Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease

In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity.Given its detri-mental health impact,early identification of at-risk individuals is crucial.MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic dysregulation.However,in large-scale epidemiological studies,liver biopsies are not feasible.The application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized software.Blood biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical.Analysis of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods.Accordingly,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.

Clinical Features and Genetic Analysis of Pediatric Patients with Alagille Syndrome Presenting Initially with Liver Function Abnormalities

Alagille syndrome （AGS） is a multisystem disorder and caused by mutations in JAG1 or NOTCH2 gene. The diagnosis of AGS is hampered by its highly variable clinical manifestations. We performed a retrospective analysis on 16 children diagnosed as having AGS in recent five years in our hospital. Cholestasis was seen in 15 patients （93.8%）, heart disease in 12 （75%）, characteristic facies in 7 （43.8%）, and butterfly vertebrae in 7 （43.8%）. Ophthalmology examination was not performed on all the patients. Further, serum biochemical parameters were compared between AGS and 16 biliary atresia （BA） patients who were confirmed by surgery. Elevated liver enzymes were seen in all the patients. Serum total cholesterol （TC） （P=0.0007）, alanine aminotransferase （ALT） （P=0.0056）, aspartate aminotransferase （AST） （P=0.0114）, gamma-glutamyl transferase （GGT） （P=0.035） and total bile acid （TBA） levels （P=0.042） were significantly elevated in AGS patients compared to those in BA cases. However, there were no significant differences in serum total bilirubin （TB）, conjugated bilirubin （CB） and albumin （ALB） between the two groups. We identified 14 different JAG1 gene variations and 1 NOTCH2 gene mutation in 16 Chinese AGS patients. Our study suggested clinical features of AGS are highly variable and not all patients meet the classical diagnostic criteria. It was suggested that hypercholesterolaemia and significantly elevated GGT, TBA and ALT may be helpful to diagnose AGS. Genetic testing is integral in the diagnosis of AGS.

Early complications after excision with hepaticoenterostomy for infants and children with choledochal cysts

Objective: To retrospectively study the early compli- cations of excision with hepaticoenterostomy for in- fants and children with choledochal cysts. Methods: We analyzed 16 patients with early posto- perative complications out of 173 patients with con- genital choledochal cysts aged 27 days to 14 years (mean 2.4 years) who had undergone excisional pro- cedures and biliary tract reconstruction. Results: The early complications included bile leak- age (10 patients), abdominal wall dehiscence (3), and hepatic failure, pancreatic juice leakage and postoperative intussusception (each in 1) respective- ly. Three patients died from bile leakage and 1 from postoperative hepatic failure. No statistical differen- ces were observed between the procedures of biliary tract reconstruction with jejunal segment interposi- tion hepaticoduodenostomy and Roux-en-Y hepatico- jejunostomy (P>0.75). The morbidity was signifi- cantly higher in infants below 1 year than in children (P<0.005). Prevention and treatment of the com- plications were discussed. Conclusion: Bile leakage and abdominal wall dehis- cence are major early postoperative complications. The morbidity of cholechal cysts is higher in infants than in children. Exploratory laparotomy should not be delayed when biliary leakage with diffuse peritoni- tis appears. The 'tension suture in the fascial space of the abdominal wall' is useful to prevent and treat wound dehiscence.

Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease

Background Hirschsprung's disease(HSCR)is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth,causing great physical and mental pain to patients and their families.Studies have shown that more than 20 genes are involved in HSCR,and most cases of HSCR are sporadic.However,the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%.Furthermore,familial HSCR patients show incomplete dominance.We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families.Methods To find published references,we used the title/abstract terms"Hirschsprung"and"familial"in the PubMed data-base and the MeSH terms"Hirschsprung"and"familial"in Web of Science.Finally,we summarized 129 HSCR families over the last 40 years.Results The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR.The primary gene factors in the syndromic families are ret proto-oncogene(RET)and endothelin B receptor gene(EDNRB).Most families show incomplete dominance and are relevant to RET,and the RET mutation has 56%pen-etrance in familial HSCR.When one of the parents is a RET mutation carrier in an HSCR family,the offspring's recurrence risk is 28%,and the incidence of the offspring does not depend on whether the parent suffers from HSCR.Conclusion Our findings will help HSCR patients obtain better genetic counseling,calculate the risk of recurrence,and provide new insights for future pedigree studies.

Novel Insights into the Pathogenesis of I-lirschsprung＇s-associated Enterocolitis

Objective： To systematically summary the updated results about the pathogenesis of Hirschsprung＇s-associated enterocolitis （HAEC）. Besides, we discussed the research key and direction based on these results. Data Sources： Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords ＂Hirschsprung enterocolitis＂, ＂Hirschsprung＇s enterocolitis＂, ＂Hirschsprung＇s-associated enterocolitis＂, ＂Hirschsprung-associated enterocolitis＂, ＂HAEC＂, and ＂EC＂. Study Selection： Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. Results： Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC. Conclusions： The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung＇s disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.

Ex utero intrapartum treatment for giant congenital omphalocele

Background To determine whether ex utero intrapartum treatment (EXIT) is an appropriate approach for managing fetuses antenatally diagnosed with giant congenital omphaloceles. Methods We retrospectively reviewed patients with omphaloceles who underwent either an EXIT procedure or a traditional repair surgery. Basic and clinical parameters including gender, gestational age, birth weight, maternal blood loss, operative times and operative complications were analyzed. During the 6–12-month follow-ups, postoperative complications including bowel obstruction, abdominal infections, postoperative abdominal distension were monitored, and survival rate was analyzed. Results A total of seven patients underwent the EXIT procedure and 11 patients underwent the traditional postnatal surgery. We found no differences in maternal age, gestational age at diagnosis, gestational age at delivery and birth weight between the two groups. In the EXIT group, the average operation time for mother was 68.3 ± 17.5 minutes and the average maternal blood loss was 233.0 ± 57.7 mL. The operation time in the EXIT group (22.0 ± 4.5 minutes) was shorter than that in the traditional group (35 ± 8.7 minutes), but the length of hospital stay in the EXIT group (20.5 ± 3.1 days) was longer than that in the traditional group (15.7 ± 2.5 days,P < 0.05). During the follow-up, one patient in the EXIT group had an intestinal obstruction, one developed abdominal compartment syndrome and one died in the traditional group. Conclusions In our experience, EXIT is a safe and effective procedure for the treatment of giant congenital omphaloceles. However, more experience is needed before this procedure can be widely recommended.

Comparison of different noninvasive diagnostic methods for biliary atresia: a meta-analysis

Background:This study was undertaken to retrospectively analyze the accuracy of different methods in differentiating biliary atresia from neonatal jaundice.Methods:A search was made in MEDLINE,and the Web of Science for relevant original articles published in English;methodological quality of the included studies was also assessed.Two reviewers extracted data independently.Studies were pooled,summary receiver operating characteristics curve and diagnostic odds ratio(DOR)with corresponding confi dence intervals were calculated.Results:For diagnosis of biliary atresia,ultrasonography(US),hepatic scintigraphy(HBS),and magnetic resonance cholangiography(MRCP)had a pooled sensitivity of 74.9%(range:70.4%-79.1%),93.4%(range:90.3%-95.7%)and 89.7%(range:84.8%-93.4%),a specificity of 93.4%(range:91.4%-95.1%),69.2%(range:65.1%-73.1%)and 64.7%(range:58.0%-71.0%),a positive likelihood ratio of 12.16(range:6.41-23.08),3.01(range:2.15-4.20)and 3.10(range:1.59-6.06),a negative likelihood ratio of 0.23(range:0.13-0.38),0.13(range:0.06-0.25)and 0.16(range:0.06-0.44),DOR of 72.56(range:27.34-192.58),29.88(range:12.82-69.64)and 32.48(range:8.22-128.29),with an area under the curve of 0.96,0.91,and 0.92,and Q value of 0.90,0.85,and 0.85,respectively.Conclusions:US,HBS and MRCP can be very useful for the diagnostic work-up of neonatal cholestasis.To improve the sensitivity and specificity,several additional measures can be used.