Natural History and Management of Congenital Hepatic Hemangiomas

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CA Ostertag-Hill et al. J Pediatr 2025;281:114523. The Natural History of Congenital Hepatic Hemangiomas

Background: “Hemangiomas remain the most common tumor of the liver in newborns and infants…A subtype classification system for hepatic hemangioma (HH) was first proposed based on our Liver Hemangioma Registry in 2007, delineating focal, multifocal, and diffuse HH…Focal hepatic lesions correspond to congenital hemangiomas whereas multifocal and diffuse lesions represent infantile hemangiomas.”

Methods: This was a retrospective review of 96 infants over an 18 year period (2004-2022). Patients with infantile HH were excluded.

Key Findings:

  • 32% were diagnosed prenatally, 23% developed heart failure, and 23% developed respiratory failure
  • There was a balanced sex distribution (50% for each gender)
  • Common clinical features included transient anemia (n = 23/48, 48%) and thrombocytopenia (n = 30/53, 57%).
  • On average, patients demonstrated 43% residual HH volume at 12 months and 16% residual volume at 24 months
  • No difference in time to 50% HH volume reduction between patients with and without medical therapy was observed
  • Larger hemangioma volumes were associated with an increased risk of anemia (P = .005) and thrombocytopenia (P < .001)
  • There was not a significant association between HH volume and congestive heart failure (CHF) or cardiomegaly. For example, the HH volume was 824 mL vs 579 mL (P=0.689) in those with and without CHF, respectively

Discussion Points:

  • “Congenital HH is present at birth and typically does not undergo postnatal growth”
  • “Congenital HH occurs equally in males and females and is immunonegative for GLUT-1. This stands in contrast to infantile hepatic and cutaneous hemangioma, which exhibits an early proliferative phase followed by gradual involution”
  • “HH size at diagnosis was associated with respiratory failure but not with the development of cardiomegaly or CHF, suggesting intralesional shunting may not be related to absolute tumor volume. Hence, all HH regardless of size should be assessed for shunting by doppler US”
  • “We advocate consideration of cross-sectional imaging and/or biopsy if patients with presumed congenital HH do not follow the expected clinical behavior of early signs of involution”
  • “Although corticosteroids and propranolol have proven benefit for infantile HH, we
    demonstrate that there was no significant difference in the rate of congenital HH involution between patients who had received medical therapy and those that did not”
  • “Medical therapy does have a role in the medical management of high-output heart failure occurring secondary to shunting. If refractory to pharmacologic therapy, these patients
    should undergo embolization of symptomatic intrahepatic shunts”
The practice algorithm for evaluation and management of congenital HH suggested by the authors. *Obtain baseline labs and repeat as needed. Repeat CBC if lesion increases in size during
monitoring period and there is concern for intralesional bleeding. Repeat AFP as necessary to rule out hepatoblastoma. TFTs indicated if unclear whether congenital HH or infantile HH
.

My take: This is a very useful study. It is important to distinguish congenital HH from infantile HH. Even in those with congenital HH, “a subset of patients develop life-threatening complications including respiratory failure and CHF that warrant directed medical management.”

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.

Long-term Efficacy and Safety of Upadacitinib for Ulcerative Colitis

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R Panaccione et al. The Lancet Gastroenterology & Hepatology. 2025; 10: 507 – 519. Open Access! Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study

Methods: U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study that enrolled patients (n=369) aged 16–75 years with a confirmed diagnosis of moderately to severely active ulcerative colitis; patients who had a clinical response in the induction studies were eligible to enter the U-ACHIEVE maintenance study. Patients not in clinical remission originally randomly assigned to upadacitinib 15 mg were eligible to escalate to upadacitinib 30 mg, those originally randomly assigned to upadacitinib 30 mg continued on upadacitinib 30 mg, and those originally assigned to placebo were eligible to escalate to upadacitinib 15 mg in a masked way

Key findings:

  • In the as-observed population, 84 (71%) of 118 patients receiving upadacitinib 15 mg were in clinical remission at week 48, as were 130 (67%) of 193 receiving upadacitinib 30 mg
  • By week 96, 69 (76%) of 91 patients receiving upadacitinib 15 mg and 104 (74%) of 141 of those receiving upadacitinib 30 mg were in clinical remission
  • The most common adverse events of special interest were hepatic disorder, lymphopenia, creatine phosphokinase elevation, serious infection, neutropenia, and herpes zoster
mNRI indicates modified non-responder imputation analysis response

My take: This study shows a good durable (3 year) response to upadacitinib treatment with both 15 mg and 30 mg dosing.

Related blog posts:

    Eosinophilic Esophagitis: Once vs Twice Daily Steroid Treatment

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    CC Reed et al. Clin Gastroenterol Hepatol 2025; 23: 946-953. Open Access! Daily or Twice Daily Treatment With Topical Steroids Results in Similar Responses in Eosinophilic Esophagitis

    Methods: This was a retrospective cohort study using the UNC EoE Clinicopathologic Database of newly diagnosed patients with EoE treated with a tCS who had a follow-up endoscopy with biopsy. In total, there were 522 patients, including 195 pediatric patients (<18 yr). 122 patients received once daily dosing and 400 patients received twice daily dosing.

    At our center, patients are typically treated on a clinical basis with either oral viscous budesonide or fluticasone from a multidose inhaler, with daily doses ranging from 1–2 mg for budesonide and 440–1760 μg for fluticasone based on patient size and at the discretion of the provider.

    Key findings:

    • Global symptomatic response (78% vs 76%; P = .82), posttreatment eosinophil count (20.8 vs 25.6; P = .21), posttreatment EoE Endoscopic Reference Score (2.2 vs 2.2; P = .92), and histologic response (<15 eos/hpf; 56% vs 58%; P = .66) did not differ by dosing frequency
    • Candida was less frequent with daily dosing (2% vs 8%; P = .04)

    My take: This study suggests that once daily dosing can be as effective as twice daily dosing. It may be that the total dose administered may be more important than the frequency. More studies are needed to confirm these results.

    Related blog posts:

    Mediterranean Diet’s Impact on Crohn’s Disease Outcomes

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    Methods: In this prospective cohort study, consecutive adults (n=271) from 2 large IBD centers in Israel with newly diagnosed CD were recruited and followed prospectively. MED adherence was assessed by repeated food frequency questionnaires (FFQs) using a predefined inflammatory bowel disease Mediterranean diet score (IBDMED score), alongside validated MED adherence screeners. Crohn’s disease activity index (CDAI), C-reactive protein, fecal calprotectin, and microbial composition (16S-ribosomal RNA sequencing) were assessed each visit. Baseline serum and fecal samples were analyzed for targeted quantitative metabolomics.

    Demographic/Clinical data indicate 68% received biologics and 40% receiving immunomodulators. 32% received 5-ASA medications (despite lack of proven efficacy)

    Key findings:

    • Adherence to MED was associated with a noncomplicated CD course, and inversely correlated with CDAI, fecal calprotectin, C-reactive protein, and microbial dysbiosis index (all P < .05)
    • Increasing adherence to MED over time correlated with reduced CDAI and inflammatory markers (P < .05)
    • Adherence to MED correlated with a beneficial microbial cluster of commensals and short-chain fatty acid producers including Faecalibacterium, and with plant metabolites, vitamin derivatives, and amino acids 
    • Adherence to MED in the cohort group was comparable to the general non-IBD population in Israel

    Limitations: This was an observational study rather than an interventional study with a control group. Thus, the results could be influenced by reverse causality

    In the associated commentary by Abreu et al, it is noted that in Israel, “MED is more commonplace than in the US and other Western countries…Godny et al found that IBD patients had an average MED adherence score of 7.8, which is similar to that of the general non-IBD population in Israel; in contrast, the average MED adherence score in the US is 4–5.Godny et al’s CD patients consumed an average of 21 g of fiber per day; in a study we just completed, American CD patients consumed less than half that amount.13 Indeed, the baseline diets of American IBD patients are characterized by high amounts of saturated animal fat and almost no fresh fruits and vegetables…Another difference between the Israeli population and the typical American population is body mass index (BMI). The average BMI of patients in this study was 21.9 kg/m2 (interquartile range 20–25.3 kg/m2). This contrasts with the average BMI of the general US population of 30 kg/m2.”

    My take: This study shows an association between MED diet and better outcomes/less complications in adults with Crohn’s disease. Eating a good diet is an important part of treatment.

    Additional notes on dietary scores: “The IBDMED screener positively scored high consumption of MED-recommended dietary components such as fruits, vegetables, olive oil, legumes, nuts and seeds, and fish. It also positively scored low consumption of MED non-recommended dietary components such as red and processed meat, soft drinks, and sweets. To this we added several dietary features based on previous data associated with microbial composition and function. These included a positive score for plant diversity27 by scoring for different colors in the diet, consumption of fermented foods28 (specifically yogurt), and inclusion of starchy vegetables like potato in the whole grain category to promote diversity in the carbohydrate-rich food group, as well as support butyrate producers as we had previously shown.29 In addition, we aimed to positively score for relatively low UPF intake. To this end, we evaluated the average intake of sweets, snacks, sweet and savory pastries, soft drinks, and foods and drinks containing artificial sweeteners.”

    Related blog posts:

    Also, from Kim Beall, Cofounder and Managing Director of Nutritional Therapy for IBD:

    “If you haven’t been to the website recently, we have expanded the recipe database to over 1,000 recipes with many filterable aspects and we’ve just released a new nutrition tool, the IBD Nutrition Navigator to facilitate nutrition conversations between providers and patients to find the right nutritional starting point. This is a project led by Dr. Ananthakrishnan and a dedicated team of pediatric and adult medical advisors in a two year long development process. Many have told us this is a useful tool particularly for those less familiar with nutrition in IBD. We’re excited about it’s potential to integrate nutrition in practice, with “an option for every patient”. We appreciate your support in sharing our information, tools, and resources to advance IBD nutrition care.” Here’s the link to their website:

    How HLA DQA1*05 and Combination Therapy Modulate Treatment Outcomes in Children with Crohn’s Disease

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    J Adler et al. Am J Gastroenterol 2025; 120: 1076-1086. HLA DQA1*05 and Risk of Antitumor Necrosis Factor Treatment Failure and Anti-Drug Antibody Development in Children’s with Crohn’s Disease.

    This was a prospective, double-blind, placebo-controlled trial with 204 patients examining the clinical outcomes of anti-TNF with or without methotrexate (COMBINE).

    Key findings:

    • Treatment failure in HLA DQA1*O5: A trend toward increased treatment failure among HLA DQA1*05-positive participants was not statistically-significant (hazard ratio 1.58; P = 0.08).
    • HLA DQA1*05 and Treatment Failure Rate: During the followup period, HLA DQA1*05-positive patients had a 35% failure rate compared to 26% for those who were HLA DQA1*05-negative (P=0.098). The overall failure rate was 30%
    • Methotrexate Combined with HLA DQA1*05 Effect: Patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05-positive patients on placebo (hazard ratio 0.31, 95% CI 0.13-0.70; P = 0.005).
    • Anti-TNF Medication Comparison: Treatment failure was similar between infliximab and adalimumab, 29% and 33% respectively
    • Antidrug antibodies (ADA): A trend toward increased ADA development among HLA DQA1*05-positive participants was not significant (odds ratio 1.96, P = 0.09). The addition of methotrexate to the treatment regimen mitigated the risk of treatment failure among individuals positive for HLA DQA1*05 and reduced the odds of developing ADA by 90%.
    • Rate of ADA: “After further stratification, HLA DQA1*05-negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05-positive patients on placebo (odds ratio 0.12; P = 0.008).”

    Discussion Points:

    • “A retrospective by Fuentes-Valenzuela et al …found that if patients underwent proactive TDM, there was no increase in the rate of treatment discontinuation among those who were HLA DQ-A105 positive compared with HLA DQ-A105 negative”
    • “The totality of evidence suggests that HLA DQ-A1*05 seems to confer a risk of both immunogenicity and treatment failure, particularly among infliximab-treated patients. Furthermore, this risk may be mitigated by the use of proactive TDM and/or concomitant immunomodulators.”

    My take (borrowed in part from authors):  “40% of patients were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate.” The use of combination therapy (methotrexate with anti-TNF) was associated with the lowest failure rates.

    Also, unrelated article: DA Carlson et al. Gastroenterology 2025; 168: 1114-1127. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Congratulations to Dr. Garza from our group who was one of the authors

    Related blog posts:

    Dr. Arun Singh: Tips and Tricks to Managing Celiac Disease

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    Recently Dr. Arun Singh gave our group a terrific update on Celiac Disease. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

    Key points:

    • Celiac disease (CD) global prevalence is about 1.4%, though there are ‘pockets’ with much higher rates (~3% prevalence in Colorado). This equates to more than 3 million Americans with CD
    • There is a huge gluten free diet market of ~$7 billion. This market includes CD, nonceliac gluten sensitivity (NCGS) and those with wheat allergies
    • Many patients have atypical symptoms which can include ADHD, brain fog, headaches, and elevated LFTs. Many have silent CD with no symptoms
    • Higher risk groups include family members (~10% risk for 1st degree, ~80% risk for identical twin), autoimmune diseases (thyroid, diabetes, others), and genetic disorders (Down syndrome, Williams syndrome, Turner syndrome)
    • Transient elevation of TTG IgA is common. In TEDDY study, 19% had TTG IgA spontaneously normalize. Thus, a single abnormal lab is not reliable
    • Genetic testing can be a useful adjunct in a few specific situations, including prior to instituting a gluten challenge
    • 1-3% of those with celiac disease may be negative for HLA-DQ2 and HLA-DQ8
    • If a gluten challenge is needed, 12 weeks is ideal. However, if poorly tolerated, then consider endoscopy earlier and Dr. Singh recommends checking in with family 4-6 weeks into the challenge
    • Endoscopy recommendations: Taking a single biopsy per pass can improve orientation when obtaining duodenal biopsies (bulb and distal portion, 5-6 in total)
    • NASPGHAN has not updated comprehensive guidelines for CD in 20 years
    • A survey of NASPGHAN members indicated that ~40% utilize a “no-biopsy” approach in patients. Dr. Singh noted that the accuracy of this approach, based on data from North America, may be about 96%
    • Drug trials for CD require a biopsy-confirmed diagnosis
    • Surveillance practice is quite variable. Important to follow growth and serology. CHOP approach includes surveillance for type 1 DM
    • Followup endoscopy to assess mucosal healing is not the current standard of care but could be helpful in some patients
    • Among patients with potential CD, about 30% develop CD over time. Thus, these patients should be monitored (yearly labs, f/u scope after 2 years)
    • Nonresponsive/refractory CD: start with nutrition assessment, often needs a f/u scope before consideration of budesonide therapy (9 mg x 12 weeks) or gluten contamination elimination diet

    Related blog posts:

    Risks of GLP-1RA Therapy Related to Endoscopy: Three Studies and GLP1RA Nutrition Pearls

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    A recent Nutrition Pearls with one of our nutritionists, Baily Koch, as a moderator was very good: Christy Figueredo – Navigating GLP-1 Use in Pediatrics (episode 33, 58 minutes)

    A Faccisorusso et al. Clin Gastroenterol Hepatol 2025; 23: 715-725. Open access! Effects of Glucagon-Like Peptide-1 Receptor Agonists on Upper Gastrointestinal Endoscopy: A Meta-Analysis

    This is one of three articles discussing the issue of GLP-1RAs and potential complications with upper endoscopy. Faccisourruso et al performed a meta-analysis that included 13 studies (of 177 studies) involving a total of 84,065 patients.

    Key findings:

    • Patients receiving GLP-1RA therapy exhibited significantly higher rates of retained gastric contents (RGC) (OR, 5.56)
    • Rates of aborted and repeated procedures were higher in the GLP-1RA user group. The absolute risk of aborted procedure was 1% in GLP-1RA users compared to 0.3% in non-users. The absolute risk of a repeated procedure was 2% vs 1% respectively.
    • No significant differences were found in AE and aspiration rates between the 2 groups (OR, 4.04 and OR, 1.75 respectively). The absolute risk of aspiration was 0.3% in GLP1-RA users compared to 0.2% in non-GLP1-RA group
    • Adverse events were higher in GLP-1RA users (0.3%) compared to non-users (0.1%)

    In their discussion, the authors note that an “individualized approach based on the indication of GLP-1RA use (withholding the drug in patients with diabetes could lead to more harm)…a potential stragegy could be to place patients on a liquid diet the day before endoscopy, thus prolonging the duration of fasting for solid for at least 12 hours.”

    The related articles:

    My take: The totality of these studies confirms the increased risk of retained gastric contents in patients receiving GLP-1RAs. This in turn increases the need to abort/reschedule cases and may result in very a low increased risk of aspiration. To mitigate this risk, it may be sufficient to implement a liquid diet the day before endoscopy (avoiding solid foods for at least 12 hours prior to endoscopy). This is in agreement with the recent AGA Rapid Clinical Practice Update (see post below).

    Related article on utility of GLP-1RAs: David Kessler, NY Times  5/7/25: In a World of Addictive Foods, We Need GLP-1s

    “Like millions of others, I was caught between what the food industry has done to make the American diet unhealthy and addictive and what my metabolism could accommodate.

    We may now be at the brink of reclaiming our health. New and highly effective anti-obesity medications known as GLP-1s have revolutionized our understanding of weight loss and of obesity itself. These drugs alone are not a panacea for the obesity crisis that has engulfed the nation, and we should not mistake them for one. But their effectiveness underscores the fact that being overweight or obese was never the result of a lack of willpower…

    GLP-1s are revolutionary drugs that can drastically reduce caloric intake and improve health in a way I didn’t expect I would ever see. Now we need to complete that revolution by taking on the food industry and its engineered foods that are contributing to some of the most harmful health issues America faces today.”

    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.

    VISION 5-Year Study Results: Safety of Vonoprazan in Erosive Esophagitis

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    N Uemura et al. Clin Gastroenterol Hepatol 2025; 23: 748-757. Open Access! Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study

    Background: Potassium-competitive acid blockers, such as vonoprazan, provide more potent gastric acid suppression than proton pump inhibitors. However, long-term safety data are lacking for vonoprazan in patients with healed erosive esophagitis. This study with 208 patients provides long-term data on the use of a vonoprazan.

    Methods: Open-label study. Patients with erosive esophagitis (EE) received induction therapy (once daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). 

    Key findings–Adverse effects:

    • No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was 1 adenoma in each group
    • At week 260, significantly more patients taking vonoprazan vs lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%)
    • proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar
    • Median serum gastrin levels were higher with vonoprazan treatment vs lansoprazole (625 pg/mL vs 200 pg/mL)

    Key finding –Efficacy:

    • Overall, the cumulative EE recurrence over 260 weeks was lower in the vonoprazan group (10.8% ) vs the lansoprazole group (38.0%) (P = .001)  

    Discussion Points:

    • “Annual endoscopies and biopsies performed in the VISION study are considered objective approaches for detecting upper gastrointestinal diseases and variable lesions, as well as gastric mucosa morphological changes in areas without endoscopically apparent lesions…Although the proportions of patients with parietal cell protrusion and foveolar hyperplasia were higher in the vonoprazan group than in the lansoprazole group over 5 years, the clinical significance of these findings is unclear.”
    • “The safety profiles of vonoprazan and lansoprazole were also comparable, suggesting that long-term use of vonoprazan is as safe as PPIs.”

    My take: This study provides some reassurance regarding the risk of using vonoprazan & other potassium-competitive acid blockers. The benefits of controlling erosive esophagitis may outweigh potential safety risks of long-term use. Nevertheless, it will be a while before this class of medications is used extensively in the pediatric age group.

    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.

    Head-to-Head: Tirzepatide Outperforms Semaglutide

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    LA Aronne et al. NEJM 2025; DOI: 10.1056/NEJMoa2416394. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity

    Methods: In this phase 3b, open-label, controlled “SURMOUNT-5” trial, adult participants (n=751) with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks

    Key findings:

    Discussion Points:

    “With both treatments in our trial, as weight reduction increased, greater improvements occurred in cardiometabolic risk factors, including blood pressure, glycemia, and lipid levels, which is consistent with the findings in previous reports.17 The mean differences between tirzepatide and semaglutide in the cardiometabolic risk factors may be clinically relevant considering that reductions in systolic blood pressure of 2 to 5 mm Hg have been shown to reduce the risk of cardiovascular events.”

    ” As typically observed with incretin-based therapies, gastrointestinal adverse events were predominantly mild to moderate in severity, occurred mostly during dose escalation, and led to treatment discontinuation more often with semaglutide than with tirzepatide.”

    My take (borrowed from the authors):  “Treatment with tirzepatide, a dual GIP and GLP-1 receptor agonist, was superior to treatment with semaglutide, a selective GLP-1 receptor agonist, with respect to reduction in body weight and waist circumference.”

    Related blog posts: