Takuji Fujisawa

Accuracy of the Stool Antigen Test for the Diagnosis of Childhood Helicobacter pylori Infection: A Multicenter Japanese Study

OBJECTIVE:The 13C-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 13C-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 manufacturers instructions, an absorbance at 450/630 nm of <0.100, ≥0.120, and 0.100–0.119 was defined as negative, positive, and indeterminate, respectively. Based on the 13C-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 13C-UBT at 2 or 3 months of follow-up.RESULTS:13C-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 ≤5, 6–10, and ≥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.

Diagnostic accuracy of the 13C-urea breath test for childhood Helicobacter pylori infection: a multicenter Japanese study

OBJECTIVES:In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value.METHODS:A total of 220 Japanese children aged 2–16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS).RESULTS:Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean Δ 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5‰. The overall sensitivity and specificity at a cutoff value of 3.5‰ were 97.8% (95% CI = 92.1–99.7%) and 98.5% (95% CI = 96.4–100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (≤5, 6–10, and ≥11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001).CONCLUSIONS:The 13C-UBT with a cutoff value of 3.5‰ is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.

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

BackgroundAlthough 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.MethodsThis 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.ResultsThe 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).ConclusionsH. 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.

Epidemiology of Helicobacter pylori infection in children: A serologic study of the Kyushu region in Japan

Background : The prevalence of Helicobacter pylori infection in children varies as a function of socioeconomic development, with low rates in developed countries and high rates in developing countries. The prevalence of H. pylori infection in Japanese children is unknown.

Profile of urinary bile acids in infants and children : developmental pattern of excretion of unsaturated ketonic bile acids and 7β-hydroxylated bile acids

Unusual bile acids, such as unsaturated ketonic and 7β-hydroxylated bile acids, have been detected in urine early in life. To elucidate the normal profiles of usual and unusual urinary bile acids in the neonatal and pediatric periods, we measured the concentrations of 28 kinds in urine from normal newborns, infants, and children by gas chromatography-mass spectrometry. The mean total bile acid/Cr ratio in 7-d-old infants was significantly higher than in subjects of other age groups (birth, 2-4 mo, 5-7 mo, 11-12 mo, 2-3 y, 9-14 y, and adult) (p < 0.05). Relatively large amounts of unusual bile acids were detected during infancy, especially during the period up to 1 mo of age. At that time, 1β,3α,7α,12α-tetrahydroxy-5β-cholan-24-oic, 7α,12α-dihydroxy-3-oxo-5β-chol-1-en-24-oic, and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids were predominant among the unusual urinary bile acids present. Moreover, the levels of 3α,7β,12α-trihydroxy-5β-cholan-24-oic acid increased significantly after 2-4 mo of age. These results indicate that bile acid synthesis and metabolism in the liver of developing infants are significantly different from that occurring in the liver of adults. Significant amounts of urinary isomerized 7β-hydroxylated bile acids were detected after late infancy, probably because of changes in the intestinal bacterial flora response to a change in nutrition. We describe, for the first time, evidence of the epimerization of the 7α-hydroxyl group of cholic acid, which may be unique to human development.

Hepatitis C virus RNA present in saliva but absent in breast‐milk of the hepatitis C carrier mother

In order to examine whether saliva and breast‐milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast‐milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1‐ to 3‐month intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast‐milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast‐milk is not likely to be a source of mother‐to‐child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.

Helicobacter pylori and TT virus prevalence in Japanese children

BackgroundThe major transmission route of Helicobacter pylori, oral-oral or fecal-oral, remains to be established. TT virus (TTV), a recently discovered microbe that is prevalent in healthy persons, is believed to be mainly transmitted by nonparenteral routes. The purpose of this study was to test the hypothesis that these two microorganisms have a common mode of transmission.MethodsWe investigated the seroprevalence of H. pylori and TTV in a cross-sectional study of 454 healthy Japanese children from birth to age 15 years, living in five different geographic areas. Determination of H. pylori status was based on the presence of specific serum IgG and IgA antibodies, determined using enzyme immunoassays. TTV DNA was detected and the titer was determined using semiquantitative polymerase chain reaction with heminested primers.ResultsThe overall prevalences of H. pylori and TTV were 12.2% and 21.6%, respectively. An age-related increase of prevalence was shown for H. pylori (P ≪ 0.001), but not for TTV (P = 0.23). Titers of TTV DNA significantly decreased with age (P = 0.02). There were significant geographic differences in TTV prevalence (P ≪ 0.001), but not in H. pylori seroprevalence (P = 0.33). There was no true correlation between the prevalence of these two organisms (Φ coefficient = −0.02 and P = 0.66). ConclusionsAlthough Japanese children frequently acquire both H. pylori and TTV, especially in early childhood, their acquisition appears to be independent.

A 13C-urea breath test in children with helicobacter pylori infection: assessment of eradication therapy and follow-up after treatment.

Purpose. Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, for assessment of the efficacy of eradication therapy, and for post-treatment follow-up in children. Methods. Seventy-two patients who underwent endoscopy for symptoms related to the upper gastrointestinal tract were examined by rapid urease test, histology, and culture. The patients were also studied with serology and UBT. Results. Forty-seven of the 72 patients were diagnosed with H. pylori infection, based on the results of biopsy-based tests and serology. As an initial diagnostic test to detect H. pylori infection, the sensitivity of the UBT was 95%, which was comparable with that of histology (94%), rapid urease test (96%), and serology (91%) and was greater than that of culture (79%). The specificity of the UBT was 100%, which was comparable with that of the other four tests. The efficacy of eradication therapy was assessed by biopsy-based tests and the UBT in 24 H. pylori-positive patients. For this purpose, the sensitivities of UBT and histology were 100%, while the sensitivities of culture and the rapid urease test were 88%. The specificity was 100% for all of these tests. Eleven patients were assessed by biopsy-based tests and UBT after more than 6 months of post-treatment follow-up. There were no discordances between the results of the UBT and those of the biopsy-based tests in any of the patients. Conclusions. The UBT may be useful for detecting H. pylori infection in children with upper gastrointestinal tract symptoms, for assessment of the efficacy of eradication therapy, and for the follow-up evaluation of patients after the therapy.

Helicobacter pylori seropositivity in patients with severe neurologic impairment.

The objective of this study was to assess the prevalence of Helicobacter pylori seropositivity in institutionalized patients with severe neurologic impairment. Anti-H. pylori immunoglobulin G antibody in serum was measured in 196 institutionalized Japanese patients using enzyme linked immunosorbent assay, taking an antibody level >50 units/ml as evidence of H. pylori seropositivity. Patient age pattern and duration of institutionalization were examined for the relationships with H. pylori seropositivity. We also examined for seroconversion indicating new H. pylori infection in initially negative patients 1 year later. Positivity for H pylori infection among institutionalized patients was also compared with positivity among patients living at home. H. pylori seropositivity was present in 81.1% of subjects. Prevalence of H. pylori seropositivity increased with both age and duration of institutionalization. The serum level of anti-H. pylori immunoglobulin G antibody in patients over 20 years old was consistently high, approximately twice that of subjects less than 10 years of age. Of 38 patients initially negative for H. pylori infection, 18 (47.4%) had become positive at 1 year. H. pylori seropositivity was significantly more prevalent among institutionalized patients than among patients living at home (P < 0.0001). This study confirms that high H. pylori seropositivity rates are found among institutionalized patients with severe neurologic impairment. Our observations suggest person to person transmission, with fecal to oral, salivary secretion and respiratory droplet routes possibly being important pathways.

Urinary 7α-hydroxy-3-oxochol-4-en-24-oic and 3-oxochola-4,6-dien-24-oic acids in infants with cholestasis

BACKGROUND/AIMS Urinary 3-oxo-delta4 bile acids have been detected in infants who ultimately died of liver disease. We used qualitative and quantitative methods to compare urinary 3-oxo-delta4 bile acids in liver disease, determining their composition and evaluating the prognostic implication in patients of various ages with various liver diseases. METHODS Gas chromatography-mass spectrometry was used to measure 3-oxo-delta4 bile acids in the urine of patients and healthy controls. RESULTS Patients with a deficiency of 3-oxo-delta4-steroid 5beta-reductase and acute hepatic failure exhibited a significantly higher percentage of 3-oxo-delta4 bile acids in total bile acids in urine than the healthy controls or other patient groups, including those with neonatal cholestasis or biliary atresia (p<0.0001). The urinary 3-oxo-delta4 bile acids in patients with 3-oxo-delta4-steroid 5beta-reductase deficiency who had a poor prognosis were mainly 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid. CONCLUSIONS Our results indicate that an increase in the 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid in the urine of patients with hepatobiliary disease indicates a poor prognosis.