Category Archives: Pediatric Gastroenterology Liver Disease

AASLD Practice Statement on the evaluation and management of metabolic dysfunction–associated steatotic liver disease in children

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S Xanthakos et al. Hepatology 2025; 82: 1352-1394. AASLD Practice Statement on the evaluation and management of metabolic dysfunction–associated steatotic liver disease in children (Behind paywall)

The review of pediatric MASLD addresses epidemiology, pathophysiology, natural history, screening, diagnosis, treatment, comorbidity management, outcome monitoring, and transition of care. It also discusses the implications of the 2023 nomenclature revision, which emphasizes evaluating both hepatic steatosis and cardiometabolic risk factors.

Some key points:

  • Box 1 outlines numerous (32) research priorities, including the need for prospective longitudinal cohort studies.
  • “Globally, the estimated prevalence of MASLD in children is 7.6%, making it the most common cause of chronic liver disease in children”
  • Figure 4 describes the interplay between risk factors for MASLD included genetic predisposition, prenatal factors and environmental exposures
  • Figure 5 summarizes comorbid conditions which include obstructive sleep apnea, prediabetes/diabetes, cardiovascular disease (dyslipidemia, hypertension, left ventricular hypertrophy), anxiety/depression, reduced bone mineral density, renal dysfunction and polycystic ovarian syndrome. Table 6 summarizes evaluation and initial management with most of these conditions. Yearly screening for diabetes in children with MASLD is recommended.
  • ALT remains most common screening test with >26 U/L for adolescent males and >22 U/L for adolescent females having optimal sensitivity (>80-85%). We recommend “screen for MASLD in children aged 10 years or older with overweight and cardiometabolic risk factors or family history or obesity.” Annual screening recommended if at risk.
  • Table 2 provides a long list of medications which may promote weight gain. These include antihistamines, steroids, some contraceptives, anticonvulsants, antidepressants, antipsychotics, methotrexate, and doxycycline

Diagnostic evaluation:

  • Diagnosis of MASLD requires confirmation of steatosis (by imaging or biopsy) in addition to the presence of at least one cardiometabolic risk factor. ALT elevation with a cardiometabolic risk factor is insufficient.
  • “Consider liver biopsy in cases where there is uncertainty, especially if ALT levels are persistently elevated (>2 times the ULN)”
  • Table 3 lists inborn errors of metabolism and monogenetic diseases which may cause childhood-onset steatotic liver disease. Evaluation of inborn errors of metabolism should be considered if atypical signs or symptoms, such as early onset (<3 yrs), rapidly progressive, absence of obesity, or other organ involvement (especially neurological)
  • Table 4 summarizes imaging modalities to assess steatosis and fibrosis in children. Only MRI-PDFF has been validated in children (for steatosis)
  • Table 5 describes BMI classification in children (WHO and AAP)
  • Lifestyle treatments are detailed including diet (reduction of added sugars, Mediterranean diets) and exercise
  • Emerging medications are reviewed. However, practice statement notes “No pharmacotherapies are currently recommended or approved as specific treatments for MASLD or MASH in children…Medications approved for use in children ages 12 years and older to treat obesity or type 2 diabetes may be considered for children with MASLD.”

My take: This is a comprehensive practice guidance. It emphasizes an extensive diagnostic evaluation. The threshold for liver biopsy is relatively low in this guidance. As more data emerges, it is likely that more emphasis will be placed on the use of pharmacotherapies.

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.

Living-Donor Transplant Availability Lifts All Boats

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“A rising tide lifts all boats” has been used to express the sentiment that a good economy is beneficial to all. However, this has been criticized as not all boats are lifted equally and some boats are a lot nicer than others. I was thinking about this expression with these recent publications. The articles indicate that the availability of living donor liver transplant (LDLT) is clearly beneficial to the recipients but also is helpful, in a lesser way, to others on the transplant list as well.

Researchers analyzed data from 474 pediatric candidates listed for liver transplants at a single center from 2001 to 2023 (Toronto).

Key findings:

  • The pLDLT group had a higher likelihood of receiving a liver transplantation (adjusted HR: 1.38)  a lower risk of dying without a transplant (adjusted HR: 0.11)
  • Survival rates from the time of listing were significantly better in the pLDLT group compared to the pDDLT (on live donor) at 1—(98.6% vs. 87.6%), 5—(96.6% vs. 84.4%), and 10—(96.6% vs. 83.1%) years
  • Having a potential live donor was linked to a 72% reduction in mortality risk (adjusted HR: 0.28)
  • The waiting time for deceased donation shortened. This correlated with increased LDLT utilization, suggesting LDLT not only improved outcomes but also shortened wait times even for pDDLT patients

From the associated editorial:

  • “LDLT continues to be underutilized in the United States with only 15% of all pediatric LTs being LDLTs.1… In 2024, only 6 pediatric centers across the United States performed 5 or more LDLTs.6…”
  • “Black and African-American and Hispanic candidates and those with public insurance are half as likely to undergo LDLT compared with Caucasian candidates and those with private insurance.7,8“
  • “In a survey of over 200 parents of pediatric candidates and recipients of LT, only 72% reported knowing the steps to gain access to LDLT, and only 69% knew that donor costs were covered by the recipient’s insurance.7“
  • The authors recommend collaboration between centers offering LDLT and those that don’t so that more patients could benefit

My take: More use of LDLT will result in better outcomes.

Related blog posts:

Clever Study: Hepatic Steatosis is Common in Overweight/Obese Children in First Four Years of Life

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AO Glenn et al. JPGN 2025;81:679–682. Sonographic evidence of hepatic steatosis is highly prevalent in at-risk children under 4 years of age

This study had a clever design: the authors examined the liver findings from overweight/obese children (n=168) who underwent renal ultrasounds to help determine the frequency of hepatic steatosis. Quantification of the hepatorenal index (HRI) by ultrasound has been shown to provide moderate diagnostic performance for detecting hepatic steatosis in children. (Ref: Frankland MP et al. Diagnostic performance of ultrasound hepatorenal index for the diagnosis of hepatic steatosis in children. Pediatr Radiol. 2022; 52(7): 1306-1313)

This design helped avoid a selection bias present in most studies which have examined ultrasonography in children with elevated liver enzymes. The authors did try to correlate the imaging findings with blood tests. Serum laboratory data were available for 50 patients at a mean interval of 115 days (0–366) from the ultrasound examination.

Key findings:

  • 91 (54%) patients had an abnormally elevated HRI (>1.75). An abnormally elevated HRI was present in 58% (50/86) of patients with overweight and 50% (41/82) of patients with obesity
  • Of the 12 patients with abnormal ALT, 5 (42%) had an abnormal ultrasound HRI and 7 (58%) had a normal ultrasound HRI

Discussion points:

“MASLD can occur at a very young age and should be considered in at-risk patients. Importantly, only 21% (5/24) of the patients with imaging evidence of steatosis and available labs had elevated ALT and 58% (7/12) of patients with an elevated ALT did not have imaging evidence of steatosis, suggesting that ALT may not be a useful biomarker for MASLD screening at this age.”

My take: Hepatic steatosis is likely present in about half of children with early onset overweight/obesity. ALT values are often normal in this cohort.

Related blog posts:

The Rocky Mountains, Landers Peak by Albert Bierstadt at the Metropolitan Museum of rt

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.

Related blog posts:

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.

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

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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