Analysis of autoimmune hepatitis with acute presentation in the early stage of illness.

BACKGROUND AND AIM: There is no gold standard for making the diagnosis of autoimmune hepatitis (AIH), and the diagnosis of acute onset AIH (A-AIH) is most challenging. A-AIH sometimes develops into acute liver failure with poor prognosis if the diagnosis is delayed. Therefore, it is most important for the better prognosis to diagnose non-severe A-AIH early and treat appropriately. However, features in the early stage of A-AIH are unclear. We examined initial characteristics of non-severe A-AIH in detail and tried to find novel clinical features for the early diagnosis. METHODS: Clinical, biochemical, immunological, radiological, and histological features of 71 patients (54 women, mean age 57.9 ± 14.3 years) with non-severe A-AIH admitted to community hospitals between 2001 and 2022 were analyzed retrospectively. RESULT: Forty-six had no symptom on onset and liver injuries were discovered by regular medical checkups. The mean duration from onset to consultation was 25.0 ± 29.3 days. Liver histology showed acute hepatitis in 59% and chronic hepatitis in 41%. Patients with symptoms revealed more male sex (P = 0.039), higher alanine aminotransferase (P < 0.001), higher total bilirubin (P < 0.001), and higher rate of histological acute hepatitis (P = 0.0013) than those without symptoms significantly. Male sex, presence of symptoms on onset, occurrence of jaundice in the course, and histological acute hepatitis were correlated. CONCLUSIONS: Sixty-five percent of non-severe A-AIH patients were asymptomatic on onset, suggesting that A-AIH would develop insidiously and present a longer clinical course than that reported. Male patients more often revealed true acute hepatitis clinically, biochemically, and histologically than female ones.

Efficacy and safety of biosimilar infliximab in bio-naïve patients with Crohn's disease.

BACKGROUND AND STUDY AIMS: The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease. PATIENTS AND METHODS: This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration. RESULTS: The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups. CONCLUSION: The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease.

Risk factors of unintentional piecemeal resection in endoscopic mucosal resection for colorectal polyps ≥ 10 mm.

This study aimed to investigate the lesion and endoscopist factors associated with unintentional endoscopic piecemeal mucosal resection (uniEPMR) of colorectal lesions ≥ 10 mm. uniEPMR was defined from the medical record as anything other than a preoperatively planned EPMR. Factors leading to uniEPMR were identified by retrospective univariate and multivariate analyses of lesions ≥ 10 mm (adenoma including sessile serrated lesion and carcinoma) that were treated with endoscopic mucosal resection (EMR) at three hospitals. Additionally, a questionnaire survey was conducted to determine the number of cases treated by each endoscopist. A learning curve (LC) was created for each lesion size based on the number of experienced cases and the percentage of uniEPMR. Of 2557 lesions, 327 lesions underwent uniEPMR. The recurrence rate of uniEPMR was 2.8%. Multivariate analysis showed that lesion diameter ≥ 30 mm (odds ratio 11.83, 95% confidence interval 6.80-20.60, p < 0.0001) was the most associated risk factor leading to uniEPMR. In the LC analysis, the proportion of uniEPMR decreased for lesion sizes of 10-19 mm until 160 cases. The proportion of uniEPMR decreased with the number of experienced cases in the 20-29 mm range, while there was no correlation between the number of experienced cases and the proportion of uniEPMR ≥ 30 mm. These results suggest that 160 cases seem to be the minimum number of cases needed to be proficient in en bloc EMR. Additionally, while lesion sizes of 10-29 mm are considered suitable for EMR, lesion sizes ≥ 30 mm are not applicable for en bloc EMR from the perspective of both lesion and endoscopist factors.

Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000.

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Clinical Features Focusing on Extraintestinal Manifestations in Japanese Patients with Inflammatory Bowel Diseases: Far East 1000.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) can develop extraintestinal manifestations (EIMs) during the disease course, which sometimes impact their quality of life. OBJECTIVES: This study aimed to clarify the prevalence and types of EIMs using a hospital-based IBD cohort in Japan. METHODS: A patient cohort with IBD was established in 2019, as participated by 15 hospitals in Chiba Prefecture of Japan. Using this cohort, the prevalence and types of EIMs, which are defined based on previous reports and the Japanese guidelines, were investigated. RESULTS: This cohort enrolled 728 patients, including 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). Of these patients with IBD, 10.0% were identified with one or more EIMs (57 (10.5%) with UC and 16 (8.6%) with CD). Arthropathy and arthritis were the most common EIM in 23 (4.2%) patients with UC, followed by primary sclerosing cholangitis (PSC) (2.6%). Arthropathy and arthritis were also the most common in patients with CD, but no cases of PSC were observed. EIMs were more frequently observed in patients with IBD treated by specialists than in those treated by non-specialists (12.7% vs. 5.5%, p = 0.011). The incidence of EIMs in patients with IBD was not significantly different over time. CONCLUSIONS: The prevalence and types of EIMs in our hospital-based cohort in Japan did not significantly differ from those reported in previous or Western studies. However, the incidence might be underestimated due to the limited ability of non-IBD specialists to discover and describe EIMs in patients with IBD.

X-ray induced luminescence spectroscopy for DNA damaging intermediates aided by a monochromatic synchrotron radiation.

PURPOSE: To identify the bonding sites of initial radiation interaction with DNA and to trace the following chemical reaction sequences on the pathway of damage induction, we carry out a spectroscopy XIL (X-ray induced luminescence) using soft X-ray synchrotron radiation. This is a nondestructive analysis of the excited intermediate species produced in a molecular mechanism on the damage induction pathway. MATERIALS AND METHODS: We introduce aqueous samples of UMP (uridine-5'-monophosphate) in the vacuum by the use of a liquid micro-jet technique. The luminescence in the region of UV-VIS (from visible to ultraviolet) radiation induced after the absorption of monochromatic soft X-ray by aqueous UMP is measured with sweeping the soft X-ray energy in the region of 370-560 eV. RESULTS: The enhanced XIL intensities for aqueous UMP in the region of soft X-ray of 410-530 eV (in "water window" region) are obtained. The enhancement of XIL intensities in the UV-VIS region, relative to the water control, is explained by the excitation and ionization of a K-shell electron of nitrogen atoms in the uracil moiety. The enhanced XIL intensities do not match the structure of XANES (X-ray absorption near-edge structure) of the aqueous UMP. This suggests that the XIL intensities reflect the quantum yields of luminescence, or the quantum yields for conversion by UMP of an absorbed X-ray into UV-VIS radiation. In this paper, spectra of luminescence are shown to be resolved by combining low pass filters. The filtered luminescence spectra are obtained at the center of gravity (λc) of the band pass wavelength regions at λc = 270nm, 295 nm, 340 nm, 385 nm, 450 nm, and 525 nm., which show a trend similar to the fluorescence of nucleobases induced by ultraviolet radiation. CONCLUSION: It is concluded that the origin of the observed XIL is the hydrated uracil moiety in aqueous UMP, decomposition of which is suppressed by the migration of excess charge and internal energy after the double ionization due to Auger decay.

The long-term effect of biologics in patients with ulcerative colitis emerging from a large Japanese cohort.

To gain a better understanding of the effects of biologics, we evaluated clinical outcomes in patients with moderate to severe exacerbations of ulcerative colitis (UC). This retrospective, multicenter study retrieved the entire clinical courses of UC patients who began treatments between 2004 and 2018. All exacerbations and clinical parameters, including treatment details for exacerbations and both remission and re-exacerbation dates, were identified during the observation period. Two different endpoints, the cumulative incidence rates of surgical resection and re-exacerbation, were evaluated separately in moderate to severe exacerbation events. Among 1401 patients, 1626 exacerbation events were determined according to a partial Mayo score (remission: < 2, mild: 2-4, moderate: 5-7, and severe: > 7). During the observation period, as administration rates of biologics increased, both surgical resection and hospitalization rates decreased, for 959 moderate to severe exacerbation events. We confirmed that biologics significantly reduced the cumulative re-exacerbation rate in moderate to severe exacerbation events during the study period compared with suboptimal therapies (a 0.507-fold decreased risk according to COX regression analysis, P < 0.001). However, they had not enough impact in reducing the cumulative incidence rate of surgical resection in moderate to severe exacerbation events that were corticosteroid-refractory or dependent (a 0.878-fold decreased risk according to COX regression analysis, P = 0.606). Biologics may improve remission duration, but these agents had no significant impact in reducing the risk of surgical resection in moderate to severe active UC.

Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19.

Although the importance of virus-specific cytotoxic T lymphocytes (CTL) in virus clearance is evident in COVID-19, the characteristics of virus-specific CTLs related to disease severity have not been fully explored. Here we show that the phenotype of virus-specific CTLs against immunoprevalent epitopes in COVID-19 convalescents might differ according to the course of the disease. We establish a cellular screening method that uses artificial antigen presenting cells, expressing HLA-A*24:02, the costimulatory molecule 4-1BBL, SARS-CoV-2 structural proteins S, M, and N and non-structural proteins ORF3a and nsp6/ORF1a. The screen implicates SARS-CoV-2 M protein as a frequent target of IFNγ secreting CD8+ T cells, and identifies M198-206 as an immunoprevalent epitope in our cohort of HLA-A*24:02 positive convalescent COVID-19 patients recovering from mild, moderate and severe disease. Further exploration of M198-206-specific CD8+ T cells with single cell RNA sequencing reveals public TCRs in virus-specific CD8+ T cells, and shows an exhausted phenotype with less differentiated status in cells from the severe group compared to cells from the moderate group. In summary, this study describes a method to identify T cell epitopes, indicate that dysfunction of virus-specific CTLs might be an important determinant of clinical outcomes.

Analysis of non-severe acute onset autoimmune hepatitis according to the presence of radiological heterogeneity.

AIM: Diagnosis of acute onset autoimmune hepatitis (A-AIH) has been difficult in that patients may not have typical clinicopathological features of AIH. In our previous reports of severe and fulminant AIH, two-thirds of them showed radiological heterogeneity: hepatic heterogeneous hypoattenuation on unenhanced computed tomography (CT) reflecting heterogeneous distribution of massive hepatic necrosis (severe centrilobular necrosis), which would be beneficial for the diagnosis. In the present study, we analyzed non-severe A-AIH patients with or without radiological heterogeneity and tried to find novel clinical features for supporting the early diagnosis. METHODS: Clinical, biochemical, immunological, radiological and histological features of 42 patients with non-severe A-AIH at community hospitals between 2010 and 2020 were analyzed. RESULTS: Of 42, 28 patients on whom CT scans were performed and who could be fully analyzed were enrolled. Five patients showed hepatic heterogeneous hypoattenuation on unenhanced CT. There was no significant difference in clinical, biochemical, immunological and histological features at diagnosis between the two groups according to the presence of radiological heterogeneity, although mean minimum prothrombin time activity during the course was lower in patients with heterogeneity without statistical significance (p = 0.080). All responded to treatment well and achieved initial remission within 3 months. CONCLUSIONS: It is possible that patients with non-severe A-AIH show radiological heterogeneity reflecting centrilobular necrosis which is one of important diagnostic features of A-AIH. Accordingly, radiological heterogeneity might be beneficial for the diagnosis of A-AIH in combination with conventional clinicopathological features if it is detected in the absence of features suggestive of other liver diseases.

Long-term observation of acute-onset autoimmune hepatitis presenting clinically and radiologically as acute hepatitis.

BACKGROUND: There is yet no gold standard for the diagnosis of acute-onset autoimmune hepatitis (A-AIH), especially histologically acute AIH. As a result, long-term observation of A-AIH has been difficult and the nature is not well known. We retrospectively analyzed the clinicopathological features of A-AIH over a long prospective follow-up period. METHODS: Clinical, biochemical, immunological and pathological features of 30 patients (21 female, mean age 55.1 ± 13.1 years) with non-severe A-AIH "without signs of clinical and radiological chronicity" admitted to a community hospital between 2001 and 2015 who were prospectively followed for more than 2 years were analyzed retrospectively. RESULTS: Liver histology of 45% showed acute and 55% chronic hepatitis. Mean age was older, prothrombin time activity was higher, AIH scores before treatment were lower in histologically acute hepatitis than histologically chronic hepatitis significantly. Liver fibrosis was not coarse, but delicate with severe activity in most patients showing chronic hepatitis defined by our strict criteria. Median (range) follow-up period was 6.9 (2.1-16.2) years. Six (20%) patients experienced episode of relapses. All were alive at the last follow-up point. Corticosteroid was continued at 2.5-5 mg/day until the study end point without serious side effects in most patients. Serial change of alanine aminotransferase levels, immunoglobulin G levels and anti-nuclear antibody titers did not show statistical difference between histologically acute and chronic hepatitis. CONCLUSION: Rapid progression of fibrosis could occur in A-AIH. Treatment response and long-term prognosis were good, and not different between patients with histologically acute and chronic hepatitis.

Nationwide survey of Helicobacter pylori treatment for children and adolescents in Japan.

BACKGROUND: To prevent gastric cancer, a test-and-treat strategy for Helicobacter pylori has been proposed. This retrospective study assessed the clinical features, efficacy and safety of treatment for H. pylori infection in children and adolescents. METHODS: Questionnaires concerning the clinical features and treatment of H. pylori in children and adolescents were sent to doctors in 2013. It included questions on patient background, H. pylori-associated disease, first- and second-line treatment, success or failure of eradication, resistance to antibiotics, and occurrence of adverse events. In 2014, serious adverse events associated with treatment were analyzed. RESULTS: Invitation letters and questionnaires were sent to 1097 doctors, of whom 409 (37.3%) participated. Finally, 332 patients (mean age, 11.6 ± 3.4 years; male, n = 200) treated from 1997 to 2013 were analyzed. H. pylori-associated gastritis, iron deficiency anemia, and duodenal ulcer occurred most frequently. Success rates for first- and second-line treatments were 73.1% and 79.6%, respectively. Seventy-six H. pylori strains were analyzed for resistance to amoxicillin (AMPC) and clarithromycin (CAM), and 64 were analyzed for resistance to metronidazole (MNZ). CAM resistance was most frequent, occurring in 43.4% of patients; that of MNZ was 21.9%. Adverse events were observed in 13.8% of cases. In total, 587 cases of H. pylori infection were analyzed and no serious adverse events were observed. CONCLUSIONS: Treatment for H. pylori in children and adolescents is safe, but further studies on treatment regimens should be conducted to improve eradication rates and monitor increasing CAM resistance.

High level of persistent liver injury is one of clinical characteristics in treatment-naïve acute onset autoimmune hepatitis: experience in a community hospital.

BACKGROUND: There is, as yet, no gold standard for making the diagnosis of acute onset autoimmune hepatitis (A-AIH). Novel histological characteristics have been reported, but etiologies other than AIH could show similar histological pattern. We attempted to determine what clinical characteristics we should consider as A-AIH different from other etiologies, and to whom histological characteristics should be applied for the diagnosis. METHODS: Clinical, biochemical, immunological and pathological features of 46 patients (35 women, mean age 55.9 ± 14.2 years) with non-severe A-AIH admitted to a community hospital between 2001 and 2015 were analyzed. RESULTS: Immunoglobulin G level was normal in 28%, and anti-nuclear antibody titer was < × 80 in 28%. Liver histology of 49% showed acute form and 51% chronic one. Centrilobular necrosis/collapse and/or plasma cell accumulation, rosette formation were characteristic for A-AIH. High levels of alanine aminotransferase persisted in 21 patients who could be observed for equal to or more than 4 weeks before the start of treatment. CONCLUSIONS: Long persistence of high levels of alanine aminotransferase would be one of clinical features for considering A-AIH along with conventional features. Histological diagnostic features should be applied for such patients. Guidelines for diagnosing A-AIH should be urgently drawn up.

Analysis of infectious complications and timing for emergency liver transplantation in autoimmune acute liver failure.

BACKGROUND: Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT. METHODS: Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed. RESULTS: Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10­41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01). CONCLUSIONS: Two-week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve.

Effects of Arm Bracing on Expiratory Flow Limitation and Lung Volume in Elderly COPD Subjects.

BACKGROUND: Although it is useful for COPD patients to relieve their dyspnea by bracing their arms, the relationships between the arm bracing posture and expiratory flow limitation (EFL) and lung volume are unknown. Whether arm bracing affects dyspnea, EFL, and lung volume in elderly COPD patients was investigated. METHODS: Sixteen elderly subjects (median [interquartile range] age 81 [77-85] y) with stable COPD (percent-of-predicted FEV1 50.9 [31.3-64.9] %) and 16 age-matched healthy subjects were studied. Breathing patterns, EFL, lung volume, SpO2 , and heart rate during quiet breathing were randomly evaluated in 3 standing postures: erect, leaning forward, and arm bracing. Dyspnea was also assessed for each posture with a Borg dyspnea score at the end of the test. RESULTS: Lung volume was significantly higher with arm bracing than with the other postures in both groups (P < .05). Breathing patterns, SpO2 , and pulse rate were not significantly different among the 3 postures in both groups. However, EFL and Borg dyspnea scores were significantly lower with arm bracing than with the other postures in COPD subjects (P < .01). CONCLUSIONS: The decreased EFL in the arm bracing position may be caused by breathing at a higher lung volume than in the erect position, which may be one of the factors relieving dyspnea in elderly COPD patients.

Nitrogen K-edge x-ray absorption near edge structure of pyrimidine-containing nucleotides in aqueous solution.

X-ray absorption near edge structure (XANES) was measured at energies around the N K-edge of the pyrimidine-containing nucleotides, cytidine 5'-monophosphate (CMP), 2'-deoxythymidine 5'-monophosphate (dTMP), and uridine 5'-monophosphate (UMP), in aqueous solutions and in dried films under various pH conditions. The features of resonant excitations below the N K-edge in the XANES spectra for CMP, dTMP, and UMP changed depending on the pH of the solutions. The spectral change thus observed is systematically explained by the chemical shift of the core-levels of N atoms in the nucleobase moieties caused by structural changes due to protonation or deprotonation at different proton concentrations. This interpretation is supported by the results of theoretical calculations using density functional theory for the corresponding nucleobases in the neutral and protonated or deprotonated forms.

Study of the mechanisms of a Japanese traditional fermented medicine in the improvement of constipation.

BACKGROUND AND AIM: Gut Working Tablet (GWT) is a Japanese traditional fermented medicine based on Aspergillus oryzae NK-fermented grain germ. Although GWT has been used by patients with constipation, the mechanism has not been investigated. The aim of this study was to examine the possible mechanisms of the effect of GWT on constipation. METHODS: The effect of GWT water extracts on gut contractility using ileum strips from guinea pig and on the growth of Bifidobacterium longum were examined in vitro. The 14 Sprague Dawley rats were administered loperamide at 10 mg/day per kg for 3 days. They were fed with and without 5% of GWT before and during administration of loperamide. Number of stools and weight of feces were measured before and during administration of loperamide. The concentrations of short-chain fatty acids (SCFAs) in the feces and cecal contents were measured by gas chromatography. RESULTS: GWT water extracts dose-dependently induced ileal contractile responses, which were inhibited by atropine. The growth of B. longum was increased in the presence of GWT water extracts in a dose-dependent manner (P < 0.01 vs control). The decrease in both the number and weight of feces caused by loperamide was improved by GWT administration (P < 0.05 vs loperamide). The decrease in the butyric acid concentration in feces and cecal contents induced by the administration of loperamide was inhibited by GWT (P = 0.035 and 0.018). CONCLUSION: GWT water extracts may induce cholinergic-like stimulation and promote the growth of probiotics. Furthermore, GWT water extract contributed to normalization of colonic SCFAs. These results may explain, at least in part, the beneficial effects of GWT on constipation.

Association between serum long-chain n-3 and n-6 polyunsaturated fatty acid profiles and glomerular filtration rate assessed by serum creatinine and cystatin C levels in Japanese community-dwellers.

BACKGROUND: Plasma concentration of n-3 polyunsaturated fatty acids (PUFAs) has been reported to be associated with renal function in Western populations. However, few studies have investigated the association between serum long-chain n-3 and n-6 PUFA profiles and renal function in a Japanese population with high marine-derived long-chain n-3 PUFA intake. METHODS: A cross-sectional study was performed in 549 Japanese rural community-dwellers aged 40 to 64 years. In adjusted analysis of covariance, we assessed the relationship between estimated glomerular filtration rate (eGFR) and tertiles of serum long-chain n-3 and n-6 PUFA profiles ([eicosapentaenoic acid {EPA} + docosahexaenoic acid {DHA}]:arachidonic acid [AA]). GFR was estimated by Japanese specific equations using serum creatinine and cystatin C (eGFRcre and eGFRcys). Using multivariate-adjusted linear regression models, we also assessed the relationships between eGFRs and several n-3 and n-6 PUFAs, which have been suggested to be associated with renal function. RESULTS: In all participants, higher dietary fish intake as assessed by a semi-quantitative questionnaire was associated with higher serum value of (EPA+DHA):AA. Participants in the higher (EPA+DHA):AA tertiles had non-significantly higher eGFRcre and significantly higher eGFRcys (P = 0.016). In addition, eGFRcys in T2+T3 of (EPA+DHA):AA was significantly higher than that in T1 (adjusted mean eGFRcys, T1: 87 ml/min/1.73 m(2), T2+T3: 91 ml/min/1.73 m(2); P < 0.01). Among the PUFAs, only (EPA+DHA) was significantly associated with eGFRcys. CONCLUSIONS: Serum (EPA+DHA):AA, which reflects an individual's fish intake, might be associated with eGFRcys in Japanese community-dwellers.

Severe and fulminant hepatitis of indeterminate etiology in a Japanese center.

AIM: The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF. METHODS: We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively. RESULTS: Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients. CONCLUSION: There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies.

Low prevalence and incidence of Helicobacter pylori infection in children: a population-based study in Japan.

BACKGROUND: Infection of Helicobacter pylori mainly occurs in childhood. In Japan, incidence of gastric cancer is still high in the senior citizen population, but little is known about the current H. pylori infection status among children or their family members. METHODS: As a population-based study, the prevalence of H. pylori infection and change in infection status over a 1-year interval in children were determined. Family members of some participants were also invited to participate in the study to determine their infection status. All children of specific ages attending 16 schools in Sasayama, Hyogo Prefecture, were invited to participate. H. pylori infection was determined by the stool antigen test and diagnosis confirmed by polymerase chain reaction and the urea breath test. RESULTS: Helicobacter pylori prevalence was 1.9% among 689 children aged 0-8 years in 2010 and 1.8% among 835 children aged 0-11 in 2011. No feco-conversion was observed in 430 children aged 0-8 years (170 were aged 0-4 years) who provided follow-up stool samples after 1 year. The prevalence of infection was 6% (2 of 33) and 38% (6 of 16) in mothers of negative and positive probands (p = .04), respectively, and 12% (3 of 25) and 50% (8 of 16) (p = .01), respectively, in fathers. CONCLUSION: Helicobacter pylori prevalence in Japanese children is approximately 1.8%, which is much lower than that reported in Japanese adults. New infection may be rare. Parent-to-child infection is thought to be the main infection route of the infrequent infection for children in Japan.

Evaluation of a stool antigen test using a mAb for native catalase for diagnosis of Helicobacter pylori infection in children and adults.

Non-invasive diagnosis of Helicobacter pylori infection is important not only for screening of infection but also for epidemiological studies. Stool antigen tests are non-invasive and are convenient to identify H. pylori infection, particularly in children. We evaluated the stool antigen test, which uses a mAb for native catalase of H. pylori developed in Japan. A total of 151 stool samples were collected from participants (52 children and 99 adults) of the Sasayama Cohort Study and stored between -30 and -80 °C. The stool antigen test used was Testmate pylori antigen (TPAg), and was performed according to the manufacturer's instructions. Furthermore, we conducted a quantitative real-time PCR test and compared the PCR results with those of the TPAg test. When compared with the results in real-time PCR, the sensitivity of TPAg was 89.5 % overall, 82.7 % for children and 92.4 % for adults, and the specificity was 100 %. The accuracy was 93.4 % overall, 90.4 % for children and 94.9 % for adults, and there was no significant difference in the accuracy of TPAg between children and adults. Five of 28 children (18 %) and five of 38 adults (13 %) were PCR positive with negative TPAg results. Four of five children with positive PCR and negative TPAg results were given a (13)C-urea breath test and all four children tested negative. No significant correlation was observed between the TPAg results and DNA numbers of H. pylori in faeces among children or adults. A stool antigen test (TPAg) using a mAb for native catalase is useful for diagnosis of H. pylori in children and adults. Additionally, this test has particularly high specificity.