Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children.

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.

Granulomas in Pediatric Liver Biopsies: Single Center Experience.

BACKGROUND: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. METHODS: Single-center retrospective study of GPLB. RESULTS: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum. CONCLUSION: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.

Biomarkers of fibrosis and portal hypertension in Fontan-associated liver disease in children and adults.

BACKGROUND: Fontan-associated liver disease (FALD) refers to structural and functional changes of the liver caused by the physiology of the Fontan palliation. Currently, liver biopsy is the gold standard to assess liver fibrosis of FALD. AIM: Investigate biomarkers correlating with severity of liver biopsy fibrosis in FALD. METHODS: A retrospective study of post-Fontan patients ≥ 10 years of age who underwent liver biopsy was conducted. Advanced liver disease (ALD) was defined as bridging fibrosis and/or cirrhosis on liver biopsy. AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) and Liver Stiffness Measurement (LSM) from FibroScan were used as non-invasive fibrosis scores. RESULTS: Sixty-six patients (26/47; 55.3% adults and 13/19 children; 68.4%) had ALD on biopsy. ALD was associated with lower platelet count (151 vs. 198 K/uL, p = 0.003), higher APRI (0.64 vs. 0.32, p = 0.01), higher FIB-4 (0.64 vs. 0.32, p = 0.02). Liver fibrosis score correlated with APRI (0.34, p = 0.02) and FIB-4 (0.47, p = 0.001) in adults. LSM had a high sensitivity at 81.3% with 45.5% specificity at a cut-off 18.5 kPa. CONCLUSIONS: APRI and FIB-4 had modest discrimination to identify adults with advanced liver disease, but not children, indicating that these values may be followed as a marker of FALD progression in older patients.

Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD.

BACKGROUND & AIMS: PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD. METHODS: A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG). RESULTS: PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both). CONCLUSIONS: Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.

Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and gluconeogenesis in mice.

The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via de novo lipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in both gluconeogenesis and DNL. We examined the effects of hepatocyte-specific mitochondrial pyruvate carrier (MPC) deletion on the fasting-refeeding response. Rates of DNL during refeeding were impaired by hepatocyte MPC deletion, but this did not reduce intrahepatic lipid content. During fasting, glycerol is converted to glucose by two pathways; a direct cytosolic pathway and an indirect mitochondrial pathway requiring the MPC. Hepatocyte MPC deletion reduced the incorporation of 13C-glycerol into TCA cycle metabolites, but not into new glucose. Furthermore, suppression of glycerol and alanine metabolism did not affect glucose concentrations in fasted hepatocyte-specific MPC-deficient mice, suggesting multiple layers of redundancy in glycemic control in mice.

Comparative analysis of whole vs. split liver transplantation in infants.

BACKGROUND: Liver transplantation (LT) in infants can be challenging due to their small size and small vasculature. Although both whole LT (WLT) and split LT (SLT) have been described in infants, the head-to-head comparison of these techniques in this population is sparse. METHODS: We retrospectively analyzed the records of all patients with age ≤1 year at Indiana University between 2016 and 2022. All SLT were left lateral segment grafts split in situ. RESULTS: A total of 24 infants were transplanted, with 11 SLT and 13 WLT. The median follow-up time was 52.1 months. Donor and recipient characteristics were comparable except for donor age (19 years vs. 2 years; p < .01) and weight (64 kg vs. 14.2 kg; p < .01). Early allograft dysfunction, primary nonfunction, and hepatic artery thrombosis developed more frequently in the WLT group. There were no biliary complications. There were two early deaths (2 and 4 days) in the WLT group. One-year graft survival (100% vs. 77%; p = .10) and patient survival (100% vs. 85%; p = .18) were numerically higher in the SLT group. CONCLUSIONS: SLT with LLS offers a safe and viable option for liver transplantation in infants and is associated with a trend toward superior outcomes. SLT should be considered as a strategy to reduce waitlist times for infants in the absence of small, deceased donors for WLT.

Effects of hepatic mitochondrial pyruvate carrier deficiency on de novo lipogenesis and glycerol-mediated gluconeogenesis in mice.

The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via de novo lipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in both gluconeogenesis and DNL. We examined the effects of hepatocyte-specific mitochondrial pyruvate carrier (MPC) deletion on the fasting-refeeding response. Rates of DNL during refeeding were impaired by liver MPC deletion, but this did not reduce intrahepatic lipid content. During fasting, glycerol is converted to glucose by two pathways; a direct cytosolic pathway essentially reversing glycolysis and an indirect mitochondrial pathway requiring the MPC. MPC deletion reduced the incorporation of 13C-glycerol into TCA cycle metabolites but not into newly synthesized glucose. However, suppression of glycerol metabolism did not affect glucose concentrations in fasted hepatocyte-specific MPC-deficient mice. Thus, glucose production by kidney and intestine may compensate for MPC deficiency in hepatocytes.

Characterization of Biomarkers of Hemostasis and Bleeding-Related Outcomes in Children With Cirrhosis.

OBJECTIVES: We aimed to evaluate differences in laboratory tests, bleeding, transfusions, and thrombosis between (1) children without and with cirrhosis and (2) children and adults with cirrhosis, and to correlate thromboelastography (TEG) parameters with biomarkers of hemostasis, bleeding, and transfusions in children and adults with cirrhosis. METHODS: This single-center, retrospective study included 20 children without cirrhosis, 40 children with cirrhosis, and 40 adults with cirrhosis who underwent a liver transplant (LT). We collected demographic data, preoperative laboratory values, and intraoperative TEG parameters. Biomarkers of hemostasis just prior to the start of LT surgery were analyzed including international normalized ratio (INR), platelet, fibrinogen level, R time, K time, alpha angle (α), and maximum amplitude (MA). We also collected outcome data including blood loss, transfusion requirements, and thrombosis. RESULTS: A significantly higher proportion of children with cirrhosis had abnormal PT ( P = 0.001), platelet ( P = 0.001), K time ( P = 0.02), and MA ( P = 0.05) compared to children without cirrhosis. The incidences of thrombosis, bleeding events, blood loss or PRBC transfusion were not significantly different between these 2 groups. A significantly higher proportion of adults with cirrhosis had abnormal R time ( P = 0.01) and alpha angle ( P = 0.01) than children with cirrhosis. CONCLUSIONS: Children with cirrhosis had defects in fibrinogen and platelets compared to children without cirrhosis at time of LT; however, these abnormalities did not translate into higher rates of bleeding in the former. Adults with cirrhosis had more defects in clotting factors compared to children with cirrhosis.

Mitochondrial pyruvate carrier inhibitors improve metabolic parameters in diet-induced obese mice.

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved insulin sensitivity, hyperinsulinemic-euglycemic clamp studies did not detect enhanced insulin action in response to 7ACC2 treatment. Rather, our data suggest acute glucose-lowering effects of MPC inhibition may be due to suppressed hepatic gluconeogenesis. Finally, we used reporter sensitive to pyruvate to screen a chemical library of drugs and identified 35 potentially novel MPC modulators. Using available evidence, we generated a pharmacophore model to prioritize which hits to pursue. Our analysis revealed carsalam and six quinolone antibiotics, as well as 7ACC1, share a common pharmacophore with 7ACC2. We validated that these compounds are novel inhibitors of the MPC and suppress hepatocyte glucose production and demonstrated that one quinolone (nalidixic acid) improved glucose tolerance in obese mice. In conclusion, these data demonstrate the feasibility of therapeutic targeting of the MPC for treating diabetes and provide scaffolds that can be used to develop potent and novel classes of MPC inhibitors.

Characteristics, risk factors, and outcomes of neutropenia after liver or kidney transplantation in children.

BACKGROUND: While prior adult studies have shown that approximately 20%-38% of subjects undergoing solid-organ transplant develop neutropenia, similar analyses in pediatric subjects are scarce. METHODS: We conducted a retrospective chart review of liver transplant (LT) and kidney transplant (KT) recipients at our center during the period 2008-2018. All of the KT and none of the LT subjects during this time period had induction with either anti-thymocyte globulin (ATG) or basiliximab at time of transplant. Neutropenia was defined as absolute neutrophil count (ANC) value ≤1000/mm3 . RESULTS: One hundred subjects with LT and 82 subjects with KT were included. The incidence of neutropenia within the first year of transplant in KT was higher compared to LT (54.8% vs 39%, p = .01). The median number of hospitalizations (p = .001) and infectious complications (p = .04) was significantly higher only in the KT subjects who developed neutropenia (compared to those who did not). Multivariate analysis identified factors associated with severity of liver disease at transplant, namely h/o upper gastrointestinal bleeding (p = .02), weight deficit (p = .01), and pre-LT ANC (p = .01), along with high or moderate risk cytomegalovirus status (p = .05) as predictors of neutropenia in LT subjects. Female gender (p = .03) predicted neutropenia, while BK virus infection was protective for neutropenia (p = .04) in KT subjects. CONCLUSIONS: The incidence of and morbidity associated with neutropenia within 1 year post-transplant is higher in KT subjects compared to LT subjects. The likely reason for this is the use of induction therapy (ATG, basiliximab) at the time of transplant in KT subjects.

The Relationship Between Sleep Disturbance and Disease Activity in Pediatric Patients With Inflammatory Bowel Disease.

OBJECTIVE: The aim of this prospective cross sectional study was to assess the prevalence of sleep disturbance in children with inflammatory bowel disease (IBD), including the relationships between sleep, inflammatory markers, and disease activity of pediatric patients with IBD. METHODS: Pediatric patients with IBD and parents were enrolled in the study. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Pediatric Daytime Sleepiness Scale, and the Adolescent Sleep Wake Scale (ASWS) surveys. Parents completed the Child Sleep Habits Questionnaire (CSHQ). Disease activity for Crohn disease (CD) was determined by the Pediatric Crohn Disease Activity Index and the Pediatric Ulcerative Colitis Activity Index was used to define disease activity in ulcerative colitis (UC)/indeterminate colitis patients. RESULTS: Fifty-three pediatric patients with IBD (38 CD, 12 UC, and 3 indeterminate colitis) participated in the study. The significant correlations between the CSHQ and Pediatric Crohn Disease Activity Index (P = 0.002) and the PSQI and Pediatric Ulcerative Colitis Activity Index (P = 0.04) were found. Youth with UC and indeterminate colitis significantly reported more sleep disturbance than patients with CD, (P = 0.03, 0.05, and 0.04; PSQI, Pediatric Daytime Sleepiness Scale, ASWS, respectively). Patients self-reported significantly more sleep disturbance than was observed by parents (P < 0.0001). This study showed the significant correlations between CSHQ score compared to erythrocyte sedimentation rate and albumin (P = 0.001 and 0.03, respectively). CONCLUSIONS: Results suggest that increased disease activity is associated with adverse effects on sleep quality. Based on the results of this study, pediatric patients with IBD should be screened for sleep disturbance.

Clostridium difficile colitis complicating Kawasaki disease in children: Two case reports.

Clostridium difficile infection is increasingly diagnosed in children with a wide clinical spectrum ranging from asymptomatic carriage to fulminant colitis. Symptomatic patients typically present with diarrhea, with or without blood, fever, and abdominal pain. Kawasaki disease, a vasculitis of unknown etiology, occurs primarily in young children. Establishing the diagnosis of Kawasaki disease can be challenging given the lack of a confirmatory diagnostic test or pathognomonic features as well as the appearance of symptoms over time rather than simultaneously. In addition, commonly occurring nonspecific associated symptoms, such as diarrhea and abdominal pain, may confound the clinical presentation. We present two cases of children with Kawasaki disease presenting with fever and Clostridium difficile colitis to illustrate the importance of keeping a high index of suspicion for Kawasaki disease.

The Characteristics of Esophageal Multichannel Intraluminal Impedance-PH Measurements in Infants Experiencing Brief Resolved Unexplained Events.

BACKGROUND: Brief Resolved Unexplained Events (BRUE) is defined as a sudden, brief and now resolved episode characterized by color change, altered respirations, change in tone, and altered level of responsiveness. This study aims to identify the characteristics of esophageal Multichannel Intraluminal Impedance-pH (MII-pH) monitoring in infants who have experienced a BRUE. METHODS: This study was a retrospective review of records of infants younger than 12 months who presented to the University of South Alabama Children's and Women's Hospital with an admission diagnosis of BRUE. Patients who underwent esophageal MII-pH monitoring between October 2015 and February 2017 and diagnosed with BRUE were initially included in this study. RESULTS: Fifty-three infants (preterm 25, term 28) who experienced a higher risk BRUE were included in our study. The mean age at diagnosis was 2.25 ± 2.07 months. Apnea (41/53; 77.4%) was the most common manifestation of BRUE. Non-acid reflux events were the most common findings in the MII-pH studies (66%). MII-pH results showed 6/53 (11%) acid reflux, 17/53 (32%) non-acid reflux and 12/53 (23%) both acid/nonacid reflux and 18/53 (34%) were normal. There were significant differences in the longest acid reflux episode and the Reflux Symptom Sensitivity Index (RSSI) of coughing/choking/gagging between preterm and term infants. The Reflux Symptom Index (RSI), RSSI and Reflux Symptom Association Probability (RSAP) were significantly correlated with each other in all symptoms (pain/fussiness, coughing/choking/gagging and vomiting). CONCLUSIONS: Among infants experiencing a higher risk BRUE, esophageal MII-pH monitoring revealed acid or nonacid reflux in 2/3 of patients.

The Relationship between Sleep Disturbance, Quality of Life and Psychosocial Functioning in Pediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: Pediatric patients with inflammatory bowel disease (IBD) are at risk for psychiatric symptoms that impact quality of life (QoL) and psychosocial functioning. Sleep disturbance has been reported to impose adverse effects on host defense mechanisms by affecting the magnitude and characteristics of the inflammatory response. The current study sought to assess the relationships among sleep disturbance, QoL, and psychosocial functioning in children with IBD. METHODS: Pediatric IBD patients completed multiple measures of sleep and daytime functioning as well as measures of QoL and psychosocial functioning. The parents completed complementary measures of sleep, QoL, and psychosocial functioning. The HRQOL results for subjects with IBD were compared to a healthy control group. RESULTS: Fifty-three children with pediatric IBD and their parents were enrolled in the study. QoL was positively associated with sleep quality, based on significant negative correlations between QoL and both sleep quality and daytime sleepiness scales (r = -0.62, -0.57; p value <0.001, respectively). Patients with CD reported significantly better QoL and psychosocial functioning than patients with UC. The QoL was similar between IBD patients and healthy controls. CONCLUSIONS: The present study suggests that a positive association exists between sleep functioning and QoL in pediatric patients with IBD. Patients with pediatric IBD should be screened for sleep disturbance, QoL and psychosocial functioning. Prevention and intervention strategies of sleep disturbance aimed at improving QoL and psychosocial functioning in children with IBD should be developed and evaluated.

Short article: The endoscopic and histologic findings of infants who have experienced brief resolved unexplained events.

INTRODUCTION: A brief resolved unexplained event (BRUE) describes an event associated with a change in muscle tone, color, respiration, and responsiveness that is unexplained after an appropriate examination. Some infants with higher risk BRUE may undergo endoscopy as part of their evaluation. OBJECTIVE: This retrospective study aimed to identify the endoscopic findings in infants who have experienced a higher risk BRUE. We also compared the characteristics, prenatal, natal, and postnatal risk factors between 23 infants who underwent endoscopic evaluation and 23 race-matched/sex-matched/term-matched/preterm-matched infants who did not undergo endoscopic evaluation. METHODS: This was a retrospective descriptive study. Infants were identified from a query of medical records using the ICD-10 code for BRUE (R68.13). RESULTS: Of 119 infants with BRUE, 23 infants with higher risk BRUE underwent an esophagogastroduodenoscopy and flexible sigmoidoscopy. Apnea (87%) was the most common presentation of BRUE. Most were female (57%) with a mean age at BRUE presentation of 2.73 months. We found 10 (43.5%) term infants and 13 (56.5%) preterm infants in our study. There were no significant differences in characteristics, prenatal, natal, and postnatal risk factors between the infants who underwent endoscopy and those who did not undergo endoscopy. The most common abnormal endoscopic finding was lymphonodular hyperplasia (LNH) associated with eosinophilia in the rectosigmoid colon. The proportion of females in the LNH group was significantly higher than the non-LNH group. CONCLUSION: Rectosigmoid LNH and eosinophilia, which are associated with milk soy protein intolerance (MSPI), were the most common findings on endoscopic evaluation. Although there is no proof of causation between MSPI and BRUE, MSPI should be considered in the differential diagnosis for higher risk BRUE.

Correlation of Gastroesophageal reflux disease Assessment Symptom Questionnaire to impedance-pH measurements in children.

BACKGROUND: Esophageal multichannel intraluminal impedance-pH monitoring has become one of the preferred tests to correlate observed reflux-like behaviors with esophageal reflux events. The Gastroesophageal reflux disease Assessment Symptom Questionnaire is a validated tool used to distinguish infants with gastroesophageal reflux disease from healthy children. The aim of this study was to determine whether the Gastroesophageal reflux disease Assessment Symptom Questionnaire composite symptom scores and individual symptom scores correlate with outcomes in esophageal multichannel intraluminal impedance-pH monitoring. METHODS: A total of 26 patients with gastroesophageal reflux disease-associated symptoms, aged 0-2 years, for whom both esophageal multichannel intraluminal impedance-pH monitoring and Gastroesophageal reflux disease Assessment Symptom Questionnaire survey results were available were included in the study. Gastroesophageal reflux disease Assessment Symptom Questionnaire score data were collected from a 7-day recall of parent's responses about the frequency and severity of gastroesophageal reflux disease symptoms, which determined the individual symptom scores. The composite symptom scores is the sum of all individual symptom scores. Multichannel intraluminal impedance-pH study results were compared to Gastroesophageal reflux disease Assessment Symptom Questionnaire data using Pearson correlation. RESULTS: Among 26 patients, a total number of 2817 (1700 acid and 1117 non-acid) reflux episodes and 845 clinical reflux behaviors were recorded. There were significant correlations between the reflux index and the individual symptom scores for coughing/gagging/choking (r2 = 0.2842, p = 0.005), the impedance score and individual symptom scores for coughing/gagging/choking (r2 = 0.2482, p = 0.009), the reflux symptom index for acid reflux-related coughing/gagging/choking and the individual symptom scores for coughing/gagging/choking (r2 = 0.1900, p = 0.026), the impedance score and individual symptom scores for vomiting (r2 = 0.1569, p = 0.045), and the impedance score and the composite symptom scores (r2 = 0.2916, p = 0.004). However, there were no significant correlations between fussiness, irritability, or abdominal pain-related multichannel intraluminal impedance-pH results and the individual symptom scores for abdominal pain. CONCLUSION: The impedance scores from multichannel intraluminal impedance-pH studies correlate with coughing/gagging/choking and vomiting in infants with gastroesophageal reflux disease. There are no significant correlations among the reflux index and impedance score versus the Gastroesophageal reflux disease Assessment Symptom Questionnaire scores for abdominal pain. We conclude that in infants with gastroesophageal reflux disease, multichannel intraluminal impedance-pH studies are more likely to demonstrate an association between gastroesophageal reflux disease and symptoms of coughing, gagging, or choking compared to an association between gastroesophageal reflux disease and pain in infants.

Association of autoimmune hepatitis type 1 in a child with Evans syndrome.

Autoimmune hepatitis (AIH) is a progressive liver disease that is often associated with extrahepatic autoimmune disorders. Evans syndrome (ES) is a rare autoimmune disorder, which is characterized by immune thrombocytopenia and autoimmune hemolytic anemia. Association of AIH with ES is rare, especially in children. We report a 3-year-old female with a past medical history of ES who presented with jaundice and significant transaminitis due to AIH type 1. She required multiple treatments with steroids as well as azathioprine, intravenous immunoglobulin and a course of rituximab.

Short article: Etiologic profile and endoscopic findings in immunocompromised children and adolescents with gastrointestinal bleeding.

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the potential causes of increased morbidity and mortality in immunocompromised patients, but data on characteristics of GIB in immunocompromised children are sparse. OBJECTIVES: This study aimed to identify the etiology, endoscopic, and histologic findings of GIB in immunocompromised children. DESIGN: This was a retrospective descriptive study. PATIENTS: We identified 33 patients (aged<20 years) and 45 GIB episodes related to GIB between January 2007 and April 2015 from a tertiary care and teaching hospital. RESULTS: The mean age at endoscopy was 10.7±4.6 years. Most common indications for endoscopy were melena in upper GIB and hematochezia in lower GIB. The median delay of duration between GIB presentation to endoscopy was 3 days. All except one child had at least one endoscopic abnormality. The most common cause of upper GIB was cytomegalovirus (CMV)-related gastrointestinal disease (35%), followed by esophageal varices (26%), and the most common cause of lower GIB was CMV-related gastrointestinal disease (55%). Fourteen percent of patients died during upper GIB episodes and 15% died during lower GIB episodes. CONCLUSION: Among immunocompromised individuals aged younger than 20 years presenting with GIB, CMV-related gastrointestinal disease is the most prevalent in our study population. However, the etiology of immunocompromised state needs to be taken into consideration when evaluating these children presenting with GIB.

Henoch-Schönlein without Purpura: A Case Report and Review Literature.

Henoch-Schönlein purpura (HSP) is a multi-organ vasculitis involving skin, joints, gastrointestinal tract, and kidneys. The present study reported a 5-year-old boy presenting with intense abdominal pain, bloody diarrhea, and protein-losing enteropathy. Investigations for infectious enteritis were negative. Esophagogastroduodenoscopy showed swelling and erythematous mucosa with hemorrhagic spots at duodenal bulb to the third part of duodenum. Histopathology of endoscopic biopsies revealed non-specific duodenitis. HSP was suspected, based on duodenitis and the presence of inflammatory markers without identifiable causes. Corticosteroid was started resulting in marked improvement of his clinical symptoms. Two weeks later, he developed nephrotic-range proteinuria, thus kidney biopsy was performed. Renal histology was consistent with IgA nephropathy, supporting the diagnosis of HSP This report emphasizes that patients with HSP may not always show visible purpura, and the diagnosis requires a high index of suspicion. GI endoscopy and renal biopsy may be helpful for the diagnosis in selected patients presenting with atypical presentations.