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Pediatric cholestatic liver disease: Successful transition of care

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Release date: July 1, 2019
Expiration date: June 30, 2020
Estimated time of completion: 1 hour

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ABSTRACT

With recent medical advances, more patients with childhood-onset liver disease and more pediatric liver transplant recipients are surviving into adulthood, generating distinctive challenges to adult primary care providers. Young adults with pediatric liver disease are a unique cohort of patients with different evaluation and monitoring strategies, treatment, complications, and comorbidities. This creates a critical need for successful transition of these patients into adult care, with incorporation of a formal transitional model and multidisciplinary team.

KEY POINTS

  • The causes of cholestasis in children are different from those in adults, with genetic inherited causes more common in childhood.
  • Cholestasis in children can be caused by biliary tract obstruction such as in biliary atresia or defects in forming and excreting bile acids and other components of bile.
  • With the growing number of people with childhood-onset liver disease surviving into adulthood, it is important for internists to be aware of unique problems and challenges in continuing management of this population.
  • In addition to medical comorbidities, these patients may also have impaired psychosocial functioning and quality of life.


 

References

Thanks to advances in medical science and our understanding of inherited and acquired liver disease, many more children with acquired or congenital liver disease survive into adulthood than they did 2 decades ago. Improvements in immunosuppression and surgery have increased the chances of pediatric liver transplant recipients reaching adulthood, with a survival rate of 75% at 15 to 20 years.1

Cholestasis in children can be caused by biliary tract obstruction.

Figure 1. Cholestasis in children can be caused by biliary tract obstruction such as in biliary atresia (top) or defects in forming and excreting bile acids and other components of bile (bottom).

The causes of cholestasis in children are different from those in adults (Figure 1). Pediatric cholestasis is caused either by genetic defects that affect the process of synthesis, processing, or secreting bile, or by mechanical obstruction of the biliary tract, the classic example being biliary atresia.

With the growing number of adult patients with pediatric-onset liver disease, internists and adult hepatologists need to be aware of these liver diseases and develop expertise to manage this challenging group of patients. Moreover, young adults with pediatric-onset chronic liver disease pose distinct challenges such as pregnancy, adherence to medical regimens, and psychosocial changes in life.

These patients need a “transition of care” rather than a “transfer of care.” Transition of care is a multifaceted process that takes the medical, educational, and psychosocial needs of the patient into consideration before switching their care to adult care physicians, whereas transfer of care is simply an administrative process of change to adult care without previous knowledge of the patients.2

Implications of some childhood-onset liver diseases in adulthood
In this article, we discuss relatively common types of inherited childhood-onset cholestatic disease and their implications and management in adulthood (Table 1). Other acquired or rare cholestatic diseases are beyond the scope of this article.

BILIARY ATRESIA

Biliary atresia is a progressive inflammatory fibrosclerosing cholangiopathy of unknown cause. Its prevalence varies with geographic location, ranging from 1 in 6,000 to 1 in 19,000, with the highest prevalence in Taiwan.3

Biliary atresia usually presents within the first few weeks of life, with progressive cholestasis leading to failure to thrive and to fat-soluble vitamin deficiency. Approximately 20% of patients have congenital splenic, gastrointestinal, genitourinary, cardiac, and venous malformations.4,5 Untreated, biliary atresia progresses to end-stage liver disease and death within 2 years.

The first-line treatment for biliary atresia is to establish biliary outflow with the Kasai procedure (hepatic portoenterostomy), in which a jejunal limb is anastomosed in a Roux-en-Y with the liver. The outcomes of the Kasai procedure depend on the timing of surgery, so timely diagnosis of biliary atresia is crucial. When the Kasai procedure is performed within 60 days of birth, biliary flow is achieved in up to 70% of patients; but if performed after 90 days, biliary flow is achieved in fewer than 25%.6

Long-term outcomes of biliary atresia in patients with their native liver have been reported in a few studies.

In a French study,7 743 patients with biliary atresia underwent the Kasai procedure at a median age of 60 days. Survival rates were 57.1% at 2 years, 37.9% at 5 years, 32.4% at 10 years, and 28.5% at 15 years. In other studies,4–9 the 20-year transplant-free survival rate ranged from 23% to 46%. Therefore, at least one-third of children with biliary atresia survive to adulthood with their native liver.

Implications of biliary atresia in adulthood

Although the Kasai procedure improves biliary outflow, up to 70% of patients develop complications of biliary atresia such as progressive fibrosis, cirrhosis, portal hypertension, cholangitis, and hepatocellular carcinoma, even after a successful Kasai procedure.10

Portal hypertension with evidence of splenomegaly, thrombocytopenia, or ascites is found in two-thirds of long-term survivors of biliary atresia with a native liver, with variceal hemorrhage occurring in 30%.11 Therefore, patients with biliary atresia who have evidence of portal hypertension should be screened for varices with upper endoscopy on an annual basis. Management of variceal hemorrhage in these patients includes the use of octreotide, antibiotics, variceal ligation, and sclerotherapy; primary prophylaxis can be achieved with beta-blockers and endoscopic variceal ligation.12

Cholangitis is frequent, occurring in 40% to 60% of biliary atresia patients after the Kasai procedure, and about one-fourth of these patients have multiple episodes.13 The number of episodes of cholangitis negatively affects transplant-free survival.14 Patients with cholangitis should be adequately treated with oral or intravenous antibiotics depending on the severity of presentation. The role of prophylaxis with antibiotics remains unclear.15

Pulmonary complications such as hepato­pulmonary syndrome and portopulmonary hypertension can also occur in biliary atresia patients with a native liver. It is important for physicians to be aware of these complications and to screen for them, for example, with agitated saline echocardiography for hepatopulmonary syndrome and with echocardiography for portopulmonary hypertension. Timely screening is crucial, as the outcome of liver transplant depends on the severity at the time of transplant in these conditions, especially portopulmonary hypertension.

Hepatocellular carcinoma has been rarely reported in children with biliary atresia,16 so well-defined guidelines for screening in young adults with biliary atresia are lacking. Most centers recommend screening with ultrasonography of the abdomen and alpha-fetoprotein measurement every 6 months or annually starting soon after the Kasai procedure, since hepatocellular carcinoma has been reported in children as young as age 2.16

Transplant. Adult hepatologists are faced with the challenging task of deciding when it is time for transplant, balancing the long-term complications of biliary atresia with the risk of long-term immunosuppression after transplant. In addition, young adults with these complications may have preserved synthetic function, resulting in low Model for End-Stage Liver Disease (MELD) scores, which may complicate the process of listing for transplant.

Neurocognitive deficits are reported in children with biliary atresia,17 but young adults with biliary atresia generally have reasonable cognitive function and prospects for education and employment.

Pregnancy with successful outcomes has been reported.8

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