Rare Liver Disease Drug Gives Five-Year-Old Relief From Agonizing Itch

"Since the symptoms appeared, not a single day passed without my child crying herself to sleep. She scratched her whole body, so her face and ears were always covered with scabs. She couldn't sleep properly and was always exhausted. I never knew she could laugh so much and be so playful."

The mother of Yeon-ji (5, pseudonym), speaking at Seoul Asan Medical Center's Children's Hospital outpatient clinic on the 13th, wiped away tears as she said, "A miraculous drug has completely transformed our family's life."

Yeon-ji was born with complex cardiac malformations, including a narrowed section of the aorta, requiring extensive hospitalization. Just as her family breathed a sigh of relief after successful heart surgery, warning signs emerged in her liver and biliary system. Jaundice persisting beyond two weeks prompted blood tests revealing direct bilirubin levels and bile acid concentrations dozens of times above normal ranges.

Only after consulting with Dr. Oh Seok-hee, a professor of pediatrics at Seoul Asan Medical Center, did the family learn the precise diagnosis: Alagille Syndrome, a rare genetic disorder that significantly reduces the number of bile ducts in the liver. As of 2021, only 136 patients had been diagnosed with the condition in South Korea.

The disease was previously estimated to occur in one in 70,000 newborns, but advances in genetic diagnostics have increased the identified prevalence to approximately one in 30,000. Most Alagille Syndrome patients develop symptoms within three months of birth, presenting as jaundice, cholestasis, severe itching, and progressive liver failure.

"It's like having harsh detergent chronically accumulating inside the liver," Dr. Oh explained. "Patients experience pain as if thousands of ants were crawling over their bodies, biting and stinging them."

The condition stimulates itch-receptor sensory nerve fibers in the peripheral nervous system, causing itching and pain so severe that most patients experience sleep deprivation. Prolonged suffering impairs children's physical and emotional development, while parents caring for restless children through sleepless nights also develop sleep disorders.

Approximately 95% of patients have cardiac abnormalities in addition to liver problems, with lower frequencies of skeletal, ocular, and facial complications.

Until recently, liver transplantation remained the only definitive treatment. Choleretic agents, liver enzyme inducers, and bile acid sequestrants showed minimal clinical effectiveness.

"When parents endure the hellish routine of watching their child scratch and cry through the night, they eventually break down physically and emotionally, pleading for a liver transplant," Dr. Oh said. "When symptoms became severe, we had no choice but to hospitalize children and sedate them with narcotic sleeping pills. As physicians, we felt utterly helpless."

Only about 40% of pediatric Alagille Syndrome patients retain their native liver into adulthood. Yeon-ji's symptoms had deteriorated beyond the effectiveness of narcotic sedatives, placing her on the deceased-donor liver transplant waiting list since 2023.

The family's desperate situation changed dramatically in September 2024 when Yeon-ji was prescribed Livmarli (maralixibat), an ileal bile acid transporter (IBAT) inhibitor approved for cholestatic pruritus in Alagille Syndrome patients aged three months and older. Taken orally each morning 30 minutes before eating, the liquid formulation blocks bile acid reabsorption from the small intestine to the liver, increasing excretion through feces.

Clinical research published in The Lancet showed that more than 80% of patients experienced significant improvements in bile acid levels and itching after 18 weeks of Livmarli treatment. Long-term follow-up over six years demonstrated that Livmarli reduced the risk of hepatic decompensation, liver transplantation, and death by nearly 70%.

However, the drug's cost presented a significant barrier. Internationally, Livmarli costs approximately 30 million won ($21,000) per bottle, with annual expenses reaching 100 million to 200 million won depending on patient weight. Most parents investigating direct importation through the Korea Orphan Drug Center abandoned the effort upon learning the astronomical price.

Yeon-ji was selected for the pharmaceutical company's compassionate use program, enabling early treatment. Her bile acid concentration, which had risen to nearly 40 times normal levels, approached normal within six months. Her itching improved, ending her sleep deprivation, and liver transplantation became unnecessary.

More encouraging still, Livmarli became covered by national health insurance in January 2025, substantially reducing patient costs. While the domestic price remains approximately 29 million won per bottle, eligible patients pay only 10% through the special calculation system. Additional support based on income level is available through the rare disease medical expense assistance program.

"A game-changer has emerged that completely transforms the treatment paradigm for Alagille Syndrome, where transplantation was once the only answer," Dr. Oh emphasized. "The earlier we control bile acid levels, the better the chances of minimizing liver damage and avoiding transplantation, so we must work to identify suspected patients early."

He added: "A simple blood test checking direct bilirubin levels can help prevent the need for liver transplantation. If a child's eyes or skin show jaundice symptoms persisting beyond two weeks, parents must consult a pediatric specialist."