Pediatric liver transplants have an extremely high success rate. However, with this brass ring in mind, the period between diagnosis and transplant can be a missed opportunity to optimize recovery and a build a better quality of life for the child.
A group of pediatric gastroenterologists within the North American Society for Pediatric Gastroenterology Hepatology & Nutrition (NASPGHAN) joined forces to recommend ways to maximize patients’ health during this critical interim
“Children with end-stage liver disease who require liver transplantation are a group with diverse needs,” said coauthor Saeed Mohammad, M.D., M.S., a liver transplant specialist at Monroe Carell Jr. Children’s Hospital at Vanderbilt.
“After transplantation, we have set protocols. However, between diagnosis and transplantation — which could be months or years — what can we do to improve their care and quality of life?
“Liver conditions are complicated by lots of nuances, so we thought it was important to share what we know about impactful treatment in nutrition, medical management and surgical management.”
With this goal in mind, the team focused on children whose liver disease began in infancy. Then they reviewed the available treatments and identified areas of unmet need.
Personalized Evaluation and Management
Most children facing transplant have congenital biliary atresia. The resulting condition, cholestasis, causes the impaired flow of bile from the liver to the small intestine and may result in multiple organ dysfunction and end-stage liver disease .
“These are chronic conditions, so we need to optimize medical management to improve the patient’s quality of life, provide nutritional support, and reduce bile-acid toxicity to potentially slow disease progression and avoid or manage infectious complications,” Mohammad said.
The condition’s heterogeneous etiologies and disease pathways can make medical management a challenge. Children with liver disease may need unique therapies based on the severity of liver injury, the underlying etiology, timing of diagnosis, and genetic variability.
“Disease severity can vary within the same disease, based on the timing of diagnosis and treatment,” Mohammad said.
Supporting Growth
Malabsorption of nutrients is a top concern with these patients, with inherent barriers to nutrient absorption, higher energy demands, and energy dysregulation.
“Large studies show that patients who are malnourished have worse transplantation outcomes, even at one-year post-transplant,” Mohammad said. “They are in the ICU longer and tend to have infections and other complications.”
“Large studies show that patients who are malnourished have worse transplantation outcomes.”
He says physical growth interrupted by the transplant may resume, but typically lags behind normal levels. The effort to optimize nutrients, calories and absorption can be a monumental task.
Patients face nausea and vomiting triggered by chronic inflammation, along with early satiety, poor lymphatic drainage, and accumulation of fluid in the abdominal cavity known as ascites. And these are just some of the impediments to reaching nutritional goals.
“We make recommendations for how many calories they should get, the best way to give those calories, and the easiest way that they can absorb the nutrients,” Mohammad said.
He suggests that monitoring improvement can be confounded by ascites and enlargement of organs that skew body mass estimates to underestimate the degree of malnutrition present.
“We recommend the mid-upper-arm circumference measurement and triceps skin fold thickness as more reliable ways of determining growth,” he said.
The article also includes granular recommendations for determining muscle mass loss and guidance on lipids and other screenings.
Medical Management
Pruritus (itching) is one of the side effects of cholestasis that can tremendously affect patients’ quality of life.
“It can be hard to tell when a baby is itchy, so when you suspect pruritus, you need to ask the family questions about whether the baby is inconsolable a lot of the time or restless at night,” Mohammad said. “This may be the first symptom of liver disease, and awareness and early referral matter a great deal.”
The newest drug class on the market to target pruritus is the ileal bile acid transporter (IBAT) inhibitors, which have demonstrated a solid profile in safely reducing both pruritus and serum bile acids in many children with the most common forms of liver disease. The hope is that new drugs targeting bile acid receptors, now under development, will fill an unmet need for second-line therapies.
The team also reviewed encouraging results from prospective trials on medical therapies to slow disease progression.
Surgical Management
The Kasai procedure continues to be the gold standard for biliary atresia to reduce toxic bile build-up and pruritus.
However, the team discussed other surgical strategies that can improve pruritus and sometimes defer or avoid the need for transplant, including partial external biliary diversion.
“Improvement in pruritus after partial external biliary diversion can occur in between 76 and 81 percent of patients with progressive familial intrahepatic cholestasis,” he said. “However, we hope that the newer medical therapies will diminish the need for any surgical procedure.”
Comfort and Readiness
Mohammad is active efforts to raise rates of living-donor liver transplantation but also makes the goal of improving early detection and raising quality of life a major focus of his work.
“What we want to avoid is health care providers thinking: ‘You’re eventually going to need a transplant, so we’re going to just monitor you until then,’” he said.
“We hope this will provide pediatricians and gastroenterologists with some condensed and updated information they can use to actively help their patients thrive.”
“We hope this will provide pediatricians and gastroenterologists with some condensed and updated information they can use to actively help their patients thrive.”
