Pediatric cholestatic liver disease: Successful transition of care
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.
PEDIATRIC LIVER TRANSPLANT RECIPIENTS WHO SURVIVE INTO ADULTHOOD
Adolescent rebellion poses risks
Outcomes of liver transplant in children and adolescents have improved tremendously in the past 2 decades with advances in surgical techniques, pre- and postoperative management, organ preservation, and immunosuppression. Now, most pediatric liver transplant recipients survive into adulthood, creating a unique challenge for internists and adult care hepatologists.41
In rebellious adolescents and young adults, risk-taking behavior, nonadherence to immunosuppressive medications, alcohol intake, and substance abuse increase the risk of graft rejection and loss. Current immunosuppressive drugs such as calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil, sirolimus, and corticosteroids have drastically decreased rejection rates in compliant patients.41 Educating patients on the importance of taking their medications and avoiding alcohol and drug abuse is especially important for adolescents and young adults, as rates of nonadherence are high in these age groups.
Although pregnancy is usually successful after liver transplant, it should be considered high-risk due to reported complications such as graft rejection, diabetes, preeclampsia, sepsis, prematurity, and low birth weight. Conception should be avoided for at least 1 year after transplant.42 Appropriate counseling with regard to pregnancy and contraception is important.
There is no consensus on breastfeeding, but it is considered safe in women on low-dose calcineurin inhibitors.43
Life is better with a new liver, but patients have special needs
Liver transplant is life-saving and improves quality of life. However, long-term pediatric liver transplant recipients face challenges such as strict adherence to medications and follow-up visits, avoiding exposure to infections, and fear of graft rejection.
Chronic liver disease in children leads to failure to thrive, growth failure, and even delayed puberty, which resolve in most patients after liver transplant before adulthood in the absence of other comorbidities.44 However, these patients are reported to have lower psychosocial functioning and more psychiatric disorders such as anxiety or posttraumatic disorder.41,44
Therefore, a psychologist or other mental health professional should be part of the management team from the time of pretransplant assessment to identify mental health problems and the need for adjustments before liver transplant. Ongoing psychosocial assessment after liver transplant is equally important to identify risks such as drug or alcohol abuse, depression, posttraumatic stress disorder, and medication nonadherence, all of which can negatively affect posttransplant outcome.45
In addition, assessment of family functioning and structure is important for good long-term outcomes posttransplant; therefore, a social worker should also be a part of the transplant team. Psyschosocial assessment tools can identify high-risk candidates who would benefit from earlier intervention to avoid any negative impact posttransplant.
Neurocognitive development can be delayed in children with chronic liver disease, and the delay may persist even after liver transplant, with reported impairments in intellectual ability, language, verbal, and visuospatial functioning skills.41 In spite of this, a recent study found that more than half the study patients were employed at a median follow-up of 24 years from liver transplant and a median age of 27.46
Remarkably, pediatric liver transplant recipients have reported quality of life comparable to that in the general population,47 and even better than in patients with other chronic illnesses.48
Long-term medical comorbidities in pediatric liver transplant recipients
Favorable outcomes such as long-term survival and good quality of life in pediatric liver transplant recipients are lessened by late complications such as portal vein thrombosis or biliary strictures needing interventions, chronic graft rejection, adverse effects of immunosuppression, and recurrence of the disease.
Split-liver transplant—splitting a deceased-donor allograft to provide grafts for 2 recipients—has revolutionized liver transplant by increasing the donor pool and thereby decreasing waitlist mortality rates, especially in pediatric candidates. Despite this advantage, split-liver transplant is technically challenging and associated with increased perioperative complications compared with whole-liver transplant, especially in adult recipients. Recently, experienced centers have reported favorable outcomes with split-liver transplant comparable to those with whole-liver transplant; therefore, split-liver transplant should be considered after careful evaluation of donor organ and recipient clinical status.49
Old age in the recipient can also adversely affect liver transplant outcomes.50
Interestingly, even in patients whose clinical course is unremarkable and biochemical values are normal, graft hepatitis or fibrosis of unknown cause with progression to cirrhosis has been described in the decade after transplant.41
Chronic rejection with eventual graft loss may be related to nonadherence in adolescents and can be reduced with use of an additional immunosuppressant such as sirolimus or mycophenolate. Chronic kidney disease can occur in about one-third of liver transplant recipients secondary to renal disease associated with primary disease (like Alagille syndrome), hepatorenal syndrome, and most importantly, use of calcineurin inhibitors.45
Components of the metabolic syndrome such as type 2 diabetes, obesity, nonalcoholic fatty liver disease, hypertension, and dyslipidemia are also seen in long-term pediatric liver transplant survivors. Internists are advised to screen for these comorbidities so that interventions can be applied early to improve long-term health outcomes and graft survival.
Of importance, multiple studies have shown a 2-fold increase in the rates of de novo malignancy in liver transplant recipients, including solid-organ and lymphoproliferative cancers, probably due to long-term immunosuppression. Posttransplant lymphoproliferative disorder occurs at lower rates than with other solid-organ transplants; its incidence is greatest in pediatric patients and in the first 12 to 18 months after transplant.51
