Biliary atresia (BA) is a fibro-obliterative disease process of unknown etiology affecting the biliary tract in infants. BA eventually leads to cirrhosis and is the leading cause of liver transplantation in infants. Since changes in the intestinal microbiome are associated with chronic liver disease in adults, the authors of this study looked for similar issues occurring in infants with BA. Research previously done by this group has demonstrated increased alpha-diversity of pathogenic intestinal bacteria with an associated decrease in potential beneficial bacteria in children with BA who had underwent hepatoportoenterostomy (the “Kasai procedure” (KP)) and had worse surgical outcomes. This current study evaluated gut bacterial translocation and intestinal barrier function in children with BA.

Infants with BA were recruited in a prospective manner and were assessed at 6 weeks, 12 weeks, and 24 weeks post-KP. Prior to KP, all infants had standard blook work and demographics obtained. They also underwent liver biopsies to assess for fibrosis. After KP, standard blood work for liver disease as well as hepatic elastography studies were obtained. Additionally, blood and stool specimens were obtained to assess for intestinal barrier function and evidence of bacterial translocation.  

A total of 55 infants with BA were recruited for the study for which 33 infants had no jaundice at 6 months after KP while the rest of the patient group continued to have jaundice. Patient demographics were similar between the two groups. Liver transplantation occurred in 24 of the 55 infants by 2 years of age for which 91% of those infants requiring liver transplantation had no clearance of jaundice by 6 months after KP. At least one episode of cholangitis occurred with 26 of the 55 infants by 6 months after KP for which 64% of these specific infants were still jaundiced at 6 months after KP.  

A comparison occurred between patients who were cleared of jaundice after KP and those that did not clear jaundice after KP. Although markers for intestinal barrier function and bacterial translocation were similar between the two patient groups prior to KP, differences were noted very soon after KP. At 6 weeks post KP, intercellular adhesion molecule 1 (ICAM-1), interleukin-4 (IL-4), and claudin-3 were significantly elevated in the patient group with continuing jaundice after KP.  By 12 weeks post KP, ICAM-1, IL-8, IL-1ß, and claudin-3 were significantly elevated in the patient group with continuing jaundice after KP. By 24 weeks post KP, ICAM-1, IL-2, IL-6, IL-8, IL-1ß, tumor necrosis factor alpha (TNF-ɑ), and vascular cell adhesion molecule 1 (VCAM-1) were significantly elevated in the patient group with continuing jaundice after KP.

Univariate analysis done at 6 weeks post KP demonstrated that elevated levels of total bilirubin, serum aspartate aminotransferase (AST), ICAM-1, and claudin-3 were significantly associated with persistent jaundice. A multivariate analysis demonstrated that elevated levels of ICAM-1 and claudin-3 were significantly associated with jaundice at 24 weeks post KP. VCAM-1, ICAM-1, TNF-ɑ, lipopolysaccharide (LPS), and intestinal fatty acid binding protein (IFABP) all increased significantly from before KP to 24 weeks post KP in patients who remained jaundiced. A significant correlation of total bilirubin levels after KP was found with ICAM-1 levels at 6 weeks post KP; with ICAM-1, IL-8, IL-1ß levels at 12 weeks post KP; and with ICAM-1, IL-8, IL-1ß, IL-6, IL-2, and VCAM-1 levels at 12 weeks post KP.

In terms of fibrosis correlation, only ICAM-1 was significantly associated with an elevated AST-to-platelet ratio prior to KP although liver histology prior to KP was not associated with ICAM-1 levels. ICAM-1 and VCAM-1 were significantly associated with an elevated AST-to-platelet ratio and liver stiffness measured by elastography at 6 weeks post KP.  IL-1ß, TNF-ɑ, IL-8, IL-4, and IL-2 were significantly associated with an elevated AST-to-platelet ratio at 12 weeks post KP.  Only ICAM-1 was associated with an elevated liver stiffness measurement as measured by elastography at 24 weeks post KP. D-lactate (used to demonstrate bacterial translocation) was significantly associated with hepatic fibrosis only at 12 weeks post KP.

In terms of markers of bacterial translocation and inflammation, lipopolysaccharide binding protein (LBP) levels were significantly correlated with IL-6 and TNF-ɑ at 6 weeks post KP; were significantly correlated with D-lactate and ICAM-1 at 12 weeks post KP; and were significantly correlated with IL-6 and IL-17 at 24 weeks post KP. Using 16S rRNA amplicon sequencing, the most common bacteria identified in fecal specimens at all time points post KP included Enterococcus, Clostridium, Fusobacterium,and 10 other bacterial species. Finally, elevated fecal calprotectin levels were significantly associated with severity of jaundice in infants at 24 weeks post KP.

This study demonstrates that gut inflammation and potential bacterial translocation into the bloodstream of infants with BA who undergo KP may be associated with worse surgical outcomes. The authors point out that claudin-3, which is a biomarker for tight junction integrity, may be an effective screening tool to determine potential outcomes after KP in children with BA.

Jain V, Nulty J, Alexander E, Buford C, Davenport M, Chokshi S, Riva A, Dalby M, Verma A, Hall L, Yuksel M, Dhawah A. Claudin-3, Lipopolysaccharide Binding Protein, and Jaundice Clearance in Infants with Biliary Atresia. Journal of Pediatrics 2025; 286: 114703.

Using H. pylori Antibiotic Sensitivity to Drive Treatment in Children

Helicobacter pylori (H. pylori) is a gram-negative bacteria associated with gastric infections worldwide. Besides causing gastritis and peptic ulcer disease, a chronic infection by this bacterium can lead to gastric adenocarcinoma and MALT lymphoma. Antibiotic therapy is essential for curing this infection, and it would be especially important to identify a correct antibiotic regimen as H. pylori is associated with a high rate of antibiotic resistance. The authors of this study evaluated the efficacy of susceptibility-guided treatment (SGT) compared to empirical therapy (ET) for H. pylori.

This retrospective study occurred at a single tertiary care children’s hospital in the United States.  All included patients had a history of a biopsy-proven initial H. pylori infection and had received antibiotic treatment. All patients were treated for H. pylori using the 2016 Joint ESPGHAN / NASPGHAN guidelines for treatment of H. pylori in children (see https://www.naspghan.org/files/Joint_ESPGHAN_NASPGHAN_Guidelines_for_the.33.pdf).

All patients treated either by ET or by SGT underwent testing for H. pylori eradication by either fecal antigen screening or by repeat esophagogastroduodenoscopy (EGD) with biopsy.

A total of 238 patients were diagnosed with an initial H. pylori infection over a 5-year period (2019 to 2024). After excluding patients who had received no therapy, had no H. pylori culture sent, or had a culture with no bacterial growth, a total of 218 patients were left for which 95 patients underwent ET and 123 patients underwent SGT. Mean patient age was 13.6 ± 4.8 years, and 50.9% of patients were male. The most common endoscopic finding was gastritis in 92.7% of patients with 100% of patients having gastritis on histology. Antibiotic resistance was present in 45.5% of H. pylori cultures with the most common single antibiotic resistance being clarithromycin at 26.8%. The most common dual antibiotic resistance was clarithromycin and metronidazole at 10.6%. No cultures demonstrated resistance to tetracycline. The most common treatment for H. pylori in the study was clarithromycin-based triple therapy which was used in 41.3% of patients. Subsequent eradication was achieved in 80.7% of patients.

Age, sex, and ethnicity were not associated with antibiotic treatment failure in patients treated with either ET or SGT. However, patients categorized as “white” had significantly higher eradication rates. Treatment failure rates were significantly higher in those infections associated with amoxicillin resistance as well as in infections associated with clarithromycin-metronidazole dual resistance. Amoxicillin use was significantly associated with eradication while a history of prior amoxicillin, clarithromycin, and metronidazole use were significantly associated with treatment failure.  

Eradication was significantly higher in those patients treated using SGT (89.4%) compared to ET (70.2%). Univariate analysis demonstrated that patients who received amoxicillin during therapy, received clarithromycin during therapy, received metronidazole during therapy, or had received any of these three antibiotics in the past were significantly less likely to achieve eradication with no other factors reaching significance. Multivariate analysis demonstrated that amoxicillin use was the sole factor associated with H. pylori eradication.  

This study clearly demonstrates that H. pylori eradication was superior when using SGT. Amoxicillin bacterial resistance and prior use of antibiotics seemed to be a significant issue in preventing eradication in this patient population. Obtaining H. pylori cultures to drive directed antibiotic therapy is recommended and should be more widely available.

Chan C, Bousvaros A, Goldsmith J, Liu E, Bonilla S. Antimicrobial Susceptibility-Guided Treatment is Superior to Empiric Therapy for Helicobacter pylori Infection in Children. Journal of Pediatric Gastroenterology and Nutrition. 2025; 81: 1133-1141.