Category Archives: Pediatric Gastroenterology Liver Disease

Should All Pediatric Patients with Hepatitis B Undergo Routine Surveillance for Hepatocellular Carcinoma?

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C Rajan et al. JPGN Reports: November 2021 – Volume 2 – Issue 4 – p e124. Open Access: Hepatocellular Carcinoma in the Absence of Cirrhosis in a Child With Inactive Chronic Hepatitis B Infection

In this case study, the authors “describe an unusual case of a child with chronic hepatitis B infection who developed HCC in the absence of active hepatitis or cirrhosis.” Based on their case report, they advocate for “regular HCC surveillance for all children with chronic hepatitis B, regardless of presence or absence of hepatitis or cirrhosis.”

However, the authors suggestions to expand surveillance to all children with hepatitis B is NOT aligned with current expert opinion (by most experts). This potential recommendation deserves (deserved) more commentary in their discussion. The AASLD recommends offering surveillance when the risk of HCC is at least 1.5% per year and the incidence is greater than 0.2% per year, which includes patients with cirrhosis and some non-cirrhotic hepatitis B carriers [7]. In a study from Taiwan (blog post: HBV Vaccination Prevents Cancer), the authors showed the beneficial effects of vaccination: HCC incidence per 105 person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. This study also showed how rare HCC cases are in children; thus, showing benefit of vaccination was impressive.

The AASLD guidelines on HCC (Link to PDF: Diagnosis, Staging, and Management of
Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for
the Study of Liver Diseases) notes the following high risk categories:

My take: This case report is helpful in emphasizing the risk of HCC in patients with HBV, even in those without significant risk factors. However, at this time most experts do not recommend surveillance in those with a low risk of developing HCC.

Related blog posts:

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.

Genetic Underpinnings of Acute Liver Failure in Children

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R Hegarty et al. J Pediatrics; 236: 124-130. Open Access: Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology

Background: “Despite the progress made over the last 40 years the rate of indeterminate cases [of acute liver failure] remains ~30%”

Methods: The authors identified 41 children (<10 yrs) with DNA sample availability who were admitted to King’s College Hospital, London, with ALF of indeterminate etiology (2000-2018). In addition, trio exome sequencing was performed on 4 children admitted during 2019.

Key Findings:

  • Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively
  • The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings.

My take: Genetic testing for underlying metabolic/metabolic disorders is important to further determine the reasons for ALF. Given the potential need for liver transplantation, obtaining these results quickly will be crucial. In addition, interpretation of the results in some cases will be difficult.

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NASPGHAN Toolbox App

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Patrick Reeves passed along the following helpful information about the NASPGHAN toolbox:

The NASPGHAN Fellows committee, working in close partnership with the NASPGHAN Technology and Training committees, has developed an App named, “The NASPGHAN Toolbox”.

The App is equipped with ready access to: clinical calculators, guidelines and algorithms, medication guides, patient education resources, and more. You can access the Toolbox via its URL (https://toolbox.naspghan.org/) on your phone or computer.

The NASPGHAN team hopes this will enhance your day-to-day patient care of children with gastrointestinal disorders.

Some highlights:

Some screenshots:

Oral Pan-Genotypic HCV Drugs Approved For Children Starting at Age 3 Years

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AAP News (Nov 2021): First oral pan-genotypic HCV drugs approved for children as young as 3 years

“The Food and Drug Administration (FDA) has approved Epclusa (sofosbuvir and velpatasvir) and Mavyret (glecaprevir and pibrentasvir) for treatment of chronic hepatitis C virus (HCV) infection in pediatric patients as young as 3 years. These products are the first all-oral, pan-genotypic (genotypes 1-6) HCV treatment regimens for pediatric patients 3 years and older…Both products are available as oral tablets and as newly approved oral pellets in dosing strengths suitable to accommodate the recommended weight-based dosing in pediatric patients.”

From HCVGuidelines.org (updated September 2021):

The following images are from Abbvie patient-provider handouts. I do not receive any funding from any pharmaceutical company but think these instructions are useful.

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.

Recurrent PSC in Children After Liver Transplantation

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M Martinez et al. Hepatology 2021; 74: 2047-2057. Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study

In this retrospective study, the authors examined recurrent PSC (rPSC) in children who had undergone liver transplantation (LT) with 3 yrs of median followup. Key findings:

  • rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively
  • Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01)
  • After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04)

My take: rPSC, not surprisingly, was associated with a more agressive, immunoreactive phenotype prior to LT characterized by younger age, faster progression to end-stage liver disease, higher prevalence of IBD and more frequent/difficult allograft rejection

Related blog posts:

Bahamas (courtesy of Mark Martin)

Anonymous Nondirected Liver Donors

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D Yoeli et al. Liver Transplantation 2021; 27: 1392-1400. Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series

This case series of 13 nondirected liver donors (ND-LLDs) (from 2012-2020) helps highlight this increasing trend of motivated donors who do not have a predetermined recipient. The Scientific Registry of Transplant Recipients documented 105 patients who underwent a living donor liver transplantation (LDLT) from ND-LLDs 2000-2019, with 39 in 2019 alone.

Key points:

  • While the article states that carefully selected ND-LLDs at high volume centers have excellent outcomes, the associated editorial (pg 1373-74) notes that there is a 0.2% living donor operative mortality. And, a significant number experience negative physical and socioeconomic effects of donation
  • The authors advocate more use of SPLIT livers to increase the donor pool (currently at 10 centers) to lower pediatric deaths on the waitlist
  • The authors note that the likelihood of receiving a LT is increased at high-volume pediatric centers (85%) compared to low-volume centers (41%). “Center expertise and volume is an important consideration…especially true for pediatric liver transplantation, which is relatively infrequent…551 [in 2019]” compared to 8345 adult liver transplants.

The commentary places some context regarding the donors.

  • 70% had previously donated a kidney (“Repetitive donor disorder?”)
  • Yet, “in some sense, nondirected donors may be the best qualified donors, as they are free of coercion”
  • The authors advocate for a “safe, well-informed” process and for national guidelines to address risks and the components of evaluation, medical and psychosocial

My take: It is amazing how much some individuals are willing to sacrifice to help others, especially in age when some react so harshly to being asked to consider the needs of their community.

Related blog posts:

Hyde Farm, Marietta, GA

Good News for Vitamin K

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T Rooimans et al. Gastroentol 2021; 161: 1056-1059. Open Access PDF: Novel Orally Formulated Mixed Micelles Optimize Vitamin K Absorption Under Bile-Deficient Conditions

This study, using a rat animal model, demonstrated how gastro-resistant mixed micelles (MMs) could be used to overcome the limitations of current prophylactic vitamin K formulations which are associated with failures in newborns with unrecognized cholestatic liver diseases (1:2,500 live births).

Key findings:

  • Under cholestatic conditions, gastro-resistant formulations greatly improved vitamin K absorption.
  • Pathophysiology: “Our data provide an explanation why: unstabilized MMs will aggregate during gastric passage, once aggregated vitamin K will not be sufficiently resolubilized upon a subsequent pH increase”

My take: It is likely that these gastro-resistant MMs would be effective in pediatric patients. If proven in clinical trials, this would reduce bleeding events in infants and lower bleeding risks in those with chronic liver disease while obviating the need for parenteral Vitamin K.

Related blog posts: 

Hyde Farm, Marietta GA
From Eric Topol’s Twitter Feed

Hepatology Shorts: Glycosylation Disorders, MMF hepatotoxicity & Wilson’s Disease

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R Colantuono et al. JPGN 2021; 73: 444-454. Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Key points:

  • There are over 130 different types of CDG with 41 that have liver involvement; 7 with a hepatopathy and 34 with in the context of multisystem disease.
  • Transferrin isoform analysis (Isoelectric focusing or high-performance liquid chromotography) detects about 50% of the CDGs; hence, genetic panel or exome sequencing is needed for diagnosis in many cases.

M Warren et al. JPGN 2021; 73: 463-470. Mycophenolate Mofetil Hepatotoxicity Associated With Mitochondrial Abnormality in Liver Transplant Recipients and Mice

Key points:

  • 4 cases of MMF hepatoxicity are presented along with EM changes which revealed unequivocal mitochondrial abnormalities similar to those seen in primary and secondary mitochondrial disorders
  • MMF hepatotoxicity was confirmed in mouse study showing that MMF caused various stress changes in the mitochondria
  • Conclusion: Although MMF is safe for the majority of patients, MMF can cause mitochondrial stress, which may trigger more severe mitochondrial abnormalities in a small subset which can be evident with EM.

E Couchonnal et al JGPN; 73: e80-e86. Pediatric Wilson’s Disease: Phenotypic, Genetic Characterization and Outcome of 182 Children in France

This study examined the clinical data from 182 pediatric patients. WD was diagnosed at a mean age of 10.7 years. Overall survival at 20 years of followup was 98% and patient and transplant-free survival was 84% at 20 years.

Improvement in Hepatitis C Mortality Rates from 2005 to 2017

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EW Hall et al. Hepatology 2021; 582-590. Open Access. County-Level Variation in Hepatitis C Virus Mortality and Trends in the United States, 2005-2017

The authors used county-level HCV death rates and assessed trends in HCV mortality from 2005 to 2013 and from 2013 to 2017; the study is derived from mortality data from the National Vital Statistics System.

Key Findings:

  • Nationally, the age-adjusted HCV death rate peaked in 2013 at 5.20 HCV deaths per 100,000 persons and decreasing to 4.34 per 100,000 persons in 2017
  • There was heterogeneity in HCV mortality with the highest rates being concentrated in the West, Southwest, Appalachia, and northern Florida. 80% of counties had improvement in HCV mortality

My take: This study showed widespread improvement trends in HCV death rates from 2013 to 2017 and provides benchmarks for further progress. However, other studies have shown increasing rates of HCV tied to opioid crisis which could impact long-term outcomes as well.

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How Often Does a Fatty Liver Start in Infancy?

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K McNelis et al. JPGN Reports; 2021: 2(3):e113. Open Access: Hepatic Steatosis in Infancy: The Beginning of Pediatric Nonalcoholic Fatty Liver Disease?

In this retrospective study of 65 healthy infants (<3 months of age, median age 2 months) who had CT scans performed due to trauma, the authors investigated the frequency of a fatty liver.

Key findings:

  • Depending on the criteria used, 23% or 26% of infants had evidence of fatty liver on CT scan
  • The prevalence of maternal obesity and/or diabetes was 11% (of the 65 pregnancies) but there was no significant difference in maternal risk factors between infants with and without evidence of steatosis

My take: Whether the fatty liver seen on CT scans in this infant cohort persists and evolves to adolescent and adult fatty liver disease is unknown but intriguing.