Imaging and endoscopic tools in pediatric inflammatory bowel disease: What’s new?

Pediatric inflammatory bowel disease(IBD)is a chronic inflammatory disorder,with increasing incidence and prevalence worldwide.There have been recent advances in imaging and endoscopic technology for disease diagnosis,treatment,and monitoring.Intestinal ultrasound,including transabdominal,transperineal,and endoscopic,has been emerging for the assessment of transmural bowel inflammation and disease complications(e.g.,fistula,abscess).Aside from surgery,IBD-related intestinal strictures now have endoscopic treatment options including through-the-scope balloon dilatation,injection,and needle knife stricturotomy and new evaluation tools such as endoscopic functional lumen imaging probe.Unsedated transnasal endoscopy may have a role in patients with upper gastrointestinal Crohn’s disease or those with IBD with new upper gastrointestinal symptoms.Improvements to dysplasia screening in pediatric patients with longstanding colonic disease or primary sclerosing cholangitis hold promise with the addition of virtual chromoendoscopy and ongoing research in the field of artificial intelligence-assisted endoscopic detection.Artificial intelligence and machine learning is a rapidly evolving field,with goals of further personalizing IBD diagnosis and treatment selection as well as prognostication.This review summarized these advancements,focusing on pediatric patients with IBD.

Pediatric stricturing Crohn's disease

Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Health Systems Strengthening to Tackle the Global Burden of Pediatric and Congenital Heart Disease: A Diagonal Approach

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience

BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Home-Nebulized Inhaled Glucocorticoid Therapy in Pediatric Respiratory Diseases

Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and October 2023 were selected as study subjects and randomly divided into the control group and the observation group,30 cases each.The control group was provided with conventional treatment only,while the observation group was provided with home-nebulized inhalation glucocorticosteroid treatment,and the treatment effects,clinical symptom relief time,disease recurrence rate,and treatment satisfaction of the children’s families were recorded and compared between the two groups.Results:A comparison of the two groups in terms of gender and age showed that the differences were not statistically significant(P>0.05).In terms of clinical efficacy,the total effective rate of the observation group was 90.00%,which was significantly higher than that of the control group of 66.67%(P<0.05).Compared with the control group,the disappearance time of the clinical symptoms of the observed group was significantly shortened(P<0.05).In addition,the satisfaction scores of the families of the children in the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Home-nebulized inhalation glucocorticoid therapy shows significant clinical efficacy in pediatric respiratory diseases,significantly reduces the time of disappearance of clinical symptoms,and improves the satisfaction of patients’families,which provides an effective treatment option for children.

Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders

The clinical scenario of pediatric liver disease is becoming more intricate due to changes in the disease spectrum,in which an increasing number of inherited/metabolic liver diseases are reported,while infectious diseases show a decreasing trend.The similar clinical manifestations caused by inherited/metabolic diseases might be under-recognized or misdiagnosed due to nonspecific characteristics.A delayed visit to a doctor due to a lack of symptoms or mild symptoms at an early stage will result in late diagnosis and treatment.Moreover,limited diagnostic approaches,especially liver biopsy,are not easily accepted by pediatric patients,leading to challenges in etiological diagnosis.Liver dysfunction due to inherited/metabolic diseases is often caused by a variety of metabolites,so precision treatment is difficult;symptomatic treatment is a compelling option for inherited disorders.

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease:A retrospective observational study

BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pediatric liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two groups.AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019.ALF and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient survival.RESULTS Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for ALF.The ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD group.Post-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF group.Once the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.

Infliximab vs adalimumab:Points to consider when selecting antitumor necrosis factor agents in pediatric patients with Crohn’s disease

Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.

Study of the Management of Children with Major Sickle Cell Disease in Pediatric Emergencies at the Gabriel Toure University Hospital

Objective: To study the epidemiological, clinical and therapeutic aspects of sickle cell disease in children admitted to the pediatric emergency department of the Gabriel Toure University Hospital. Materials and methods: This was a prospective study over 12 months in sickle cell children aged 6 months to 15 years. Results: The frequency of sickle cell disease was 4.67% with 71.1% of SS form. The age range of 60 - 120 months predominated with 43.4% and the sex ratio 1.4. Vaso-occlusive crises (VOC) were the most frequent reason for consultation (50.6%) and osteoarticular pain was the main symptom followed by fever and pallor with respectively 67.5%, 60.2%, 39.8%. The pain subsided in less than 72 hours in 39.8% and hyper hydration was performed in 85.1% of patients. Analgesic treatment was given in 90.4%, antibiotic therapy in 51.8% and phenotyped red blood cells transfusion was performed in 36.1%. The average duration of treatment was 10 days. Conclusion: Vaso-occlusive crisis remains the main reason for consultation in sickle cell disease children at Gabriel Toure University Hospital. The management consisted, in addition to the correction of the triggering factors, of hyper hydration and the administration of analgesics and blood products.

Gastric IgG4-related disease mimicking a gastrointestinal stromal tumor in a child: A case report

BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric patients.To our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a child.We describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based approaches.Therefore,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary surgery.CASE SUMMARY The patient suffered from epigastric pain for several days.Panendoscopy and computed tomography scan revealed a submucosal tumor.Differential diagnoses included GIST,leiomyoma,teratoma,and mucinous adenocarcinoma.However,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach disease.CONCLUSION We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

Systemic immune-inflammation index combined with pediatric appendicitis score in assessing the severity and prognosis for paediatric appendicitis

BACKGROUND Pediatric appendicitis is a common cause of abdominal pain in children and is recognized as a significant surgical emergency.A prompt and accurate diagnosis is essential to prevent complications such as perforation and peritonitis.AIM To investigate the predictive value of the systemic immune-inflammation index(SII)combined with the pediatric appendicitis score(PAS)for the assessment of disease severity and surgical outcomes in children aged 5 years and older with appendicitis.METHODS Clinical data of 104 children diagnosed with acute appendicitis were analyzed.The participants were categorized into the acute appendicitis group and chronic appendicitis group based on disease presentation and further stratified into the good prognosis group and poor prognosis group based on prognosis.The SII and PAS were measured,and a joint model using the combined SII and PAS was constructed to predict disease severity and surgical outcomes.RESULTS Significant differences were observed in the SII and PAS parameters between the acute appendicitis group and chronic appendicitis group.Correlation analysis showed associations among the SII,PAS,and disease severity,with the combined SII and PAS model demonstrating significant predictive value for assessing disease severity[aera under the curve(AUC)=0.914]and predicting surgical outcomes(AUC=0.857)in children aged 5 years and older with appendicitis.CONCLUSION The study findings support the potential of integrating the SII with the PAS for assessing disease severity and predicting surgical outcomes in pediatric appendicitis,indicating the clinical utility of the combined SII and PAS model in guiding clinical decision-making and optimizing surgical management strategies for pediatric patients with appendicitis.

Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand

BACKGROUND Thus far,genetic analysis of patients clinically diagnosed with glycogen storage diseases(GSDs)in Thailand has not been reported.AIM To evaluate the clinical and biochemical profiles,molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD.METHODS Children aged<18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited.Whole-exome sequencing(WES)was performed to identify the causative gene variants.Medical records were assessed.RESULTS All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia(n=1),III(n=3),VI(n=3),and IX(n=1).A total number of 10 variants were identified including G6PC(n=1),AGL(n=4),PYGL(n=5),and PHKA2(n=1).AGL had two novel variants.The clinical manifestations were hepatomegaly(n=8),doll-like facies(n=3),wasting(n=2),and stunting(n=5).All patients showed hypoglycemia,transaminitis,and dyslipidemia.The mainstay of treatment was cornstarch supplementation and high-protein and low-lactosefructose diet.After a median follow-up time of 9.59 years,height turned to normal for age in 3/5 patients and none had malnutrition.Liver enzymes,blood sugar,and lipid profiles improved in all.CONCLUSION Hepatomegaly,transaminitis,and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology.Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment,prognosis,and long-term care.

Optimizing growth in pediatric renal transplant recipients: An update

Growth retardation is a significant complication observed in pediatric renal transplant recipients,originating from a multifactorial etiology.Factors contributing to growth impairment encompass pre-transplant conditions such as primary kidney disease,malnutrition,quality of care,growth deficits at the time of transplantation,dialysis adequacy,and the use of recombinant human growth hormone.Additionally,elements related to the renal transplant itself,such as living donors,corticosteroid usage,and graft functioning,further compound the challenge.Although renal transplantation is the preferred renal replacement therapy,its impact on achieving final height and normal growth in children remains uncertain.The consequences of growth delay extend beyond the physi-ological realm,negatively influencing the quality of life and social conditions of pediatric renal transplant recipients,and ultimately affecting their educational and employment outcomes.Despite advancements in graft survival rates,growth retardation remains a formidable clinical concern among children undergoing renal transplantation.Major risk factors for delayed final adult height include young age at transplantation,pre-existing short stature,and the use of specific immunosuppressive drugs,particularly steroids.Effective management of growth retardation necessitates early intervention,commencing even before transplantation.Strategies involving the administration of recombinant growth hormone both pre-and post-transplant,along with protocols aimed at minimizing steroid usage,are important for achieving catch-up growth.This review provides a comprehensive outline of the multifaceted nature of growth retardation in pediatric renal transplant recipients,emphasizing the importance of early and targeted interventions to mitigate its impact on the long-term well-being of these children from birth to adolescence.INTRODUCTION Children with chronic kidney disease(CKD)endure frequent hospitalizations and ongoing treatment,which significantly affect their quality of life.One of the most noticeable effects of CKD in children is poor growth,with stunted height being a common sign of chronic malnutrition.Growth assessment involves regularly measuring weight and height/length and comparing these against z-score charts,along with other anthropometric indicators like head circumference and mid-upper arm circumference.Data from the North American Pediatric Renal Trials and Collaborative Studies(NAPRTCS)registry shows that over 35%of children enrolled had stunted growth at the time of admission,with growth impairment being more severe in younger children(58%in those aged under 1 year,compared to 22%in those aged over 12 years).Additionally,the same data revealed that growth impairment worsens as the severity of the disease increases.Although recent advances in science have enabled better outcomes for children with CKD,in resource-limited settings,numerous children are still deprived of achieving optimal growth owing to the disease and its related factors.Stunting is a key indicator of chronic growth impairment in children.A study by Wong et al[1]in the United States Renal Data System found that each SD decrease in height among children with stage V CKD is linked to a 14%increase in the risk of death[1].Similarly,research by Furth et al[2]using data from the NAPRTCS indicated that children with a height standard deviation score(SDS)of-2.5 face a relative hazard of death of 2.07.Stunting also correlates with increased hospitalizations.A study in the United States followed 1112 pediatric patients with end-stage renal disease from 1990 to 1995.It showed that children with severe or moderate growth failure had higher hospitalization rates compared to those with normal growth.Specifically,the relative risk for hospitalization was 1.14(95%CI:1.1-1.2)for those with moderate growth failure and 1.24(95%CI:1.2-1.3)for those with severe growth failure,even after adjusting for age,sex,race,cause,and duration of end-stage renal disease,and treatment type[2](dialysis or transplant).The growth of a child significantly affects his/her psychological and overall well-being as an adult.Short children are often embarrassed by peers,and it has been observed that height influences employment status,with unemployment being more prevalent among stunted individuals.Further,marital opportunities can be fewer among stunted individuals[3].Hence,all measures to achieve adequate growth should be attempted in children with CKD,regardless of whether they undergo transplantation.

Response to strict and liberalized specific carbohydrate dietin pediatric Crohn's disease

AIM: To investigate the specific carbohydrate diet(SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease(CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple(diet alone, antibiotics or 5-ASA) or SCD with immunomodulators(corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.RESULTS: The mean age at start of the SCD was 11.8 ± 3.0 years(range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo(range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization(P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

Efficacy of early treatment with infliximab in pediatric Crohn’s disease

AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and maintenance therapy for the first year, and were treated with azathioprine after 1 year. All patients were followed for at least 24 mo. Efficacy was determined by the relapse rate using the pediatric Crohn’s disease activity index score in each group at 12 and 24 mo. RESULTS: At the 1 year follow-up, the relapse ratee, Mi Jin Kim, Hae Jeong Lee, Yon Ho Choe (23.1%, 3 of 13 patients) in group C was lower than that (61.5%, 8 of 13 patients) in group B (P = 0.047). At the 2 years follow-up, the relapse rate (38.5%, 5 of 13 patients) in group C was lower than that (76.9%, 10 of 13 patients) in group B (P = 0.047). Adverse events in group C were fewer than in groups A and B. CONCLUSION: Early induction with infliximab at diagnosis, known as "top-down" therapy, was effective for reducing the relapse rate compared to conventional therapies for at least 2 years.

Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review

Upper gastrointestinal(UGI) tract involvement of inflammatory bowel disease(IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis(UC), atypical UC, Crohn's disease(CD) and IBD unclassified.Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid(non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD,is histologically characterized by increased intraepithelial lymphocytes(> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis,villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.

Inflammatory bowel disease in pediatric and adolescent patients:A biomolecular and histopathological review

Crohn&#x02019;s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) with both overlapping and distinct clinical, pathological and biomolecular features. It has been suggested that pediatric IBD is a distinct disease entity, with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD. The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities. For clinicians and pathologists convenience, practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.

Understanding the pathophysiological mechanisms in the pediatric non-alcoholic fatty liver disease: The role of genetics

Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.