The Presence of Ganglionic Acetylcholine Receptor Antibodies in Sera from Patients with Functional Gastrointestinal Disorders: A Preliminary Study.

BACKGROUND: Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. OBJECTIVE: To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. MATERIALS AND METHODS: We measured autoantibodies against the gnAChR α3 and ß4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. RESULTS: Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. CONCLUSIONS: We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.

Endoscopic intragastric balloon therapy for 15 years in Japan: Results of nationwide surveys.

INTRODUCTION: Endoscopic intragastric balloon (IGB) placement has been performed in Japan since 2004. The nationwide surveys were repeatedly carried out to confirm the effectiveness and safety of IGB in Japan. We herein present the accumulated results. METHODS: Twenty-six Japanese endoscopists personally imported products of the BioEnterics Intragastric Balloon (BIB)/Orbera system after completing the training courses in Japan. Mail surveys were posted to them every 2 years from 2010. This study included the accumulated data of the six surveys, and excluded data from non-Japanese patients and the Orbera365 data. RESULTS: Between 2004 and 2019, 399 obese Japanese patients underwent IGB treatment using the BIB/Orbera system. The incidence rates of early removal of IGB within 1 week and complications due to IGB were 4.8% and 6.1%, respectively. The average percent excess weight loss (%EWL) and percent total weight loss (%TWL) at IGB removal were 46.6% and 11.5%, and successful weight loss, defined as %EWL ≥ 25% or %TWL ≥ 10%, was achieved in 65.6% or 54.5% of the patients, respectively. Multivariate analyses revealed that older age and larger saline filling volume were independent predictors of successful weight loss. At 1 year after IGB removal, successful weight loss defined by the %EWL and %TWL was maintained in 44.7% and 34.1% of the patients, respectively. CONCLUSION: IGB therapy using the BIB/Orbera system has been safely and effectively performed in Japan. The successful weight loss may be associated with older age and larger saline filling volume.

MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection.

The outcome of antiviral therapy is associated with viral and host factors. In the present study, the association between MHC class I-related chain B (MICB) genotypes and therapeutic response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy was investigated in hepatitis C virus (HCV)-infected patients. In total, 107 patients with chronic HCV infection (74 with HCV serotype 1 and 33 with serotype 2) were enrolled. Genotyping of MICB single-nucleotide polymorphism (SNP) rs3828913 and interleukin-28B (IL28B) SNP rs8099917 was performed using TaqMan® SNP genotyping assays. The genotype distribution of the MICB alleles was: CC, 79.4%; CA, 17.8%; and AA, 2.8%. Sustained virological response (SVR) was achieved by 55.1% (59/107) of the HCV patients. The SVR rate of patients with MICB major (CC) alleles was 62.3% and this rate was significantly higher than that of the patients with MICB minor (CA and AA) alleles (27.2%) (P=0.0068). A multivariate logistic model showed that the MICB major genotype was an independent factor contributing to SVR (OR, 4.47; 95% CI, 1.46-13.70; P=0.009). In addition, the MICB genotype was identified as the sole independent factor contributing to SVR and non-virological response in HCV serotype 1 patients with the IL28B major genotype. In HCV serotype 2 patients, the MICB genotype was the sole significant factor contributing to SVR (OR, 30.68; 95% CI, 2.72-346.3; P=0.006). In conclusion, the MICB genotype is a strong predictive factor for virological response to PEG-IFN/RBV therapy in HCV patients.

Interleukin-28B genotypes determine response to pegylated-interferon plus ribavirin therapy in patients with hepatitis C virus infection.

We recently reported that the interleukin (IL)-28B major genotype is a predictor of early suppression of the hepatitis C virus (HCV) at 12 weeks in response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy. The present study investigated the relationship between IL-28 genotypes and the virological response to PEG-IFN/RBV therapy at 24 and 48 weeks. Genotypes of the IL-28B rs8099917 T>G single nucleotide polymorphism were determined in 177 patients with HCV infection. Among them, 56 patients with HCV1 infection were treated with PEG-IFN/RBV. The frequency of the IL-28B major allele (TT) was 73.8% in patients with HCV serotype 1 and 86.3% in patients with HCV serotype 2. The rate of HCV-RNA positivity was significantly lower at 48 weeks in patients with the IL-28B major allele compared to patients with the IL-28B minor allele (TG or GG). The rate of HCV-RNA positivity at 24 weeks tended to be lower in patients with the IL-28B major allele, but there was no statistical significance (P=0.059). The sustained virological response (SVR) rate was 45.9% in patients with the IL-28B major allele, but 13.3% in patients with the IL-28B minor allele. The SVR correlated with the IL-28B major allele (OR=7.13, P=0.010), early virological response (OR=33.3, P=0.008), HCV-RNA ≤ 6.3 log IU/ml (OR=81.2, P=0.009) and γ-GTP ≤ 47 IU/l (OR=49.4, P=0.027). The IL-28B genotype is a significant pre-treatment predictor of the response to PEG-IFN/RBV therapy at 48 weeks in patients with HCV infection.

Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients.

Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV-induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The genotypes of the ITPA rs1127354 single nucleotide polymorphism were determined in 179 patients with HCV infection. Among them, 52 patients were treated with PEG-IFN/RBV. The frequency of the ITPA major allele (CC) was 76.3% and that of the minor allele (CA and AA) was 23.7%. A rapid decrease in Hb levels during the initial 4 weeks was observed in patients with the ITPA major allele (CC), but not in patients with the ITPA minor allele (C/A and AA). Hb levels at 4 weeks were significantly lower in patients with the ITPA major allele than the levels in patients with the minor allele. Out of the 41 patients, 6 (14.6%) with ITPA major allele had Hb levels <10 g/dl and 11 patients (26.8%) had a decline in Hb of >3 g/dl. None of the patients with the ITPA minor allele had such data. There were no significant differences in virological responses of HCV-RNA between patients with the ITPA major allele and those with the minor allele. In conclusion, the ITPA genotypes may be a useful marker for prediction of RBV-induced anemia.

Interleukin-28B polymorphisms are associated with an early viral response in patients receiving hepatitis C therapy.

Prediction of the efficacy of pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy against hepatitis C (HCV) infection is valuable for determining its applications. This study investigated the relationship between the early response of HCV to PEG-IFN/RBV therapy and the inter-leukin (IL)-28B genetic polymorphism in patients with HCV infection. The genotypes of IL-28B rs8099917 T>G single nucleotide polymorphism were determined in 144 patients with HCV infection. Among them, 59 were treated with PEG-IFN/RBV. The frequency of IL-28B TT homozygosity was 75.2% in patients with HCV serotype 1 and 84.6% in patients with serotype 2. Multivariate analysis showed that IL-28B TT homozygosity (P=0.014) and the platelets number (P=0.030) was associated with the early suppression of HCV-RNA at 12 weeks after the start of PEG-IFN/RBV therapy. The IL-28B polymorphism was a significant pre-treatment predictor of the response to PEG-IFN/RBV therapy in patients with HCV infection.

Spectra of functional gastrointestinal disorders diagnosed by Rome III integrative questionnaire in a Japanese outpatient office and the impact of overlapping.

BACKGROUND AND AIMS: The aim of this study was to establish the spectra of functional gastrointestinal disorders (FGID) in a Japanese outpatient office in Rome III. METHODS: The Rome III Diagnostic Questionnaire for Adult Functional GI Disorders was translated into Japanese and an automated analyzing program was made according to the scoring algorithm of the questionnaire. Among 1378 patients who visited the outpatient office of the Social Insurance Shiga Hospital between May 2007 and April 2009, 112 serial patients who had symptoms possibly originating from the gastrointestinal (GI) tract, but did not have evidence of organic disease, were recruited. The subjects answered the questionnaire, and the answers were analyzed with the automatic analyzer. RESULTS: During the study period, 94 of the 112 patients were diagnosed as having active FGID. Non-overlapping FGID was diagnosed in 41 (43.6%) of those. Of the 41 non-overlapping FGID patients, the most frequent diagnosis was irritable bowel syndrome (IBS) in 13 patients. Including overlapping cases, 165 FGID were diagnosed in 94 patients. The most frequent diagnosis was IBS in 33 patients (35.1%), the second was functional dyspepsia (FD) in 29 (30.9%) and the third was functional constipation in 21 (22.3%). The most frequent FGID overlapping with IBS was FD (36.4%), and the most frequent FGID overlapping with FD was IBS (41.4%). Of the 29 FD patients, 20 (69.0%) had functional bowel disorders. CONCLUSION: The most frequent FGID was IBS in both overlapping and non-overlapping FGID patients. IBS and FD were the most frequent combinations in overlapping FGID. Most cases of FD are possibly parts of functional bowel disorders.