What to Expect After Pediatric Liver Transplantation: Cognitive Function and Quality of Life

A recent study (D Ohnemus et al. Liver Transplantation 2020; 26: 45-56, editorial 9-11) examined health-related quality of life (HRQOL) and cognitive functioning approximately 15 years after liver transplantation (LT).

Study details:

Median age 16 years.  Original group was a SPLIT research cohort recruited from 20 centers and then tested at multiple time points; for this study, 8 sites of the original 20 were included.  It is noted that patients with serious neurologic injury were excluded. Among an initial group of 108, there were 79 available for potential enrollment.  In this group, 65 parent surveys were completed and 61 child surveys.

Key findings:

  • For cognitive and school functioning, 60% and 51% of parents reported “poor” functioning, respectively (>1 SD below the health mean).  41% of children rated their cognitive function as poor.
  • Adolescents’ self-reported overall HRQOL was similar to that of healthy children; in contrast, parents rated their teenage children as having significantly worse HRQOL than healthy children in all domains.
  • The cognitive score in the poor functioning group at the latest time point was lower than at first time point measurement (ages 5-6 years and at least 2 years after LT), “suggesting that difficulties intensified in adolescence for those who have problems in early childhood.”
  • Almost half had received special educational services.

The editorial notes that the PedsQL Cognitive Functioning Scale scores used by the investigators were considered subjective.  “The more objective PedsPCF scores fell within the normal range.”

My take: This report indicates that a majority of children are likely to have some cognitive deficits and many are likely to have reduced HRQOL following liver transplantation; in addition, if these problems are detected at a younger age, they are likely to persist.

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Useful Data on Cholangitis Following Kasai Portoenterostomy

A recent retrospective study (SH Baek et al. JPGN 2020; 70: 171-77) provide useful information on cholangitis following a Kasai portoenterostomy in patients (n=160) with biliary atresia (BA).

Key points:

  • 126 of 160 (79%) had at least one episode of cholangitis during the study period (2006-2015).  Median followup was 49 months in those who had cholangitis compared to 33 months for those who did not develop cholangitis.
  • Age at time of Kasai: 63 days in those with cholangitis and 55 days in those without (P=0.42)
  • 76% of patients had recurrent cholangitis
  • Yield from blood culture was 9%.  In those with culture-proven cholangitis, Enterococcus faecium was most common pathogen (28%), followed by E. coli (15%), Enterobacter cloacae (11%), and Klebsiella pneumoniae (9%)
  • In their institution, there was a fairly-low susceptibility of gram-negative bacteria to cefotaxime (8/21, 38%). Almost all gram-negative isolates were susceptible to meropenem.
  • In their institution, there was fairly-low susceptibility of gram-positive organisms to ampicillin (8/19, 42%) and 100% susceptibility to vancomycin.
  • The authors noted that their empiric choice for treatment had been cefotaxime but this has now been reviewed; and a newer regimen, “a frequent alternative,” is the use of vancomycin along with an aminoglycoside.

It is worth noting that Up-to-Date has several recommended regimens for acute cholangitis (in adults).  For lower-risk infections, the authors recommend either a single agent like piperacillin-tazobactam or dual therapy with specific cephalosporins (eg. cefotaxime, ceftriaxone) and metronidazole.  For higher-risk infections, the Up-to-Date recommendations include meropenem or piperacillin-tazobactam as single agents or one of two cephalosporins (cefepime or ceftazidime) along with metronidazole.

My take: Cholangitis is common after biliary atresia.  Familiarity with changing susceptibility, particularly local patterns, will help optimize outcomes.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

 

 

Neurodevelopmental Outcomes: Biliary Atresia

A recent study from the Netherlands (LH Rodijk et al. J Pediatr 2020; 217: 118-24) which included 46 children provides data on the suboptimal neurodevelopmental outcomes of children with biliary atresia (BA).  This cohort did not exclude children born prematurely or those with a history of intracranial hemorrhage; the children had undergone Kasai portoenterostomy (KPE) between 2002-2012 and had a median age of 11 years.

Key findings:

  • 36 of 46 (78%) had undergone liver transplantation
  • Median age at time of KPE was 60 days
  • 12 (25%) received special education (vs. 2.4% in ‘normal’ population)
  • Motor outcomes were affected with up to half scoring low on motor skills
  • Total IQ was 91 (compared with 100 in norms)
  • There were no significant differences in the cognitive outcomes of the patients with their native livers compared to those who had undergone liver transplantation (*small sample size)

Potential explanations:

  • Detrimental affects of cholestasis
  • Major surgery/anesthesia may result in impaired neurodevelopment

My take: This study documents a fairly high rate of neurodevelopmental problems in children with BA.  The information we need now –how to mitigate this.

VL NG et al. J Pediatr 2018; 196: 139-47. This study with 148 children examined the neurodevelopmental outomes of young children with biliary atresia (ChiLDRen Study). Key finding: Children with their native livers were at increased risk for neurodevelopmental delays at 12 and 24 months.  This risk was more than 4-fold increased among those with unsuccessful Kasai procedure.

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Liver Shorts -January 2020

S Nagai et al. Clin Gastroenterol Hepatol 2019; 17: 2759-68. For patients who underwent liver transplantation during 2016–2017, a significantly lower proportion of patients with NASH survived for 1 year after transplantation than patients with HCV (P = .004) or ALD (P < .001). 1-year patient survival rates: NASH 90.4%, HCV 92.8%, ALD 93.5%. Full Text: Increased Risk of Death in First Year After Liver Transplantation Among Patients With Nonalcoholic Steatohepatitis vs Liver Disease of Other Etiologies

JE Squires et al. JPGN 2020; 70: 79-86.  Using a prospective, longitudinal database, this study from ChiLDReN network with 93 children with biliary atresia and native liver found that NO increased prevalence of neurodevelopmental delays. Markers of advanced liver disease (high bilirubin/GGT for those ≤5 yrs, and portal hypertension for those >5 years) did negatively affect neurodevelopmental measures.

C Jaramillo et al. JPGN 2020; 70: 87-92.  This pilot study with 21 patients found that degree of fibrosis, quantified by collagen hybridizing peptide, at time of Kasai, was associated with the risk of requiring a liver transplantation by age 4 years.  Total bilirubin >2 mg/dL and Albumin ❤ g/dL at 3 months post-Kasai were also associated significantly with need for liver transplantation.

H-S Chen et al. Hepatology 2019; 70: 1903-12. In this study from Taiwan with 182 children (median age of 10.6 at enrollment) with hepatitis B and a normal ALT, a baseline anti-HBc titer of >500 IU/mL was associated with spontaneous HBeAg seroconversion with hazard ratio of 2.81.  Over the median follow-up of 19.8 years, 85 subjects (46.7%) had HBeAg seroconversion. Thus, anit-HBc reflects anti-HBV immune response in the HBeAg-positive patients with normal ALT.

Development of Primary Sclerosing Cholangitis in Pediatric Patients with Inflammatory Bowel Disease

A recent study (A Chandrakumar et al. J Pediatr 2019; 215: 144-51) followed 190 children with inflammatory bowel disease from 2011 to 2018 in a longitudinal population-based cohort in Manitoba and examined the development of primary sclerosing cholangitis (PSC).  The diagnosis of PSC was made on discretion of the treating physician; thus, only a subset of patients underwent extensive evaluations for PSC.

Key findings:

  • 9 developed PSC-UC (9/95) and overall 11 developed PSC-IBD (11/190)
  • Among children with PSC-UC, 8 had high GGT (>50) at baseline and only 1 had a normal GGT at baseline.
  • All UC patients who developed PSC were diagnosed withing 6 months of their UC diagnosis.
  • At baseline, 22 patients with UC had an elevated GGT and 73 had a normal GGT.  Thus, about one-third of patients with an elevated GGT developed PSC (possibly more as all patients were not subjected to extensive testing)

My view: This study reinforces two concepts: 1) GGT is valuable as a screening test 2) PSC (often asymptomatic) is fairly common in UC and needs to be considered especially in the first year of diagnosis.  What this study does not do is help us figure out what should be done about children with asymptomatic PSC as there are no proven therapies.

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Year in Review: My Favorite 2019 Posts

Yesterday, I listed the posts with the most views.  The posts below were the ones I like the most.

General/General Health:

Nutrition:

Liver:

Endoscopy:

Intestinal Disorders:

 

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

Most Popular Posts of 2019

The following are the most viewed posts from the past year:

Wishing friends, family and colleagues a healthy and happy New Year.

Morning in Sandy Springs, GA