Question: A 9-year-old girl presented with epigastric pain, postprandial vomiting, anorexia, and poor weight gain for 6 months. On examination, she was less than the fifth percentile for height, weight, and body mass index. An esophagogastroduodenoscopy (EGD) report from 3 months before arrival to our hospital revealed erythematous gastric mucosa with ulcerations and edema of the pyloric canal. She was treated for Helicobacter pylori and cytomegalovirus (CMV) without improvement. Laboratory results showed the following: White blood cell count 4.4 × 109/L (27.3% neutrophils, 64% lymphocytes, 6.6% monocytes, 1.4% eosinophils, 0.7% basophils), hemoglobin 9.5 g/dL, mean corpuscular volume 82 fL, red cell distribution width 24.2%, platelet count 556 × 109/L, total protein 4.7 g/dL, and albumin 2.5 g/dL. Review of records showed negative anti-neutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies (ASCA), and tissue transglutaminase immunoglobulin (Ig)G and IgA. Serum total IgA levels were normal. Upper gastrointestinal series showed thickened gastric folds and narrowing of the pyloric canal (Figure A). Repeat EGD showed erythematous and friable mucosa, superficial ulcerations, and nodularity (Figure B–E). Friability, ulceration, and scarring of the prepyloric area and pylorus were appreciated; therefore, the duodenum was not able to be visualized. Colonoscopy was unremarkable. Histologic sections of the gastric biopsy specimens are shown in Figures F–I. What is the diagnosis? Look on page 905 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histopathologic examination of the gastric biopsy specimens showed erosive active chronic gastritis with patchy destruction and microabscesses of the deep gastric glands with relative sparing of the superficial mucosa. There was extension of inflammation into the submucosa. Granulomas, intestinal metaplasia, H pylori, and CMV infection were not present. A diagnosis of gastric Crohn's disease was made. Crohn's disease with predominant gastric involvement is rare in children. Diagnosis is considered after excluding other causes of gastritis and gastric outlet obstruction, such as nonsteroidal antiinflammatory drug use, Ménétrier disease, and infections such as H pylori and CMV. Endoscopic findings include nodularity (93%), aphthous ulcers (64%), thickened antral folds (64%), linear ulcerations (55%), and antral narrowing (43%).1Danzi J.T. Farmer R.G. Sullivan B.H. et al.Endoscopic features of gastroduodenal Crohn's disease.Gastroenterology. 1976; 70: 9-13Abstract Full Text PDF PubMed Scopus (112) Google Scholar Thiopurines are the preferred treatment for symptomatic gastroduodenal Crohn's disease. Endoscopic balloon dilation of strictures is avoided because of the high rate of recurrence.2Matsui T. Hatakeyama S. Ikeda K. et al.Long-term outcome of endoscopic balloon dilation in obstructive gastroduodenal Crohn's disease.Endoscopy. 1997; 27: 90-93Google Scholar Surgical resection of strictures is also avoided since recurrence and complications such as perforation are common.3Murray J.J. Schoetz D.J. Nugent F.W. et al.Surgical management of Crohn's disease involving the duodenum.Am J Surg. 1984; 147: 58-65Abstract Full Text PDF PubMed Scopus (98) Google Scholar Our patient was initially treated with prednisolone. A gastrojejunal tube was placed for gastric venting and jejunal feeds. She was tapered off prednisolone after one year and has achieved remission on 6-mercaptopurine for the past 4 years. Her gastrojejunal tube was removed 2 years after presentation. She is currently a thriving 14-year-old who is gaining weight appropriately and performing well in school with plans to attend college. The authors thank Parakrama T. Chandrasoma, MD, for his expert advice and assistance with this manuscript.

Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.

POSTERSALT decline (p = 0.0055).Null response was associated independently with the use of 180 mg/wk peginterferon alfa-2a (p = 0.0075), a higher baseline body mass index (p = 0.0016), and lower declines in: haemoglobin, platelets and body weight, during 12 weeks of treatment (all p < 0.0001) in addition to well known baseline predictors.The mean cumulative dose of peginterferon and ribavirin was high with >90% of the target dose for all response groups.Conclusions: Less decline in platelets, haemoglobin and body weight associated with null-response suggests the lack of a systemic response to peginterferon.The use of 360 mg/wk peginterferon alfa-2a (40KD) increased the likelihood for full response at week 12 and indicates that higher doses of peginterferon alfa-2a may be able to overcome the blunted interferon response in non-responder patients.Further studies on even earlier on-treatment predictors of response in the non-responder CHC population are warranted.

The role of Helicobacter pylori in the pathogenesis of peptic ulcer disease, gastritis and gastric malignancy is an area of intense investigation. The epidemiology of H. pylori suggests that the initial infection may occur in childhood. Although there is a strong association between H. pylori infection and peptic ulcer disease in children, the importance of H. pylori in the production of non-specific recurrent abdominal pain and the appropriate approach to therapy remain controversial.

Objective To assess the contribution of protein-losing enteropathy to AIDS-associated hypoalbuminemia. Design Prospective assessment of patients with AIDS. Setting An urban county hospital (Los Angeles & University of Southern California Medical Center. USA). Patients Four groups of patients with AIDS were studied: (1) patients with normal serum albumin (≥ 3.9g/dI) and normal bowel habits; (2) patients with normal serum albumin and diarrhea (≥ four loose or watery stools per day for ≥ 2 weeks); (3) patients with hypoalbuminemia (≤ 3.0g/dI) and normal bowel habits; and (4) patients with hypoalbuminemia and diarrhea. Main outcome measure Fecal α1-antitrypsin concentration was used as a measure of protein loss in the gut. Results Patients with hypoalbuminemia had a significantly higher mean fecal α1-antitrypsin concentration than those with normal albumin (10.8 ± 3.0 mg/g dry stool versus 2.4 ± 0.4 mg/g dry stool; P ≤ 0.001). Although mean fecal α1-antitrypsin concentrations were similar in patients with and without diarrhea in the normal albumin group, patients with hypoalbuminemia and diarrhea had signficantly higher levels of fecal α1-antitrypsin than those with hypoalbuminemia and normal bowel habits (17.3 ± 5.8 mg/g dry stool versus 4.6 ± 1.0 mg/g dry stool; P = 0.009). Twelve out of 36 (33%) patients with normal albumin had elevation of fecal α1-antitrypsin compared with 33 (70%) of 47 patients with hypoalbuminemia (P ≤ 0.001). Linear regression analysis showed a significant negative correlation between serum albumin and fecal α1-antitrypsin concentration (r = −0.38; P ≤ 0.001). Fecal α1-antitrypsin was significantly higher in patients with mucosal disease visualized at upper endoscopy or flexible sigmoidoscopy than in those without gross abnormalities (13.5 ± 5.8 mg/g dry stool versus 2.4 ± 0.7 mg/g dry stool; P = 0.005). Conclusion Protein-losing enteropathy is common in patients with AIDS and may contribute to the development of hypoalbuminemia in these patients.

BACKGROUND:Malabsorption and deficiency of vitamin E causing neurological degeneration are common consequences of chronic childhood cholestatic liver disease. The objective of this study was to determine the long-term efficacy and safety of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in correcting vitamin E deficiency in children with chronic cholestasis who were unresponsive to other forms of oral vitamin E. METHODS:Sixty vitamin E-deficient children with chronic cholestasis unresponsive to 70-212 IU.kg-1.day-1 of oral vitamin E were entered into a trial at eight centers in the United States. After initial evaluation, treatment was started with 25 IU.kg-1.day-1 of TPGS. Vitamin E status, neurological function quantitated by a specific scoring system, and clinical and biochemical parameters were monitored during therapy. RESULTS:All children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 after a mean of 2.5 years of therapy. No adverse effects were observed. CONCLUSIONS:TPGS (20-25 IU.kg-1.day-1) appears to be a safe and effective form of vitamin E for reversing or preventing vitamin E deficiency during chronic childhood cholestasis.

Dietary protein-induced colitis is a frequent cause of rectal bleeding in infants. The exact pathogenic mechanism is unknown but the disorder has been thought to be due to an allergic response. Rectal mucosal edema and eosinophilia are typically found but there are no specific markers currently available. Because eosinophil degranulation, as evidenced by the release of major basic protein, has been implicated in hypersensitivity disorders, we aimed to assess major basic protein deposition as a marker of dietary protein-induced colitis occurring in young infants. Suction rectal biopsies from five infants aged 1 to 7 months with findings consistent with dietary protein-induced colitis were compared histologically with five age matched controls who underwent rectal biopsies to rule out Hirschsprung's disease. An established indirect immunofluorescent staining method was used to identify tissue major basic protein. Comparable rectal deposition of major basic protein was found for the controls and colitic patients. Mucosal eosinophilia but not mast cell content was more prominent in the colitic patients (P < .05) than in the controls. Some of the colitic infants had elevated serum IgE levels (1 of 5), positive RAST for milk (2 of 5), and peripheral blood eosinophilia (1 of 5). Our findings do not support the concept that dietary protein-induced colitis of infancy is due solely to an immediate hypersensitivity response. The results also indicate that major basic protein is probably not a marker or likely primary mediator of this disorder.

The prevalence of abnormal values of initial screening laboratory tests was assessed for 24 children who eventually proved to have Crohn's disease. The screening tests included in this analysis were fecal alpha 1-antitrypsin (FA) concentration, erythrocyte sedimentation rate (ESR), total leukocyte count, serum albumin level, hemoglobin concentration, and qualitative testing of stool for the presence of blood. Of the 24 patients, 21 had abnormal FA values, 17 had anemia, 19 had an increased ESR, 14 had hypoalbuminemia, rectal bleeding was found in 8, and none had leukocytosis. All 24 patients had at least one abnormal screening test value; the most frequently abnormal result was the FA concentration. Pediatric patients without elevated FA values, anemia, a high ESR, bloody stools, or hypoalbuminemia are unlikely to have active Crohn's disease.

Total parenteral nutrition (TPN) in children is associated with the complicating syndromes of cholestasis and cholelithiasis. The causes of these syndromes are not completely clear. Gastrointestinal hypomotility associated with enteral fasting may be involved in the pathogenesis of both syndromes. We compared weanling rabbits maintained solely on TPN with chow pair-fed and free-fed controls over a 10-day period. Gastrointestinal transit time, assessed with a solid marker technique, was significantly greater in the TPN-treated animals. No difference in intestinal or biliary bacterial flora was demonstrated by aerobic or anaerobic cultures. Gallbladder bile contained a higher percentage of lithocholic acid, unconjugated bilirubin, and total calcium in the TPN-treated animals. Markers of hepatic dysfunction were elevated in the serum of the TPN-treated animals. Mild steatosis and edema were the only histologic differences in the livers of the TPN-treated animals. We conclude that gastrointestinal hypomotility associated with enteral fasting plays a role in the pathophysiologic changes leading to TPN-associated hepatobiliary dysfunction. This dysfunction may be mediated by an increase in the absolute and relative concentrations of lithocholic acid in the bile of TPN-treated animals.

SUMMARYWe evaluated [99mTc]diisopropylphenyl‐carbamoylmethylimidodiacetic acid ([99mTc]DISIDA) cholescintigraphy with measurement of duodenal fluid radioactivity collected by the string test in patients with neonatal cholestasis. Twenty‐six infants with prolonged jaundice and acholic stools were studied prospectively. Twelve patients had neonatal hepatitis, 12 biliary atresia, and one each Alagille syndrome and α1‐antitrypsin deficiency liver disease. All infants except the biliary atresia patients and four of the neonatal hepatitis patients revealed bowel activity on scan 6 h after tracer administration. At 24 h, three of these latter patients with neonatal hepatitis and two of the patients with biliary atresia revealed bowel activity. String radioactive counts for neonatal hepatitis ranged from 99,574 to 967,205 cpm (374,504 ± 232,210 cpm; mean ± SD) and for biliary atresia from 8,342 to 370,346 cpm (117,149 ± 98,698 cpm; mean ± SD). While neither test alone was capable of correctly differentiating among all patients, those patients with biliary atresia had either a negative hepatobiliary scan at 24 h or string radioactive count below 197,007 cpm. Disparity between the hepatobiliary scan and the string radioactive counts mandates further diagnostic investigation. These data suggest that simultaneous administration of the string test with hepatobiliary scintigraphy is advantageous in the evaluation of infants with chole‐static jaundice.

We provided partial peritoneal alimentation to a 1.69-kg 11-month-old premature infant who had no available central venous access, depleted peripheral venous access, and gastrointestinal dysfunction. A cuffed silastic catheter was surgically inserted into the suprahepatic space. An alimentation solution was continuously infused into the peritoneum for 28 days to supplement peripheral venous and nasogastric alimentation and contributed 42 +/- 15% of total calories daily. Weight gain was achieved, but complications included hypoglycemia, hypophosphatemia, intravascular dehydration, catheter site leakage, ascites, and hydrocele. At autopsy 11 months later, lipid accumulation was present in the upper peritoneum and the hilar regions of the lungs secondary to preexisting lymphatic obstruction. Partial peritoneal alimentation may be feasible when other access routes are inadequate, but lymphatic obstruction is a contraindication to the peritoneal administration of lipid emulsions.

G.G.C. has received com M.C. has served on th served on the board o and Enteral Nutrition; her institution has rec collaborative and Prov pensation from Child L.A.G. has received c received compensatio employment, expert t stocks/stock options; LLC, consulted to No received or has grants Institutes of Health, th holds equity interest in has received compens Fibrosis Foundation; M Abbott Laboratories, Foundation, the Natio Diseases/National Ins ticals; E.A.R. has rece sionalism & Ethical institution has receive as the medical editor has received compen Pharmaceuticals, and Nutrition; J.T. has rec Pediatrics, Prometheu conflicts of interest. Copyright # 2012 by E Hepatology, and Nut Gastroenterology, He DOI: 10.1097/MPG.0b01

Septo-optic dysplasia (SOD), an unusual clinical syndrome associated with intrahepatic cholestasis, is a cause of false-positive hepatobiliary scintigraphy in patients with neonatal jaundice. Use of the criterion of absence of [99mTc]IDA activity in the gastrointestinal tract by 24 hr, as well as application of the more recently used criterion of normal hepatic extraction, failed to differentiate patients with biliary atresia from those with SOD. Septo-optic dysplasia has clinical and scintigraphic features unique from other causes of conjugated hyperbilirubinemia. Identification of the patients with SOD, in a group of 44 infants being evaluated for neonatal jaundice, improved the overall specificity of hepatobiliary scintigraphy in neonatal jaundice from 65% to 79% and accuracy in identification of patients with biliary atresia from 82% to 90%. Recognition of SOD is important to prevent unnecessary surgical exploration of these patients.

We used a highly specific method, alkaline methanolysis-high performance liquid chromatography, for determining the concentration and patterns of the unconjugated and esterified bilirubin fractions in the sera of pediatric patients with hepatobiliary disease. Bilirubin-protein conjugates were assayed using a new method that selectively removes bilirubin reversibly bound to protein, allowing measurement of the tightly bound bilirubin-protein conjugates by use of a diazo method. Fifty-two serum samples from children with varying bilirubin concentrations and diagnoses were studied. Whereas no conjugated pigment was detectable in the serum samples of healthy children or in individuals with Gilbert syndrome or Crigler-Najjar syndrome, bilirubin monoester and diester conjugates and bilirubin-protein conjugates were present in the sera of children with cholestatic liver disease, and accounted for 69% +/- 15% of the total bilirubin in these samples. Bilirubin fractional analysis was incapable of differentiating extrahepatic biliary obstruction from hepatocellular disease, because of overlap between the groups. The presence of bilirubin-protein conjugates in serum always coincided with detection of bilirubin monoester and diester conjugates. The distribution of bilirubin and its conjugates in sera provides a sensitive, although nonspecific, measure of hepatic disease.