Society Of Hepatology Research Articles

P1092 Real-life durability and utilization of biologics in pediatric inflammatory bowel disease: results from Italian society of pediatric gastroenterology, hepatology and nutrition (SIGENP) IBD registry

Abstract Background Long-term data on the efficacy and safety of biologics in pediatric inflammatory bowel disease (IBD) are crucial for guiding clinicians in optimizing their use. This study aims to evaluate real-life durability, usage patterns, and factors influencing treatment discontinuation in pediatric IBD. Methods This registry-based study analyzed data of patients from the IBD registry of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) who started biologic therapy between 2009 and 2022, with a minimum 1-year follow-up. Results 1184 patients (749 Crohn’s Disease [CD], 437 Ulcerative Colitis or IBD-undetermined [UC/IBD-U]) were retrieved. The median follow-up was 43 months (IQR 28-64). Infliximab was the first biologic in 807 patients (68%) followed by adalimumab in 378 patients (31%). 393 patients (33%) received a second-line biologic, 107 (9%) a third-line and 24 (2%) a fourth-line. At last follow-up, 544 patients (47%) had discontinued the first biologic, with a median time to discontinuation of 14 months (IQR 5-27). Main reasons were loss of response (36%) followed by primary non-response (33%) and infusion reactions (13%). For first-line biologics, treatment durability was superior in patients who received adalimumab compared to infliximab (Figure 1a) and in patients managed with TDM (Figure 2b). In the multivariate analysis risk factors for first biologic discontinuation were age < 6 years (HR 1.8, 95%CI 1.3-2.4), UC/IBD-U (HR 1.4, 95%CI 1.1-1.8), moderate/severe disease activity (HR 1.3, 95%CI 1.1-1.6) and Infliximab vs adalimumab (HR 2.1; 95% CI 1.6-2.7) while the use of TDM emerged as protective, significantly lowering the risk (HR 0.50; 95% CI 0.40-0.63). Combination therapy did not influence biologic durability (HR 0.95; 95% CI 0.77-1.18). Conclusion strategies for optimizing treatment efficacy of biologics in pediatric IBD should be tailored considering patients age, IBD type and severity and integrating TDM in patients’ management. The contribution of concomitant immunomodulation in the pediatric setting might be negligible.

P1014 Anti-TNF-alpha biosimilar cross and reverse-switching in pediatric IBD: Preliminary real-world data from the SIGENP IBD Working Group

Abstract Background Due to the increasing number of pediatric IBD patients receiving anti-TNF-alpha, multiple switching between biosimilars has become part of everyday clinical practice, although it is not yet officially recommended. A multicenter, nationwide retrospective study to determine the safety and effectiveness of multiple switching is currently underway within the IBD Working Group of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Methods Data from all pediatric IBD patients on anti-TNF-alpha treatment (IFX, ADA) who made one or more switches from one biosimilar to another (cross-switch) or from one biosimilar to the originator (reverse-switch) from 2013 to present have been collected. Safety was the primary study objective. These data are preliminary as data collection is still ongoing in additional centers. Results To date, three centers have collected data on 89 patients who underwent at least one cross- or reverse-switch 13.7 months (7-23.5) after starting biologic therapy: 51 with IFX (significantly more for UC and IBDU patients than CD patients, p<0.01) and 38 with ADA (significantly more in CD than in UC/IBDU patients, p<0.01). Twenty-one (23.6%) patients were switched twice, four (4.5%) three times, at 5.2 months (2-14.7) and 16.4 months (5.1-18.7), respectively since the previous switch. 84 were cross-switches and 5 were reverse-switches. The switch was non-medical in most cases (n=86, 89%) and medical in the remaining cases (due to adverse events). The median follow-up time was 3.6 years (2.2–6.4) from the start of biologic therapy. An acute infusion reaction occurred in 6/89 (6.7%), 1/21 (4.8%) and 1/4 (25%) patients after the first, second and third switches, respectively. Multiple switching was associated with a relapse in 2/89 (2.2%) and 2/21 (9.5%) after the first and second switching, respectively. No between-group differences in reactions or flares were noted between IFX and ADA. Conclusion Multiple switching biosimilars are a reality in the current practice in pediatric IBD. This practice does not appear to have any effect on the course of the disease, but further data are pending. References de Ridder L, Assa A, Bronsky J, et al. Use of biosimilars in pediatric inflammatory bowel disease: an updated position statement of the pediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2019;68:144–153. doi:10.1097/MPG.0000000000002141 Mysler, E., Azevedo, V.F., Danese, S. et al. Biosimilar-to-biosimilar switching: what is the rationale and current experience?. Drugs 81, 1859–1879 (2021). https://doi.org/10.1007/s40265-021-01610-1 Cohen, H.P., Hachaichi, S., Bodenmueller, W. et al. Switching from one biosimilar to another biosimilar of the same reference biologic: a systematic review of studies. BioDrugs 36, 625–637 (2022). https://doi.org/10.1007/s40259-022-00546-6 Dipasquale V, Pellegrino S, Ventimiglia M, Cucinotta U, Citrano M, Graziano F, Cappello M, Busacca A, Orlando A, Accomando S, Romano C; Sicilian Network for Inflammatory Bowel Disease. Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease. Eur J Gastroenterol Hepatol. 2022 Oct 1;34(10):1007-1014. doi: 10.1097/MEG.0000000000002408 Dipasquale V, Pellegrino S, Ventimiglia M, Citrano M, Graziano F, Cappello M, Busacca A, Orlando A, Accomando S, Romano R; Sicilian Network for Inflammatory Bowel Disease. Adalimumab biosimilar in pediatric inflammatory bowel disease: a retrospective study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). Healthcare (Basel). 2024 Feb 4;12(3):404. doi: 10.3390/healthcare12030404 Dipasquale V, Cicala G, Spina E, Romano C. Biosimilars in Pediatric Inflammatory Bowel Diseases: A Systematic Review and Real Life-Based Evidence. Front Pharmacol. 2022 Mar 17;13:846151. doi: 10.3389/fphar.2022.846151

Evaluation of the Frequency of HLA-DQ2/DQ8 Genes Among Patients with Celiac Disease and Those on a Gluten-Free Diet.

Celiac disease (CD) is a chronic, permanent, gluten-dependent disease that manifests itself with inflammation of the small intestine and malabsorption in genetically predisposed individuals with HLA-DQ2 and -DQ8 (human leukocyte antigen) histocompatibility antigens. The diagnostic criteria for celiac disease have undergone numerous modifications over the years. The aim of the study is to evaluate the frequency of HLA-DQ2/DQ8 genes in a group of patients with celiac disease diagnosed in 1980-2010 in order to verify the primary diagnosis of CD. The study group included 50 patients, 13 men and 37 women, who had been diagnosed with celiac disease many years ago based on histopathological criteria and improvement of health condition after receiving a gluten-free diet. The control group consisted of 31 healthy volunteers, 18 women and 13 men. All subjects underwent a genetic analysis assessing the presence of histocompatibility antigens HLA-DQ2.2, -DQ2.5, and -DQ8, along with the assessment of alleles encoding the α and β subunits of the antigens, according to European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines from 2020, using the EUROarray technique at EUROIMMUNE®. In the study group, 12 (24%) patients did not meet the genetic criteria. Among the remaining patients (Group 1) with celiac disease, the presence of HLA-DQ2.5 (50.0% vs. 9.68%; p < 0.01) and the co-occurrence of both alleles of HLA-DQ2 (31.6% vs. 6.45%; p < 0.05) were detected significantly more frequently than in the control group. Among patients with celiac disease, the prevalence of HLA-DQ8 was also slightly more frequent (13.2% vs. 3.23%; p > 0.05). Patients who did not meet the genetic criteria for celiac disease (Group 2) had a single string α-HLA-DQ2.5 significantly more often than control subjects (66.67% vs. 38.71%; p < 0.05). Among patients with celiac disease diagnosed before 2010, based on the 2020 ESPGHAN criteria, it is advisable to verify the previous diagnosis, taking into account genetic criteria.

Synopsis of European Society of Pediatric astroenterology, Hepatology and Nutrition (ESPGHAN) Guidelines (2024) on the Diagnosis and Treatment of Eosinophilic Esophagitis.

The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2024 guidelines on eosinophilic esophagitis in children provide a systematic approach to the diagnosis and management of this rising disease entity in children. We present a concise update of the guideline to simplify management protocols, thus improving patient outcome.

Fecal Calprotectin Determination in a Cohort of Children with Cow's Milk Allergy.

Cow's milk allergy (CMA) is the most common food allergy among children. An oral food challenge (OFC) remains a mainstay of the diagnosis of CMA, especially for the non-IgE-mediated type; however, this test can be risky and time-consuming. Hence, there is a need to identify biomarkers. Fecal calprotectin (FC) showed variable results, with good reliability and reproducibility in CMA patients. In this prospective study, we enrolled 76 children (aged 5-18 months) with CMA-related gastrointestinal and cutaneous symptoms following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Clinical assessments included history, physical examination, skin prick tests, and IgE assays. FC levels and the Cow's Milk Related Symptom Score (CoMiSS) were measured in 51 patients pre (T1) and post-diet (T2), with a subgroup analysis of 15 patients with elevated baseline FC (>50 mg/kg). The results showed that FC levels significantly decreased after the elimination diet (median: 30 mg/kg at T1, 16 mg/kg at T2; p < 0.01). In the subgroup with higher FC levels, median values dropped from 90 mg/kg to 33 mg/kg (p < 0.01). CoMiSS also improved (median: 8.50 at T1, 3.00 at T2; p < 0.01). Linear regression analysis showed no correlation between FC values and the CoMiSS at T1 and T2. In conclusion, the reduction in FC value after an elimination diet suggests that it could be considered a possible biomarker of bowel inflammation in CMA patients. Further studies are necessary to confirm these data and to evaluate and standardize the use of FC for diagnosis and follow-up of CMA.

Consensus on the management of liver injury associated with targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma ( version 2024)

With the widespread application of systemic treatments for hepatocellular carcinoma, liver injury caused by molecular targeted drugs and immune checkpoint inhibitors has become a common clinical problem. The Chinese Society of Hepatology organized relevant domestic experts to summarize and analyze the adverse liver reactions and diagnosis and treatment progress related to systemic treatment of liver cancer at home and abroad, and formulated the "Consensus on the management of liver injury associated with targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma," aiming to provide reasonable suggestions and decision-making references for clinical physicians in liver disease and related specialties in the monitoring, diagnosis, prevention and treatment of liver injury during the treatment of targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma, so as to enable more liver cancer patients to benefit from targeted immune therapy.

Erratum to: Practice Recommendations for Metabolic Dysfunction Associated Steatotic Liver Disease by the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN)

Erratum to: Practice Recommendations for Metabolic Dysfunction Associated Steatotic Liver Disease by the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN)

Prevalence and outcomes of arthritis in pediatric IBD: A multicenter study from the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition.

The aim of the present study was to assess prevalence and disease outcomes of arthritis in a nationwide cohort of pediatric patients with inflammatory bowel disease (IBD). We collected data of pediatric IBD patients experiencing arthritis from the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition IBD registry. We gathered baseline and one-year follow-up data on concomitant IBD and arthritis diagnosis. 150 patients [(99 Crohn's Disease (CD), 51 Ulcerative Colitis (UC) and Unclassified IBD (IBDU)] with arthritis out of 3061 (1301 CD and 1760 UC) patients were identified, with an overall prevalence of 4.9 %. Arthritis was more frequent in CD than in UC (7.6 % vs 2.9 %, p < 0.01). Peripheral arthritis was more frequently diagnosed in patients with active IBD than in those with quiescent disease (94.6 % vs 67.3 %, p < 0.01). At one-year follow-up, clinically active IBD was independently associated with lower peripheral arthritis remission rates, whereas it did not impact axial arthritis remission. The presence of additional EIMs was associated with lower IBD clinical remission rates. Clinically active IBD impacts peripheral arthritis but not axial one, whose activity appeared to be independent by intestinal disease. The presence of additional EIMs has a negative prognostic impact on IBD course.

Discrepancy between Mexican paediatricians and ESPGHAN experts regarding cow's milk allergy

AbstractObjectivesCow's milk allergy (CMA) is a common food allergy in infants. Guidelines and recommendations for the diagnosis and management of CMA are based on scientific review of the available evidence. However, real‐world situations may oblige clinicians to adapt a different attitude.MethodsThis paper evaluated the opinion of 42 Mexican paediatricians on the 73 statements presented in the recent position paper of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Voting on the statements and their interpretation were identical for both groups (online and anonymous). Both groups were unaware of the other's outcome at the moment of the voting.ResultsWhile the ESPGHAN group accepted all 73 statements, the Mexican group rejected 19 statements. Two rejections were due to the mean and median being below the predefined and agreed‐upon cut‐off, and 17 were due to over 75% of participants disagreeing with the statements. The greatest discrepancy was observed regarding the role of vitamin D in preventing CMA.ConclusionWhile opinions on the prevalence, diagnosis and management of CMA were comparable between European paediatric gastroenterologists and Mexican general paediatricians for the majority of statements, significant differences were observed. It is essential to gather information from various regions and healthcare levels to enhance the impact of recommendations.

Publications by the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition Members in PubMed-indexed Journals (1st June to 31st August 2024)

Publications by the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition Members in PubMed-indexed Journals (1st June to 31st August 2024)

Accuracy of International Guidelines in Identifying Normal Liver Histology in Chinese Patients With HBeAg-Positive Chronic HBV Infection.

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection.

Comparison of the ability between dual-energy X-ray absorptiometry and bioelectrical impedance analysis for diagnosing low skeletal muscle mass and sarcopenia in patients with chronic liver disease.

Sarcopenia and osteoporosis adversely impact the clinical outcomes of patients with chronic liver disease (CLD). The Japan Society of Hepatology (JSH) sarcopenia criteria utilize bioelectrical impedance analysis (BIA) for assessing muscle mass rather than dual-energy X-ray absorptiometry (DXA), which can simultaneously diagnose these comorbidities. We investigated the correlations and interchangeability between the appendicular skeletal muscle mass index (ASMI) values determined using BIA and DXA and evaluated the diagnostic ability of DXA for sarcopenia and osteosarcopenia in patients with CLD. This cross-sectional study included 173 patients with CLD. Sarcopenia was defined as low ASMIBIA according to the JSH and Asian Working Group for Sarcopenia (AWGS) criteria (ASMIBIA cutoff) or low ASMIDXA according to the AWGS criteria (ASMIDXA cutoff) and low handgrip strength. For women, a provisional cutoff value was set for ASMIDXA using the ASMIBIA cutoff (ASMIDXA-altered cutoff). We found that ASMIBIA and ASMIDXA were significantly correlated (r=0.921; P<0.001). The Bland-Altman plots demonstrated substantial agreement between ASMIBIA and ASMIDXA, with a mean difference of 0.0116kg/m2. The prevalence rates of sarcopenia and osteosarcopenia diagnosed using the ASMIBIA cutoff were 26.0% and 17.3%, respectively. The kappa coefficients for the prevalence of sarcopenia and osteosarcopenia were 0.759 and 0.775 between ASMIBIA cutoff and ASMIDXA cutoff and 0.780 and 0.806 between ASMIBIA cutoff and ASMIDXA-altered cutoff, respectively. The utilization of DXA can facilitate the comprehensive assessment and management of musculoskeletal comorbidities in patients with CLD.

Guideline for the Prevention and Treatment of Metabolic Dysfunction-associated Fatty Liver Disease (Version 2024).

With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the "Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)". The new edition, titled "Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)", offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.

Concise guidelines for the clinical management of thrombocytopenia in cirrhosis

Thrombocytopenia in cirrhosis is causing puzzlement in clinical practice. Therefore, in order to help clinical practitioners grasp quickly and standardize the diagnosis and treatment of thrombocytopenia in cirrhosis, liver fibrosis, and portal hypertension, the Group of the Chinese Society of Hepatology of the Chinese Medical Association has organized relevant field experts to formulate the "Concise Guidelines for Clinical Management of Thrombocytopenia in Cirrhosis" with aim of providing guidance for the clinical diagnosis and treatment.

Rational application of the ESPGHAN 2022 recommendations for the follow-up of the paediatric coeliac patient: consensus document of scientific societies (SEGHNP, AEPAP, SEPEAP, SEEC, AEG, SEPD, SEMFYC, SEMG and SEMERGEN)

Coeliac disease is a common condition for which the only current treatment is a gluten-free diet. Adherence to this diet is not always easy and is associated with a reduction in quality of life for the patient and their family. Non-adherence is associated with complications of varying severity. The lack of control at the outpatient care level in a high percentage of these patients evinces the need to improve follow-up protocols and the approach to care delivery with coordination of paediatric gastroenterology units (PGU) and primary care paediatricians. With this aim in mind, the present document was developed by consensus to offer a set of recommendations adapted to our region, based on the recent recommendations published by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and with participation of the pertinent scientific societies, including those concerning the adult population, for the management and follow-up of adolescents and the transition to adult care.

Philippine guidelines on the dietary primary prevention of allergic diseases in children.

In response to the continual increase in the prevalence of pediatric allergic diseases in the Philippines, the Philippine Society of Allergy, Asthma, and Immunology (PSAAI) and the Philippine Society of Pediatric Gastroenterology, Hepatology, and Nutrition (PSPGHAN) have published guidelines on the dietary prevention of allergic diseases in children. This guideline aims to update the previous guideline recommendations for clinicians on the use of dietary interventions for the prevention of allergic disease in children. Following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach specified in the Department of Health Manual for Clinical Practice Guidelines development, we systematically searched for and appraised clinical practice guidelines and systematic reviews on topics formulated and prioritized by a Steering Committee, which comprised of members of the PSAAI and PSPGHAN. In the absence of an existing systematic review, a de novo systematic review was conducted. A multisectoral consensus panel reviewed the evidence summaries and formulated recommendations through a formal consensus method. The recommendations made by the consensus panel were based on the available evidence on the benefits and harm of the intervention, as well as the cost, feasibility, acceptability, and availability. Several research gaps exist, resulting in low levels of certainty of evidence on most dietary recommendations for the prevention of pediatric allergic diseases.

Chinese guidelines for the diagnosis and treatment of hereditary hemochromatosis

Hereditary hemochromatosis is an iron overload disease caused by mutations in iron-regulating genes, resulting in excessive iron deposition in organs such as the liver, heart, skin, pancreas, and gonads, leading to corresponding multi-system damage. This condition is relatively common in European and American populations, primarily caused by mutations in the HFE gene; however, it is rare in China and other Asian countries, almost exclusively due to mutations in non-HFE genes. Clinical features include unexplained chronic hepatitis or cirrhosis, accompanied by elevated serum ferritin and/or increased transferrin saturation. MRI shows iron deposition in the liver, liver biopsy reveals iron accumulation in hepatocytes, and genetic testing facilitate the diagnosis of this disease. Repeated phlebotomy is the first-line therapy for this condition. For those who cannot tolerate phlebotomy, iron chelation therapy may be used, and patients who progress to end-stage liver disease will require liver transplantation. To assist clinicians in making informed decisions on the diagnosis and treatment of hereditary hemochromatosis, the Chinese Society of Hepatology, Chinese Medical Association has invited experts from clinical medicine, molecular genetics, pathology, imaging, and methodology to systematically summarize the advancement in this field and collaboratively develop the current guidelines.

Chinese guidelines on the management of hepatic encephalopathy in cirrhosis (2024)

With the progress of basic and clinical research on hepatic encephalopathy in cirrhosis over the world, Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise the 2018 "Chinese Guidelines on the Management of Hepatic Encephalopathy in Cirrhosis". New guideline provides the recommendations for clinical diagnosis, treatment, primary and secondary prevention of hepatic encephalopathy in cirrhosis.

Practice Recommendations for Metabolic Dysfunction–Associated Steatotic Liver Disease by the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN)

Practice Recommendations for Metabolic Dysfunction–Associated Steatotic Liver Disease by the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN)

Diagnosis and management of eosinophilic esophagitis and esophageal food impaction in adults : Aposition paper issued by the Austrian Society of Gastroenterology and Hepatology (ÖGGH).

This position paper deals with an expert consensus on diagnosis and management of eosinophilic esophagitis and esophageal food impaction issued by the Austrian Eosinophilic Esophagitis Network, aworking group under the patronage of the Austrian Society of Gastroenterology and Hepatology (ÖGGH). In need of astandardized approach on the management of EoE, recommendations were made based on international guidelines and landmark studies.