Category Archives: Pediatric Gastroenterology Liver Disease

Rectal Budesonide for Biliary Atresia After Kasai Procedure

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S Langreen et al. JPGN 2025;81:626–633. Rectal budesonide: A potential game changer after Kasai hepatoportoenterostomy

Background: After the START trial in 2014, it seemed that enthusiasm for post-operative steroids for biliary atresia had waned. The START study did not find that steroids improved outcomes after Kasai hepatoportoenterostomy (HPE). Subsequently, though, there have been observational reports of using steroids in a customized fashion to improve outcomes. Langreen et al add to this literature by examining their use of rectal budesonide (2 mg) for 3 months in a retrospective cohort (n=142) with a historical control (n=137). Jaundice-free native liver survival (jfNLS) was assessed at 6 months, 2 years, 5 years, and 10 years post-Kasai.

Key findings:

  • Improvements were noted in jfNLS at 6 months (53% vs. 39%) , 2 years (45% vs. 22%), 5 years (40% vs. 23%) and 10 years (32% vs. 13%)
  • These benefits were exclusive to patients with nonsyndromic BA
  • No serious adverse effects were identified with budesonide

Rationale for rectal budesonide: The authors note that “a single dose of budesonide foam contains about 2 mg of budesonide, equivalent to 25 mg of prednisolone or 20 mg of methylprednisolone…In our series, no serious steroid associated adverse effects were recorded, possibly due to the first pass after rectal administration.”

Limitations: “The retrospective nature of our data analysis allows for variability in the follow‐up protocols, potential biases (historical control group, change of surgeons) and confounding factors cannot be entirely ruled out.”

Kaplan–Meier curve comparing native liver survival between the study and control groups
over a 10‐year follow‐up.. Study group—blue. Control group—orange.

My take: The START study with 140 participants was well-designed and did not find a benefit with systemic steroids. However small differences in outcomes can be difficult to identify. Rectal budesonide may improve outcomes. A randomized, double-blind, placebo-controlled trial would be more definitive.

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Warnings of Hepatitis B Vaccine Policy Shift

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Despite the enormous benefits of hepatitis B vaccination, it appears that this administration has its sights on changing the policy of administration at birth.

NY Times 9/16/25: C.D.C. Vaccine Advisers May Limit Hepatitis B Shots for Newborns

An excerpt:

Committee members, some of whom are vaccine skeptics, are likely to recommend restricting the use of the shots at birth or delaying them until later in childhood…

“Unless the mother is hepatitis-B-positive, an argument could be made to delay the vaccine for this infection,” Martin Kulldorff, the committee’s chair, said at its previous meeting in June.

Vaccine experts at the C.D.C., who normally would be deeply involved in preparing for this week’s meeting, have been sidelined and given no more information than the public about the meeting’s agenda or possible outcomes…

Before 1991, when newborns were not all vaccinated for hepatitis B, about 20,000 babies became infected each year. Routine immunization at birth cut the number of newborn infections … There are now fewer than 20 children per year who acquire the disease from their mothers.

Only about half of the cases before 1991 were a result of transmission from an infected mother. The other half “weren’t getting it from becoming sex workers, and they weren’t getting it from being intravenous drug users,” Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said…

From 2015 to 2017, about 21,000 infants were born to pregnant women with hepatitis B antibodies, but fewer than half were identified through prenatal screening, according to the C.D.C.

My take: If routine immunization at birth is stopped, there will be a lot more hepatitis B infections and subsequent complications. Some infections will be acquired at birth and some later due to missed opportunities to provide protection later on.

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Brooklyn Botanic Garden

Ultrasonography to Distinguish Biliary Atresia from Alagille Syndrome

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AM Upton et al. J Pediatr Gastroenterol Nutr. 2025;81:212–216. The “maximum echogenicity” at the right portal vein: Biliary atresia versus Alagille syndrome

See related ultrasound study from last week: Improving Ultrasound Examination to Identify Biliary Atresia

Background/Methods: One way clinicians can distinguish between biliary atresia and Alagille syndrome is with a positive “triangular cord sign.” This ultrasound finding refers to a thickened echogenicity at the anterior aspect of the right portal vein…the maximum echogenicity at the anterior aspect of the right portal vein (“maximum echogenicity” or “MxE”) was measured in a group of infants with cholestasis (Cohort 1, n=64) and in another group of infants with Alagille syndrome (Cohort 2, n=30).

Key findings:

  • “Thin echogenicity at the anterior aspect of the right portal vein may help distinguish between biliary atresia and Alagille syndrome…None of the 12 infants with biliary atresia in Cohort 1 had a MxE < 1.0 mm”
  • “A MxE < 1.0 mm could help identify Alagille syndrome. 2 of the 64 infants with cholestasis in Cohort 1 had a MxE < 1.0 mm. Both infants were eventually diagnosed with Alagille syndrome. In the Cohort 2 infants with Alagille syndrome, 16 of 30 infants had a MxE < 1.0 mm”
Infant with biliary atresia
Infant with Alagille Syndrome

Discussion Point:

“Infants with Alagille syndrome can have smaller bile ducts which may be inapparent on invasive testing such as cholangiography. As a result, they may be presumptively diagnosed with biliary atresia and inappropriately treated with the Kasai portoenterostomy. Unfortunately, these infants have poorer outcomes compared to infants with Alagille syndrome who do not receive the Kasai portoenterostomy.” Thus, distinguishing Alagille from biliary atresia is very important.

My take: This study shows that MxE (a refinement of what has previously been called the triangular cord sign) on ultrasound may help distinguish biliary atresia from Alagille syndrome. As this is a single-center study, it will be important to determine if this ultrasound finding can be replicated in other centers and whether the finding is operator-dependent.

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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

Infliximab for Autoimmune Hepatitis

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C Efe et al. Hepatology 2025; 81: 1660-1670. Efficacy and safety of infliximab in patients with autoimmune hepatitis

In this multicenter retrospective study, there were two groups of patients with autoimmune hepatitis (AIH) who received infliximab treatment:

  • Group 1 (n=20) had failed standard, second-line (mycophenolate mofetil and 6-mercaptopurine) or third-line (tacrolimus or cyclosporine) therapy.
  • Group 2 (n=22), infliximab was given for treatment of concomitant extrahepatic autoimmune diseases. Only 6 of these patients had active AIH at time of initiation of infliximab therapy

Key findings:

  • Overall, 65% (17/26) of the patients with active AIH achieved complete biochemical remission* (CR) on infliximab.  This included CR in 75% (6/8) of nonresponders to second-line and in 46% (6/13) of failing third-line therapy.
  • *CR defined as normalization of serum transaminases and IgG levels
  • Five patients developed anti-infliximab antibodies, 1 had an allergic reaction and 4 had a lack of control of a concurrent autoimmune disorder, prompting discontinuation of infliximab

My take: While a randomized controlled trial would be better, this study demonstrates that infliximab is an option for AIH, especially in those with concurrent immune-mediated disorders and in those not responding to standard therapy. It is worth noting that infliximab can paradoxically induce an autoimmune hepatitis and stopping infliximab therapy can be curative in these patients (we recently had such a case).

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PRO and CON: All Pediatric Transplant Centers Should Have Living Donor Liver Transplant Option

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S Zielsdorf et al. Liver Transplantation 2025; 31: 832-835. PRO: All pediatric transplant centers should have LDLT as an option

Zielsdorf et make a compelling argument that all liver transplant patients should have access to LDLT. By improving access to transplantation, transplant recipients are in better health at the time of LDLT and have better outcomes. This also results in fewer deaths on the waiting list, even for patients who do not receive a LDLT.

The authors note that “whether LDLT is a superior option in and of itself or is instead a proxy for higher volume and more experienced centers, with associated better outcomes, may not be entirely feasible to tease out from the data.”

N Galvan et al. Liver Transplantation 2025; 31: 836-839. CON: LDLT should not be a requirement for pediatric transplant programs

Galvan et al counter with their good statistics from their large-volume center in Houston. In their center, 91% of the liver transplants performed over a decade were size-matched, whole organ allografts. They attribute some of their success to their central U.S. location allowing them to access more donors without compromising warm ischemia time. Other factors that make LDLT less viable at their center include lack of Medicaid reimbursement for living donor operations (51% of their patients rely on public insurance) and concern that the donor is oftentimes a primary caregiver.

They note that most programs in U.S. “are low-volume centers, that is, <5 pediatric liver transplants/year, making up 75% of the pediatric centers in the country that account for 38.5% of the pediatric cases…Experience is garnered by volume, and so the question,…is whether it is worth consolidating small-volume programs.”

My take: LDLT is an important tool to improve outcomes. The ability to access LDLT and technical variant grafts could be life-saving for a patient. Thus, from a public policy standpoint, it would make more sense to have fewer high-volume liver transplant centers that offer these options. Centers, like Houston, which have improved organ availability/acceptance and main high-volume, are the exception and not the rule with regard to outcomes.

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Dr. William Balistreri: Whatever Happened to Neonatal Hepatitis (Part 2)

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Recently Dr. Balistreri gave our group an excellent lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

Key Points:

  • Producing enough bile acids and recycling bile acids in enterohepatic circulation is crucial for bile acid flow. In addition, there are ‘good’ bile acids like cholic acid that have trophic properties and ‘bad’ bile acids like lithocholic acid that cause liver toxicity
  • In addition to defects in the metabolic pathway of bile acids, discoveries identified defects in the membrane transporters (eg. FIC1, BSEP, MDR3), trafficking proteins (eg. MYO5B, VPS33B), nuclear control receptors (eg. FXR), and tight junction proteins (eg. TJP2). Tight junction protein defects are associated with bile leakage from bile canaliculus
  • Alagille syndrome, a disorder of embryogenesis, related to JAG1-NOTCH2 signaling pathways affects organs throughout the body
  • Many of these genetic mutations are now being identified in adults with unexplained liver diseases (eg. intrahepatic cholestasis of pregnancy and cryptogenic cirrhosis)
  • Cholestasis panels and whole exome sequencing are important tools
  • Ileal bile acid transporter (IBAT) inhibitors have emerged as important therapies for conditions like Alagille which were previously treated with biliary diversion

Cholestasis Evaluation:

See blog post: Identifying Biliary Atresia in Infants: New Guidelines

Baby with Carbamoyl-phosphate synthetase 1 (CPS1) deficiency (urea cycle defect)

My take: This lecture really shows how the field of pediatric liver disease has been a puzzle. Now one can see how almost all of the pieces of the puzzle work together.

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Increased Mortality in Pediatric Steatotic Liver Disease Plus One

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From UCSD 4/28/25: Children with Liver Disease Face Dramatically Higher Risk of Early Death (via Jeff Schwimmer’s X feed)

The findings, published April 22, 2025 in Hepatology, the scientific journal of the American Association for the Study of Liver Diseases, come from the Longitudinal InVestigation Evaluating Results of Steatosis (LIVERS) study, which followed 1,096 children over an average of 8.5 years. Nearly half of all deaths in the cohort were liver-related, and the overall mortality rate was 40 times higher than that of similar peers in the general U.S. population...

The retrospective cohort study used medical records and National Death Index data to follow children ages 2 to 18 who were diagnosed with MASLD between 2000 and 2017. Over an average of 8.5 years of follow-up, 3.4% of children had died…

In addition to the risk of early death, many children in the study developed serious health problems while still in their teens or twenties. These included high blood pressure (14%), obstructive sleep apnea (9.5%) and type 2 diabetes (7.3%). Problems with blood fats, such as high triglycerides or low HDL, were even more common — making dyslipidemia, the presence of abnormal levels of fats (lipids) in the blood, the most frequent complication overall.

Link to study: JB Scwimmer et al Hepatology ():10.1097/HEP.0000000000001357. Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study

My take: Since this was a retrospective single center study, the severity of the findings may be different with a more-representative national cohort. Nevertheless, this study shows that MASLD has serious consequences including premature death and numerous comorbidities.

Related article: J Panganiban et al. Obesity Pillars 2025: 14. https://doi.org/10.1016/j.obpill.2025.100164. Open Access! Metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity: An Obesity Medicine Association (OMA) and expert joint perspective 2025. This Obesity Medicine Association (OMA) Expert Joint Perspective is a comprehensive review (~28 pages) of steatotic liver disease (SLD), metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH) in children with obesity.

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Triple Therapy for Cystic Fibrosis May Improve Liver Damage

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S Diemer et al. JPGN 2025; DOI: 10.1002/jpn3.70050. Open Access! The effect of elexacaftor–tezacaftor–ivacaftor on liver stiffness in children with cystic fibrosis

In this retrospective study, 12 of 21 patients had cystic fibrosis hepato-biliary involvement (CFHBI). The authors examined the liver stiffness after administration of the new and highly potent CF transmembrane conductance regulator modulator therapy, elexacaftor–tezacaftor–ivacaftor (ETI). All of the patients in this cohort had normal liver enzymes.

Key findings:

  • Analyzing liver stiffness in CwCF with CFHBI showed a decline to 5.7 kPa median (IQR: 3.9–7.1) during ETI treatment, and this decline was statistically significant (W = −60, n = 12, p = 0.0161) (Figure 3B) (after at least 3 months of ETI treatment)
Liver stiffness over time in patients with CFHBI

Discussion Points:

“Our findings of a clear improvement of liver stiffness in CwCF and CFHBI during ETI treatment is in line with the recently published study by Terlizzi et al.28  Calvo et al. prospectively investigated liver stiffness and liver enzyme development in a single-centre cohort with a starting point before ETI and a follow-up at 1, 3 and 6 months on ETI…A significant overall reduction in mean liver stiffness was found at 6 months, and already after 1 month of ETI, a decline in liver stiffness was observed in those with values ≥5 kPa.29“

My take: Liver stiffness is a biomarker for chronic liver damage. Longer term studies will be needed to determine how important triple therapy is for liver health in persons with cystic fibrosis. Thus far, there has not been improvement in the number of patients with CF needing a liver transplant; however, there has been a marked improvement in the need for lung transplantation.

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Advancements in Pediatric Cholestatic Liver Disease Management

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KR Mysore et al. J Pediatr Gastroenterol Nutr. 2025;80:549–558. Recent advances in the management of pediatric cholestatic liver diseases

This is a useful review summarizing advances in the management of cholestatic diseases.

Treatment with IBAT inhibitors:

“Improvement in both pruritus and serum BAs/bilirubin levels has been associated with improved event‐free survival and 6‐year transplant‐free survival in ALGS patients treated with maralixibat. Additionally, this class of medication improved overall growth of the patient by improving mean height and weight Z scores that may be related to reduced impact of high serum bile acid levels on the growth axis although further studies are needed to better define the mechanism responsible for this out-come. This finding suggests these parameters could be used as surrogate end‐points for disease severity in diseases like ALGS or PFIC, where the time course to develop the need for LT commonly occurs over many years.”

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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.

Essential Learning Objectives in Pediatric Gastroenterology (and All Subspecialties) for Pediatricians and in Pediatric Residency Training

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T Aye et al. J Pediatr 2025; 277, 114380. (Open Access!) Subspecialty Perspectives on the Education Needs for Pediatrics Residency Training

Background: The Council of Pediatric Subspecialties (CoPS) created a list of 3 to 5 learning objectives that each subspecialty believes are the most important practical skills for the general pediatrician and recommends be included in general pediatrics, medicine-pediatrics, and other combined residency program curricula… The Subspecialty Perspectives on (pediatrics) Training (SPoT) action team within CoPS asked each subspecialty representative, most of whom were fellowship program directors at the time, in collaboration with their subspecialty colleagues, to provide a list of 3 to 5 practical learning objectives that should be expected of graduating pediatric residents and practicing general pediatricians in the evaluation and management of conditions related to their subspecialty.

Recommendations for Pediatric Gastroenterology:

My take: This article identifies four of the most important areas in pediatric gastroenterology. If I were to add a fifth, given the wide variety of problems in our field, it would be to know how to quickly reach out to a pediatric gastroenterologist when you need advice.

This article is worth a quick look to see if you have the essential knowledge in all pediatric subspecialty fields (Table 1). One of the most important that relates to pediatric gastroenterology is in the allergy section: “Identify the importance of avoiding indiscriminate testing for food allergy without an appropriate clinical history concerning for IgE mediated food allergy.”