Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis

Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.

Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease

Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.

Real-world effectiveness and safety of adalimumab in Korean patients with intestinal Behcet’s disease: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter study

Background/Aims@#The short- and long-term effects of adalimumab (ADA) on Korean patients with intestinal Behcet’s disease (BD) for remain unclear. Therefore, a multicenter study was performed to evaluate the efficacy and safety of ADA in Korean patients with intestinal BD in a real-world setting. @*Methods@#The medical records of 67 patients with BD prescribed ADA between January 2012 and December 2020 at five referral centers in Korea were retrospectively analyzed and the safety and efficacy of ADA within 52 weeks were assessed. To evaluate the clinical efficacy of ADA, the Disease Activity Index for Intestinal BD (DAIBD) and representative blood biochemical markers were compared at 0, 12, 24, and 52 weeks of ADA treatment. @*Results@#During the follow-up period of 52 weeks, 46 patients continued ADA treatment. The cumulative drug survival rate was 83.5%. The DAIBD score decreased over the study period (p < 0.001). Moreover, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum albumin levels significantly improved at 12, 24, and 52 weeks of ADA treatment (all, p <0.05). @*Conclusions@#As ADA is effective for refractory intestinal BD with few safety concerns in real-world situations, it is a potential treatment option for Korean patients with intestinal BD.

Animal models of inflammatory bowel disease: novel experiments for revealing pathogenesis of colitis, fibrosis, and colitis-associated colon cancer

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a lifelong disease that manifests with chronic intestinal inflammation, sequential fibrosis, and an increased risk of colitis-associated colon cancer (CAC). The combined effects of genetic, immunological, environmental, and microbial factors render it difficult to determine the specific mechanism underlying the induction and perpetuation of IBD. Various animal models of IBD have contributed enormously to the understanding of IBD pathogenesis in terms of genomics, transcriptomics, proteomics, microbiome, and drug development of novel therapeutics. Although comprehensive research on IBD has been enabled by advanced technologies, such as genetically engineered models, there is a great need to develop relevant in vivo models of colitis and fibrosis. Here, we review 4 categories of animal models of acute and chronic intestinal inflammation, fibrosis, and CAC: chemically induced, genetically engineered, T cell transfer, and spontaneous gene mutation models.

Infectious complications in patients with inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting

Background/Aims@#Infectious complications are major concerns when treating patients with inflammatory bowel disease (IBD). This study evaluated clinical differences across countries/regions in the management of infectious diseases in patients with IBD. @*Methods@#A multinational online questionnaire survey was administered to participants at the 8th meeting of the Asian Organization for Crohn’s and Colitis. The questionnaire included questions regarding surveillance, diagnosis, management, and prevention of infection in patients with IBD. @*Results@#A total of 384 physicians responded to the questionnaire. The majority of Korean (n=70, 63.6%) and Chinese (n=51, 51.5%) physicians preferred vancomycin to metronidazole in the treatment of Clostridium difficile infection, whereas more than half of the Japanese physicians (n=62, 66.7%) preferred metronidazole. Physicians in Korea (n=88, 80.0%) and China (n=46, 46.5%) preferred a 3-month course of isoniazid and rifampin to treat latent tuberculosis infection, whereas most physicians in Japan (n=71, 76.3%) favored a 9-month course of isoniazid. Most Korean physicians (n=89, 80.9%) recommended hepatitis B virus (HBV) vaccination in patients lacking HBV surface antigen, whereas more than half of Japanese physicians (n=53, 57.0%) did not consider vaccination. @*Conclusions@#Differences in the diagnosis, prevention, and management of infections in patients with IBD across countries/regions reflect different prevalence rates of infectious diseases. This survey may broaden understanding of the real-world clinical settings across Asian countries/regions and provide information for establishing practical guidelines to manage patients with IBD.

Impact of Crohn’s Disease on the Survival of Patients with Small-Bowel Adenocarcinoma in Korea: A Bicenter Cohort Study

Background/Aims@#Owing to the low prevalence of small-bowel adenocarcinoma (SBA), data on the impact of Crohn’s disease (CD) on the survival of patients with SBA are lacking. Therefore, we investigated this issue in this study. @*Methods@#In this bicenter cohort study, patients with histologically confirmed SBA were retrospectively enrolled and classified into two groups: sporadic SBA and CD-associated SBA. Patients with duodenal SBA were excluded. Overall survival, disease-free survival, and factors associated with survival were analyzed. @*Results@#Of 128 patients with SBA, 115 had sporadic SBA and 13 had CD-associated SBA. Ileal involvement and poorly differentiated tumors were more common in the CD-associated SBA group than in the sporadic SBA group (ileal involvement, 53.8% vs 22.6%; poor differentiation, 46.2% vs 14.8%; both p<0.05). In survival analysis, overall survival showed no statistical difference between the sporadic SBA and CD-associated SBA groups (p=0.370). However, when stratified by stage, the adjusted overall survival of the CD-associated SBA group was lower in patients with an advanced disease stage (p=0.029). Disease-free survival showed the same tendency, albeit without clinical significance (p=0.097). CD (hazard ratio [HR], 2.308; p=0.047), older age (≥65 yr) at SBA diagnosis (HR, 2.766; p=0.001), and stage III/IV disease (HR, 3.151; p<0.001) were factors associated with mortality. @*Conclusions@#The overall survival of patients with CD-associated SBA did not differ from that of patients with sporadic SBA. However, as CD is an independent risk factor for mortality, vigilant surveillance in high-risk patients may be crucial.

Concomitant ankylosing spondylitis can increase the risk of biologics or small molecule therapies to control inflammatory bowel disease

Background/Aims@#Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes. @*Methods@#Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients’ electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised. @*Results@#The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863–9.021; P< 0.001) and Crohn’s disease (odds ratio, 3.552; 95% confidence interval, 1.590–7.934; P= 0.002). @*Conclusions@#Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.

Osteoporosis Is Associated with an Increased Risk of Colorectal Adenoma and High-Risk Adenoma: A Retrospective, Multicenter, Cross-Sectional, Case-Control Study

Background/Aims@#The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. @*Methods@#A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. @*Results@#A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). @*Conclusions@#Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma

Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice / 대한소화기학회지

Background/Aims@#Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). @*Methods@#After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. @*Results@#A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. @*Conclusions@#TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Clinical Course of COVID-19 in Patients with Inflammatory Bowel Disease in Korea: a KASID Multicenter Study

In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea.

Risk of Diabetes in Subjects with Positive Fecal Immunochemical Test: A Nationwide Population-Based Study

Background@#Positive fecal immunochemical test (FIT) results have been recently suggested as a risk factor for systemic inflammation. Diabetes induces inflammation in the gastrointestinal tract via several ways. We investigated the association between FIT results and the incidence of diabetes. @*Methods@#A total of 7,946,393 individuals aged ≥50 years from the National Cancer Screening Program database who underwent FIT for colorectal cancer (CRC) screening from 2009 to 2012 were enrolled. The primary outcome was newly diagnosed diabetes based on the International Classification of Disease 10th revision codes and administration of anti-diabetic medication during the follow-up period. @*Results@#During a mean follow-up of 6.5 years, the incidence rates of diabetes were 11.97, 13.60, 14.53, and 16.82 per 1,000 personyears in the FIT negative, one-positive, two-positive, and three-positive groups, respectively. The hazard ratios (HRs) for the incidence of diabetes were 1.14 (95% confidence interval [CI], 1.12 to 1.16; HR, 1.21; 95% CI, 1.16 to 1.27; and HR, 1.40; 95% CI, 1.28 to 1.55) in the one-positive, two-positive, and three-positive FIT groups compared with the FIT negative group, respectively. The effect was consistent in individuals with normal fasting blood glucose (adjusted HR 1.55 vs. 1.14, P for interaction <0.001). @*Conclusion@#Positive FIT results were associated with a significantly higher risk of diabetes, suggesting that the FIT can play a role not only as a CRC screening tool, but also as a surrogate marker of systemic inflammation; thus, increasing the diabetes risk.

Clinicopathological Characteristics of Asymptomatic Young Patients with Gastric Cancer Detected during a Health Checkup / 대한소화기병학회잡지

BACKGROUND/AIMS: The Korean National Cancer Screening Program recommends biennial gastric cancer screening for patients aged ≥40 years. This study compared the characteristics of asymptomatic young gastric cancer patients aged <40 years, whose cancer was detected during a health checkup (screening group), with those whose disease was detected because of symptoms (diagnostic group). METHODS: Data were collected retrospectively from 84 subjects who underwent a gastroduodenoscopy before the age of 40 years and who were diagnosed with gastric cancer from January 2006 to February 2017 in three tertiary centers in Korea. The clinicopathological characteristics, including age, sex, stage, location, pathology, and survival, were compared according to the purpose of endoscopy (screening group, n=23 vs. diagnostic group, n=61). RESULTS: The median age of the screening group was higher than that of the diagnostic group (37 vs. 35 years, p=0.027), as was the proportion of early gastric cancer cases (78.3% vs. 29.5%, p<0.01), curative endoscopic treatment or operation rate (95.7% vs. 52.5%, p<0.01), and the overall survival (p<0.01). Poorly differentiated or signet ring cell carcinoma was less common in the screening group than in the diagnostic group (56.5% vs. 83.6%, p=0.006). The sex ratio, smoking status, family history of gastric cancer, Helicobacter pylori infection status, and tumor location were similar in the two groups. CONCLUSIONS: Screening gastroduodenoscopy may enable the early detection of gastric cancer and prolong survival in patients <40 years of age.

Clinicopathological Characteristics of Asymptomatic Young Patients with Gastric Cancer Detected during a Health Checkup / 대한소화기학회지

BACKGROUND/AIMS: The Korean National Cancer Screening Program recommends biennial gastric cancer screening for patients aged ≥40 years. This study compared the characteristics of asymptomatic young gastric cancer patients aged <40 years, whose cancer was detected during a health checkup (screening group), with those whose disease was detected because of symptoms (diagnostic group).METHODS: Data were collected retrospectively from 84 subjects who underwent a gastroduodenoscopy before the age of 40 years and who were diagnosed with gastric cancer from January 2006 to February 2017 in three tertiary centers in Korea. The clinicopathological characteristics, including age, sex, stage, location, pathology, and survival, were compared according to the purpose of endoscopy (screening group, n=23 vs. diagnostic group, n=61).RESULTS: The median age of the screening group was higher than that of the diagnostic group (37 vs. 35 years, p=0.027), as was the proportion of early gastric cancer cases (78.3% vs. 29.5%, p<0.01), curative endoscopic treatment or operation rate (95.7% vs. 52.5%, p<0.01), and the overall survival (p<0.01). Poorly differentiated or signet ring cell carcinoma was less common in the screening group than in the diagnostic group (56.5% vs. 83.6%, p=0.006). The sex ratio, smoking status, family history of gastric cancer, Helicobacter pylori infection status, and tumor location were similar in the two groups.CONCLUSIONS: Screening gastroduodenoscopy may enable the early detection of gastric cancer and prolong survival in patients <40 years of age.

Periostin in Mature Stage Localized Scleroderma

BACKGROUND: Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare. OBJECTIVE: To investigate the expression of periostin and other molecules in localized scleroderma. METHODS: A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy. RESULTS: Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p=0.013), diffuse periostin positivity (42.9% vs. 0%, p=0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p=0.001) in patients than in the controls. CONCLUSION: Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma.

Five-Alpha Reductase Inhibitor and Breast Cancer Risk in Men: A Systematic Review

No abstract available.

Comparison of the Efficacies of Parenteral Iron Sucrose and Oral Iron Sulfate for Anemic Patients with Inflammatory Bowel Disease in Korea

BACKGROUND/AIMS: The optimal route for iron administration in anemic patients with inflammatory bowel disease (IBD) has not been determined. The aim of this study was to compare the efficacies of parenteral and oral iron therapy in IBD patients in Korea. METHODS: A retrospective multicenter study was performed. Patients who had been administered parenteral iron were matched to the controls with oral iron at a 1:1 ratio according to age, sex, and type of IBD. RESULTS: Patients that received parenteral iron exhibited increases in hemoglobin levels of ≥20% from the baseline at lower doses and in shorter durations (p=0.034 and p=0.046, respectively). In the multivariate analysis, parenteral iron therapy appeared to be more efficient than oral iron therapy, but this difference was not statistically significant (hazard ratio [HR], 1.552; 95% confidence interval [CI], 0.844 to 2.851; p=0.157). Patients with ulcerative colitis responded better to iron therapy than those with Crohn's disease (HR, 3.415; 95% CI, 1.808 to 6.450; p<0.001). Patients with an initial hemoglobin level of 10 g/dL or higher responded poorly to iron therapy (HR, 0.345; 95% CI, 0.177 to 0.671; p=0.002). CONCLUSIONS: Parenteral iron therapy appears to be more efficient than oral iron therapy. Physicians should focus on the iron deficiency of IBD patients and consider parenteral iron supplements in appropriate patient groups.

Do we need colonoscopy verification in patients with fundic gland polyp?

BACKGROUND/AIMS: The aim of this study was to evaluate the prevalence of colorectal neoplasia in subjects with fundic gland polyps (FGPs) and the relationship between FGPs and colorectal neoplasia in Korea. METHODS: We analyzed 128 consecutive patients with FPGs who underwent colonoscopy between January 2009 and December 2013. For each case, age- (±5 years) and sex-matched controls were identified from among patients with hyperplastic polyps, gastric neoplasms, and healthy controls. Clinical characteristics were reviewed from medical records, colonoscopic findings, pathologic findings, and computed tomography images. The outcome was evaluated by comparison of advanced colonic neoplasia detection rates. RESULTS: Of the 128 patients, seven (5.1%) had colon cancers and seven (5.1%) had advanced adenomas. A case-control study revealed that the odds of detecting a colorectal cancer was 3.8 times greater in patients with FGPs than in the age- and sex-matched healthy controls (odds ratio [OR], 3.80; 95% confidence interval [CI], 1.09-13.24; P =0.04) and 4.1 times greater in patients with FGPs than in healthy controls over 50 years of age (OR, 4.10; 95% CI, 1.16-14.45; P =0.04). Among patients with FGPs over 50 years old, male sex (OR, 4.83; 95% CI, 1.23-18.94; P =0.02), and age (OR, 9.90; 95% CI, 1.21-81.08; P =0.03) were associated with an increased prevalence of advanced colorectal neoplasms. CONCLUSIONS: The yield of colonoscopy in colorectal cancer patients with FGPs was substantially higher than that in average-risk subjects. Colonoscopy verification is warranted in patients with FGPs, especially in those 50 years of age or older.

Helicobacter pylori Eradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori infection induces aberrant DNA methylation in gastric mucosa. We evaluated the long-term effect of H. pylori eradication on promotor CpG island hypermethylation in gastric carcinogenesis. METHODS: H. pylori-positive patients with gastric adenoma or early gastric cancer who underwent endoscopic resection were enrolled. According to H. pylori eradication after endoscopic resection, the participants were randomly assigned to H. pylori eradication or non-eradication group. H. pylori-negative gastric mucosa from normal participants provided the normal control. CpG island hypermethylation of tumor-related genes (p16, CDH1, and RUNX-3) was evaluated by quantitative MethyLight assay in non-tumorous gastric mucosa. The gene methylation rate and median values of hypermethylation were compared after one year by H. pylori status. RESULTS: In H. pylori-positive patients, hypermethylation of p16 was found in 80.6%, of CDH1 in 80.6%, and of RUNX-3 in 48.4%. This is significantly higher than normal control (p16, 10%; CDH1, 44%; RUNX-3, 16%) (p<0.05). In the H. pylori eradication group, methylation rates of p16 and CDH1 decreased in 58.1% and 61.3% of the patients, and the median values of hypermethylation were significantly lower at one year compared with the non-eradication group. However, RUNX-3 hypermethylation did not differ significantly at one year after H. pylori eradication. The non-eradication group hypermethylation did not change after one year. CONCLUSIONS: H. pylori infection was associated with promotor hypermethylation of genes in gastric carcinogenesis, and H. pylori eradication might reverse p16 and CDH1 hypermethylation.

Circulating Ghrelin Levels and Obestatin/Ghrelin Ratio as a Marker of Activity in Ulcerative Colitis

BACKGROUND/AIMS: Ghrelin levels are known to increase in patients with ulcerative colitis (UC), but serum obestatin levels in UC patients are not well elucidated. The aim of this study was to examine the relationship between serum ghrelin and obestatin levels and disease activity in UC patients. METHODS: The serum ghrelin and obestatin levels were measured in 21 UC patients (12 with active disease and 9 in remission) using enzyme-linked immunosorbent assay. The relationship between the circulating levels of these 2 hormones and disease activity was analyzed. The colonic mucosal mRNA expression of ghrelin and obestatin was measured by quantitative reverse transcription polymerase chain reaction. RESULTS: The mean serum ghrelin values were significantly higher in patients with active disease than in patients with remission (1370.6+/-404.3 vs. 783.5+/-235.3 pg/mL, P=0.001). Colonic mucosal mRNA expression of ghrelin was also significantly higher in patients with active disease than in patients in remission (0.805+/-0.214 vs. 0.481+/-0.356, P=0.018). However, the mean serum obestatin levels and colonic mucosal mRNA expression of obestatin were not significantly different between both groups. The circulating obestatin/ghrelin ratio was significantly lower in patients with active UC than in patients in remission (0.32+/-0.08 vs. 0.58+/-0.20, P=0.001). CONCLUSIONS: The serum ghrelin levels and the obestatin/ghrelin ratio were related to the activity of UC, but serum obestatin was not related to activity of UC. The ghrelin levels and the obestatin/ghrelin ratio could serve as activity markers in patients with UC.

Cross-Regulation of Innate and Adaptive Immunity: A New Perspective for the Pathogenesis of Inflammatory Bowel Disease

No abstract available.