Category Archives: Pediatric Gastroenterology Liver Disease

What to Do with Adolescents with Common Bile Duct Stones

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Many times throughout the year we will receive a request to accept a 15-17 year old weighing more than 200 pounds with gallstones who needs to be transferred so that he/she can be cared for in a pediatric facility. The really crazy part is that some of these ‘kids’ need to transferred back to an adult facility to have an ERCP to remove the gallstones if they are lodged in the common bile duct (CBD). Very few pediatric gastroenterologists are adequately trained in ERCP.

A recent retrospective study (PC Bonasso et al JPGN 2019; 68: 64-7) shows some of the consequences of this problem –longer hospitalizations and delays in treatment. The authors compared 79 (48%) pediatric patients who required transfer compared to 85 (52%) who were managed at the tertiary care pediatric hospital.  The median age was 15 years with 42% obese and 23% overweight.

Key findings:

  • Transfer group patients had longer length of stay, median 7 days vs 5 days for non-transfer group (P< 0.0001) and more days between ERCP and surgery.
  • Transfer patients were more likely to have an MRCP (34% vs 8% for non-transfer).
  • Transfer patients were more likely to have a stent placement, 9% vs 5% (which would require a subsequent anesthetic to remove).
  • Transfer patients were more likely to have a non-therapeutic ERCP;  stone/sludge removal was 70% in transfer group vs 86% in non-transfer group. This could be related to the delay (eg. more time for stone to pass) or due to the evaluation by team not responsible for ERCP.

The authors note that there are fewer than 20 pediatric gastroenterologists trained in ERCP; this is not likely to change much in the near term due to the large number of ERCPs needed to become proficient and few options for pediatric training. Their study notes that 46% had adult gastroenterologist management for non-transfer group.

My take: This is clearly an area in need of collaboration.  More pediatric hospitals need to have adult gastroenterologists available and adult hospitals need to consider keeping some of these young adults to improve both the care and costs for these individuals.

Related blog posts:

This article was referenced previously on this blog

 

Ledipasvir-Sofosbuvir for Children 6-11 years

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Almost two years ago, the FDA approved Ledipasvir-Sofosbuvir (aka Harvoni) for pediatric patients 12-17 years of age with hepatitis C virus (HCV) infection.  Now, a recent study (KF Murray, WF Balistreri, S Bansal et al. Hepatology 2018; 68: 2158-66) is likely to expedite approval for children ages 6-11 years of age.

In this open-label study with 92 patients, 88 had genotype 1, 89 received treatment with ledipasvir-sofosbuvir without ribavirin for 12 weeks, 97% were perinatally-infected, and 78% were treatment naive.  The median age was 9 years. The dose (determined by intense pharmacokinetics) was 45 mg-200 mg (half the adult dosage). Two patients with genotype 3 HCV received ledipasvir-sofosbuvir for 24 weeks along with ribavirin.

Key findings:

  • SVR12 was 99% (91/91).  The single patient without SVR12 had relapsed 4 weeks after completing a 12 week treatment course.
  • Ledipasvir-sofosbuvir was well-tolerated; the common adverse events reported were headache and pyrexia.

The authors note that while most children are considered to have mild symptoms or are asymptomatic, some progress to have significant fibrosis or cirrhosis, a small minority develop hepatocellular carcinoma, and HCV infection can impact both cognitive development and overall health.

My take: This study confirms that effectiveness of DAA therapy with ledipasvir/sofosbuvir in children as young as 6 years of age.

Related study: F Tucci et al. Hepatology 2018; 68: 2434-37. The authors report the successful treatment with ledipasvir/sofosbuvir of an infant with both SCID and HCV infection.

Related blog posts:

Mesquite Flat Sand Dunes, Death Valley

Resolution: Eradication of Hepatitis C

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Eradication of hepatitis C virus (HCV) is going to be difficult despite the huge improvements in treatment.  One obstacle that has been highlighted previously has been the increase in HCV transmission associated with the opioid epidemic.  Another basic problem is establishing a ‘cascade of care’ that makes sure that those with HCV receive appropriate treatment and followup.

In a recent study (RL Epstein et al. J Pediatr 2018; 203: 34-40, editoria by KB Schwarz, W Karnsakul 7-8) describe the deficiencies in the followup of women in an obstetric clinic serving women with substance use disorders. The authors reviewed electronic records of 879 women over a 10 year period.  Key findings:

  • 85% of women were screened for HCV.  Of the 68% who were seropositive, only 72% had HCV RNA testing and 71% were viremic.
  • There were 404 infants born to women who were HCVB seropositive.  Only 45% of these infants completed AAP-recommended perinatal HCV screening.

In the commentary, the authors point to the suboptimal rates of followup.  They note that there is a “huge gap between infected women and the linkage of their infected progency to care.” Furthermore, the AASLD has recommended that “all children with HCV infection in age groups for which direct-acting antiviral agents are approved should be treated.”

My take: this study identifies gaps in followup and treatment that need to be addressed systematically if we are to realize the goal of HCV eradication.

Related blog posts:

Screenshot (383)

NASPGHAN Toolbox App -Review

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To all my colleagues and to others who follow this blog, I wish you a happy new year.  Thank you to all of you, especially to those who provide feedback to help improve the content and usefulness.

Recently NASPGHAN released an App, titled NASPGHAN Toolbox.  There are some very useful features but also some areas where more work is needed.

Work in progress: Many of the algorithms that are listed are dated and no longer accurate.  To list a few examples:

  • The UC Algorithm suggests holding off on anti-TNF therapy in severe disease for 7-14 days
  • The EoE Algorithm lists only diet treatments and topical steroids and does not list PPIs as a treatment option
  • The GERD guidelines are from 2001 rather than more recent recommendations

Also, this ‘algorithms’ section should probably be renamed into ‘algorithms and tables’ as a large amount of the information is not algorithmic.

What I Like:

  • Scores and Calculators for items like MELD score, PUCAI score, Mayo score
  • Extensive patient education handouts and image atlas -this could facilitate “airdrop”ing or messaging of these items to families.  (To be picky –the normal esophagus image could be better)
  • Formula charts –though the lists for infants and older children could be more comprehensive
  • Bristol charts (especially children version) -listed in algorithm section

My take: This is a very good start and a very helpful toolbox for pediatric gastroenterologists but I would not rely on the algorithms.

 

My Favorite Posts from the Past Year

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Recently, I listed the posts that had the most views in the past year –some dating back to 2012.  The following list includes less viewed but some of my favorite posts from 2018:

GI:

Nutrition:

LIVER:

Miscellaneous:

Flowers in Calgary

Most Popular Posts 2011-2018

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Since this blog’s inception, there are now more than 2500 posts; these are the most popular (most views):

Most of these posts are referenced in more recent posts on the same or similar subjects.

Near Banff

 

PEG-B-ACTIVE Study: Efficacy of Peginterferon for Children with Hep B

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A recent randomized controlled, open-label study (S Wirth et al. Hepatology 2018; 68: 1681-94) examined the use of weekly peginterferon alfa-2a (PEG) in 161 children (3-18 yrs) with immune-active HBe-Ag-positive children.  The two main groups were for those without advanced fibrosis: a PEG group (n=101) and a placebo group (n=50).  A third group enrolled 10 patients with advanced fibrosis who all received PEG. The treatment period was 48 weeks with ongoing observation for an additional 24 weeks.

Key findings:

  • The PEG group had HBeAg seroconversion of  8% at 48 weeks and 26% at 72 weeks; the placebo group had HBeAg seroconversion of 6% at both timepoints. At 72 weeks, the odds ratio was 5.43 for the PEG group and P=0.0043.
  • HBsAg clearance rates were higher in the PEG group: 8.9% vs 0% in placebo group.
  • The authors showed response (loss of HBeAg) by age and those <5 years had the highest response 43% (6 of 14).  The rate of seroconversion was 30.2% in those <12 years compared with 20.8% in those ≥12 years.
  • The authors showed response (loss of HBeAg) those with ALT values between 2-<5 had the highest response of 35% (15 of 43).
  • Adverse events were frequent –among the 101 treated patients: 49 with pyrexia, 30 with headache, 19 with abdominal pain, 15 with influenza-like illness, 14 with vomiting, 61 with ALT >5 x ULN, 25 with ALT >10 x ULN, 19 with neutropenia (ANC <750), and two with self-limited increased thyroid-stimulating hormone. These were all much higher than in the placebo group

My take: This study does not answer the question about which treatment is optimal for hepatitis B in children–direct-acting antivirals (eg. entecavir, and tenofovir) or peginterferon.  It does shows that weekly peginterferon alfa-2a was associated with HBeAg seroconversion in 26% of recipients at week 72.  Although a high number of patients experienced adverse effects, there were no new safety signals identified.

Related blog posts:

View from Parker Ridge, near Banff

Bilary Atresia Prognosis After 2-Year Survival with Native Liver

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A recent study (M Witt et al. JPGN 2018; 689-94) indicates that among patients with biliary atresia who reached 2 years of life with native liver survival (NLS), they continued to be at risk for progressive liver failure.

Key findings:

  • Upon a median follow-up of 16.4 years, NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively.
  • Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively
  • NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality.
  • Abstract Link: Prognosis of Biliary Atresia After 2-year Survival With Native Liver

My take: This data provides more precise information for families about prognosis and reinforces the need for careful followup.

Related blog posts:

Parker Ridge, near Banff

 

 

Pediatric Liver Enzyme Reference Values

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A recent study (S Bussler et al. Hepatology 2018; 1319-1330)  provides reference age-related reference values for ALT, AST, and GGT for children from 11 months of age through 16 years.  This study from Leipzig used the LIFE Child prospective longitudinal population-based cohort with 3,131 cases (normal weight).

  • Figure 2 provides age- and sex-related percentiles for ALT.  At all ages and in both genders, the 90% cutoff was ~30 IU (or less).
  • Figure 3 provides age- and sex-related percentiles for AST.  There was a negative sloping curve with both genders, such that the 90% cutoff was ~60 IU at ~1 yr and ~40 IU at ~13 yr. Females tended to have modestly higher values.
  • Figure 4 provides age- and sex-related percentiles for GGT.  At all ages and in both genders, the 90% cutoff was ~25 IU. Males tended to have modestly higher values.

These values overall are similar to previous studies. From NASPGHAN NAFLD Guidelines: For ALT: “In the United States, sex-specific biologically based cutoffs have been determined from nationally representative data and have been validated in a fairly diverse cohort. These cutoffs are 22 mg/dL for girls and 26 mg/dL for boys. A Canadian study found the upper limit of normal for ALT to be 30 mg/dL in children 1 to 12 years of age, and 24 mg/dL in those between 13 and 19 years”

Related blog post: Pediatric NAFLD Guidelines 2017

Near Banff

 

Liver Shorts November 2018

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J Ge et al. Hepatology 2018; 68: 1101-10.  This study reviewed liver donation offers between 2010 to 2014.  This study found that 5.6% of men (293/5202) and 6.2% of women (179/2899) received a pediatric donor as a first offer.  Women, but not men, who received a pediatric first offer had a lower risk of waitlist mortality than with those who received adult organ offers. The authors recommend that “offers of pediatric donor liver be prioritized to women, who are generally shorter stature, once alllocation to the entire…pediatric waitlist pool has occurred.”

CA Chapin et al. Hepatology 2018; 68: 1087-1100.  This study found that patients with indeterminate pediatric acute liver failure (iPALF) have a unique pattern of dense CD8+ T-cell infiltrate that is also perforin-positive adn CD103-positive.  These CD8+ cells are a biomarker for immune dysregulation. These CD8+ dense pattern was found in the 27 of 33 patients with iPALF; 3 had moderate and 3 had minimal staining pattern (per table 2).  The dense CD8+ pattern was seen in 3 of 9 with autoimmune hepatitis and in 1 of 14 with other liver diseases.

E-D Pfister et al. Liver Transplantation 2018; 24: 1186-98.  This study examined patient (n=338) and graft survival in the pediatric population (median age 14.0 years) with Wilson’s disease (1968-2013).  Overall, patient survival was 87% at 1 year, 84% at 5 years, and 81% at 10 years.  Though, the survival was much improved since 2009.

JA Bezzerra et al. Hepatology 2018; 68: 1163-73. This review summarized a research workshop (June 2017) focused on the clinical and research challenges for biliary atresia.

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