Metabolic dysfunction-associated steatotic liver disease:A silent pandemic

The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.

Emerging role of regulated cell death in intestinal failure-associated liver disease

Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality.It is mainly characterized by cholestasis in children and steatohepatitis in adults.Unfortunately,there is no effective approach to prevent or reverse the disease.Regulated cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver diseases.Nowadays cell death is reclassified into several types,based on the mechanisms and morphological phenotypes.Emerging evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver diseases.Recent studies have shown that different modes of RCD are present in animal models and patients with IFALD.Understanding the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in IFALD.In this review,we discuss the current knowledge on how RCD may link to the pathogenesis of IFALD.We highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.

Gut microbiota in gastrointestinal diseases:Insights and therapeutic strategies

Considering the bidirectional crosstalk along the gut-liver axis,gut-derived microorganisms and metabolites can be released into the liver,potentially leading to liver injury.In this editorial,we comment on several studies published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the roles of gut microbiota in selected gastrointestinal(GI)diseases that are prevalent,such as inflammatory bowel disease,metabolic dysfunction-associated steatotic liver disease,and hepatitis B virus-related portal hypertension.Over the past few decades,findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders.However,studies elucidating the mechanisms underlying the host-microbiota interactions remain limited.The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota.Ultimately,the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.

Longitudinal changes in body weight of breastfeeding mothers in the first year after delivery and its relationship with human milk composition:a combined longitudinal and cross-sectional cohort study

Objective:Postpartum weight retention(PPWR)is a common problem among women after childbirth.The main objectives of this study are to understand the changes in body weight of breastfeeding mothers during long-term follow-up and preliminarily explore the relationship between maternal body weight and human milk composition,including macronutrients,leptin,and adiponectin.Methods:The study included a longitudinal cohort(122 mothers),and a cross-sectional cohort(37 mothers).The human milk,maternal weight,and dietary surveys were collected in the longitudinal cohort at different follow-up time points(1-14 days postpartum,2-4 months postpartum,5-7 months postpartum,and 12-17 months postpartum).The maternal body weight was analyzed using the responses in the survey questionnaires.A milk analyzer based on the mid-infrared spectroscopy(MIRS)was used to determine milk composition,and nutrition analysis software evaluated dietary intakes.In the cross-sectional cohort,participating mothers were asked to provide blood and human milk samples and pertinent information related to maternal body composition.Maternal body composition was measured by bioelectrical impedance analysis(BIA),while ELISA analyzed leptin and adiponectin in milk and serum.Results:At 5-7 months postpartum,the PPWR of breastfeeding mothers was(2.46±3.59)kg.At 12-17 months postpartum,the PPWR was(0.98±4.06)kg.PPWR was found to be negatively correlated with milk fat content within 14 days postpartum and positively correlated at 2-4 months postpartum.In addition,the maternal weight and body muscle mass were positively correlated with leptin and adiponectin in milk.Plasma leptin was positively correlated with the mother’s body weight,body mass index(BMI),FAT percentage,and body fat mass,while plasma adiponectin did not correlate with any parameter.The results also indicate that the PPWR did not correlate with leptin and adiponectin in plasma or milk.Conclusions:Breastfeeding mothers may retain considerable weight gain one year after delivery.Human milk composition may be related to changes in maternal body weight.Leptin and adiponectin in breast milk and leptin in plasma are associated with the maternal body composition.This study supports the notion that maternal nutritional status may affect offspring health through lactation,and future research should focus on exploring weight management of postpartum mothers.

Successful treatment of acute liver failure due to Wilson’s disease: Serendipity or fortuity?

BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy:A perspective

Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.

Hepatic pseudotumor:A diagnostic challenge

Hepatic pseudotumors are rare lesions of unknown origin,characterized by the proliferation of fibrous connective tissue and inflammatory cell infiltrates.They mimic malignant lesions clinically,and radiologically,given their non-specific clinical and imaging features.The pathophysiology of hepatic pseudotumor is incompletely understood and there are no standardized criteria for diagnosis.Pseudotumors have been reported to develop in various organs in the body with the lung and liver being the most common site.Hepatic pseudotumors develop in patients with underlying triggers of liver inflammation and injury,including infections,autoimmune liver diseases,bile duct injury,or surgery.Hepatic pse-udotumors respond well to conservative treatment with antibiotics,and steroids and some may regress spontaneously,thus avoiding unnecessary resection.This condition is rewarding to treat.It is important to recognize pseudotumor as a distinct clinical entity and include it in the differential of liver masses with atypical imaging features.

Diseases of bile duct in children

Several diseases originate from bile duct pathology.Despite studies on these diseases,certain etiologies of some of them still cannot be concluded.The most common disease of the bile duct in newborns is biliary atresia,whose prognosis varies according to the age of surgical correction.Other diseases such as Alagille syndrome,inspissated bile duct syndrome,and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction.The majority of these diseases present with cholestatic jaundice in the newborn or infant period,which is quite difficult to differentiate regarding clinical acumen and initial investigations.Intraoperative cholangiography is potentially necessary to make an accurate diagnosis,and further treatment will be performed synchronously or planned as findings suggest.This article provides a concise review of bile duct diseases,with interesting cases.

Upper gastrointestinal bleeding in Bangladeshi children:Analysis of 100 cases

BACKGROUND Upper gastrointestinal bleeding(UGIB)is defined as bleeding that occurs proximal to the ligament of Treitz and can sometimes lead to potentially serious and life-threatening clinical situations in children.Globally,the cause of UGIB differs significantly depending on the geographic location,patient population and presence of comorbid conditions.AIM To observe endoscopic findings of UGIB in children at a tertiary care center of Bangladesh.METHODS This retrospective study was carried out in the department of Pediatric Gastroenterology and Nutrition of Bangabandhu Shiekh Mujib Medical University,a tertiary care hospital of Bangladesh,between January 2017 and January 2019.Data collected from hospital records of 100 children who were 16 years of age or younger,came with hematemesis,melena or both hematemesis and melena.All patients underwent upper gastrointestinal endoscopy(Olympus CV 1000 upper gastrointestinal video endoscope)after initial stabilization.Necessary investigations to diagnose portal hypertension and chronic liver disease with underlying causes for management purposes were also done.RESULTS A total of 100 patients were studied.UGIB was common in the age group 5-10 years(42%),followed by above 10 years(37%).Hematemesis was the most common presenting symptom(75%)followed by both hematemesis and melena(25%).UGIB from ruptured esophageal varices was the most common cause(65%)on UGI endoscopy followed by gastric erosion(5%)and prolapsed gastropathy(2%).We observed that 23%of children were normal after endoscopic examination.CONCLUSION Ruptured esophageal varices were the most common cause of UGIB in children in Bangladesh.Other causes included gastric erosions and prolapsed gastropathy syndrome.

Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Unique presentation of neonatal liver failure:A case report

BACKGROUND Acute fulminant liver failure rarely occurs in the neonatal period.The etiologies include viral infection(15%),metabolic/genetic disease(10%),hematologic disorders(15%),and ischemic injury(5%).Gestational alloimmune liver disease usually manifests as severe neonatal liver failure,with extensive hepatic and extrahepatic iron overload,sparing the reticuloendothelial system.Empty liver failure is a rare cause of liver failure where a patient presents with liver failure in the neonatal period with no hepatocytes in liver biopsy.CASE SUMMARY A 5-week-old male presented with jaundice.Physical examination revealed an alert but deeply icteric infant.Laboratory data demonstrated direct hyperbilirubinemia,a severely deranged coagulation profile,normal transaminase,and normal ammonia.Magnetic resonance imaging of the abdomen was suggestive of perinatal hemochromatosis.Liver biopsy showed histiocytic infiltration with an absence of hepatocytes.No hemosiderin deposition was identified in a buccal mucosa biopsy.CONCLUSION Neonatal liver failure in the absence of hepatocellular regeneration potentially reflects an acquired or inborn defect in the regulation of hepatic regeneration.

Gut microbiota predicts the diagnosis of ulcerative colitis in Saudi children

BACKGROUND Ulcerative colitis(UC)is an immune-mediated chronic inflammatory condition with a worldwide distribution.Although the etiology of this disease is still unknown,the understanding of the role of the microbiota is becoming increasingly strong.AIM To investigate the predictive power of the gut microbiota for the diagnosis of UC in a cohort of newly diagnosed treatment-naïve Saudi children with UC.METHODS The study population included 20 children with a confirmed diagnosis of UC and 20 healthy controls.Microbial DNA was extracted and sequenced,and shotgun metagenomic analysis was performed for bacteria and bacteriophages.Biostatistics and bioinformatics demonstrated significant dysbiosis in the form of reduced alpha diversity,beta diversity,and significant difference of abundance of taxa between children with UC and control groups.The receiver operating characteristic curve,a probability curve,was used to determine the difference between the UC and control groups.The area under the curve(AUC)represents the degree of separability between the UC group and the control group.The AUC was calculated for all identified bacterial species and for bacterial species identified by the random forest classification algorithm as important potential biomarkers of UC.A similar method of AUC calculation for all bacteriophages and important species was used.RESULTS The median age and range were 14(0.5-21)and 12.9(6.8-16.3)years for children with UC and controls,respectively,and 40%and 35%were male for children with UC and controls,respectively.The AUC for all identified bacterial species was 89.5%.However,when using the bacterial species identified as important by random forest classification algorithm analysis, the accuracy increased to 97.6%. Similarly, the AUC for all theidentified bacteriophages was 87.4%, but this value increased to 94.5% when the important bacteriophagebiomarkers were used.CONCLUSIONThe very high to excellent AUCs of fecal bacterial and viral species suggest the potential use of noninvasivemicrobiota-based tests for the diagnosis of unusual cases of UC in children. In addition, the identification ofimportant bacteria and bacteriophages whose abundance is reduced in children with UC suggests the potential ofpreventive and adjuvant microbial therapy for UC.

Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago.The definition,diagnosis,and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians,enabling a better understanding of this disease and more targeted treatment for patients.We describe the definition,presentation,and diagnosis of eosinophilic esophagitis including management,challenges,and future directions in children.The definition,diagnosis,and management of eosinophilic esophagitis have evolved over the last 50 years.Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients.We describe the definition,presentation,diagnosis,management,and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.

Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

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.

Vulvar Swelling in a 12-Year-Old Girl: An Early Manifestation of Crohn’s Disease

Vulvar Crohn’s disease (VCD) is a rare complication of Crohn’s disease, especially in pediatric population. An early diagnosis can result difficult if the complication does not present in conjunction with the classic gastrointestinal symptoms that characterize this disease. In this study we present the case of a 12-year-old girl whose initial symptom of Crohn’s disease was a symptomatic vulvar swelling promoted by a rectovaginal fistula. We also provide an overview of Crohn’s disease and the vulvar changes found in the course of this disease.

Capsule endoscopy in pediatrics: A 10-years journey

Video capsule endoscopy (CE) for evaluation the esophagus (ECE), small bowel (SBCE) and the colon (CCE) is particularly useful in pediatrics, because this imaging modality does not require ionizing radiation, deep sedation or general anesthesia. The risk of capsule retention appears to be dependent on indication rather than age and parallels the adult experience by indication, making SBCE a relatively safe procedure with a significant diagnostic yield. The newest indication, assessment of mucosal change, greatly enhances and expands its potential benefit. The diagnostic role of CE extends beyond the SB. The use of ECE also may enhance our knowledge of esophageal disease and assist patient care. Colon CCE is a novel minimally invasive and painless endoscopic technique allowing exploration of the colon without need for sedation, rectal intubation and gas insufflation. The limited data on ECE and CCE in pediatrics does not yet allow the same conclusions regarding efficacy; however, both appear to provide safe methods to assess and monitor mucosal change in their respective areas with little discomfort. Moreover, although experience has been limited, the patency capsule may help lessen the potential of capsule retention; and newly researched protocols for bowel cleaning may further enhance CE&#x02019;s diagnostic yield. However, further research is needed to optimize the use of the various CE procedures in pediatric populations.

Pediatric gastrointestinal bleeding: Perspectives from the Italian Society of Pediatric Gastroenterology

There are many causes of gastrointestinal bleeding(GIB) in children, and this condition is not rare, having a reported incidence of 6.4%. Causes vary with age, but show considerable overlap; moreover, while many of the causes in the pediatric population are similar to those in adults, some lesions are unique to children. The diagnostic approach for pediatric GIB includes definition of the etiology, localization of the bleeding site and determination of the severity of bleeding; timely and accurate diagnosis is necessary to reduce morbidity and mortality. To assist medical care providers in the evaluation and management of children with GIB, the "Gastro-Ped Bleed Team" of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition(SIGENP) carried out a systematic search on MEDLINE via Pub Med(http://www.ncbi.nlm.nih.gov/pubmed/) to identify all articles published in English from January 1990 to 2016; the following key words were used to conduct the electronic search: "upper GIB" and "pediatric" [all fields]; "lower GIB" and "pediatric" [all fields]; "obscure GIB" and "pediatric" [all fields]; "GIB" and "endoscopy" [all fields]; "GIB" and "therapy" [all fields]. The identified publications included articles describing randomized controlled trials, reviews, case reports, cohort studies, casecontrol studies and observational studies. References from the pertinent articles were also reviewed. This paper expresses a position statement of SIGENP that can have an immediate impact on clinical practice and for which sufficient evidence is not available in literature. The experts participating in this effort were selected according to their expertise and professional qualifications.

Hereditary pancreatitis:An updated review in pediatrics

Hereditary Pancreatitis(HP)has emerged as a significant cause of acute,acute recurrent and chronic pancreatitis in the pediatric population.Given that it presents similarly to other causes of pancreatitis,a positive family history and/or isolation of a gene mutation are vital in its designation.Inheritance patterns remain complex,but mutations involving the PRSS1,SPINK1,CFTR and CTRC genes are commonly implicated.Since being first described in 1952,dozens of genetic alterations that modify the action of pancreatic enzymes have been identified.Among children,these variants have been isolated in more than 50%of patients with chronic pancreatitis.Recent research has noted that such mutations in PRSS1,SPINK1 and CFTR genes are also associated with a faster progression from acute pancreatitis to chronic pancreatitis.Patients with HP are at increased risk of developing diabetes mellitus,exocrine pancreatic insufficiency,and pancreatic adenocarcinoma.Management follows a multi-disciplinary approach with avoidance of triggers,surveillance of associated conditions,treatment of pancreatic insufficiency and use of endoscopic and surgical interventions for complications.With significant sequela,morbidity and a progressive nature,a thorough understanding of the etiology,pathophysiologic mechanisms,diagnostic evaluation,current management strategies and future research considerations for this evolving disease entity in pediatrics is warranted.