Comparison of Risk Factors for Cholangiocarcinoma and Hepatocellular Carcinoma: A Prospective Cohort Study in Korean Adults.

Cholangiocarcinoma (CCA), especially intrahepatic CCA, is known to share several risk factors with hepatocellular carcinoma (HCC) and liver cirrhosis has been proposed as a common pathogenic factor. We aimed to identify the risk factors of CCA and to examine differences in risk factors between CCA and HCC. We followed 510,217 Korean adults who underwent health checkups during 2002−2003 until 2013 via linkage to national hospital discharge records. Hazard ratios (HRs) were calculated after adjustment for confounders. During the mean follow-up of 10.5 years, 1388 and 2920 individuals were diagnosed with CCA and HCC, respectively. Choledocholithiasis (HR = 13.7; 95% confidence interval (CI) = 7.58−24.88) was the strongest risk factor for CCA, followed by cholelithiasis (HR = 2.94) and hepatitis B virus (HBV) infection (HR = 2.71). Two of the strongest risk factors for HCC­liver cirrhosis (HR = 1.29; 95% CI = 0.48−3.45) and hepatitis C virus infection (HR = 1.89; 95% CI = 0.49−7.63)­were not significantly associated with the risk of CCA. HBV infection and diabetes increased the risk of both HCC and CCA, but the HRs were lower for CCA than for HCC (Pheterogeneity < 0.001 for HBV; Pheterogeneity = 0.001 for diabetes). The magnitudes of the effects of age, sex, obesity, alcohol consumption, and smoking on the development of both cancers were different (Pheterogeneity < 0.05 for each variable). In conclusion, choledocholithiasis, cholelithiasis, HBV, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors of CCA. Liver cirrhosis did not increase the risk of CCA. The magnitudes of the potential effects of common risk factors were generally different between CCA and HCC.

Three-dimensional Differentiated Human Mesenchymal Stem Cells Exhibit Robust Antifibrotic Potential and Ameliorates Mouse Liver Fibrosis.

Recently, three-dimensional (3D)-cultured adipose mesenchymal stem cells (ASCs) have provided an effective therapy for liver fibrosis. This study aimed to enhance the potential of human ASCs for antifibrosis or hepatocyte regeneration using a 3D culture system and investigate their therapeutic mechanism in experimental liver fibrosis. ASC-3Dc were generated in a 3D culture system and stimulated with four growth factors, namely epidermal growth factor, insulin-like growth factor (IGF)-1, fibroblast growth factor-2, and vascular endothelial growth factor-A. The expression levels of antifibrotic or hepatic regeneration factors were then measured using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The therapeutic effects of ASC-3Dc were determined using a liver fibrosis model induced by thioacetamide. Histological analysis was performed to elucidate the therapeutic mechanism. ASC-3Dc exhibited high levels of hepatocyte growth factor (HGF), IGF-1, stromal cell-derived factor (SDF)-1 genes, and protein expression. In addition, injecting ASC-3Dc significantly prevented hepatic fibrosis and improved liver function in vivo. Moreover, high numbers of ki-67-expressing hepatocytes were detected in the ASC-3Dc-injected livers. Albumin-expressing ASC-3Dc engrafted in fibrotic livers augmented HGF expression. Thus, short-term 3D-cultured ASCs may be a novel alternative to the conventional treatment for liver damage in clinical settings.

Trends of Incidence and Survival Rates of Mucosa-associated Lymphoid Tissue Lymphoma in the Korean Population: Analysis of the Korea Central Cancer Registry Database.

BACKGROUND: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) is an extranodal lymphoma that occurs at various sites in the body. There is a limited understanding of the incidence and survival rates of MALT-lymphoma. To investigate the nation-wide incidence and survival rates of MALT-lymphoma in Korea during 1999-2017, the data on MALT-lymphoma were retrieved from the Korea Central Cancer Registry. METHODS: During the time period of 1999-2017, 11,128 patients were diagnosed with MALT-lymphoma. The age and sex of the patients and the Surveillance, Epidemiology, and End Results (SEER) summary stage of the tumor were analyzed, and the relative survival rates (RSRs) were calculated. RESULTS: The age-standardized incidence rates of MALT-lymphoma in 2017 among males and females were 1.53 and 1.61 per 100,000 individuals, respectively, whereas those in 1999 among males and females were 0.21 and 0.20, respectively in Korea. The RSRs were more than 97% at 10 years post-diagnosis between 1993 and 2017. The 5-year RSRs were 87.4%, 94.8%, 97.8%, and 98.6% during 1996-2000, 2001-2005, 2006-2010, and 2013-2017, respectively. Based on SEER summary staging, the 5-year RSRs during 2013-2017 were 100.3%, 90.8%, 91.3%, and 97.9% for patients with localized, regional, distant, and unknown stages of MALT-lymphoma, respectively. CONCLUSION: Although the incidence of MALT-lymphoma is low in Korea, it has been increasing in recent years. The prognosis of MALT-lymphoma is good even at advanced stages. These findings provide useful insights to clinicians about MALT-lymphoma and inform patients about the survival rate.

HGF and IL-10 expressing ALB::GFP reporter cells generated from iPSCs show robust anti-fibrotic property in acute fibrotic liver model.

BACKGROUND: Cell therapy using hepatocytes derived from stem cells has been regarded as a promising alternate to liver transplantation. However, the heterogeneity of these hepatocytes makes them unsuitable for therapeutic use. To overcome this limitation, we generated homogenous hepatocyte like induced hepatocyte-like (iHep) cells. METHODS: iHep cells were generated from induced pluripotent stem cells (iPSCs) integrated with the albumin (ALB) reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model. RESULTS: The iHep cells expressed hepatocyte specific genes and proteins, and exhibited high levels of hepatocyte growth factor (HGF) and interleukin (IL)-10 expressions. Transplantation of iHep cells significantly decreased thioacetamide (TAA)-induced liver fibrosis, apoptotic cells in the liver, and ameliorated abnormal liver function. Liver tissues engrafted with iHep cells exhibited decreased expression of pro-inflammatory factors such as transforming growth factor (TGF)-ß, IL-6, and monocyte chemo attractant protein (MCP)-1. Furthermore, an increased number of proliferating hepatocytes and human albumin-expressing iHep cells were detected in mice liver. CONCLUSIONS: This study has investigated and proven the liver regeneration potential of genome-edited iHep cells and promises to be a strong foundation for further studies exploring cell therapy as an alternative therapeutic option for the treatment of liver fibrosis.

Directly induced hepatogenic cells derived from human fibroblast ameliorate liver fibrosis.

Recently, reprogramming technology has emerged as a fascinating tool to generate specific tissue cells. In this study, we tested the hypothesis that ultrasound-directed cellular reprogramming can generate fibroblasts into hepatogenic cells. We directly induced human dermal fibroblasts (HDFs) into hepatocyte-like cells mediated by environmental transition-guided cellular reprogramming (h/entr) using ultrasound. We confirmed the characteristics of h/entr by the expression levels of hepatocyte specific RNA and proteins. The effects of h/entr on the activation of hepatic stellate cells were analyzed using conditioned medium (CM). h/entr were transplanted into mice with acute liver fibrosis and the therapeutic effects and mechanism of liver fibrosis were determined. h/entr exhibited high levels of hepatocyte specific genes, hepatogenic (hepatocyte growth factor [HGF], colony-stimulating factor 3 [CSF-3]) and anti-inflammatory (interleukin 10 [IL-10]) factors. h/entr CM suppressed the activation of hepatic stellate cells in vitro. Transplantation of h/entr significantly delayed liver fibrosis and improved liver function. Transplantation of h/entr accelerates liver regeneration, and human albumin expressing h/entr and human Alu gene were detected in the mouse livers. This report suggests that directly induced h/entr could be one of the highly effective therapeutic options for the treatment of liver cirrhotic disease.

Clinical Features of Intra-Abdominal Abscess and Intestinal Free-Wall Perforation in Korean Patients with Crohn's Disease: Results from the CONNECT Study.

Background: In Crohn's disease (CD), intra-abdominal abscess (IA) and intestinal free-wall perforation (IP) have a common mechanism of transmural inflammation; however, their manifestation is different. Objective: This study aimed to investigate differences in the clinical features between IA and IP in Korean patients with Crohn's disease. Design: A retrospective cohort study. Setting: Thirty university hospitals and two local hospitals in Korea. Patients: Patients who were diagnosed with CD between July 1982 and December 2008 were enrolled. Main Outcome Measures: Clinical characteristics of IA and IP. Results: Among 1286 patients with CD, 147 (11.4%) had IA and 83 (6.5%) had IP. IA patients were younger than those of IP (24.2 ± 8.6 vs. 30.4 ± 11.1 years, p = 0.001). Location and behavior were significantly different between IA and IP (p = 0.035 and 0.021). In multivariate analyses, perianal fistula was not associated with increased risk of IA and IP, while intestinal stricture was associated with increased risk of IA (OR: 2.72, p < 0.0001) and IP (OR: 2.76, p < 0.0001). In subgroup analyses, 55 (36.5%) IA patients were diagnosed at the diagnosis of CD, and 92 (63.5%) during follow-up of CD, while 47 (56.6%) IP patients were diagnosed at the diagnosis of CD, and 36 (43.3%) during follow-up of CD. Conclusions: There are several differences in the clinical features of IA and IP in Korean patients with CD. The development mechanism is considered as identical, but further investigation should be needed for clinical implication.

Effect of Samryungbaekchul-san Combined with Otilonium Bromide on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Randomized Controlled Trial.

Conventional and herbal drugs are frequently used together to treat many disorders. Samryungbaekchul-san (SRS, a herbal formula) and otilonium bromide (OB, an antispasmodic agent) are widely used to treat diarrhea-predominant irritable bowel syndrome (D-IBS) in Eastern Asian countries. However, there have been no studies on the co-administration of SRS and OB. Therefore, we aimed to preliminarily assess the feasibility of SRS combined with OB for D-IBS treatment in a pilot double-blind, four-arm, parallel-group, randomized controlled trial (RCT), including 80 patients diagnosed with D-IBS according to the Rome III criteria. The patients were randomly assigned to four treatment groups and were administered drugs for eight weeks after a two-week preparatory period. Follow-up was conducted four weeks after the administration period. The primary outcome was evaluated by using a global D-IBS symptom improvement score; no statistically significant difference was observed between the groups. However, multiple logistic regression analysis of primary outcome scores shows that SRS significantly improved D-IBS symptoms (p < 0.05). For secondary outcomes, better results were observed in the SRS + OB group, in terms of symptoms, including abdominal pain, discomfort, frequency of abdominal pain, and stool form than in OB alone or placebo groups (p < 0.05). In conclusion, the co-administration of SRS and OB might be an effective and safe strategy for the treatment of D-IBS. Large-scale RCTs are warranted to further confirm and clarify these findings.

Transplantation of human adipose tissue derived-SVF enhance liver function through high anti-inflammatory property.

Although human adipose tissue-derived stromal vascular fraction (SVF) has been considered a promising source of stem cells, its characteristics relevant to treatment of a damaged liver have not been fully elucidated. In the present study, we sought to characterize the property of human SVF and determine the therapeutic utility of SVF in the liver cirrhosis model. We performed microarray, quantitative (q)-PCR experiments, and in vivo therapeutic assays using a liver cirrhotic mouse model. q-PCR results revealed that hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)-A, Interleukin (IL)-10 and microRNA (miR)-146 were more highly upregulated in SVF than in human adipose-derived mesenchymal stem cells (ASCs). The SVF culture medium (CM) inhibited the activation of hepatic stellate cells in vitro. Injection of SVF significantly suppressed TAA-induced liver fibrosis and repaired liver function by inhibition of infiltrating inflammatory cells and induction of capillary/hepatocyte regeneration in vivo. Injection of IL-10 siRNA treated SVF cells decreased anti-inflammation and anti-fibrotic effects in TAA-induced mice liver. Our data indicate that SVF show a high anti-inflammatory property for treating fibrotic liver diseases through IL-10 secretion. Therefore, SVF might be a novel therapeutic alternative for the treatment of liver cirrhosis in clinical settings.

Human Adipose Derived Stem Cells Exhibit Enhanced Liver Regeneration in Acute Liver Injury by Controlled Releasing Hepatocyte Growth Factor.

BACKGROUND/AIMS: Although mesenchymal stem cells (MSCs) provide effective therapy for liver fibrosis, there are conflicting data regarding their marginal therapeutic effects. This study aimed to enhance the potential of hepatocyte regeneration in human adipose mesenchymal stem cells (ASCs) and investigate whether they have robust therapeutic efficacy in experimental liver fibrosis. METHODS: ASCs were cultured with four cytokines (ASC-C), the expression of hepatogenic factors was detected by microarray, and the effects of conditioned medium (CM) from ASC-C on the activation of hepatic stellate cells were analyzed. The therapeutic effects and mechanism of liver fibrosis induced by thioacetamide (TAA) were determined after cell transplantation. RESULTS: ASC-C exhibited high levels of hepatogenic (HGF, G-CSF), anti-apoptotic (IGFBP-2), and chemokine (IL-8) genes and increased expression of hepatocyte specific proteins. ASC-C CM inhibited the activation of hepatic stellate cells in vitro, and injection of ASC-C significantly delayed TAA-induced liver fibrosis and improved liver function and regeneration in vivo. In addition, human albumin-expressing ASC-C were observed in the livers of recipient animals. High levels of expression of HGF and its downstream signaling molecules, including p-38, were detected in the ASC-C-injected livers. Transplantation of ASC-C exerts anti-fibrotic effects and accelerates liver regeneration. CONCLUSION: Thus, ASC-C may be a novel candidate for the enhanced treatment of liver cirrhosis in clinical settings.

Fatty liver disease and the risk of erosive oesophagitis in the Korean population: a cross-sectional study.

OBJECTIVES: To investigate an association between fatty liver disease (FLD) and erosive oesophagitis. DESIGN AND SETTING: This was a cross-sectional study of subjects selected from examinees who underwent health check-up, including oesophagogastroduodenoscopy in one hospital between 2004 and 2011. Erosive oesophagitis was classified according to the Los Angeles classification and FLD was diagnosed with ultrasonography. The anthropometric and laboratory data of the subjects were analysed using χ2 test and multivariate logistic regression. Additionally, we have analysed our data with two-stage least square estimation using the Baltagi-Chang one-way model to clarify unobserved confounding variable. PRIMARY OUTCOME MEASURE: The effect of FLD on erosive oesophagitis. RESULTS: Among the 14 723 eligible subjects, 4232 (28.7%) subjects diagnosed with FLD were classified into the fatty liver group and 10 491 (71.3%) subjects without FLD were classified into the non-fatty liver group. The incidence rate of erosive oesophagitis was significantly higher in the fatty liver group than in the non-fatty liver group (10.4%vs6.1%, p<0.0001). The multivariate analysis revealed that the fatty liver group was significantly associated with erosive oesophagitis (OR 1.19, 95% CI 1.03 to 1.37, p=0.016). CONCLUSION: FLD diagnosed by ultrasonography is an independent risk factor of erosive oesophagitis. It suggests that FLD-related metabolic abnormality may be associated with erosive oesophagitis.

IL-10-secreting human MSCs generated by TALEN gene editing ameliorate liver fibrosis through enhanced anti-fibrotic activity.

Mesenchymal stem cells (MSCs) are known for their ability to repair liver damage. However, their therapeutic potential still needs to be enhanced. In the present study, we produced genome-edited MSCs that secrete interleukin 10 (IL-10) and evaluated their therapeutic potential in a liver fibrosis model. Multiple copies of the IL-10 gene were inserted into a safe harbor genomic locus in amniotic mesenchymal stem cells (AMMs) using transcription activator-like effector nucleases (TALENs). The IL-10 gene-edited AMMs (AMM/I) were characterized by reverse transcription PCR (RT-PCR), quantitative RT-PCR (qRT-PCR), and microarray. The effects of AMM/I-conditioned cell medium (CM) on the activation of hepatic stellate cells (HSC) were analyzed in vitro and in vivo therapeutic assays were performed on a mouse liver fibrosis model. The engineered AMM/I expressed high levels of IL-10. AMM/I-CM inhibited the activation of HSC (in vitro) and TNF-α expression of T cells/macrophage derived from fibrotic liver. In addition, human IL-10 was detected in the serum of the mice transplanted with AMM/I and transplantation of AMM/I significantly inhibited thioacetamide (TAA)-induced liver fibrosis and ameliorated abnormal liver function. Furthermore, a high number of human albumin-expressing AMM/I were successfully engrafted into the liver of recipient mice. Overall, genome-edited AMMs overexpressing anti-fibrotic IL-10 might be a promising alternative therapeutic option for the treatment of liver cirrhosis.

Body mass index and the risk of acute pancreatitis by etiology: A prospective analysis of Korean National Screening Cohort.

BACKGROUND: It is unclear whether obesity increases the incidence of acute pancreatitis (AP) in the general population. Further, no study has prospectively examined the associations of the risk of AP by etiology with measured body mass index (BMI) values. METHODS: A total of 512 928 Korean participants in routine health examinations during 2002-2003 were followed up until 2013 via linkage to national hospital discharge records to assess AP incidence. Multivariable-adjusted hazard ratios were calculated using BMI measurements. RESULTS: During 10.5 mean years of follow-up, 1656 persons developed AP (337 gallstone related and 1319 non-gallstone related). Nonlinear associations were found: U-curves for total and non-gallstone-related AP and a reverse L-curve for gallstone-related AP. Each 5 kg/m2 increment in BMI increased gallstone-related AP by 123% (95% confidence interval = 48-234%) and non-gallstone-related AP by 42% (9-84%) in the range ≥ 25 kg/m2 (Pheterogeneity  = 0.068). Obese persons had a doubled risk of gallstone-related AP compared with normal-weight persons. In the range < 25 kg/m2 , BMI had inverse association with non-gallstone-related AP but no association with gallstone-related AP (Pheterogeneity  < 0.001). In subgroup analyses, for non-gallstone-related AP, hazard ratios per each 5 kg/m2 BMI increment were 0.50 (men), 0.73 (women), 0.46 (alcohol drinkers), 0.69 (alcohol non-drinkers), 0.43 (ever smokers), and 0.73 (never smokers). CONCLUSIONS: Gallstone-related AP and non-gallstone-related AP have different nonlinear associations with BMI. Higher BMI increases the risk of both gallstone-related AP and non-gallstone-related AP but more strongly for gallstone-related AP. For non-gallstone-related AP, in the range < 25 kg/m2 , BMI has inverse associations that were stronger in men, current alcohol drinkers, and ever smokers than in their counterparts.

Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status: A prospective cohort study in Korea.

BACKGROUND: To the authors' knowledge, relatively little is known regarding the interaction of risk factors for hepatocellular carcinoma (HCC) with age, sex, and liver disorder status. METHODS: The authors followed 504,646 Korean patients aged 40 to 80 years who underwent routine health checkups between 2002 and 2003 until 2013 via linkage to national hospital discharge records. RESULTS: HCC occurred in 2744 individuals. In the sex-adjusted and age-adjusted analysis, cirrhosis increased the incidence of HCC by 42-fold, followed by hepatitis B virus (21-fold), hepatitis C virus (HCV; 19-fold), male sex (4.3-fold), and each 5-year age increment (1.24-fold). In the multivariable adjusted analysis, diabetes increased the risk of HCC by 80%, alcohol consumption ≥80 g/day increased the risk by 75%, alcohol consumption of 40 to 79 g/day increased the risk by 37%, and being a current smoker increased the risk by 25%. The multivariable adjusted hazard ratios of male sex and HCV were 6.27 and 5.72, respectively, at age <50 years, but were 2.09 and 22.51, respectively, at age ≥70 years. Each 20 g/day of alcohol consumption increased the risk of HCC by 6% (P = .11), 8% (P = .02), 16% (P<.001), and 30% (P<.001), respectively, in individuals aged <50 years, 50 to 59 years, 60 to 69 years, and 70 to 80 years. In individuals without a liver disorder, body mass index was found to be positively associated with HCC, whereas patients with a liver disorder demonstrated an inverse association. Women had higher adjusted hazard ratios associated with age and cirrhosis compared with men. CONCLUSIONS: With advancing age, the effects of alcohol use and HCV on the development of HCC become stronger, whereas the effect of male sex weakens. Lifetime moderate alcohol consumption may cause HCC in the elderly. Smoking increases the risk of HCC irrespective of viral hepatitis, and diabetes increases the risk of HCC independent of cirrhosis. Cancer 2018;124:2748-2757. © 2018 American Cancer Society.

Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group.

BACKGROUND/AIMS: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. METHODS: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin 1ß (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor α (TNFA) genes of patients with AP were compared to those of normal controls. RESULTS: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN -1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (-118C>T, c47+242C>T, +3954C/T, and -598T>C) and TNFA (-1211T>C, -1043C>A, -1037C>T, -488G>A, and -418G>A). CONCLUSION: IL1RN -1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

Effect of herbal extract granules combined with otilonium bromide on irritable bowel syndrome with diarrhoea: a study protocol for a randomised controlled trial.

INTRODUCTION: Irritable bowel syndrome (IBS), known as a functional and organic gastrointestinal disorder, is a collection of symptoms that occur together and generally include pain or discomfort in the abdomen and changes in bowel movement patterns. Due to the limitations of conventional treatments, alternative IBS treatments are used by many patients worldwide. Samryungbaekchulsan (SRS), a herbal formula, has long been used for alleviating diarrhoea-predominant IBS (D-IBS) in traditional Korean medicine. Otilonium bromide (OB) is an antimuscarinic compound used to relieve spasmodic pain in the gut, especially in IBS. Although herbal formulae and Western drugs are commonly coadministered for various diseases in Korea, few clinical studies have been conducted regarding the synergic effects of these treatments for any disease, including D-IBS. METHODS AND ANALYSIS: This trial is a randomised, double-blinded, placebo-controlled, double-dummy, four-arm, parallel study. After a 2-week preparation period, 80 patients with D-IBS will be randomly assigned to one of four treatment groups consisting of SRS (water extract granules, 5 g/pack, three times a day) with OB (tablet form, one capsule three times a day) or their placebos, with treatment lasting for 8 weeks. Post-treatment follow-up will be conducted 4 weeks after the end of treatment. The primary outcome is the finding obtained using the Subject's Global Assessment of Relief method. The secondary outcomes are the severity of symptoms related to D-IBS, determined using a 10-point scale, and the change in symptoms. ETHICS AND DISSEMINATION: This trial has full ethical approval of the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS15MISV0033) and the Korean Ministry of Food and Drug Safety (30769). The results of the study will be disseminated through a peer-reviewed journal and/or conference presentations. TRIAL PROTOCOL VERSION: IS15MISV0033 version 4.0 (25 July 2016). TRIAL REGISTRATION NUMBER: KCT0001621 (approval date: 10 August 2015).

The IL-1B Genetic Polymorphism Is Associated with Aspirin-Induced PepticUlcers in a Korean Ethnic Group.

BACKGROUND/AIMS: Single nucleotide polymorphisms (SNPs) are associated with aspirin-induced peptic ulcers. However, SNPs of specific genes vary among races, and data regarding SNPs in the Korean population are scarce. In this study, we aimed to investigate the relationships between SNPs of the COX-1, IL-1ß, IL-1RN, and TNF genes and aspirin-induced peptic ulcers, as pilot research in a Korean population. METHODS: Patients who had been taking low-dose aspirin (100 mg) for at least 4 weeks were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. RESULTS: A total of 48 patients were enrolled (23 peptic ulcer patients vs 25 nonulcer controls). Three exon SNPs (IL-1ß -581C/T [rs1143627], IL-1ß -1061C/ T [rs16944], and IL-1RN -1129 [rs4251961]) and one intron SNP (IL-1ß IVS2+242C/T) were significantly different between the two groups. On the multivariate analysis after adjustments for age and sex, the CC/CT genotypes of IL-1ß -581C/ T, and the CT/TT genotypes of IL-1ß -1061C/T were positively associated with aspirin-induced peptic ulcers (odds ratio [OR], 4.6, 95% confidence interval [CI], 1.054 to 20.303, p=0.04; OR, 4.6, 95% CI, 1.054 to 20.303, p=0.04). CONCLUSIONS: The IL-1ß -581C/T and IL-1ß -1061C/T genotypes may be associated with low-dose aspirin-induced peptic ulcers in a Korean ethnic group.

Comparison of Predictive Systems in Severe Acute Pancreatitis According to the Revised Atlanta Classification.

OBJECTIVES: We aimed to compare the prognostic value of various predictors and complex scoring systems for prediction of severe acute pancreatitis (SAP) according to the revised Atlanta classification. METHODS: C-reactive protein (CRP) and procalcitonin were obtained on admission, and CRP level 24 hours after admission (CRP2) was measured. Various scoring systems including Ranson, Acute Physiology and Chronic Health Examination (APACHE II), the Bedside Index for Severity in Acute Pancreatitis, and Computed Tomography Severity Index (CTSI) were calculated. RESULTS: There were 146 patients with acute pancreatitis (mean age, 50.6 ± 18.3 years; 63% male), of which 43 patients (29.5%) received a diagnosis of moderately severe AP, and 17 patients (11.6%) received a diagnosis of SAP. In patients with moderately severe acute pancreatitis to SAP, CTSI (odds ratio [OR], 10.46; 95% confidence interval [CI], 4.3-25.43; P < 0.001), APACHE II (OR, 3.87; 95% CI, 1.18-12.64; P = 0.025), and CRP2 (OR, 4.5; 95% CI, 1.53-13.1; P = 0.006) were strongly related to moderately severe acute pancreatitis and SAP. In patients with SAP compared with mild to moderately severe AP, procalcitonin (OR, 4.36; 95% CI, 1.01-18.96; P = 0.049) was the only factor strongly associated with SAP. CONCLUSIONS: Procalcitonin was the best predictor for patients with SAP; CTSI, APACHE II, and CRP2 were valuable predictors for patients with moderately severe acute pancreatitis and SAP.

Usefulness of scheduled follow-up CT in discharged patients with acute pancreatitis.

BACKGROUND AND AIM: Follow-up computed tomography (CT) in patients with acute pancreatitis has been advocated but rarely studied. The aim of this study was to determine whether follow-up CT for acute pancreatitis might be helpful in establishing the prognosis or complications, and in determining a selected subgroup of patients for whom computed tomography could be beneficial. METHODS: Between January 2010 and December 2012, patients with acute pancreatitis who underwent follow-up CT in the outpatient department between one and three months after discharge were retrospectively enrolled. Events discovered on follow-up CT were defined as newly developed or increased pancreatic collection such as pseudocyst or walled off necrosis, and diagnosis of pancreatic cancer. RESULTS: Ultimately, 106 asymptomatic patients were enrolled (mean age 50.24 ± 16, 74.5% male, 31.1% moderately severe and severe acute pancreatitis). The median duration of follow-up CT was 69 (31-90) days. On follow-up CT, 23 patients showed events (2 pancreatic cancer, 21 increasing or developed pancreatic collections). In multivariate analysis, the predictive factors for events on follow-up CT were CTSI ≥3 (OR 4.46, CI 1.08-18.43, p = 0.039) and BISAP ≥ 2 (OR 4.83, CI 1.08-21.55, p = 0.039). CONCLUSIONS: Follow-up CT within three months after discharge may be helpful for acute pancreatitis patients with CTSI ≥ 3 points or BISAP score ≥ 2 points.

Serum HBV surface antigen positivity is associated with low prevalence of metabolic syndrome in Korean adult men.

BACKGROUND: Metabolic syndrome has clinical implications for chronic liver disease, but the relationship between chronic hepatitis B and metabolic syndrome remains unclear. The aim of this study was to determine whether hepatitis B surface antigen (HBsAg) positivity is associated with metabolic syndrome. METHODS: Data were obtained from the Third Korean National Health and Nutrition Examination Survey (KNHANES). Participant sera were tested for HBsAg. Metabolic syndrome was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III guidelines for Koreans. RESULTS: Of the 5108 participants, 209 (4.1%) tested positive for HBsAg, and 1364 (26.7%) were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome was 23.4% in HBsAg-positive men, 31.5% in HBsAg-negative men, 18.6% in HBsAg-positive women, and 23.7% in HBsAg-negative women. After adjusting for multiple factors, male participants who tested positive for serum HBsAg had an odds ratio of 0.612 (95% confidence interval [CI] 0.375-0.998) for metabolic syndrome and an odds ratio of 0.631 (95% CI 0.404-0.986) for elevated triglycerides. Women who tested positive for serum HBsAg had an odds ratio of 0.343 (95% CI 0.170-0.693) for elevated triglycerides. CONCLUSIONS: Positive results for serum HBsAg are inversely associated with metabolic syndrome in men and with elevated triglycerides in men and women. This suggests that elevated triglycerides may contribute to the inverse association between HBsAg and metabolic syndrome.