Acholic Stools Research Articles

Rhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction.

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode non-structural protein 1 (NSP1) derived from different RV strains. We found that compared to the parental simian SA11 strain that is less biliary pathogenic, SA11 containing an RRV-derived NSP1 resulted in severe biliary obstructive disease comparable to that associated with RRV infection, reflected by high levels of viral RNA and inflammation in the biliary tract, liver, and pancreas. In contrast, RRV containing an SA11-originated NSP1 showed only mild biliary obstruction comparable to what was observed during SA11 infection. Infection with a monoreassortant RRV virus carrying NSP1 from the bovine RV UK strain also showed substantially reduced viral replication in extra-intestinal organs and did not develop clinical biliary diseases. Mechanistically, RRV NSP1 seemed to promote active viral replication in hepatocytes and this expanded tropism led to enhanced infiltration of CD4 and CD8 T cells, causing immunopathology and damage in the hepatobiliary system. These results highlight an unexpectedly important role of RV NSP1 in viral replication and disease progression in extra-intestinal tissues.

Are Medical Students and Primary Health-care Professionals Aware of Neonatal Cholestasis and Acholic Stool.

Early diagnosis of biliary atresia (BA) and the timing of Kasai hepatic portoenterostomy are associated with improved survival rates of the native liver. Acholic stool is a major and earliest sign of BA. We evaluated the awareness and recognition of medical students and primary health care professionals (PHCPs) about neonatal cholestasis and acholic stool as a marker of BA. The knowledge of students and PHCP about prolonged jaundice and acholic stool was evaluated through a questionnaire. In the first step, 5 questions evaluating the knowledge of prolonged jaundice were asked. The sixth question was "Have you ever seen acholic stool before?" Following this question, stool color cards with 9 colors were shown, and participants were asked "Which of the following stool pictures would you define as acholic?" A total 724 students and 88 PHCPs were included in the study. In both groups, about half of the participants could not answer the first 4questions related to prolonged jaundice and cholestasis correctly. Twenty-four percent of the students and 11.4% of PHCP answered correctly to all of the stool colors. The rate of correct answers to acholic stool colors were approximately 43.9%-87.6% and 23.9%-86.4% for students and PHCP, respectively. Whitish acholic stool colors were better known than mild yellowish pale stool colors. The percentages of recognition were less than about 50% for these stool colors. This study showed that recognition and awareness of prolonged jaundice are low, and acholic stool is not well known. This may lead to delay in diagnosis. Considering the international success of stool color cards, using stool color cards will improve the outcomes of biliary atresia in our country as well.

Development of a diagnostic model for biliary atresia based on MMP7 and serological tests using machine learning.

To develop a machine learning diagnostic model based on MMP7 and other serological testing indicators for early and efficient diagnosis of biliary atresia (BA). A retrospective analysis was conducted on patient information from those hospitalized for pathological jaundice at Beijing Children's Hospital between January 1, 2019, and December 31, 2023. Patients with serum MMP7, liver stiffness measurements, and other routine serological tests were included in the study. Six machine learning models were constructed, including logistic regression (LR), random forest (RF), decision tree (DET), support vector machine classifier (SVC), neural network (MLP), and extreme gradient boosting (XGBoost), to diagnose BA. The area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the various models. A total of 98 patients were included in the study, comprising 64 BA patients and 34 patients with other cholestatic liver diseases. Among the six machine learning models, the XGBoost algorithm model and RF algorithm model achieved the best predictive performance, with an AUROC of nearly 100% in both the training and validation sets. In the training set, these two algorithm models achieved an accuracy, precision, recall, F1 score, and AUROC of 1. Through model interpretation analysis, serum MMP7 levels, serum GGT levels, and acholic stools were identified as the most important indicators for diagnosing BA. The nomogram constructed based on the XGBoost algorithm model also demonstrated convenient and efficient diagnostic efficacy. Machine learning models, especially the XGBoost algorithm and RF algorithm models, constructed based on preoperative serum MMP7 and serological tests can diagnose BA more efficiently and accurately. The most important influencing factors for diagnosis are serum MMP7, serum GGT, and acholic stools.

Effectiveness of oral methylprednisolone as adjuvant therapy for clinical improvement, biochemical markers, and inflammation in infants with cholestasis

AimsThis study analyzed the effectiveness of methylprednisolone in improving jaundice, bilirubin levels, liver function tests, and inflammatory biomarkers in infants with cholestasis. MethodsThe randomized, actively controlled, parallel‐group trial (ISRCTN45080388 registry) was conducted from November 2022 to May 2023 in Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, on infants with cholestasis. The ethics committee of Dr. Soetomo General Academic Hospital, Surabaya approved the study protocol. Infants 14 days to 3 months old, with cholestasis followed by acholic stool, dark urine, and hepatomegaly were included in the trial. Participants were randomly assigned to methylprednisolone 2 mg/kg/day twice daily or to placebo twice daily for two weeks. Ursodeoxycholic acid (10 mg/kg) was administered to all patients thrice daily. Clinical examination and laboratory measurements (direct and total bilirubin, Aspartate aminotransferase (AST), Alanine transaminase (ALT), Gamma-glutamyl transferase (GGT), and inflammatory biomarker) were performed at baseline and after 2‐week treatment. Measurement of inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β, and ANCA) was performed using enzyme-linked immunoassays. Data distribution was checked for normality. Analysis was carried out using SPSS ver. 21 with p significant <0.05. ResultsIn total, 40 participants were randomized to methylprednisolone (n = 20; mean age 8.39 ± 3.11 weeks) and placebo (n = 18; 2 drop out; mean age 8.98 ± 2.80 weeks) groups. At baseline, the methylprednisolone treatment and placebo groups significantly differed in gender (p = 0.02) but not in clinical, laboratory examination, or inflammatory biomarker levels. The methylprednisolone group had direct bilirubin 8.36 ± 4.84 mg/dL; total bilirubin 10.40 (2.70–33.25) mg/dL; AST 187.05 (42.00–911.00) U/L; ALT 170.43 ± 134.43 U/L; IL-2 171.29 (73.70–378.57) ng/L; IL-4 119.57 ± 59.69 ng/L; IL-6 71.74 ± 29.83 ng/L; IL-10 138.15 ± 70.62 ng/L; IFN-γ 42.54 ± 12.17 ng/L; TGF-β 316.58 (163.68–606.16) ng/L; ANCA 1.70 (0.66–3.25) ng/L. After two weeks of treatment, direct bilirubin, total bilirubin, AST, IL-10, and IFN-γ levels were significantly lower in the methylprednisolone group (p < 0.05) than those in the placebo group. No serious adverse events were reported. ConclusionMethylprednisolone was efficacious in reducing 2‐week bilirubin levels. These results support the hypothesis that the immunological process is involved in cholestasis. Further studies with larger sample sizes are needed to confirm the bile duct anti-inflammatory effect of methylprednisolone in cholestasis as an opportunity for new therapies to prevent the immunopathological process of cholestasis to biliary atresia.

Steroid therapy in extrahepatic cholestasis suggestive of biliary atresia: A case report

Background: Biliary atresia is a fibroinflammatory disease obstructing the extrahepatic biliary system. Biliary atresia is the leading cause of cholestasis in infants and the cause of end-stage liver disease in the first two years of life. Surgical treatment with Kasai portoenterostomy has been performed but has not eliminated the need for liver transplantation. The consideration of adjuvant steroid therapy for suppressing the fibro-inflammatory process in the bile ducts may improve the outcome of extrahepatic cholestasis. Case Presentation: A case of a 2-month 7-day-old boy with a chief complaint of jaundice with suspicion of biliary atresia. Jaundice started 1 week after birth, followed by acholic stools, yellow-brown urine, distended abdomen, hepatomegaly, and visible abdominal veins. Laboratory examination revealed an elevated level of direct bilirubin (cholestasis) in combination with elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and Gamma-glutamyl transferase (GGT), hypoalbuminemia, and reactive of IgG and IgM CMV. A percutaneous liver biopsy was performed and showed extrahepatic cholestasis with mild fibrosis consistent with biliary atresia. The patient was treated with oral methylprednisolone and ursodeoxycholic acid (UDCA). After 12 weeks of therapy, the patient was free of jaundice and darkening of stool color, followed by a normal bilirubin level. Conclusion: In young infants with extrahepatic cholestasis suggestive of biliary atresia, steroid administration resulted in clinical and laboratory improvement. The involvement of the immune response in the pathogenesis of biliary atresia may suggest new therapeutic targets for biliary atresia, such as steroids for improving the outcome of biliary atresia in young infants.

Assessments at week 2 and 3 in Term Newborns Diagnoses with Prolonged Jaundice

Introduction: Jaundice is one of the most common problems at neonatal period and seen in 60-70% of all newborns at first days of life. Prolonged jaundice is defined as hyperbilirubinemia persisting at the end of week 2 in term newborns. In this study, we reviewed term newborns diagnosed with prolonged jaundice. It was aimed to demonstrate delaying laboratory evaluations for a week in infants with favorable clinical presentation can prevent unnecessary tests in majority of newborns. Materials and methods: The study included full-term newborns who presented after day 14 of life and diagnosed with prolonged jaundice at neonatology outpatient clinic of Health Sciences University, Keçiören Teaching and Research Hospital in 2016. Overall, 336 infants with prolonged jaundice were screened. The infants with congenital anomaly, those with findings of sepsis or severe infection, those with history of intrauterine infection, those with history of acholic stool and those with no available data were excluded. In 180 patients included, clinical evaluations, bilirubin levels and advanced test results were assessed at baseline and weekly follow-up. Findings: Of the infants included, 51.7% were boys while 48.3% were girls. The most common blood type was A Rh (+). There was ABO incompatibility alone in 24 infants (14.2%), Rh incompatibility alone in 6 infants (3.5%) and ABO plus Rh incompatibility in 3 infants (1.2%). In 130 infants, total bilirubin was studied on both week 2 and 3. At week 3, total bilirubin value was ≥10 mg/dl in only 36 infants (27.7%) while it was decreased below 10 mg/dL in 94 infants (72.3%). Urinary tract infection (UTI) was detected in 7 of 38 infants with available tests at week 2. Two of 6 infants with UTI had other clinical signs of UTI. Mean total bilirubin value was 17.9 mg/dL in 5 infants. A significant correlation was found between UTI and vomiting, breastfeeding and feeding pattern (p

DIFFERENCES OF BIRTH WEIGHT AND ONSET OF ACHOLIC STOOL BETWEEN EXTRAHEPATIC AND INTRAHEPATIC CHOLESTASIS

Background: Biliary atresia (extrahepatic cholestasis) and neonatal hepatitis (intrahepatic cholestasis) are two main causes of cholestasis. It is important to distinguish the type of cholestasis for determine management. Patient with intrahepatic cholestasis have birth weight lower than extrahepatic cholestasis. Onset of acholic stool in extrahepatic cholestasis usually appear in 15-30 days of first life. The aim of the study to identify differences of birth weight and onset of acholic stool between the type of cholestasis. Method: A retrospective study on cholestasis children aged under 2 years was conducted at Dr. Soetomo General Academic Hospital from January 2012 to December 2016. A thorough history of birth weight and onset of acholic stool were undertaken. Based on histopatology liver biopsy patients were classified into twogroups: I (extrahepatic cholestasis) and II (intrahepatic cholestasis). Result: Statistical analysis of Mann Whitney U was used with p&lt;0.05 being significant. A total of 84 children were included, 55% were male. 40 children suffered from extrahepatic cholestasis (mean age 4.8 ± 2.6 months old) and 44 children suffered from intrahepatic cholestasis (mean age 2.9 ± SD 3.8 months old). The mean birth weight between extrahepatic and intrahepatic cholestasis were 2813 ± 704 gram vs 2717 ± 577 gram) (p=0.29). The mean onset of acholic stool between extrahepatic and intrahepatic cholestasis were 43.0 ± 60.6 days vs 26.6 ± 39.7 days (p=0.27). Conclusion : There is no difference of birth weight and onset of acholic stool between extrahepatic and intrahepatic cholestasis.

A Multicenter Pilot Study of Biliary Atresia Screening Using Digital Stool Color Imaging.

The presence of alcoholic stool in biliary atresia (BA) patients is the basis of a stool color card (SCC), a screening tool that has led to more patients receiving Kasai portoenterostomy earlier. This study aimed to evaluate the color image processing of stool images captured using smartphones. We propose that measuring digital color parameters is a more objective method for identifying BA stools and may improve the sensitivity of BA screening. A prospective study was conducted in five hospitals in Thailand between October 1, 2020, and December 31, 2021. Stools from infants presenting with jaundice, acholic stool, or dark-colored urine were photographed. Digital image color analysis was performed, and software was developed based on the color on the original SCC. Sensitivity and specificity for predicting BA stools were compared between the SCC and the software. Of 33 infants eligible for data collection, 19 were diagnosed with BA. Saturation and blue were two potential digital color parameters used to differentiate BA stools. The receiver operating characteristic curve was used to determine the optimum cutoff point of both values, and when saturation ≤56 or blue ≥61 was set as a threshold for detecting BA stool, high accuracy was achieved at 81.8% and 78.8%, respectively. Digital image processing is a promising technology. With appropriate cutoff values of saturation in hue, saturation, value and blue in red, green, blue color models, BA stools can be identified, and equivocal-colored stools of non-BA patients can be differentiated with acceptable accuracy in infants presenting with jaundice.

Choledochal cysts: surgical treatment in newborns and infants

To improve postoperative outcomes in newborns and infants with choledochal cysts and to determine the indications for surgery. There were 13 children aged 0-3 months with choledochal cyst who underwent reconstructive surgery between 2019 and 2023. In all children, choledochal cyst was associated with cholestasis. Acholic stool was observed in almost half of the group (n=7). All children underwent cyst resection and Roux-en-Y hepaticoenterostomy. Symptoms of cholestasis regressed in all patients. Mean surgery time was 128±27 min. There were no complications. Enteral feeding was started after 1-2 postoperative days, abdominal drainage was removed after 6.2±1.6 days. Mean length of hospital-stay was 16±3.7 days. Adequate bile outflow is one of the main principles. For this purpose, anastomosis with intact tissues of hepatic duct should be as wide as possible. Roux-en-Y loop should be at least 40-60 cm to prevent postoperative cholangitis. Drug-resistant cholestasis syndrome and complicated choledochal cysts (cyst rupture, bile peritonitis) are indications for surgical treatment in newborns and infants. When forming Roux-en-Y hepaticoenterostomy, surgeon should totally excise abnormal tissues of the biliary tract to prevent delayed malignant transformation.

CLINICAL AND LABORATORY ASPECTS IN DIAGNOSTICS OF THE FUNCTIONAL STATE OF THE HEPATOBILIARY SYSTEM IN PRETERM INFANTS

Resume. The insufficient information content of existing methods of diagnosis and treatment, the high incidence of complications, and the growing prevalence of digestive diseases in children in Ukraine justify the necessity for in-depth research in order to deepen understanding of the pathophysiological mechanisms underlying organ pathology with the ultimate goal of improving medical care for newborns.&#x0D; The aim of this study is to assess clinical and laboratory parameters characterizing the functional state of the hepatobiliary system in preterm infants.&#x0D; Participants and methods. The main group included 68 preterm infants of gestational age 32-33/6 weeks who had clinical signs of severe perinatal pathology; the comparison group involved 27 basically healthy infants of gestational age 34-36/6 weeks. A comprehensive examination of newborns with an assessment of the severity of perinatal pathology and a set of generally accepted biochemical blood parameters was performed. The research was conducted in compliance with the basic provisions of GCP (1996), the Council of Europe Convention on Human Rights and Biomedicine (April 4, 1997), the World Medical Association Declaration of Helsinki on the Ethical Principles of Scientific Medical Research Involving Human Subjects (1964-2008). The research protocol was approved by the Commission on Biomedical Ethics of Bukovinian State Medical University (Protocol No. 5 of 12.09.2015). Statistical processing of the study results was performed using the STATISTICA software (StatSoft Inc., USA, Version 10) MedCalc program (https://www.medcalc. org/index.php). Comparison of quantitative indicators with a normal distribution was performed using the Student's t-test at a statistical significance of p&lt;0.05.&#x0D; Results and Discussion. With a burdened somatic history, unfavorable factors of pregnancy and childbirth in the mother, severe forms of diseases in preterm infants in the early neonatal period are accompanied by clinical signs of disorders of the functional state of the hepatobiliary system, in particular, an enlargement of the liver, hepatosplenic syndrome, edema, meteorism, jaundice, hemorrhagic manifestations, such as gastrointestinal bleeding, acholic stools, and hypoglycemia. Laboratory markers of severe functional hepatoniliary disorders include decreased levels of total protein, bilirubin, and glucose; increased levels of urea and cholesterol; reduced enzymatic activity of aspartate aminotransferase and lactate dehydrogenase. A significant decrease in the activity of the enzymes alanine aminotransferase and γ-glutamine transaminase and a decrease in the activity of alkaline phosphatase and Ca2+ level were also observed.&#x0D; Conclusions. The obtained results of clinical and laboratory parameters indicate the necessity to study the main pathophysiological syndromes of hepatobiliary system dysfunction in perinatal pathology, considering morphological and functional characteristics in preterm infants.

The Successful Administration of Steroid in Extrahepatic Cholestasis

Biliary atresia is the most common cause of liver transplantation in children. Kasai surgery is still a bridging therapy for biliary atresia, but patients are often late for treatment. Based on the currently proposed theory, biliary atresia results from a progressive inflammatory process and progresses to fibrosis of the bile ducts. A case of a 1.5-month-old boy with prolonged jaundice followed by acholic stools and dark urine was presented. He had cholestasis, elevated GGT levels, and a liver biopsy suggesting extrahepatic cholestasis. He was treated with methylprednisolone, ursodeoxycholic acid, and vitamin supplementation was started orally. After steroid therapy, direct bilirubin levels decreased rapidly to 0.55 mg/dl on day 14. Jaundice, acholic stools, cholestasis, and liver function tests were improved. Therapeutic opportunities based on the pathogenesis of inflammation in biliary atresia using steroids may provide new opportunities for non-surgical management of biliary atresia in the early phase of the disease.

Infantile Kaposiform hemangioendothelioma in a female patient complicated with severe obstructed jaundice: a case report

BackgroundKaposiform hemangioendothelioma (KHE) is a rare locally aggressive vascular neoplasm that occurs mainly in the pediatric population. KHE usually originates just underneath the skin and affects deeper tissues through infiltrative growth; however, visceral tissue involvement is quite rare.Case presentationAn 8-month-old girl with jaundice and acholic stool was referred to our hospital for further evaluation of a hepatoduodenal ligament tumor. A blood examination revealed high bilirubin and liver enzyme levels, but no signs of coagulopathy. The first attempt at a diagnostic surgical procedure did not provide sufficient diagnostic information. However, the histopathological diagnosis of the cystic duct excised in the second surgery indicated KHE. Therefore, in our case, KHE was considered a cause of obstructive jaundice. Sirolimus (rapamycin) was initiated, and the patient was discharged 7 months after admission.ConclusionsIn cases of atypical hypervascular lesions in the abdominal cavity, especially in the pediatric population, it is important to consider the possibility of KHE, and surgical intervention with proper strategies is required for diagnosis, followed sequentially by promising treatments.

Questioning Diagnostic Value of Serum Matrix Metalloproteinase 7 for Biliary Atresia

Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing biliary atresia (BA). This study aimed to assess the diagnostic accuracy of serum MMP7 in BA in the Middle Eastern population. In this cross-sectional study, neonates and infants with direct hyperbilirubinemia admitted to Namazi referral hospital, Shiraz, Iran, were studied. Baseline demographic and clinical characteristics and blood samples were obtained on admission. MMP7 serum concentration was measured using an enzyme-linked immunosorbent assay (ZellBio GmbH, Ulm, Germany). 44 infants with a mean age of 65.59 days were studied. Of these patients, 13 cases were diagnosed with BA, and 31 cases' cholestasis related to other etiologies. Serum MMP7 concertation was 2.13ng/mL in the BA group and 1.85ng/mL in the non-BA group. MMP7 was significantly higher in those presented with either dark urine or acholic stool. The predictive performance capability of the MMP7 was not significant in the discrimination of BA from the non-BA group based on receiver operating characteristic curve analysis (area under curve: 0.6, 95% confidence interval: 0.45-0.75). In the optimal cut of point 1.9, the sensitivity and specificity were 84.6% and 45.1%, respectively. Further combination of MMP7 with Gamma-glutamyl transferase (GGT), alkaline phosphatase, direct and total bilirubin, and dark urine or acholic stool was not remarkably boosted the diagnostic accuracy of the test. Interestingly, GGT at a cut-off point of 230 U/L was 84.6% sensitive and 90.3% specific for BA. Our results are not consistent with previous studies on this subject. Considering more conventional and available tests like GGT besides conducting future studies with greater samples and different geographical areas is recommended.

Protocols of Investigation of Neonatal Cholestasis-A Critical Appraisal.

Neonatal cholestasis (NC) starts during the first three months of life and comprises extrahepatic and intrahepatic groups of diseases, some of which have high morbimortality rates if not timely identified and treated. Prolonged jaundice, clay-colored or acholic stools, and choluria in an infant indicate the urgent need to investigate the presence of NC, and thenceforth the differential diagnosis of extra- and intrahepatic causes of NC. The differential diagnosis of NC is a laborious process demanding the accurate exclusion of a wide range of diseases, through the skillful use and interpretation of several diagnostic tests. A wise integration of clinical-laboratory, histopathological, molecular, and genetic evaluations is imperative, employing extensive knowledge about each evaluated disease as well as the pitfalls of each diagnostic test. Here, we review the difficulties involved in correctly diagnosing the cause of cholestasis in an affected infant.

S1818 Rare Sequelae of Obstructive Jaundice: Hyperferritinemia and Bile Cast Nephropathy

Introduction: Obstructive jaundice occurs due to a physical blockage in the biliary outflow tract or external compression. While jaundice and scleral icterus are common symptoms initially, long term sequelae include severe systemic manifestations from the buildup of various compounds normally excreted in bile such as bilirubin. Case Description/Methods: A 67-year-old male smoker presented with 3 weeks of pruritus, acholic stools, dark urine, nausea, vomiting, and 20-pound weight loss. Physical exam was notable for jaundice and scleral icterus, LUQ and epigastric tenderness to palpation, but lacked hepatosplenomegaly, ascites or other stigmata of cirrhosis. Liver function tests showed AST 486 IU/L, Alk Phos 1419 IU/L, Alt 600 IU/L, and total bilirubin >30.0 mg/dL with direct bilirubin >10.0 mg/dL. Ferritin was >7500 ng/mL with decreased transferrin of 159 mcg/dL. Hepatitis panel and malignancy/autoimmune markers were negative. CMP showed BUN 74 mg/dL, and creatinine 5.1 mg/dL with 2+bilirubin on urinalysis and microscopic analysis showing pigmented renal tubular cells, bilirubin crystals, and waxy casts suggestive of ATN due to bilirubin damage and possible CKD given waxy casts (Table). CT abdomen reported severe intra and extra hepatic biliary duct dilation with CBD of 17 mm and abrupt tapering with pancreatic head fullness confirmed with MRCP. On day 2, ERCP showed a tight 15mm distal biliary stricture. A small sphincterotomy followed by balloon dilation allowed for placement of a CBD stent with excellent drainage of dark green bile. Following ERCP, patient had a drop of liver function tests and ferritin levels, gradual improvement in BUN and creatinine, and was discharged in stable condition on hospital day 6. On day 16, EUS revealed a hypoechoic area within the periampullary area with atypical cells in brushings collected during repeat ERCP (Figure). Discussion: Iron and iron binding proteins have been shown to be excreted in bile, primarily in iron excess. Our patient showed a large increase in ferritin signifying the potential role of biliary excretion of excess ferritin, with unknown ramifications. Additionally, severe biliary tree obstruction led to markedly elevated bilirubin, overwhelming renal clearance leading to severe tubular damage. With alleviation of obstruction, there was a steady decrease in ferritin and return to normal baseline renal function. Further research is needed to clarify both the consequences of excess ferritin in biliary obstruction and the significance of excess bilirubin in renal injury.Figure 1.: a) Ampulla prior to ERCP on day 2 shows no periampullary abnormality. b) Day 16 - Endoscopic Ultrasound showing narrowing of distal common bile duct with hypoechoic intraductal area. c) Bile casts and bilirubin crystals seen on microscopy. Table 1. - Patient’s Laboratory test results on and post admission Laboratory Values Reference Range Day 1 Day 5 (3 days post-ERCP) Day 21 AST 13 – 39 IU/L 486 187 18 ALT 7 – 52 IU/L 600 315 27 Alkaline Phosphatase 34 – 104 IU/L 1419 886 160 Total Bilirubin 0.3 - 1.2 mg/dL >30.0 13.0 4.4 Albumin 3.5 - 5.2 g/ 3.0 2.9 3.4 BUN 7 – 25 mg/dL 74 64 18 Creatinine 0.5 - 1.2 mg/dL 5.1 2.90 1.01 WBC 4 – 11 K/cmm 13.8 17.7 10.1 Hgb 13.7 - 17.5 g/dL 11.9 9.4 8.5 Ferritin 24 – 336 >7500 4677 976 Transferrin 300 to 360 mcg/dL 159 233 Iron 50 - 182 ug/dL 126 61 Iron Saturation 57% 19% TIBC 250 – 450 ug/dl 233 326 Urine Bilirubin Negative 2+ Negative Urobilinogen 0.0 - 2.0 EU/dL 4.0 < 2.0 PT 9.1 - 13.2 sec 26.6 12.8 PTT 23.3 - 36.6 SEC 42.0 33.0 INR 0.8 - 1.2 2.3 1.1 Alpha-1-Antitrypsin (ATT) 83 – 199 mg/dL 256 Ceruloplasmin 18– 36 mg/dL 51 Carcinoembryonic Antigen (CEA) 0.0 - 3.0 ng/mL 3.9

S2958 Do Not Trust the Internet: Acute Liver Failure Secondary to DILI From Online Hormones Versus Stimulant Use in a Transgender Patient

Introduction: Approximately half of acute liver failure cases in the United States are from drug-induced liver injury (DILI), a process modulated by the interplay between host, environment, and agent. Here, we present a case of DILI from unsupervised feminizing hormones versus stimulant use. Case Description/Methods: A 27 year old transgender (M to F) woman with history of anxiety, depression, and attention deficit hyperactivity disorder (ADHD) presented with 3 weeks of jaundice, abdominal discomfort, acholic stools, and memory issues after consuming several drugs purchased from international websites. Due to severe anxiety, she did not seek endocrinology evaluation for hormone guidance, instead ordering estrogen and anti-androgen therapy to transition on her own. She had been on estradiol for 5 years and cyproterone acetate intermittently for 4 years, restarted 9 months prior with N-methyl cyclazodone for ADHD. All 3 agents were discontinued at the onset of jaundice, but she then began copious water and laxative intake—“to flush the bilirubin out of [her] body”—along with that of milk thistle and delta-8 THC extract. Pertinent labs included AST 485, ALT 668, T. Bili 52.8, AP 140, INR 3, and K of 2.3. Chronic liver disease workup was negative. Biopsy revealed severe hepatocyte dropout with associated marked cholestasis and mixed portal inflammatory cell infiltrate including eosinophils, features consistent with DILI (Figure). Hospital course involved hematemesis, spontaneous bacterial peritonitis, Ogilvie’s syndrome, acute tubular necrosis requiring continuous renal replacement therapy, paraphimosis, and, ultimately, acute liver failure. Given severely compromised hepatic function with transplant the only option for viable recovery, patient was listed as category 1a with a MELD score of 37. She underwent orthotopic liver transplantation complicated by hemorrhage from a vein near the porta hepatis, which was repaired. She was started on tacrolimus, mycophenolate, prednisone, fluconazole, valganciclovir, and bactrim with recommendations to defer hormone replacement therapy for 1 year post-transplant. Discussion: Those with gender dysphoria may turn to the internet to relieve the distress caused by mismatch between biological sex and gender identity. Unfortunately, the online market is rife with unregulated information and products. In consuming such, physician supervision is imperative, and lack thereof lead our self-medicating patient to incur multiorgan insult, notably dire hepatic dysfunction requiring transplant.Figure 1.: Patient’s histopathology with hematoxylin and eosin staining (A) versus trichrome staining (B) demonstrating severe hepatocyte dropout with inflammatory cell infiltrate.

S3161 Sickle Cell Hepatopathy: A Rare Complication of Sickle Cell Anemia

Introduction: Sickle cell hepatopathy (SCH) describes the spectrum of hepatobiliary complications seen in sickle cell disease (SS). The etiology is multifaceted; repeated sickling causes liver vaso-occlusion and sinusoidal obstruction, which contributes to ischemic hepatic damage. SCH treatment is supportive; it includes supplemental oxygen, intravenous fluids and exchange transfusions. We present the diagnosis and management of a rare case of SCH. Case Description/Methods: Our patient is a 30-year-old male with SS anemia complicated by avascular necrosis of the shoulder, infrequent pain crises and cholecystectomy, who presented to our ED with fevers >100.4F, abdominal pain, acholic stools, dark urine and jaundice. Initial workup showed transaminitis, cholestasis, with an alkaline phosphatase 189, ALT 104, AST 145 and a total bilirubin 46.5. Abdominal ultrasound and CT did not show any acute hepatic causes for these lab abnormalities. Fevers prompted an infectious workup; viral hepatitis markers and blood cultures were negative. Autoimmune processes were ruled out with normal ANA, ASMA and immunoglobulins. He was given supportive care via intravenous fluids. The fevers resolved, but his abdominal pain and jaundice persisted. His t-bili increased without any evidence of infection or renal failure. Hepatology was concerned that he had intrahepatic cholestasis as a result of his SS. They recommended an exchange transfusion and considered a liver transplant. Our patient had many antibodies in his blood, increasing the risk of complications from an exchange transfusion. We deferred a liver biopsy due to the known increased risk of bleeding in SS patients and a lack of impact on management. We continued supportive care, and his liver function improved. Discussion: Acute sickle cell hepatopathy can range from an intra-hepatic sickle cell crisis, acute liver sequestration, and intrahepatic cholestasis; treatments include supportive care and exchange transfusions. Severe cases may require a liver transplant. We were initially concerned for acute intrahepatic cholestasis for our patient, however, his fevers did not persist and he did not have evidence of multi-organ system failure. There was also no evidence of worsening of sickling on a peripheral smear. If his lab abnormalities and symptoms worsened, we would consider doing exchange transfusions or a liver transplant. He improved with conservative measures, and this is an example of a rare complication of a serious disease.

S2933 BRIC Type 3? A Case of Benign Recurrent Intrahepatic Cholestasis Unlinked to ATP8B1 and ABCB11

Introduction: Benign Recurrent Intrahepatic Cholestasis (BRIC) is a genetic disorder with two common subtypes: BRIC I (mutated ATP8B1 gene), and BRIC II (mutated ABCB11 gene). Diagnosis requires high degree of suspicion and is confirmed by genetic testing. There are rare cases where patients lack both of the typical mutations. We present a patient with clinical, lab and histological evidence of BRIC without the usual mutations. Case Description/Methods: A 17-year-old male with no medical history presented with yellow eyes, pruritus, and acholic stools for six weeks, without triggering illness or stress. He denied fatigue, fevers, rash, dizziness, nausea, vomiting, diarrhea, constipation, arthralgias, melena, hematochezia, or hematemesis. He had no tattoos, blood transfusions, or allergies. He denied medications, alcohol, smoking, and drug use. On exam, he was icteric, with normal abdominal exam, and Alkaline Phosphatase 370 U/L, ALT 96 U/L, AST 66 U/L, and conjugated bilirubin of 6.7 mg/dL. Serological tests were normal, including antibodies for hepatitis A/B/C, CMV, EBV, HIV; alpha-1 antitrypsin; ceruloplasmin; iron, transferrin, C28Y/H63D mutations; TSH; antinuclear, anti-smooth muscle, anti-liver kidney microsomal, anti-mitochondrial antibodies; serum tissue transglutaminase; urine chlamydia and gonorrhea. Liver ultrasound had no biliary dilation. Genetic testing revealed negative ATP8B1 and ABCB11. Nonfocal liver biopsy showed bland cholestasis with coarse granular material in dilated bile canaliculi, compatible with a disorder of intrahepatic cholestasis, with morphologically similarities to biopsies seen in BRIC. He received ursodiol and symptoms improved. He stopped ursodiol after discharge and presented six months later with similar lab abnormalities. Repeat serological workup was normal. He received ursodiol and symptoms resolved again (Figure). Discussion: Diagnostic criteria for BRIC include episodes of jaundice separated by a symptom-free interval of at least six months, lab and histological evidence of non-inflammatory cholestasis, non-dilated biliary ducts, and no other explanatory causes. Our patient satisfied these diagnostic criteria. Some evidence indicates the presence of additional disease loci for low γ-GT BRIC, explaining why some patients diagnosed with BRIC on clinical and histopathologic evidence lack usual mutations in ATP8B1 or ABCB11. This disorder is informally termed “BRIC 3”; it is unclear which genes are implicated in this form and further research is needed.Figure 1.: Histopathologic appearance of the liver biopsy. Bland centrilobular cholestasis with coarse granular biliary material within dilated bile canaliculi, without any significant inflammation, bile duct damage, or ductular reaction.

Management Strategies for Choledochal Cysts in Infants and Children Our Experience at Department of Pediatric Surgery ,L.R.H, Peshawar

Objective: This study aims to understand more about choledochal cysts and how they are managed in children under 12 years old. Setting and Design: A Descriptive Study at Department of Pediatric surgery L.R.H. Hospital Peshawar. Method and Material: The most common kind of malformation of the biliary tree in Pakistan is choledochal cyst malformation (C.C.M.). Congenital choledochal anomalies range from asymptomatic to life-threatening cholangitis or pancreatitis. Surgeons now recommend total cyst ectomy and bilioentenric anastomosis. This five-year research examines. Clinical presentation, blood and laboratory testing, imaging, surgery, and predictive data were evaluated from case records. Twenty-three children with choledochal cysts were treated between January 2019 and December 2021, and their clinical presentation, diagnostic tests, and treatments were recorded. ERCP or a cholangiogram confirmed choledochal cysts after ultrasound diagnosis (P.O.C.). Before surgery, children with cholangitis received antibiotics and percutaneous transhepatic biliary drainage (excision of the cyst and jejunal loop interposition hepaticoduodenostomy) Results: Twenty-three patients were analyzed; eight presented with chronic abdominal pain, five with a history of cholangitis, two with acute cholangitis, four with biliary peritonitis, and one with a history of pancreatitis. Following cyst excision, Roux-en-Y hepaticojejunostomy (RYHJ) was performed in 13 patients, and hepaticoduodenostomy (H.D.) was performed in 4 patients. One example of congenital choledochal malformation type II was treated with cyst excision and drainage because cholangitis and jaundice threatened the patient's life. The median age was 3, and the gender distribution was about even. Of the patients who sought care, 18 presented with jaundice, 15 with abdominal discomfort, 12 with fever, and 9 with a mass in their stomach. Only four people had all three symptoms of characteristic jaundice, pain, and lump. Overall, the results of both ERCP in 7 patients and P.O.C. in 14 cases were favorable. There were two distinct clinical presentations: I infantile form (less than a year), which included nine infants with jaundice in all, acholic stool in 7, lump abdomen in 4, but only one with classical triad; and (ii) childhood form (more than a year), which included twelve patients with abdominal pain, jaundice, and cholangitis. Twenty patients had a type I cyst, and three had a type Iva cyst. Only two kids said no to surgery, while the rest went through with it. Only three newborns were lost during surgery, but the other 18 did well following their follow-up visits (median 25 months). Six had extrahepatic biliary atresia, two had congenital hepatic fibrosis, and one had congenital biliary cirrhosis. Practical implication: Our study will provide a new data to the health care providers about choledochal cysts and how they are managed in children under 12 years old Conclusions: However, total cyst removal and Roux en Y hepaticojejunostomy (RYHJ) anastomosis is the definitive treatment of Congenital Choledochal Malformation. However, several other temporary therapies are also necessary at various phases of the illness. Their criticality—evolutionary stages may differentiate two types of choledochal cysts from infancy through adulthood. The prognosis is favorable following surgery, but early identification and referral are critical for reducing the risk of complications and mortality. Keywords: Choledochal cyst, ERPC, H.D., RYHJ, and C.C.M. (Endoscopic retrograde cholangiopancreatography)

Biliary atresia-An experience from the first pediatric liver transplant center in Pakistan.

Biliary atresia (BA) is the most common cause of neonatal cholestatic syndrome. The true incidence of BA in Pakistan is largely unknown. This study aimed to report the clinical features, age at diagnosis and outcomes of biliary atresia from the first pediatric liver transplant center in Pakistan. The study was done in Shifa International hospital from 2013 to 2020. All babies who had biliary atresia confirmed by laboratory investigation were included. Demographic data, age of presentation, clinical presentation, supporting investigations like liver function tests, ultrasound abdomen, HIDA scan and liver biopsy were noted. Outcome related to Kasai portoenterostomy, liver transplant, complications and immunosuppressant agents were noted. A total of 42 children were included, 23 (54.7%) males and 19 (45.2%) were females. Jaundice was seen in all patients (100%) followed by acholic stools (81%). Associated malformations were noted in 6 (14.2%) patients. Liver function tests confirmed obstructive cholestasis (p 0.04). Kasai was done in 19 (45%) patients only, living donor liver transplant was performed in 6 (14%) patients. Age range of transplant patients was from 3months to 1year. Indication for liver transplant was failed Kasai in 1(16.7%) patient and chronic liver disease in 5 (83.3%) patients. LDLT survivors were 10months to 1year of age at the time of transplant, mean age was 10.6months. Maximum survival noted so far is 7 years. Acute complications seen post-transplant were sepsis (three patients), surgical site infections (two patients), biliary leaks and acute cellular rejection in one patient each. Chronic graft rejection, portal vein stricture needing stenting was done in one patient. All patients underwent LDLT from related donors wih no donor related mortality. All are deceased patients were yonger and had advanced disease. BA remains third most commo indication of transplant in our center. Liver transplant is the only lifesaving procedure after failed Kasai or as primary liver transplant due to advance liver disease. The advent of liver transplantation services offers survival and improving outlook of the disease.