A Multicenter Prospective Survey on Early-Onset Inflammatory Bowel Disease in Japan.

INTRODUCTION: The incidence of early-onset inflammatory bowel disease is increasing in Japan. OBJECTIVE: This study aimed to analyze the treatment and progress of early-onset inflammatory bowel disease. METHODS: This prospective survey evaluated the data of 43 patients aged <8 years who were diagnosed with inflammatory bowel disease (IBD) from the time of diagnosis to 36 months after registration. RESULTS: A total of 12 patients with Crohn's disease (CD), 21 with ulcerative colitis (UC), and 3 with unclassified IBD were enrolled. The mean disease onset age was 3 years and 7 months. Colon and anal lesions were present in 100 and 50% of patients with CD, respectively. Granulomas were detected in 5 patients (41.7%). Dietary elimination including elemental diet was performed in all patients. Eleven patients (91.7%) were in remission by initial induction therapy, and 72.7% maintained remission for 36 months. Three patients (14.3%) with UC had familial history, 71.4% had pancolitis-type UC, and 66.7% exhibited disease of moderate severity. Colectomy was performed in 4 patients (21.1%). Eighteen patients (85.7%) were in remission by initial induction therapy; however, only 15.8% maintained remission for 36 months. Anal complication was more prevalent in infantile-onset IBD than in childhood-onset IBD (p = 0.014). CONCLUSIONS: Among Japanese patients aged <8 years who were diagnosed with IBD, colitis-type disease was more common in CD and pancolitis was more common in UC. As the courses of several patients were severe, identifying primary immunodeficiency appears to be necessary to confirm background disease.

Growth impairment in individuals with citrin deficiency.

Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD), and adult-onset type II citrullinemia (CTLN2). Owing to a defect in the NADH-shuttle, citrin deficiency impairs hepatic glycolysis and de novo lipogenesis leading to hepatic energy deficit. To investigate the physiological role of citrin, we studied the growth of 111 NICCD-affected subjects (51 males and 60 females) and 12 NICCD-unaffected subjects (five males and seven females), including the body weight, height, and genotype. We constructed growth charts using the lambda-mu-sigma (LMS) method. The NICCD-affected subjects showed statistically significant growth impairment, including low birth weight and length, low body weight until 6 to 9 months of age, low height until 11 to 13 years of age, and low body weight in 7 to 12-year-old males and 8-year-old females. NICCD-unaffected subjects showed similar growth impairment, including low birth weight and height, and growth impairment during adolescence. In the third trimester, de novo lipogenesis is required for deposition of body fat and myelination of the developing central nervous system, and its impairment likely causes low birth weight and length. The growth rate is the highest during the first 6 months of life and slows down after 6 months of age, which is probably associated with the onset and recovery of NICCD. Adolescence is the second catch-up growth period, and the proportion and distribution of body fat change depending on age and sex. Characteristic growth impairment in citrin deficiency suggests a significant role of citrin in the catch-up growth via lipogenesis.

Detailed genetic analyses of the HN gene in human respirovirus 3 detected in children with acute respiratory illness in the Iwate Prefecture, Japan.

We performed detailed genetic analyses of the partial hemagglutinin-neuraminidase (HN) gene in 34 human respirovirus 3 (HRV3) strains from children with acute respiratory illness during 2013-2015 in Iwate Prefecture, Japan. In addition, we performed analyses of the evolutionary timescale of the gene using the Bayesian Markov chain Monte Carlo (MCMC) method. Furthermore, we analyzed pairwise distances and performed selective pressure analyses followed by linear B-cell epitope mapping and N-glycosylation and phylodynamic analyses. A phylogenetic tree showed that the strains diversified at around 1939, and the rate of molecular evolution was 7.6 × 10-4 substitutions/site/year. Although the pairwise distances were relatively short (0.03 ±â€¯0.018 [mean ±â€¯standard deviation, SD]), two positive selection sites (Cys544Trp and Leu555Ser) and no amino acid substitutions were found in the active/catalytic sites. Six epitopes were estimated in this study, and three mouse monoclonal antibody binding sites (amino acid positions 278, 281, and 461) overlapped with two epitopes belonging to subcluster C3 strains. Bayesian skyline plot analyses indicated that subcluster C3 strains have been increasing from 2004, whereas subcluster C1 strains have declined from 2004. Based on these results, Iwate strains were divided into two subclusters and each subcluster evolved independently. Moreover, our results suggested that some predicted linear epitopes (epitopes 3 and 5) are candidates for an HRV3 vaccine motif. To better understand the details of the molecular evolution of HRV, further studies are needed.

Pediatric-onset Chronic Nonspecific Multiple Ulcers of Small Intestine: A Nationwide Survey and Genetic Study in Japan.

We performed a Japanese nationwide survey of pediatric-onset chronic nonspecific multiple ulcers of the small intestine between January 2000 and July 2013 in 176 institutions of pediatric surgery or pediatric gastroenterology and clarified the clinical features associated with genetic abnormalities in the Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) gene. A total of 4 cases (3 girls and 1 boy) were diagnosed in this series, which had to be differentiated from Crohn disease, Behçet disease, tuberculosis, or drug-induced enteropathy. Clinical symptoms appeared in infants and accurate diagnosis required several years. Medical therapies for inflammatory bowel disease were administered in all patients; however, 2 of the 4 patients had mutation in the SLCO2A1 gene which are responsible for primary hypertrophic osteoarthopathy, and underwent strictureplasty or ileal resection after long-term follow-up. Pediatric gastroenterologists should include this new entity in the differential diagnosis of small intestinal ulcers and inflammatory bowel disease.

A 4-year-old girl with chronic nonspecific multiple ulcers of the small intestine diagnosed by double-balloon endoscopy.

We present the youngest patient reported to date with chronic nonspecific multiple ulcers of the small intestine (CNSU) diagnosed by double-balloon endoscopy (DBE). A 3-year-old girl was referred to our department with a 2-year history of iron-deficiency anemia. Failure to thrive and hypoproteinemia were also noted, and stool occult blood tests had been persistently positive. However, the C-reactive protein level and erythrocyte sedimentation rate were not elevated. Esophagogastroduodenoscopy and double-contrast enema revealed no abnormality in the colon and terminal ileum. Retrograde DBE was performed when the patient was 4 years old. Linear ulcerations arranged in an oblique or circular pattern were present at 3 sites between 55 and 65 cm from the ileocecal valve. Microscopic examination showed nonspecific inflammatory changes, and no granuloma was present. Based on the clinical and endoscopic findings, the patient was diagnosed as having CNSU. The youngest previously reported patient with CNSU was 7 years old, whereas our present patient was diagnosed at the age of 4 years. In pediatric cases of obscure gastrointestinal bleeding, it may be necessary to be aware of small bowel disease.

Characteristics of inflammatory bowel disease with an onset before eight years of age: a multicenter epidemiological survey in Japan.

BACKGROUND AND AIM: Pediatric inflammatory bowel disease (IBD) has not been rare in Japan since the 1990s. The present study attempted to define the epidemiological and clinical characteristics of early-childhood IBD in Japan in comparison with results from Western countries. METHODS: Among children diagnosed as having IBD between January 1998 and December 2008, those showing onset before 8 years of age were investigated retrospectively. A questionnaire survey was carried out at 45 facilities throughout Japan, and 80 cases were reported from 27 facilities. On the basis of the final diagnosis, 24 patients with Crohn's disease (CD) and 47 patients with ulcerative colitis (UC) were analyzed. RESULTS: Among the patients with CD, the age at onset was less than 1 year in 62.5%. On the basis of the Montreal classification, 87.5% of CD cases involved the colon, and 63.8% of UC cases were pancolitis. Coexisting conditions such as congenital diseases (five cases) and cerebral palsy (four cases) were present before the onset of IBD. Growth failure was more severe (P < 0.05) at diagnosis in CD patients than in UC patients. Familial occurrence within first-degree relatives was observed in eight families among 45 patients with UC, compared with none among the CD patients (P < 0.05). CONCLUSION: Our results suggest that, in Japan, the pathogenesis of IBD in infants and children may differ from that in Western countries, and that the characteristics of early childhood-onset IBD are distinct from those of school age-onset IBD.

Intestinal microbiota and secretory immunoglobulin A in feces of exclusively breast-fed infants with blood-streaked stools.

Episodes of blood-streaked stools are not uncommon in exclusively breast-fed infants under 6 months of age. Such bleeding is thought to be associated with food protein-induced proctocolitis, however the pathomechanism remains unclear. The aim of this study was to investigate intestinal microbiota and secretory immunoglobulin A in the feces of exclusively breast-fed infants with blood-streaked stools. Fecal specimens from 15 full-term infants with blood-streaked stools and 15 breast-fed healthy infants were studied and the results compared. All infants had been delivered vaginally and exclusively breast-fed. The fecal microbiota were investigated by phylogenetic analysis combined with culture methods for some bacterial species, and feces were assessed for the presence of fecal secretory immunoglobulin A by enzyme-linked immunosorbent assay. Phylogenetic cluster analysis revealed four major clusters of fecal bacteria, cluster A being found only in healthy infants. The Bacteroides fragilis group was observed more frequently in controls than in patients (P < 0.05). In the controls, the predominant species belonging to the Enterobacteriaceae group was Escherichia coli, whereas in the patients it was Klebsiella (P < 0.05). Concentrations of secretory immunoglobulin A were high in one third of the healthy controls. In conclusion, the pathomechanism of rectal bleeding in exclusively breast-fed infants may be related to differences in the composition of their intestinal flora.

Leukocytapheresis in pediatric patients with ulcerative colitis.

OBJECTIVE: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. PATIENTS AND METHODS: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. RESULTS: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. CONCLUSIONS: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.

Urinary sulfated bile acid analysis for the early detection of biliary atresia in infants.

BACKGROUND: Measurement of urinary sulfated bile acid (USBA) is a non-invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). METHODS: We determined the USBA-to-creatinine ratio (USBA/cr) in 1148 infants at 10-40 days after birth. All infants were followed until the 3- to 4-month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. RESULTS: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow-up period. CONCLUSION: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false-positive rate is decreased by improving the methods for sample collection and urine storage.

Histological findings in the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency.

AIM: To characterize the histological features of the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), we studied specimens from 30 patients diagnosed with NICCD by genetically analyzing the SLC25A13 gene. METHODS: Liver biopsy specimens were subjected to hematoxylin-eosin, Azan, and Berlin-blue staining. RESULTS: Most specimens showed varying degrees of fibrosis. The degree of inflammation varied among the specimens, with half showing moderate or severe inflammatory changes. Fat deposition in hepatocytes was observed in almost all of the specimens, and severe fatty liver was noted in 20 (67%) of them. There was a mixture of two types of hepatocytes with macrovesicular or microvesicular fat droplets, and cholestasis was observed at a rate of 77%. Hemosiderin deposition, mostly mild and localized in periportal hepatocytes and macrophages in portal areas, was observed in 57% of the specimens. CONCLUSION: A combination of mixed macrovesicular and microvesicular fatty hepatocytes and the above-described findings, such as fatty liver, cholestasis, necroinflammatory reaction and iron deposition, are almost never observed in other liver diseases in infants and adults. We believe that NICCD is a disease with characteristic hepatopathological features.

Novel diagnostic approach to citrin deficiency: analysis of citrin protein in lymphocytes.

Citrin deficiency induces two clinical features; namely neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type II citrullinemia. Hypercitrullinemia is the most characteristic feature, whereas there are non-citrullinemic individuals. Diagnosis of citrin deficiency is performed by genetic analysis, although the 12 known mutations in the alleles are not detected in about 15% of cases. Thus, we aimed to examine citrin protein in lymphocytes isolated from peripheral blood as an alternative diagnostic method. We examined 38 children having an episode of cholestatic liver dysfunction, 8 heterozygotes, and 11 healthy individuals. All subjects were evaluated for citrin protein by Western blotting and for the 12 known mutations by gene analysis. Citrin protein was detected in 15 of 38 children with cholestatic liver dysfunction. Fourteen of them were negative for 12 known mutations in both alleles, whereas one patient was found to have a known mutation in one allele. Citrin protein was absent in 23 of the 38 patients. Among these 23, gene analysis diagnosed citrin deficiency in 19, whereas 2 patients were later revealed to be NICCD with novel mutations. In the remaining 2 patients, who exhibit the clinical features of NICCD, a known mutation was detected in one allele but no mutation was identified in another allele. Citrin protein was also detected in the 8 heterozygotes and 11 healthy individuals. We disclosed that citrin was deficient in lymphocytes among patients with citrin deficiency. Analysis of citrin is useful to diagnose citrin deficiency even in patients without known mutations or hypercitrullinemia.

Guidelines for the treatment of Crohn's disease in children.

This paper shows guidelines for the treatment of Crohn's disease in children by the Working Group of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (Chair: Yuichiro Yamashiro) and the Japanese Society for Pediatric Inflammatory Bowel Disease (Chair: Akio Kobayashi). The points in which these guidelines differ from those for adult patients are as follows. (i) Total enteral nutrition in the form of an elemental formula is indicated as primary therapy for children with Crohn's disease at onset as well as the active stage. Oral mesalazine is used together. (ii) Total parenteral nutrition (TPN) with oral mesalazine is required for children with serious illness. The use of a corticosteroid should be withheld for at least 1 week after TPN has been started. (iii) When TPN is not considered to be effective, additional corticosteroid is used. Full doses of corticosteroid should be used for at least 2 weeks after clinical improvement has been achieved, and then the dose of the corticosteroid should be tapered carefully. (iv) When surgery is indicated in pediatric patients with stricture or fistula formation and complicated by persistent growth failure despite medical therapy, the optimum time for surgery is thought to be before epiphyseal plates have been closed.

Association between gastric atrophy and Helicobacter pylori infection in Japanese children: a retrospective multicenter study.

The purpose of this study was to determine whether Helicobacter pylori infection and mucosal inflammation result in gastric atrophy in Japanese children. A total of 196 patients ages 1-16 years were retrospectively studied: 131 patients were infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney system. In both the antrum and corpus, H. pylori-infected patients showed significantly higher degrees of inflammation and activity of gastritis, compared with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P < .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and 0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the antrum showed significantly higher degrees of H. pylori density, inflammation and activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was significantly correlated with activity, whereas in the corpus, atrophy correlated with H. pylori density, inflammation, and activity. H. pylori-induced gastric inflammation can cause atrophy in Japanese children, predominantly in the antrum. It remains to be determined whether H. pylori-infected children with gastric atrophy are at increased risk for gastric cancer.

Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.

A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.

Results of triple eradication therapy in Japanese children: a retrospective multicenter study.

BACKGROUND: Large-scale clinical trials in children are lacking concerning Helicobacter pylori eradication therapies. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapies in Japanese children. METHODS: This was a retrospective analysis of the first- and second-line PPI-based triple therapies from pediatric gastrointestinal units between 1996 and 2003. Data collected included doses and duration of regimens, drug compliance, success or failure of eradication, ulcer healing, and symptom response of those with dyspepsia and no ulcers. The results of antibiotic susceptibility tests were also reported in cases where these were performed. RESULTS: A total of 149 pediatric patients (mean age, 12.6 years) were studied, including 123 patients who received first-line therapy: 115 received a PPI plus amoxicillin and clarithromycin (PAC) and 8 received a PPI plus amoxicillin and metronidazole (PAM). Overall eradication rates of the first-line PAC and PAM therapies were 77.4% and 87.5%, respectively ( P = 0.68). All 14 patients with failed PAC therapy received the second-line PAM regimen, resulting in an eradication rate of 100%. Mild side effects were reported only in PAC regimens (13.8%). Primary resistance to amoxicillin, clarithromycin, and metronidazole was detected in 0%, 34.7%, and 12.5% of the strains, respectively. The PAC regimen showed a high eradication rate for clarithromycin-susceptible strains (91.7%), but was relatively ineffective for resistant strains (40.0%) ( P < 0.01). Eradication of H. pylori was associated with ulcer healing and symptomatic improvement among those with gastritis only (both; P < 0.001). Among 17 patients with iron-deficiency anemia, post-treatment hemoglobin levels were higher than the pretreatment levels ( P < 0.001). CONCLUSIONS: The PAC regimen is effective in children. Clarithromycin resistance is associated with eradication failure. Metronidazole is a good substitute for clarithromycin as the second-line option for children.

The prevalence of Helicobacter pylori in Japanese children with gastritis or peptic ulcer disease.

BACKGROUND: Although Helicobacter pylori infection is typically acquired in childhood, the role of H. pylori infection in gastroduodenal diseases in childhood remains to be defined. The purpose of this study was to evaluate the prevalence of H. pylori infection in children with gastritis, duodenal ulcer, and gastric ulcer. METHODS: This was a retrospective analysis of 283 Japanese children (mean age, 11.5 years) with non-nodular gastritis ( n = 73), nodular gastritis ( n = 67), duodenal ulcer ( n = 100), and gastric ulcer ( n = 43). H. pylori status was based on biopsy tests. Clinical symptoms at the time of endoscopy were analyzed with regard to a possible association with the infection. RESULTS: The prevalence of H. pylori in non-nodular gastritis, nodular gastritis, duodenal ulcer, and gastric ulcer was 28.8%, 98.5%, 83.0%, and 44.2%, respectively. H. pylori was significantly linked to duodenal ulcer and gastric ulcers in the age group of 10-16 years, but not in the age group of 9 years and under. In children with H. pylori infection, nodular gastritis was observed in 26.3% of gastric ulcer patients and in 74.7% of duodenal ulcer patients ( P < 0.001). H. pylori infection was significantly associated with the prevalence of anemia ( P < 0.05). CONCLUSIONS: H. pylori is the most important causal factor for the development of duodenal ulcer in childhood. While H. pylori infection appears to be a risk factor in gastric ulcer, other causes are responsible for most cases. Nodular gastritis is the most common type of H. pylori gastritis in childhood. Chronic infection with H. pylori is associated with anemia.

Granulocyte adsorptive apheresis for pediatric patients with ulcerative colitis.

Granulocytapheresis (GCAP) has produced efficacy in adult patients with ulcerative colitis (UC) by adsorbing activated granulocytes and monocytes/macrophages. We retrospectively investigated efficacy and safety of GCAP in pediatric patients with active UC. Twelve steroid-refractory children (12.2 +/- 3.1 years old) were treated with GCAP, one session/week for 5-10 consecutive weeks. In 8 patients, clinical symptoms improved after two GCAP sessions. Normal body temperature, stool frequency, and disappearance of blood in stool were seen after 24.3 +/- 11.5 days. The endoscopic grade improved from 2.6 +/- 0.3 to 0.4 +/- 0.2. One patient who initially responded, developed bloody diarrhea later and 2 cases remained unchanged. The dose of steroid was tapered during GCAP therapy by 50%. No serious adverse effects were noted. Four of 8 cases relapsed 3.5 +/- 2.2 months after the last GCAP while on maintenance therapy, the other 4 were in remission up to 22.8 +/- 18.1 months. In conclusion, GCAP appears to be effective and well tolerated in children with steroid-refractory UC.

Accuracy of the stool antigen test for the diagnosis of childhood Helicobacter pylori infection: a multicenter Japanese study.

OBJECTIVE: The (13)C-urea breath test (UBT) has been accepted as a reliable noninvasive test for detecting Helicobacter pylori infection. Recently, another noninvasive test, a new enzyme immunoassay for H. pylori antigens in stool, has been widely investigated for its clinical usefulness. The purpose of this multicenter study was to evaluate the diagnostic accuracy of the stool antigen test in Japanese children. METHODS: A total of 264 children (148 male and 116 female; mean age 9.2 yr, range 2-17 yr) who underwent (13)C-UBT and the stool antigen test were studied. The diagnosis in these patients was gastritis (n = 49), gastric ulcer (n = 4), duodenal ulcer (n = 24), recurrent abdominal pain (n = 43), and other conditions (n = 144). The stool antigen test was performed using the HpSA ELISA (Premier Platinum HpSA, Meridian Diagnostics). According to manufacturer's instructions, an absorbance at 450/630 nm of <0.100, > or =0.120, and 0.100-0.119 was defined as negative, positive, and indeterminate, respectively. Based on the (13)C-UBT with a cutoff value of 3.5 per mil, the performance of HpSA was studied. In 21 patients who received eradication therapy, the HpSA was performed at baseline and at 1, 2, and 6 months after completion of therapy. Eradication of H. pylori was confirmed by (13)C-UBT at 2 or 3 months of follow-up. RESULTS: (13)C-UBT showed that 76 children were infected with H. pylori and 188 were not infected. In these same children, HpSA results were positive in 77 children, negative in 183, and indeterminate in four. The overall sensitivity, specificity, and accuracy of the test were 96.0% (95% CI = 88.6-99.2%), 96.8% (95% CI = 94.2-99.3%), and 96.5% (95% CI = 94.3-98.8%), respectively. There were no significant differences in these results among age groups of < or =5, 6-10, and > or =11 yr. Receiver operating characteristic curve analysis demonstrated that the best cutoff value of absorbance at 450/630 nm was 0.110. When a single cutoff value of 0.110 without indeterminate results was used, the sensitivity, specificity, and accuracy were 96.1% (95% CI = 90.8-99.7%), 96.3% (95% CI = 93.6-99.0%), and 96.2% (95% CI = 93.9-98.5%), respectively. In 19 patients in whom H. pylori was successfully eradicated, HpSA results were negative at 1 month of follow-up and remained negative through 6 months. CONCLUSIONS: The HpSA is an accurate test for the detection of H. pylori infection in all age groups of children.

Antibiotic resistance of Helicobacter pylori strains in Japanese children.

The resistance of Helicobacter pylori to the recently available antibiotic treatment regimens has been a growing problem. We investigated the prevalence of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin among 51 H. pylori isolates from Japanese children. In addition, the mutations of the corresponding gene were studied by PCR and restriction fragment length polymorphism analysis. Primary resistance to clarithromycin, metronidazole, and amoxicillin was detected in 29, 24, and 0% of strains, respectively. The eradication rates in clarithromycin-susceptible and -resistant strains were 89 and 56%, respectively (P < 0.05). The prevalence of strains with acquired resistance to clarithromycin (78%) was higher than that of strains with primary resistance (P < 0.01). Among the clarithromycin-resistant strains studied, 92% showed cross-resistance to azithromycin. No acquired resistance to amoxicillin was demonstrated. The A2144G mutation in the 23S rRNA gene was detected in 11 of 12 (92%) clarithromycin-resistant strains tested, whereas the mutation was not detected in any of the 15 susceptible strains. The deletion of the rdxA gene was not demonstrated in any of the strains. The results indicate that a high prevalence of clarithromycin-resistant strains is associated with eradication failure. Testing of susceptibility to clarithromycin is recommended.