Distribution of liver stiffness in non-alcoholic fatty liver disease with higher fibrosis-4 index than low cut-off index.

BACKGROUND AND AIM: In the condition of high prevalence of non-alcoholic fatty liver disease (NAFLD), a new diagnostic algorithm to efficiently identify NAFLD patients with significant fibrosis is urgently required. We evaluated the predictive ability of the fibrosis-4 index (FIB-4 index) for significant liver fibrosis (F ≥ 2) in a cohort of Japanese patients with NAFLD. METHODS: We prospectively calculated the FIB-4 index in patients who were incidentally diagnosed as fatty liver in medical checkups and then conducted liver stiffness measurement by vibration-controlled transient elastography (VCTE) only in patients in whom the FIB-4 index was more than the low cut-off index (> 1.45). RESULTS: Of the 5929 people who underwent medical checkups, a total of 1374 people were identified as having fatty liver. Among these, we performed VCTE in 106 patients in whom the FIB-4 index was higher than 1.45. The distribution of the fibrosis stage as estimated by VCTE in the patients was as follows: F0, 52.8%; F1, 10.3%; F2, 21.6%; F3, 11.3%; and F4, 3.7%. The positive predictive value of the FIB-4 index for detecting NAFLD with significant fibrosis was 36.6%. The minimum value of the FIB-4 index was constant for each estimated fibrosis stage. CONCLUSIONS: This is the first prospective study to evaluate the usefulness of the FIB-4 index as the first step to screen NAFLD patients with significant fibrosis. In Japan, addition of one further step that combined with the FIB-4 index is necessary to meaningfully reduce the number of patients needing liver stiffness measurement or liver biopsy.

Initial clinical trial of a novel hemostat, TDM-621, in the endoscopic treatments of the gastric tumors.

BACKGROUND AND AIM: The feasibility of TDM-621, the synthetic infectious agent-free peptides, was tested in hemostasis of the bleeding after endoscopic treatments of the gastric tumors. METHODS: The patients who underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) were enrolled in the present study. The subject of hemostasis was the oozing after the EMR or ESD. The hemostatic effect, the secondary hemorrhage from one postoperative day to the day before discharge and operability were studied. RESULTS: The hemostatic effects were assessed in 12 patients. It was "remarkably effective" in 11 patients and "effective" in 1 patient. The operability was "very easy" in two patients, "easy" in eight patients and "acceptable" in two patients. No secondary hemorrhage was observed in all of 12 patients. No adverse effect considered to be related to TDM-621 was observed. CONCLUSION: It was shown that hemostasis using TDM-621 was feasible after endoscopic treatments of the gastric tumors without any technical trouble or adverse event.

Persistent oxidative stress in the corpus mucosa is evoked by long-term treatment of H. pylori-infected patients with proton pump inhibitors.

BACKGROUND/AIMS: To examine the influence of long-term treatment of H. pylori-infected patients with proton pump inhibitors (PPI) on the toxic oxidant production in the stomach. METHODOLOGY: Eight H. pylori-positive patients with gastric ulcer were enrolled, and tissue samples were obtained endoscopically from the antrum and corpus. The tissue contents of neutrophil myeloperoxidase (MPO) and oxygen-derived free radicals were quantified by ELISA and chemiluminescence (ChL) assay. The H. pylori density in the tissue specimens was scored by immunohistochemistry and the mucosal infiltration by neutrophils and monocytes was scored by histopathology. The effects of PPI on these parameters were evaluated by oral administration of lansoprazole (LPZ) at the dose of 30mg od for 8 weeks, followed by 15mg for 24 weeks. RESULTS: Eight-week treatment with LPZ significantly increased the corpus ChL by 400%, which remained unchanged at this level during the subsequent 24 weeks, but the antrum ChL decreased slightly following LPZ-treatment. No significant changes in the mucosal MPO activity or the histologically determined parameters of H. pylori density and neutrophil/monocyte infiltration were observed in either portion of the stomach. CONCLUSIONS: The mucosal oxidative stress level significantly increased in the corpus mucosa after long-term treatment with LPZ, which may be independent of inflammatory cell infiltration.

Is there a link between food and intestinal microbes and the occurrence of Crohn's disease and ulcerative colitis?

The pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) is not fully understood. The interaction between intestinal environmental factors of food and intestinal microbes and the immunological system of hosts seems to be an important aspect. We have reviewed the relationship of the daily consumption of dietary animal meat and fats, dairy products, sugar, and other factors that may be linked to the occurrence of CD and UC from the literature and Japanese epidemiological data. In the present study, we reviewed the association between food and intestinal microbes and other factors contributing to the occurence of inflammatory bowel disease (IBD) from epidemiological data and case-control studies of IBD in the literature that appeared on Medline, and assessed the reports of intestinal microbes involved in the occurrence of IBD. We found several papers describing the positive association of animal meat and sweets and sugar with the occurrence of CD and UC. An analysis of Japanese epidemiological data suggested that the registered number of patients with CD or UC started to increase more than 20 years after an increased daily consumption of dietary animal meat and fats, and milk and dairy products, and after a decreased consumption of rice. Many studies implied a positive role of intestinal microbes in the occurrence of IBD. Intestinal environmental factors, such as Westernized food and intestinal microbes, seem to be involved in the increased occurrence of IBD.

Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.

BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have been used in patients with Crohn's disease (CD) and ulcerative colitis (UC) for reducing the dose of steroids and maintaining remission. However, some patients treated with 6-MP/AZA develop bone marrow suppression, one of the most serious side effects. The aim of this study was to evaluate the efficacy and safety of low-dose AZA (0.6-1.2 mg/kg per day) for maintaining remission in patients with UC. We also investigated the relationship between bone marrow suppression and thiopurine methyltransferase ( TPMT) mutation in the Japanese population. METHODS: Study 1. To investigate the frequency of TPMT mutation, findings for 82 patients among 141 patients with UC or CD who were treated with AZA or 6-MP were analyzed retrospectively. Polymerase chain reaction (PCR) methods were used to analyze allele mutations of the TPMT gene. Study 2. A multicenter prospective trial was performed. The subjects were 22 patients with UC with presence of remission for 3 months or more. They were treated with 50 mg/day of AZA, and we evaluated the remission rate at 6 months, adverse side effects, and changes in prednisone doses after the initiation of AZA. RESULTS: Study 1. Seventy-four (91%) of the 82 patients analyzed had no TPMT mutation, 7 (8%) had one mutant allele, and 1 (1%) had two mutant alleles. Of the total of 141 patients, 4 (44%) of the 9 patients who were treated with 50 mg/day of 6-MP or 100 mg/day of AZA developed bone marrow suppression, although no mutation of TPMT was seen in any of these patients. On the other hand, 8 (6%) of the 132 patients who were treated with 30 mg/day of 6-MP or 50 mg/day of AZA developed bone marrow suppression. Seven of 8 patients (88%) who developed bone marrow suppression with a low dose of AZA had a mutant TPMT allele. Study 2. In the 17 patients who could continue taking low-dose AZA for 6 months, 15 (88%) maintained remission. Of 8 patients treated with low-dose prednisone (5-10 mg/day), 3 patients (38%) could discontinue oral prednisone and 4 (50%) could reduce its dose. Six of the 22 patients (27%) had some adverse side effects. These side effects were ameliorated, or disappeared spontaneously, or disappeared with the discontinuation of AZA. CONCLUSIONS: A dose of 50 mg/day of AZA is effective and safe for maintenance of remission in the Japanese population. Investigation of the TPMT allele may be useful for predicting the appearance of bone marrow suppression, when low-dose 6-MP or AZA is given.

Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice.

BACKGROUND AND AIM: The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. METHODS: Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. RESULTS: The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+ T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+ T-cell activation in DSS-fed IL-18 Tg. CONCLUSIONS: These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice.

Dietary fat attenuates the benefits of an elemental diet in active Crohn's disease: a randomized, controlled trial.

OBJECTIVES: Although an elemental diet has been established as the primary treatment for patients with Crohn's disease, the influence of dietary fat on the elemental diet remains unclear. We have designed the first randomized, controlled trial for elemental diets containing different fat percentages in patients with active Crohn's disease. METHODS: Each patient was randomized to receive one of three dose levels of fat in an elemental diet (Elental) for 4 weeks: 10 patients received low fat (3.06 g/day), 10 patients received medium fat (16.56 g/day) and eight patients received high fat (30.06 g/day). The additional fat was composed of long-chain fatty acids. All patients were evaluated using the International Organization of Inflammatory Bowel Disease rating, plus C-reactive protein level and erythrocyte sedimentation rate, which were measured at weekly intervals. RESULTS: Although the International Organization of Inflammatory Bowel Disease rating, C-reactive protein level and erythrocyte sedimentation rate in the low-fat group decreased, the values in the medium- and high-fat groups fluctuated during the study. The remission rate after 4 weeks in each group was 80%, 40% and 25% for patients in the low-, medium- and high-fat groups, respectively. CONCLUSIONS: When the fat consisted of long-chain triglycerides, a high amount of this fat in the elemental diet formula decreased its therapeutic effect against active Crohn's disease.

Endoscopic classification of chronic gastritis based on a pilot study by the research society for gastritis.

BACKGROUND: Various types of classification of gastritis have been proposed, but no plausible classification has been available until now. The Research Society for Gastritis performed a pilot study to establish an endoscopic classification, taking into consideration the following: (i) ease of use; (ii) permitting everyone the common image; and (iii) presence of histopathological evidence. METHODS: One hundred and fifty-five patients were enrolled and underwent gastroscopy. Eight basic endoscopic and histological types of gastritis (superficial, hemorrhagic, erosive, verrucous, atrophic, metaplastic, hyperplastic and special types) were defined. Gastritis was endoscopically diagnosed according to the definition of the endoscopic types of gastritis. Four or more biopsy specimens were obtained from the lesser and the greater curvatures of the antrum and the corpus of each patient, and the histological findings of gastritis and Helicobacter pylori infection were assessed. The histological diagnosis of gastritis was made according to the definition of histology types of gastritis. The endoscopic and the histological diagnoses were then compared in a blinded fashion. RESULTS: Endoscopic diagnosis was 62% as sensitive as histological diagnosis for erosive gastritis, 67% for verrucous gastritis and 84% for atrophic gastritis in the antrum. In superficial gastritis, sensitivity was approximately 25% in the corpus, but only 8% in the antrum. Metaplastic and hyperplastic gastritis were correctly diagnosed only in severe cases. CONCLUSION: Five basic types of gastritis (superficial, erosive, verrucous, atrophic and special types) should be employed for the new endoscopic gastritis classification. Metaplastic and hyperplastic gastritis are considered to be subtypes of atrophic gastritis and they should be excluded from the basic endoscopic classification. A new definition of gastritis in the antrum accompanied by redness still remains to be investigated.