A new practice guideline recommends earlier referral of children with advanced liver disease for liver transplant evaluation, calls for a standardized multidisciplinary assessment and places greater emphasis on psychosocial, developmental and health equity issues throughout the transplant process. It also updates recommendations for children with acute liver failure, liver tumors, inherited metabolic disorders and other conditions that may require liver transplantation.
The guideline, published in Hepatology, was developed by the American Association for the Study of Liver Diseases in collaboration with the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the American Society of Transplantation. It updates the societies’ 2014 recommendations and includes 90 evidence-based recommendations covering the pediatric liver transplant evaluation process, from referral through waitlisting and organ allocation.
“Advances in immunosuppression, medical care, surgical techniques, living donation and outcomes have expanded both who can benefit from transplantation and how we think about the timing of referral and evaluation,” corresponding author Vicky Lee Ng, MD, FRCPC, medical director of the Pediatric Liver Transplantation, Transplant and Regenerative Medicine Center at the Hospital for Sick Children, Toronto, Ontario, Canada, told GI & Hepatology News. “Yet despite these advances, there has been considerable variation across centers in how children are evaluated for transplantation. This guideline seeks to provide an evidence-informed framework that promotes consistency while recognizing that every child and every family is unique.”
The guideline recommends a standardized transplant evaluation led by a multidisciplinary team that includes pediatric hepatologists, transplant surgeons, infectious disease specialists, anesthesiologists, intensivists, psychologists, social workers, dietitians, pharmacists, rehabilitation specialists, child life experts and transplant coordinators. In addition to determining whether a child is medically and surgically eligible for transplantation, the team should assess family readiness, developmental needs, psychosocial well-being and barriers that could affect transplant success.
“Transplant evaluation is far more than deciding whether a child is a candidate,” Dr. Ng said. “It is a process of identifying what is needed to help every child achieve the best possible outcome.” She added that working to develop this guideline “reinforced for me that transplant evaluation is best viewed as a longitudinal process rather than a single consultation. It has also changed how I frame those early conversations with families. Rather than asking, ‘Is this child ready for transplantation?’ I find myself asking, ‘What does this child need to achieve the best possible outcome?’ That shift naturally leads to earlier discussions, proactive planning, optimization of nutrition and medical care and stronger partnerships with families.”
The authors recommend comprehensive laboratory testing to determine liver disease severity, nutritional status, renal function, blood type and infectious disease risk. For kidney assessment, they recommend estimating glomerular filtration rate using the Chronic Kidney Disease in Children Under 25 equation because serum creatinine alone may underestimate renal dysfunction in children with advanced liver disease.
Abdominal ultrasound with Doppler is recommended as the first-line imaging test, with computed tomography or magnetic resonance imaging reserved mainly for surgical planning. Every child being evaluated should receive cardiopulmonary screening, including electrocardiography and echocardiography. Those with suspected pulmonary hypertension should have right-heart catheterization, and all transplant candidates should be screened for hepatopulmonary syndrome using pulse oximetry.
The recommendations emphasize that children being evaluated for liver transplantation should receive all age-appropriate vaccines before transplant whenever possible, using accelerated schedules when needed. Household members also should be fully vaccinated to help protect immunocompromised children from vaccine-preventable infections.
The updated recommendations also broaden the focus on psychosocial evaluation. In addition to assessing medical eligibility, transplant teams should evaluate caregiver understanding, medication adherence, social support, developmental and neurocognitive status and barriers such as transportation, housing instability and financial hardship. They also should monitor for disparities in transplant access and promote living donor transplantation.
An important message for clinicians is to refer children for transplant evaluation earlier rather than later. Referral is recommended once complications such as growth failure, recurrent cholangitis, severe pruritus, portal hypertension, hepatic encephalopathy, or uncorrectable coagulopathy develop. The authors note that early evaluation gives transplant teams time to optimize nutrition, coordinate care and complete the assessment before irreversible disease progression occurs.
The guidance also emphasizes rapid evaluation of children with acute liver failure. Every child should be referred immediately to a pediatric liver transplant center, with transplant programs prepared to accept urgent transfers. Early genome or exome sequencing is also recommended for unexplained cases because it identifies an underlying diagnosis in about 37% to 50% of patients and can help inform transplant decisions.
The guidance also expands disease-specific recommendations for pediatric liver transplantation. Among the updates are earlier transplantation for selected inherited metabolic disorders, earlier evaluation of unresectable hepatoblastoma and transplantation for autoimmune hepatitis or primary sclerosing cholangitis when complications persist despite treatment. Additional recommendations address cholestatic disorders, Wilson disease, intestinal failure-associated liver disease, metabolic dysfunction-associated steatotic liver disease, Budd-Chiari syndrome and liver retransplantation.
The guidance also includes several recommendations aimed at improving fairness in organ allocation. It recommends using updated Pediatric End-Stage Liver Disease-Creatinine and Model for End-Stage Liver Disease 3.0 scores for initial prioritization while preserving exception pathways for children whose clinical condition is more severe than their scores indicate. It also encourages wider use of living donor, split-liver and reduced-size grafts and supports future allocation policies that prioritize children for donor livers suitable for splitting.
According to Dr. Ng, one of the greatest challenges in developing the guideline was balancing the available evidence with the realities of clinical practice. “Many of the most important decisions in pediatric transplantation involve complex, individualized situations where high-quality pediatric data remain limited,” she said.
She and her coauthors based the guideline on a systematic review of the literature published between 2016 and early 2025. The investigators screened 881 studies, reviewed 422 full-text articles, extracted data from 298 studies and ultimately based the recommendations on evidence from 178 studies.
“If there is one message I hope readers take away, it is that transplant evaluation is not simply about determining eligibility for transplantation,” Dr. Ng said. “It is about understanding each child’s unique needs and bringing together the expertise, resources and partnership required to help every child achieve the best surgical, medical and psychosocial outcomes, whether that ultimately involves transplantation or not.”
The guideline was funded by the American Association for the Study of Liver Diseases. Several of Dr. Ng's coauthors reported research funding, consulting, advisory board participation, or honoraria from Mirum, Albireo, Gilead, Ipsen, Takeda, Merck, Viracor-Eurofins, Bridge to Life and other companies.