Combination biologic therapy in pediatric inflammatory bowel disease: Safety and efficacy over a minimum 12-month follow-up period.

OBJECTIVES: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD. METHODS: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ). RESULTS: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission. CONCLUSIONS: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.

C-Reactive Protein/Albumin Ratio at Diagnosis of Pediatric Inflammatory Bowel Disease: A Retrospective Multi-Center Study.

BACKGROUND This study aimed to evaluate the C-reactive protein-to-albumin (CRP/albumin) ratio at diagnosis of pediatric inflammatory bowel disease (IBD). MATERIAL AND METHODS Serum CRP/albumin ratio was calculated for patients with Crohn's disease (CD; n=186) and ulcerative colitis (UC; n=159) aged 3-18 years. RESULTS Patients with CD differed in CRP/albumin ratio at diagnosis in groups with quiescent, mild, moderate, and severe disease (P=0.011). CRP/albumin ratio at diagnosis was significant in differentiating patients with severe CD from quiescent disease at diagnosis (area under the curve (AUC)=0.94, odds ratio (OR)=63.4, 95% confidence interval (CI) 7.1-569.1, P<0.0001). CRP/albumin ratio at diagnosis could moderately differentiate penetrating from non-penetrating disease behavior in CD at diagnosis (AUC=0.73, OR=6.3, 95% CI 2.0-19.3, P<0.001). Furthermore, CRP/albumin ratio at diagnosis weakly differentiated IBD patients in need of biological treatment in a step-up procedure (AUC=0.58, OR=2.1, 95% CI 1.3-3.4, P=0.022) and in need of surgery (AUC=0.63, OR=3.1, 95% CI 1.4-7.2, P=0.006). For the IBD, CRP/albumin ratio at diagnosis was weakly correlated with age at first immunosuppressive treatment (rho=0.20, P=0.018), time from diagnosis to first biological treatment (rho=-0.37, P<0.001), days spent in hospital (rho=0.26, P=0.007), number of severe relapses (rho=0.31, P=0.001), and Pediatric Crohn's Disease Activity Index (rho=0.38, P=0.002). CONCLUSIONS The present findings add to previous studies carried out in adult patients and show that the CRP/albumin ratio at diagnosis was not significantly associated with the course of either CD or UC in children. However, CRP/albumin ratio could differentiate patients with severe CD from those with quiescent disease.

Effect of the Crohn's Disease Exclusion Diet (CDED) on the Fecal Calprotectin Level in Children with Active Crohn's Disease.

(1) Background: The CDED + PEN (partial enteral nutrition) is a promising method of nutritional treatment in active Crohn's disease (CD). An increase in fecal calprotectin (FCP) level­a marker of mucosal inflammation­happens to be the first evidence of Crohn's disease exacerbation that appears ahead of clinical symptoms and usually co-exists with them. In this study, we present our own experience with using the CDED + PEN in the treatment of children with CD and an increased FCP level. (2) Methods: In total, 48 children (male/female: 27/21) aged 4−17 years (median value = 13.43; IQR = 4.00) were treated with CDED + PEN between June 2019 and July 2021. The main inclusion criteria for the study was active CD defined as an FCP level ≥ 250.00 µg/g. Patients with severe clinical manifestation of CD (PCDAI >40.00), as well as ones who started any new concomitant CD treatment later than at least 4 weeks before the start of dietary intervention, were excluded from the analysis. The PCDAI and fecal calprotectin level were assessed at weeks 0 and 12. The primary endpoint was ITT normalization of FCP level, i.e., a result < 250.00 µg/g at week 12. The Wilcoxon Matched Pairs Test was used for statistical analysis. (3) Results: The normalization of the FCP level was obtained in 17 children (35.42%) and an FCP level decrease of at least 50% occurred in 26 patients (54.17%). The reduction in fecal calprotectin level between week 0 and week 12 was statistically significant with a median value of 1045.00 µg/g; IQR = 1188.00, and 363.00 µg/g; IQR = 665.00, respectively (p < 0.05). Among 29 patients who were not in clinical remission at baseline, 16 (55.17%) achieved clinical remission (PCDAI < 10.00) at week 12 and 20 (68.97%) obtained a clinical response defined as at least a 12.50 point drop in PCDAI or remission. In this group, the reduction in PCDAI between baseline and week 12 was statistically significant (median value = 20.00 points; IQR = 7.50 and 5.00 points; IQR = 5.00, respectively (p < 0.05)). All patients with a normal FCP level at week 12 were in clinical remission and 16 (94.13%) of them had a normal CRP (C-reactive protein) value. In 10 children (20.83%) the full course of 12 weeks with CDED + PEN was not completed or the concomitant therapy had been started before week 12 due to the lack of efficacy/intolerance of nutritional treatment. (4) Conclusions: The 12-week course of treatment with the CDED + PEN has a beneficial effect on the fecal calprotectin level in children with active CD. The dietary intervention led to a significant decrease in the FCP level in the studied group and to the normalization of this parameter in every third patient.

Dual Biologic Therapy in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Retrospective Study.

BACKGROUND: Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort. METHODS: Fourteen children (nine ulcerative colitis, one ulcerative colitis/IBD-unspecified, four Crohn's disease) with a disease duration of 5.2 (8 months-14 years) years, initiated dual therapy at an age of 11.7 (3-17) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab/adalimumab (VDZ + ADA), five (36%) with ustekinumab/adalimumab (UST + ADA), and three (21%) with infliximab/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up. RESULTS: A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC/IBD-unspecified, 4 CD) on the PCDAI/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 µg/g (140-10,100) to 586 µg/g (5-3410; p = 0.028) between baseline and 4 months. CONCLUSIONS: Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic options.

HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn's disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.

Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn's disease (CD) n = 214 and ulcerative colitis (UC) n = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; p = 0.012), concomitant diseases (AA vs. AG vs. GG; p = 0.015) and cutaneous manifestations (AA vs. AG/GG, p = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; p = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease (p = 0.020) and time-to-immunosuppression (p = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; p = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.

Safety and Effectiveness of Vedolizumab for the Treatment of Pediatric Patients with Very Early Onset Inflammatory Bowel Diseases.

Background: Vedolizumab (vedo) is effective for induction and maintenance of remission in adults with inflammatory bowel disease (IBD). Pediatric data are still limited, especially for the youngest children with very early onset disease (VEO-IBD). The aim of this study was to assess the safety and efficacy of vedo in VEO-IBD. Methods: We performed a retrospective review of pediatric IBD patients with VEO-IBD (defined as aged <6 years) receiving vedo. Data on demographics, disease behavior, activity, and previous treatments/surgeries were collected. Disease activity was assessed using the pediatric Crohn's disease (CD) activity index (PCDAI) for CD or pediatric ulcerative colitis (UC) activity index (PUCAI) for UC. Primary outcome was clinical response after induction therapy with vedolizumab (4th dose week). It was defined as a decrease in PCDAI of at least 12.5 points between baseline and 4th dose week for CD, and a decrease in PUCAI of at least 20 points between baseline and this time for UC. Descriptive statistics were performed to analyze the data. Results: The study included 16 patients with VEO-IBD who have received vedo: 4/16 (25%) with CD, and 12/16 (75%) with UC at the median age of diagnosis 33.7 months (6.6 months-4.5 years). Median age at vedo initiation was 6.5 years (2.2-16.5 years). Among the analyzed individuals, 56.25% had failed more than one anti-tumor necrosis factor (TNF) alfa agent. Clinical response at 4th dose week was observed in 9/16 (56.3%) patients: mean baseline PCDAI score was 34.4 ± 1.9 and 10.6 ± 1.8 after induction therapy with vedo, while PUCAI score was 26 ± 6 vs. 18 ± 8, respectively. There was improvement in patients' nutritional state: at baseline 2/16 (12.5%) children had body mass index (BMI) below 1 percentile and no child had such BMI after induction therapy with vedo. No infusion reactions or serious adverse events/infections were reported. Conclusion: Vedolizumab is safe and effective in the medical management of pediatric patients with VEO-IBD.

Premedication Does Not Influence the Incidence of Infliximab Infusion Reactions in Pediatric Patients with Inflammatory Bowel Disease-A Single Center Case-Control Study.

BACKGROUND: Infusion reactions (IRs) are the most common adverse events (AEs) of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Prophylactic premedication (PM) with corticosteroids or antihistamines prior to IFX infusions has been used in clinical practice, but its efficacy is not known. The aim of this study was to assess the influence of steroid PM on IR incidence in pediatric patients with IBD receiving IFX. METHODS: We performed a case-control study that included pediatric patients with IBD receiving IFX. Patients were divided into four subgroups according to the agent and PM they received: Remicade (original drug) + PM, and two biosimilars-Reshma +/- PM, and Flixabi-PM. At our site, until 2018, PM with steroids was used as a part of standard IFX infusion (PM+); however, since then, this method has no longer been administered (PM-). IRs were divided into mild/severe reactions. Differences between subgroups were assessed with the appropriate chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. RESULTS: There were 105 children (55 PM+, 44 male, mean age 15 years) included in the study who received 1276 infusions. There was no difference between the PM+ and PM- subgroups, either in incidence of IR (18.2% vs. 16.0% of patients, p > 0.05) or in percentage of infusions followed by IR (2.02% vs. 1.02% of infusions, p > 0.5). The OR of developing IR when using PM was 0.34, and the difference in IRs ratio in PM+ and PM- patients was not statistically significant (95% CI, 0.034-1.9). There were 11/18 (61.1%) severe IRs (anaphylactic shock) reported in all patients (both PM+ and PM-). CONCLUSION: At our site, the incidence of IR was low, and PM did not decrease the incidence of IR in pediatric patients with IBD receiving IFX. These results indicate that PM with steroids should not be a standard part of IFX infusion to prevent IR.

Apolipoprotein E variants correlate with the clinical presentation of paediatric inflammatory bowel disease: A cross-sectional study.

BACKGROUND: It has been suggested that apolipoprotein E (APOE) polymorphisms are associated with the risk of developing inflammatory bowel disease (IBD) and the early age of disease onset. However, there are no reports regarding the relationship with clinical characteristics and disease severity. AIM: To summarise that APOE polymorphisms are associated with the risk of developing IBD and the early age of disease onset. METHODS: In total, 406 patients aged 3-18 with IBD (192 had ulcerative colitis and 214 had Crohn's disease) were genotyped using the TaqMan hydrolysis probe assay. Clinical expression was described at diagnosis and the worst flare by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification). Systemic steroid intake with the total number of courses, immunosuppressive, biological, and surgical treatment with the time and age of the first intervention were determined. The total number of exacerbation-caused hospitalisations, the number of days spent in hospital due to exacerbation, the number of relapses, and severe relapses were also estimated. RESULTS: Ulcerative colitis patients with the APOEε4 allele had lower C-reactive protein values at diagnosis (P = 0.0435) and the worst flare (P = 0.0013) compared to patients with the APOEε2 allele and genotype APOEε3/ε3. Crohn's disease patients with the APOEε2 allele scored lower on the Pediatric Crohn's Disease Activity Index at diagnosis (P = 0.0204). IBD patients with APOEε2 allele spent fewer days in the hospital due to relapse (P = 0.0440). CONCLUSION: APOE polymorphisms are associated with the risk of developing IBD and the clinical expression of IBD. However, the clinical relevance of the differences identified is rather modest.

Subjective Psychophysical Experiences in the Course of Inflammatory Bowel Disease-A Comparative Analysis Based on the Polish Pediatric Crohn's and Colitis Cohort (POCOCO).

No gold standard is available to evaluate subjective psychophysical experiences in pediatric inflammatory bowel disease (IBD). We aimed to assess pain, anxiety, and limitations in social activities at diagnosis and the worst flare of the disease in relation to clinical expression, treatment and IBD severity. A total of 376 children completed the survey (Crohn's disease (CD) n = 196; ulcerative colitis (UC) n = 180). The questionnaire included 12 questions regarding pain, anxiety, and social activity, all assessed at recruitment and retrospectively at diagnosis and worst flare using a numeric rating scale. Patients that had ever been treated with systemic glucocorticosteroids scored higher in pain (p < 0.001), anxiety (p = 0.015), and social activity domains (p < 0.016) at worst flare, and the answers correlated with the number of steroid courses (p < 0.0392). The perception of social activity limitations also correlated independently with the number of immunosuppressants (p < 0.0433) and biological agents (p < 0.0494). There was no difference in retrospective perception of pain, anxiety and social activity limitations between CD and UC patients at diagnosis and the worst flare. The level of limitations in social activity correlated with hospitalisations due to relapse, days spent in the hospital, number of relapses, and severe relapses with the strongest association of rho = 0.39 (p = 0.0004). Subjective and retrospective perception of pain, anxiety, and limitations in social activity differs depending on therapy, correlates with treatment modalities, and severity measures such as hospitalisations.

The Course of Ulcerative Colitis After Pediatric Liver Transplantation for Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC) are often associated with ulcerative colitis (UC). The impact on the course of UC remains unclear, and up-to-date evidence in pediatric populations is scarce. The aim of the study was to analyze the course of UC in pediatric patients transplanted owing to PSC or ASC. MATERIAL AND METHODS: We retrospectively reviewed data from children with PSC/ASC and UC who underwent orthotopic liver transplantation (OLT). In all patients UC diagnosis was based on clinical presentation, endoscopy, and histology. RESULTS: Seventeen patients (9 female) with PSC or ASC underwent OLT from deceased donors at a median age of 16.8 years (range = 11.5-18.2 years). In 15 patients, UC was diagnosed before OLT (median age of diagnosis = 10.6 years; range = 6.6-18.0 years), and 2 patients developed UC after OLT. Ten patients (59%) presented with pancolitis on initial endoscopy. Disease activity was severe in 9 patients (53%) and most patients improved after initial treatment with steroids. Before OLT only 2 patients (13%) had severe disease activity. After OLT, 4 patients developed flares of the disease. These patients were successfully treated and remained in remission at the end of the posttransplant follow-up period (median = 3.76 years; range = 0.4-15.5 years). None of the patients developed colorectal cancer or underwent colectomy during 3.7 years of post-OLT follow-up. CONCLUSION: In our experience, the course of UC was not aggravated by OLT for PSC, and UC did not adversely affect patient or graft survival.

Insolation and Disease Severity in Paediatric Inflammatory Bowel Disease-A Multi-Centre Cross-Sectional Study.

This study was to investigate whether the clinical course of inflammatory bowel disease (IBD) in a Polish paediatric cohort fits a seasonal pattern and depends on insolation. Two hundred and fourteen patients diagnosed with Crohn's disease (CD) and 192 with ulcerative colitis (UC) aged from 3 to 18 years, were recruited in seven centres of similar latitude. The seasons were defined as winter (December-February), spring (March-May), summer (June-August), autumn (September-November). The year was also divided depending on insolation threshold (3.0 kWh/m2/day). Patients diagnosed with IBD when the isolation was >3 kWh/m2/day had poorer nutritional status than those diagnosed while insolation was below threshold (lower standardised BMI at diagnosis (-0.81 ([-1.34]-[-0.03]) vs. -0.52 ([-1.15]-0.15); p = 0.0320) and worst flare (-0.93 ([-1.37]-[-0.05]) vs. -0.66 ([-1.23]-0.17); p = 0.0344), with the need for more frequent biological treatment (45.5% vs. 32.7%, p = 0.0100). Patients diagnosed in winter were significantly younger at diagnosis (11.4 vs. 13.0; padj = 0.0180) and first immunosuppressive treatment (11.3 vs. 13.3; padj = 0.0109) than those diagnosed in other seasons. CD patients diagnosed in months with higher insolation spent more days in hospital than those diagnosed in months with lower insolation [4.6 (1.8-11.8) vs. 2.9 (1.3-6.2); p = 0.0482]. CD patients diagnosed in summer had significantly more concomitant diseases. In patients with CD, the occurrence of the worst flare was more frequent in autumn. Furthermore, the season of birth was associated with Pediatric Crohn's Disease Activity Index at worst flare and earlier surgery. In conclusion, several clinical parameters are associated with insolation, the season of diagnosis and season of birth in the clinical course of Crohn's disease.

The risk of cardiovascular complications in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, relapsing disease of unknown etiology involving gastrointestinal tract. IBD comprises two main entities: ulcerative colitis and Crohn's disease. Several studies showed increased risk of cardiovascular complications in chronic inflammatory disorders, especially during IBD relapses. Endothelium plays a role in physiologic regulation of vascular tone, cell adhesion, migration and resistance to thrombosis. Also, its dysfunction is associated with increased risk of atherosclerosis development. There are several potential links between chronic IBD-related inflammatory processes and the risk of cardiovascular disease, but insight into pathogenetic pathways remains unclear. We present the current concepts and review of adult and pediatric studies on the risk of CVD in IBD.

The level of faecal calprotectin as a noninvasive biomarker of mucosal healing in children with ulcerative colitis.

INTRODUCTION: Recently, faecal calprotectin (FC) has been used as a marker of inflammatory processes in the gastrointestinal tract, such as inflammatory bowel disease (IBD), and has served to assess and monitor disease activity, mucosal healing (MH), and disease recurrence. AIM: To assess the correlation between FC and endoscopic activity of inflammation. MATERIAL AND METHODS: This retrospective study included 81 patients with ulcerative colitis (UC), with a median age of 15 years (range: 3-18 years), who were treated in the Children's Memorial Health Institute (CMHI) between 2013 and 2015. Within the study group there were two sub-groups created: patients with Baron score = 0 (n = 34, 42%) and ≥ 1 (n = 47, 58%). RESUTS: Statistical analysis was performed using Statistica 10 software (StatSoft, USA), and the value of p ≤ 0.05 was established as a significance level. In patients with Baron score ≥ 1, significantly higher FC values and PUCAI scores were found in comparison to children with Baron score = 0. The level of FC had greater accuracy than the PUCAI score in differentiation between patients with Baron score = 0 and ≥ 1 (Z = -1.73, p = 0.082). There was a significant correlation between PUCAI score and FC (R = 0.55, p < 0.001). CONCLUSIONS: Faecal calprotectin may be a good, noninvasive biomarker of mucosal healing in paediatric patients with UC.

Tryptophan-kynurenine profile in pediatric autoimmune hepatitis.

The impairment of regulatory T cells (Tregs) is a characteristic feature of autoimmune hepatitis (AIH), and the degradation of tryptophan (Trp) to kynurenine (Kyn), by gamma interferon-induced indoleamine-2,3-dioxygenase-1 (IDO-1), is a central metabolomics check point in the differentiation of Tregs. For this reason, we investigate whether or not Kyn and IDO activity is potentially useful biomarkers in pediatric AIH.Between January 2016 and January 2017, children of AIH type-1 (AIH-1, n = 37), AIH type-2 with liver kidney microsome-1 autoantibodies (AIH-2-LKM-1, n = 8), and autoantibody-negative Wilsons Disease (WD, n = 8) and alpha-1 anti-trypsin deficiency (AATD, n = 10), were enrolled in a cross-sectional survey of Kyn and Trp levels and Kyn/Trp ratios (IDO activity) by HPLC, and neopterin levels by ELISA.The mean Kyn and mean Kyn/Trp ratios of AIH-1 with smooth muscle antigen (SMA) 1.85 µM and 27 µmole/mmole, and AIH-2-LKM-1; 1.7 µM and 28.6 µmole/mmole were lower than that of the WD; 2.2 µM p = 0.03 and 33 µmole/mmole p = 0.02 and of AATD; 2.3 µM, p = 0.02 and 55 µM, p = 0.001. Kyn/Trp ratios of AIH relapse; 23.6 µmole/mmole were lower than Kyn/Trp ratios of AIH remission; 27.6 µmole/mmole (p < 0.05). The stage of liver disease and grade of liver biopsies in AIH-1 patients negatively correlated with the Kyn/Trp ratios.The serum Kyn levels and Kyn/Trp ratio of AIH patients, within or below the normal range, indicate a trend of IDO activity lower than non-autoimmune WD or AATD. Prospective monitoring of serum tryptophan metabolomics in larger cohorts of pediatric AIH patients is required to confirm the apparent paradigm of weak IDO activity contributing to the Treg deficit and pathogenesis of pediatric AIH.