Scientific Basis for Current Hepatitis B Vaccine Strategy

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AS Lok et al. Gastroenterology. (In press) Open Access! Hepatitis B Vaccination: A Remarkable Success Story That Must Continue

For those trying to understand the success of the current HBV immunization strategy and why altering the timing of HBV vaccinations is a bad idea, this is a worthwhile article.

Key points:

  • “To date, more than 1 billion doses of HepB vaccines have been administered worldwide, and they are considered one of the safest and most effective vaccine ever made.1,2,6“
  • “Because of the high risk for chronic HBV infection, the CDC/Advisory Committee on Immunization Practices (ACIP), WHO, and health ministries of many countries recommend universal HBV vaccination of all infants beginning with a “birth dose” for newborns, preferably within the first 24 hours of birth, followed by completion of the 3-dose infant vaccination schedule…Implementation of routine infant and childhood vaccination, including birth dose HBV vaccine, prevented an estimated 210 million infections globally between 1980 and 2015.4“
  • “In 1991, with evidence showing substantial number of infants and others at risk were missed by a risk-based approach to HepB vaccination, the ACIP recommended universal HepB vaccination for all infants, with the first dose administered before hospital discharge along with hepatitis B immune globulin (HBIG) for infants born to mothers who tested positive for HBsAg or whose HBsAg status was unknown.5,6,14“
  • “In 2018, the CDC/ACIP recommendation specified that the birth dose of HepB vaccine should be administered within 24 hours of birth including for preterm infants, regardless of maternal HBsAg status.14 …Timely birth dose HepB vaccination regardless of maternal HBsAg status serves as a safety net for perinatal transmission from HBsAg-positive mothers missed by HBsAg screening programs and protects against the small but non-zero risk of HBV infections from household and other exposures for infants born to HBsAg-negative mothers.”
  • “HepB vaccination alone prevents 75% to 80% of perinatal HBV transmission.2 The addition of maternal HBsAg screening and further testing for hepatitis B e antigen or HBV DNA if HBsAg test is positive allows for additional interventions to eliminate mother-to-child transmission of HBV.”
US CDC recommendations for HBV vaccination. Decline in reported number of acute HBV infections in the United States in association with CDC recommendations for HBV vaccination, 1980–2022.

My take (borrowed in part from authors): It would be a big mistake to resume the risk-based approach to newborn HepB vaccination. “HepB vaccine is a safe and highly effective vaccine. HepB vaccination prevents an incurable chronic infection and related morbidity and mortality from cirrhosis and HCC. Indeed, HepB vaccine is the first cancer-prevention vaccine…Universal HepB birth dose vaccination regardless of maternal HBsAg status is the most effective as well as the most cost-effective strategy in eliminating HBV infection. Newborns and infants are those at highest risk of chronic HBV infection. Delaying the first dose of HepB vaccine even by a few days exposes the infants to increased risk of developing lifelong infection,18 chronic liver disease, and premature death.”

NASPGHAN has sent a letter urging the ACIP committee to continue the current immunization schedule:

“Delaying the first vaccine in the series to one-month, four years, or 12 years of age will
undermine the vaccine’s effectiveness, and relying on just screening pregnant women for
hepatitis B is insufficient.

Although some of the changes that have been discussed by ACIP sound small, they are not
grounded in new evidence and would undo more than three decades of a prevention
strategy that has nearly eliminated early childhood hepatitis B in the United States.“

Related blog posts:

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.

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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.

Post-Endoscopic Fever in Pediatric Intestinal Failure & Short Bowel Syndrome Patients

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J Hilberath et al. J Pediatr Gastroenterol Nutr. 2025;81:736–742. Open Access! Post‐endoscopic fever and infection in paediatricpatients with intestinal failure

Methods: This was a retrospective single-center observational study which included children with IF and CVC who underwent GI endoscopy between 2019 and 2024. Intravenous antibiotic prophylaxis was used in 71.2% of the procedures.

Key findings:

  • The overall post-endoscopic fever (PEF) rate was 6%, with no significant difference between the group that received prophylactic antibiotics and the group that did not. Specifically, there were 10 with PEF that had received prophylactic antibiotics and 4 that had PEF with no prophylaxis
  • No infections, including central line-associated bloodstream infections, were observed
  • 5/14 of the cases with PEF had an interventional procedure. The remainder had a diagnostic EGD, colonoscopy or both.

Interventional Cases:

Discussion Points:

  • “PEF in children with IF was 6%, which is approximately 10 times higher than the recently published 0.55% in pediatric patients following endoscopic procedures by Boster et al.” (see: Must-Read: How to Handle Post-Procedure Fevers)
  • A strength of this study was that the comparison of children with IV antibiotics versus those without was due to an institutional policy change in 2022. This helps eliminate selection bias in the determination that IV antibiotics were not beneficial in preventing PEF

My take: The high rate (6%) of PEF should be discussed with families prior to endoscopic procedures. The rate was increased (36%) in those with interventional procedures. It is reassuring that no definitive infections were identified despite the fevers.

Related blog post: Must-Read: How to Handle Post-Procedure Fevers

New Trend: Oral Medicines Replacing Injections

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  • R Bissonnette et al. NEJM 2025; 393: 1784-1795. Oral Icotrokinra for Plaque Psoriasis
  • RS Stern. NEJM 2025; 303: 1854-1855. Oral Psoriasis Therapy — For Whom and at What Cost and Risk?
  • S Wharton et al. NEJM 2025; 303: 1796-1806. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment

In the ICONIC-LEAD study (Bissonnette et al), 684 adolescents and adults participated in a DBPC trial with an oral peptide, icotrokinra, which binds the IL-23 receptor. This medication is of interest as there are ongoing trials with it for inflammatory bowel disease. Other injectable medications targeting IL-23 are already approved for IBD.

Key Findings:

The associated editorial notes that this new therapy is likely to cost ~$70,000 per year. The cost of psoriasis care has increased more than 2000% since 1997. “Because of these high prices, rebates and discounts to pharmacy benefit managers that often guide formulary preferences are likely to govern clinician’s selection of immune-based oral and parenteral therapies for psoriasis.”

In the ATTAIN-1 Trial (Wharton et al), the authors share the results of an oral GLP-1 Receptor Agonist, Orforglipron, monotherapy for obesity.

Key findings:

My take: There are similar injectable alternatives to each of these medications for psoriasis, obesity and diabetes. The availability of oral medications could reduce one barrier to treatment. Cost barriers may preclude their use in many patients when they become available. In addition, long-term outcome data are still needed.

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Microplastics Impact on Gastrointestinal Health

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DA Johnson et al. Am J Gastroenterol 2025; DOI: 10.14309/ajg.0000000000003417. Plastics: Here, There, and Everywhere: Implications for Gastrointestinal Health and Disease

This article reviews the growing health concerns regarding microplastics and nanoplastics (MNPs) specifically regarding the GI tract.

Key points:

  • “As these [plastic] products degrade, they break down into smaller particles, forming microplastics (< 5 microm) and nanoplastics (<1 microm), collectively referred to as
    MNPs”
  • “Although many plastic products are deemed recyclable, in the United States, less than 10% are actually recycled…annual global production projected to reach 1.1 billion tons by 2025. Simultaneously, over 12 billion tons of plastic wastes are expected to accumulate in landfills”
  • “The average American ingests approximately 5g of plastic per week, equivalent to 1 credit card, and 39,000–50,000 particles annually”
  • Potential association of MNPs with metabolic-associated steatotic liver disease, liver and pancreatic cancer and inflammatory bowel disease. “Studies have reported
    significantly higher levels of MNPs in patients with IBD compared with healthy controls.”

In a related article in Gastroenterology and Endoscopy News (October 2025), Dr. Johnson noted that “reduction of plastic intake from bottled water to tap water in one study reduced microplastic intake, the number of particles within human tissues, from 90,000 to 4,000…Avoid heating food in plastics…the effect of microwave increased the evidence of microplastics by over 4.2 million and the nanoplastics, 2 billion, just in three minutes in the microwave.”

My take: Something that almost everyone could agree on – they would like less plastic in their food and environment. How to achieve this is much more difficult.

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“Truly Prioritizing Child Health — The Missed Opportunities of the MAHA Commission”

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JM Perrin, TL Cheng. NEJM 2025; 393: 1869-1872. “Truly Prioritizing Child Health — The Missed Opportunities of the MAHA Commission”

This commentary welcomes the attention to child health which was a focus of the MAHA commission. This review provides perspectives on the stated policy aims and on what else is needed.

An excerpt:

The [MAHA] commission has highlighted four specific areas of concern: poor diet, environmental chemicals, lack of physical activity and chronic stress, and overmedicalization. The strategy outlined in the MAHA Commission’s recent report, however, misses real opportunities to address the chronic disease epidemic and “whole-person health”…

The MAHA Commission’s view of the state of U.S. child health ignores leading contributors to rising childhood morbidity and mortality: firearm injuries (the leading cause of death among U.S. children), drug overdoses, and motor vehicle injuries. Most striking is the commission report’s silence regarding the association of poverty with poor child health… which contributes to higher rates of asthma, obesity, and mental health conditions...

The first MAHA priority, children’s diets, has long been a concern of the U.S. child health community, particularly the intake of sugar-sweetened beverages, excessive portion sizes, and food additives. But pediatricians and researchers also know that food insecurity, food-industry marketing practices, and limited access to healthy foods are prime drivers of childhood obesity rates. Nutritious meals require money…

The MAHA strategy recommends marginal changes to the diets of U.S. children, such as reducing the use of food dyes and reducing consumption of ultraprocessed foods, even as the government is increasingly limiting public food assistance.

The commission’s focus on environmental chemicals is appropriate, given that exposures to potentially toxic chemicals in foods, household supplies, cleaning agents, farm supplies, and elsewhere have grown dramatically. The MAHA strategy provides little relief, however: a few research projects and no regulatory change…The MAHA report stops short of recommending the research and regulatory reform necessary for identifying, restricting, and mitigating harmful exposures.

Concerns about physical activity and stress are also justified. Many studies have documented alarming declines in physical activity, examined the causes and effects, and found associations with mental health and well-being… Strengthening early-childhood, school-based, and community-based physical activity programs, as well as social media strategies for promoting lifestyle changes, could improve health and reduce stress among young people, but the MAHA Commission mainly orders schools and communities to increase physical activity.

Finally, the commission has raised concerns about medications, especially stimulants and psychotropic agents…In response, the MAHA Commission primarily proposes studying prescribing patterns and “solutions that can be scaled up to improve mental health.” It does not address more fundamental ways of changing medication use…

Despite its attention to children’s health, the MAHA Commission’s lengthy list of aspirations and recommended changes is unlikely to make a real impact. Instead, next steps should include implementing policies, programs, and research supported by the strong evidence base that clinicians and investigators have built painstakingly for many years.

My take: The policies pursued by the current administration like limiting food dyes do not target the big drivers of poor health outcomes in children.

The authors of this commentary also “chaired the National Academies of Sciences, Engineering, and Medicine (NASEM) study described in “Launching Lifelong Health by Improving Health Care for Children, Youth, and Families”1 [which] provides clear, evidence-based lessons that could help in achieving MAHA objectives.”

Reference: National Academies of Sciences, Engineering, and Medicine. Launching lifelong health by improving health care for children, youth, and families. Washington, DC: National Academies Press, 2024 (https://nap.nationalacademies.org/catalog/27835/launching-lifelong-health-by-improving-health-care-for-children-youth-and-families).

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Childhood Poverty Rates: Shown is the percentage of children in households with incomes below 60% of the median national income. Data are from UNICEF and reflect averages from 2019 through 2021.

Long-Term Outcomes of Pediatric Intestinal Malrotation

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KE Corcoran et al. J Pediatr Gastroenterol Nutr. 2025;81:1166–1170. Open Access! Long-term gastrointestinal outcomes in pediatric intestinal malrotation patients following operative treatment

It is well-recognized that patients with prior intestinal malrotation have frequent GI symptoms after repair. This retrospective study with 354 children (using TriNetX EMR database) quantitates these problems compared to a control group.

Key findings:

  • Symptoms were less severe at years 3-5 post-index for IM group: constipation 29.4%, Abdominal pain 16.4%, Nausea/Vomiting 21.2%, Diarrhea 9.6%, and GERD 22.3%.

My take: While database studies have numerous limitations, it is clear that having a history of intestinal malrotation poses a significant risk of persistent GI symptoms after repair. It will be worthwhile for families to be informed of this at the time of IM repair.

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“You Still Going to be Doing This?”

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EJ Shapiro. NEJM 2025; 393: 1360-1361. “You Still Going to be Doing This?”

This commentary mirrored a lot of my recent experience. The author is startled at how patients are asking if he will still be taking care of patients in a few years and how he has enjoyed being a clinician.

Here is an excerpt:

At first, I was startled — I’d never seriously considered the timeline of my own career…Whether it was thanks to luck, sound reasoning, some resolution of my cognitive dissonance, or (least likely) an easy disposition, I mostly enjoyed the ride. Medical school flew by…every rotation opening a new world…As a resident, then a fellow, I learned the delicate balance between personal responsibility and teamwork required in caring for patients facing the range of problems…

Then…I …realized that my opinion — no discussion with the team, no attending cosignature, just mine alone — would guide this patient’s care… So many lives shared, some with laughter, less often with tears. Many of them I helped, and some I probably didn’t…

I realize the time has come to try to figure out the answer to, “Are you still going to be doing this?” But the decision doesn’t come easily. On a day-to-day basis, I love what I do, mostly because of the connections with those patients, and the nurses, techs, secretaries, medical assistants, and my partners (some of whom are now in my children’s age group). Also because medicine always changes and always fascinates.

Of course, prior authorizations, electronic medical record snafus, obtuse hospital administrators, and sometimes the clinical demands can feel oppressive… But… when I go into the exam room, close the door, greet the patient, and begin our visit, none of those structural irritants matter. We explore their situation and try to figure out how to move forward. The challenge and respect of that task never really pale…

Still, all the other passions, affections and hobbies, grandchildren, books, and mountains call out…And… I’d rather go when the reaction from the people left behind will be regret rather than relief…

I still have some things to consider before I put that full stop on my medical career, but maybe at some point the choice will become clear — like the one that long ago began it. Everything has its season.

My take: Though I am not ready to retire, I am getting the question from families about when I might and have started to think about the next season.

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“Self-Portrait with Straw Hat” at the Metropolitan Museum of Art

Dr. Jim Squires: Practical Approach to Pediatric PSC and Pointers on Unconjugated Hyperbilirubinemia (Part 2)

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Recently Dr. Squires 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.

  • Bilirubin is derived from the breakdown of red blood cells.
  • Each red blood cell contains approximately 250-300 million molecules of hemoglobin. Each molecule of hemoglobin can transport four oxygen molecule; thus a single RBC can carry one billion oxygen molecules
  • Unconjugated bilirubin binds to albumin and is taken into cell by OAT1B1 membrane transporter. Conjugation occurs in the endoplasmic reticulum.
  • Three main causes of indirect hyperbilirubinemia: defective bilirubin uptake, defective bilirubin conjugation, and hemolysis. In older patients, medications are another reason for indirect hyperbilirubinemia
  • Evaluation for hemolysis can include CBC, LDH, Haptoglobin, and retic count
  • Breastmilk jaundice (aka Lucey-Driscoll syndrome) is a different entity than “suboptimal intake jaundice” (aka breastfeeding jaundice). Suboptimal intake jaundice occurs in the fist week of life. Due to less intake, there are increased delays in meconium passage and increased reabsorption of bilirubin. Breastmilk jaundice which is much less common can result in very elevated indirect bilirubin levels.
  • With Gilbert, the molecular defect affects the promoter region of the UGT1A1 gene. Defects here are less critical than with Crigler-Najjar. For Gilbert’s, it is like there are fewer exits to reduce bilirubin. Whereas with severe forms of Crigler-Najjar, it is like all of the exits are blocked
  • Especially in the newborn period, very elevated unconjugated hyperbilirubinemia can result in kernicterus/severe neurologic sequelae. This can occur at older ages as well. The risk is related to the bilirubin to albumin ratio
  • For Crigler-Najjar, phototherapy is less effective with age and is associated with a reduction in the ratio of body surface area to plasma volume

Conclusions:

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Dr. Jim Squires: Practical Approach to Pediatric PSC and Pointers on Unconjugated Hyperbilirubinemia (Part 1)

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Recently Dr. Squires gave our group a terrific lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

Key points:

  • 2023 AASLD Practice Guidance is very helpful and Dr. Squires considers its advice akin to a ‘North Star’
  • There are several etiologies for the sclerosing cholangitis phenotype – including primary disorders and secondary causes.
  • Pancolitis is most common presentation of IBD with PSC, often with rectal sparing and backwash ileitis
  • PSC often has subclinical inflammation and poor growth. PUCAI scores typically underestimate IBD activity
  • Diagnosis can be challenging – but often “I know it when I see it”
  • MMP-7 is still being studied as a biomarker. Thus far, it appears a little better than GGT and Alk phos as a marker for biliary injury
  • ERCP should be avoided as part of diagnostic workup but is important for therapeutic intervention

Deneau et al (Hepatology 2017; 66: 518) study wit 781 children has a wealth of information on natural history. In children, 38% developed portal HTN and 25% developed biliary complications over 10 years. However, once these complications developed, the need for transplantation develops more quickly. Median survival with native liver after the development of portal HTN was 2.8 yrs and it was 3.5 yrs after development of biliary strictures

  • Cholangiocarcinoma is rare in pediatrics ~1%
  • ASC (overlap of AIH and PSC) is fairly common in children and often a manifestation of early PSC. Many evolve to PSC without overlap features. Dr. Squires counsels families that most patients will need multiple biopsies to help determine need for ongoing immunosuppression
  • In patients with IBD, some liver test abnormalities and autoimmune features may be transient. Some watchful waiting may be beneficial prior to extensive evaluation
  • Multiple factors can predispose to PSC, including EBV infection which is associated with OR 12. Genetics, environment, immune dysregulation, toxic bile acids, microbiome, leaky gut/inflammation are additional factors
  • SCOPE is very useful prognostic tool
  • Ursodeoxycholic acid (UDCA) is a first line therapy. However, if no response to treatment, it is likely not beneficial
  • Oral vancomycin has not been proven to improve liver outcomes in PSC thus far (not recommended by AASLD 2023 Practice Guidance). However, further studies are ongoing and it has been associated with improvement in IBD activity

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