross-sectional study of progressive familial intrahepatic cholestasis and Alagille syndrome,” was published in the Orphanet Journal of Rare Diseases.
Several liver diseases are marked by cholestasis, or slowed or stalled flow of bile from the liver to the intestines. When this occurs, bile accumulates to toxic levels in the liver and leaks into the bloodstream, leading to liver damage and symptoms such as jaundice (yellowing of the skin and the white part of the eyes), changes in stool color, and itching.
In children, cholestasis is often caused by genetic disorders. PFIC, caused by mutations that disrupt bile formation or transport within the liver, is estimated to occur in one in 50,000 to 100,000 live births. It accounts for 10% to 15% of pediatric cholestasis cases. Alagille syndrome, which affects an estimated one in 30,000 to 70,000 births, is caused by mutations affecting embryonic development and affects multiple organ systems. One of its hallmark features is a reduced number of bile-transporting tubes within the liver.
Survey reveals challenges families face
These cholestatic liver diseases typically begin in early infancy, and without appropriate treatment can progress to liver failure and the need for liver transplant.
Beyond their clinical impact, these diseases place a heavy burden on families due to challenges in diagnosis, ongoing treatment, and frequent hospital visits. Yet “comprehensive data on their economic and humanistic burden in China are scarce,” the researchers wrote.
To address this gap, the researchers surveyed caregivers of 70 children with PFIC and 100 children with Alagille who attended outpatient clinics at a major specialized referral center in China from January to December 2024.
Using an online questionnaire, they assessed diagnostic and treatment history, financial burden, and impact on health-related quality of life of both children and their caregivers.
The children had a median age of 3.88, 57.65% were boys, and 51.76% lived in rural areas. Nearly all families (94.71%) were covered by basic medical insurance, but access to additional financial support was limited. Most households (78.82%) reported annual incomes below 100,000 Chinese yuan (about $14,700).
The survey results revealed major challenges in disease diagnosis and management. Although symptoms appeared at a median age of 3.9 months — the most common were jaundice (91.76%), abnormal stool color (88.24%), and itching (87.06%) — diagnosis was delayed by a median of 7.3 months, to as long as 5.5 years.
In 62.35% of cases, the disease was initially misdiagnosed. Caregivers reported that patients visited a mean of nearly three healthcare institutions and underwent about five clinical visits before receiving a correct diagnosis.
Treatment, started at a median age of 11.2 months, relied largely on standard medications, most commonly ursodeoxycholic acid (sold in the U.S. as Urso and Actigall, with generics available). Access to newer therapies such as Livmarli (maralixibat) and Bylvay (odevixibat) was limited.
Most families (87.06%) reported traveling across regions to access specialized care. These travel demands were identified as a barrier to continuity of care for 39.39% of children, while 27.27% of families cited financial burden as a key obstacle to consistent follow-up.
The financial burden on families was substantial, with average annual costs of 244,700 Chinese yuan (around $36,000) per child. Direct medical expenses accounted for 60.6% of the total, with outpatient care driving the majority of costs.
The remaining costs included additional expenses, such as transportation and accommodation, along with indirect costs related to productivity loss due to caregiving responsibilities and work absenteeism.
As a result, 86.47% of families experienced catastrophic health expenditure, meaning their out-of-pocket medical costs exceeded the 40% of household income. To cope, 38.24% of families took on debt, while some relied on charitable support or crowdfunding.
Children showed moderate impairment in quality of life, and caregivers reported moderate levels of anxiety, fatigue, and depression. Children with PFIC had worse quality-of-life outcomes than those with Alagille.
Further statistical analyses showed that older age and higher family income were significantly associated with better quality of life, while greater disease severity, complications, and more frequent follow-up visits (indicating more severe disease) were linked to poorer quality of life.
“These findings establish a benchmark for families accessing specialized care, while suggesting even more severe hardships for underserved populations in remote areas who are unable to reach high-tier centers,” the researchers wrote.
Improving resource allocation and strengthening support systems could reduce family burden and improve long-term outcomes in children with rare genetic cholestatic conditions, the scientists said.
