Why Fewer Children Have Immune-Tolerant Hepatitis B Infection Than Previously

A recent study (KB Schwarz et al. JPGN 2019; 69: 588-94) highlights the chronic hepatitis B virus (HBV) phenotypes from a large pediatric North American cohort (n=371).

  • Immune-tolerant HBV was define by HBe-Ag-positivity along with normal ALT levels.
  • Inactive carrier were HBe-Ag-negative with low HBV DNA/normal ALT.
  • Chronic hepatitis B (HBeAg positive and HBeAg negative) had high HBV DNA and abnormal ALT values.
  • Indeterminant HBV had characteristics did not allow them to classified in these four categories.

Key findings:

  • If local laboratory normative values were used 36% of children would have been classified as immune-tolerant*.  However, this drops down to 12% if updated upper limits of normal (ULN) are used based on Figure 3.
  • Using updated ULN, 62% had immune active HBeAg+ disease, 12% with immune-tolerant HBV, 4% with immune-active HBeAg-negative disease, 6% with inactive carrier, and 16% indeterminant HBV.

*There are a few discrepancies between Figure 3 and the abstract data.  The abstract states that 82% would be considered to have chronic hepatitis B (this is 62% in figure 3). The abstract states that 35% were immune-tolerant based on local lab values.

The data presented were cross-sectional data at time of patient enrollment.

My take: this study shows that very few children in this cohort were immune tolerant based on more precise ULN values.  The authors note that the cohort who were immune tolerant were largely drawn from Asian children (most often infected perinatally).

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Lincoln Park, Chicago

 

Need Liver, Will Travel (2019)

A recent study (AJ Kwong et al Clin Gastroenterol Hepatol 2019; 17: 2347-55) quantifies the potential advantage of moving to receive a liver transplant. This had been discussed in 2016 blog post as well (Need Liver, Will Travel)

During the study period (2004-2016), there were 104,914 waitlist registrations.

Key findings:

  • 60.985 patients received a liver transplant during the study period
  • 2930  (2.8%) pursued listing at a distant center
  • Distant listing was associated with a 22% reductinon in the risk of death within 1 year

My take: this study highlights socioeconomic disparity in acquiring a liver transplant along with potential geographic disparities.

Related article:

“Transplantation Traffic –Geography as Destiny for Transplant Candidates” NEJM 2014; 271: 2450-52.  Describes ongoing geographic inequality in organ distribution and obstacles to improving allocation.

Related blog posts:

Botanical Garden,, Chicago

Precision Prediction of Biliary Atresia Survival

Though young age at the time of Kasai and surgical experience have been identified as factors in the long-term outcome of patients with biliary atresia (BA), why is it that some with timely intervention still fail to respond?  Conceptually, I’ve considered those who had progressive disease as probably having an intrahepatic component of their biliary disease that a Kasai operation cannot help.

New research (Z Luo, P Shivakumar, R Mourya, S Gutta, JA Bezerra. Gastroenterol 2019; 157: 1138-52) identifies genetic factors that are likely a more powerful predictor of Kasai response then the traditional clinical factors.

The science in this study is fascinating –combining genetic heat maps, and survival curves.  The prediction with a 14-gene signature is amplified with serum total bilirubin at 3 months post-Kasai.  In addition, these studies are combined with a mouse model treated with N-acetylcysteine (NAC).  Histologic changes were then assessed.

Key findings:

  • The 14-gene mRNA expression pattern predicted shorter and longer survival times in both the discovery (n=121) and validation sets (n=50) of children with BA (see figure below: red curve vs blue curve)
  • When this 14-gene expression pattern was paired with total bilirubin level 3 months after Kasai, this identified children who survived with their native liver at 24 months with an area under the curve of 0.948 in the discovery set and 0.813 in the validation set (P<.001).
  • In those with transplant-free survival, many of the mRNAs expressed had increased scores for glutathione metabolism.  Subsequently, mice with BA were treated with NAC (which promotes glutathione metabolism) & had reduced bile duct obstruction, liver fibrosis, and increased survival times.
  • In children with lower survival rates, there was increased mRNA expression of proteins encoding fibrosis genes in the liver tissues.

My take: This 14-gene signature has the potential to change our approach to children with BA.  Also, when evaluating surgical success rate, these underlying genetic factors will need to be incorporated.

Image available online

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#NASPGHAN19 Annual Meeting -Plenary Session

Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

The first speaker, Jack Gilbert, gave the William F Balistreri lecture.  Dr. Gilbert has written a book on the topic of our ‘magnificent microbiome,’ Dirt is Good.  Here are a few slides:

Related study (not discussed in the talk): A recent study (R Vasapolli et al. Gastroenterology 2019; 157: 1081-91) provided data from 21 healthy adults. Using biopsies from panendoscopy and saliva/fecal samples, the authors found that the fecal microbiome is not representative of the mucosal microbiome.  In addition, each GI region had a different bacterial community.

Christopher Forrest gave the keynote lecture on pediatric learning health systems. By collating data from large pediatric health systems, the researchers can determine more quickly how effective treatments are in all pediatric specialties.

Melvin Heyman, editor of JPGN, provided a good year in review. I only capture a few images.

#NASPGHAN19 Selected Abstracts (Part 2)

Link to full NASPGHAN 2019 Abstracts.

Here are some more abstracts/notes that I found interesting at this year’s NASPGHAN meeting.

A study (poster below) from Cincinnati found that a vedolizumab level ≥34.8 mcg/mL at week 6 (prior to 3rd infusion) predicted clinical response at 6 months

Related blog posts:

The poster below reported a high frequency of eosinophilic disorders in children who have undergone intestinal transplantation. Related blog post: Eosinophilic disease in children with intestinal failure

This study from Boston indicates that acid suppression was not associated with improved outcomes in infants with laryngomalacia (eg. lower supraglottoplasy rates or lower aspiration rates.

Related blog posts:

The study below showed that “less than half of children who started the low FODMAP diet were able to complete the elimination phase.” This indicates the need for careful dietary counseling when attempting this therapy.

Related blog posts:

The abstract below showed that the dietary intake of children with inflammatory bowel disease, who were not receiving enteral nutrition therapy, was similar to healthy control children.

The next two studies provide some pediatric experience with tofacitinib in teenagers with inflammatory bowel disease (14-18 years of age).  The first poster had 12 children and reported a 67% clinical response rate (cohort with 5 with CD, 5 with UC, and 2 with IC).  The second poster had 4 of 6 with a clinical response and 3 in remission.

Related blog posts -Tofacitinib:

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.

#NASPGHAN19 Selected Abstracts (Part 1)

Link to full NASPGHAN 2019 Abstracts.

Here are some abstracts that I found interesting at this year’s NASPGHAN meeting:

NAFLD:

  1. Off-label use of topiramate may be helpful in stabilizing weight and improving NAFLD
  2. Socioeconomic barriers are frequent in NAFLD patients (the 2nd poster did not appear to show a control population):

Primary Sclerosing Cholangitis -Use of Vedolizumab for PSC did not appear to help

Eosinophilic Esophagitis

  1. EoE is four times more likely in this cohort with inflammatory bowel disease
  2. 2nd poster describes very early-onset EoE

Inflammatory Bowel Disease:

  1. Use of infliximab in VEO IBD.  Used in 46/122 (38% of patients) and 50% had persistent use 3 years later

Enteral nutrition –poster from our group describing good tolerance of plant-based formula (with Ana Ramirez).

Celiac disease.  This poster indicates low yield of additional serology for celiac disease besides TTG IgA and serum IgA. This includes testing in young patients (< 2 years) with celiac disease.

#NASPGHAN19 Intestinal Failure Session Part 1

Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

John Kerner  Potential Role of New Fat Emulsions

Key points:

  • Both SMOFlipid and Omegaven help prevent and/or treat parenteral nutrition associated cholestasis.
  • SMOFlipid is much less expensive (see slide below) -50 gm of SMOFlipid ~$5 compared to 10 gm of Omegaven at $35, thus omegaven costs more than 30 times SMOFlipid.
  • Though SMOFlipid is not FDA approved in children, it is being used widely and allows for increased calories compared to lipid minimization with intralipid and could improve neurocognitive outcomes.
  • SMOF dosing (listed below) with goal of 3 g/kg in preterm infants.
  • Resolution of cholestasis does not mean reversal of cirrhosis.  Thus, lipid emulsion intervention at earlier stage may be important.

Bram Raphael  Getting In Line: Towards a Clinical Practice Guideline For CVC Salvage

Key points:

  • Several infections are very difficult to clear, especially yeast, enterococcus, and pseudomonas
  • Salvaging central lines may obviate the need for multi-visceral transplant which carries a 5-year ~50% mortality rate
  • Cefepime provides good gram-negative coverage; consider meropenem in those with septic shock

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.