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Background: Gastrointestinal (GI) manifestations are common in patients with diabetes complications such as autonomic neuropathy. However, the prevalence of GI symptoms before the development of diabetes complications remains unclear.Method: We performed an interview survey of functional gastrointestinal disorders in diabetes patients who visited the endocrinology clinic of a general hospital using the ROME III criteria. The investigation consisted of various questions on functional dyspepsia, irritable bowel syndrome, and functional constipation including functional defecation disorder.Results: A total of 509 patients were included in this analysis. The patients were analyzed in three groups, prediabetes patients (n = 115), diabetes patients without neuropathy (n = 275), and diabetes patients with neuropathy (n = 119). The prevalence of gastrointestinal symptoms in prediabetes patients, diabetes patients without neuropathy, and diabetes patients with neuropathy was estimated at 16.52%, 27.27%, and 23.53% for functional dyspepsia; 8.7%, 11.68%, and 16.81% for irritable bowel syndrome; and 8.85%, 11.85%, and 15.25% for functional constipation. In the subgroup analysis, postprandial distress syndrome symptoms such as postprandial fullness and early satiation were more prevalent than epigastric pain symptoms. In the constipation group, pelvic outlet obstruction symptoms such as the sensation of anorectal obstruction or blockage and manual maneuvers to facilitate defecation were more frequently observed than slow transit constipation symptomsConclusions: The prevalence of functional gastrointestinal disorders increased with diabetes severity. Diabetes-related GI symptoms appeared long before the diabetes complications

Background/Aims: Colorectal cancer incidence among patients aged ≤50 years is increasing. This study aimed to develop and validate an advanced colorectal neoplasm (ACRN) screening model for young adults aged

Hepatocellular carcinoma (HCC) is the sixth most common cause of death worldwide and the main cause of primary liver cancer. The principle problem of HCC is the poor prognosis, since advanced HCC reportedly has a median survival of only 9 months. The standard therapies are sorafenib and regorafenib, but the outcomes remain unclear. We report a 60-year-old man with advanced HCC with right adrenal gland metastasis and portal vein tumor thrombosis, who showed a complete response to multiple applications of an interdisciplinary therapy.

The purpose of this study was to investigate the effect of acute kidney injury (AKI) on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). A total of 347 HCC patients with Child-Pugh class A and pre-TACE serum creatinine (SCr) ≤1.5 mg/dL undergoing TACE as an initial therapy 2000–2014 were analyzed. Overall survival with related risk factors including AKI was investigated. We assessed AKI based on the International Club of Ascites (ICA)-AKI criteria. The mean age was 60.9 years. Of 347 patients, death was observed in 109 patients (31.4%). The mean SCr levels at pre-TACE, one day, two months, and four months after TACE were 0.9, 0.9, 0.9, and 1.1 mg/dL, respectively. The AKI within four months after TACE developed in 37 patients (11%). The AKI stages were non-AKI in 310 (89%), stage 1 in 10 (3%), stage 2 in 10 (3%), and stage 3 in 17 patients (5%). Multivariable analysis showed that the risk factors for overall survival were serum albumin ≤3.5 g/dL (hazard ratio [HR] 1.58, p = 0.027), BCLC stage B (HR 2.07, p = 0.008), BCLC stage C (HR 3.96, pp = 0.022), AKI stage 1 (HR 6.09, ppp

BACKGROUND & AIMS The relationship between cigarette smoking and nonalcoholic fatty liver disease (NAFLD) has been controversial. Most relevant studies have relied on self-reported questionnaires. We aimed to elucidate the association between smoking status and NAFLD using an objective biomarker of tobacco exposure (urinary cotinine) and self-reported questionnaire. METHODS A cross-sectional study was conducted on 160 862 asymptomatic examinees who underwent abdominal ultrasonography and urinary cotinine measurements between April 2011 and December 2015. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50 ng/mL. RESULTS The mean age of the study population was 36.1 years, and the proportion of men was 51.7%. The proportions of self-reported and cotinine-verified current smokers were 17.6% and 17.7% respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of NAFLD (adjusted odds ratio [AOR], 1.10; 95% confidence interval [CI], 1.06-1.14). Moreover, among the current smokers, the risk of NAFLD increased with an increase in the amount of cigarette smoking (

Background/aims Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance. Methods Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included. Results Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naive patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log10hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log10HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log10HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance. Conclusions Clinical characteristics of patients who developed ETV resistance were higher log10HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.

The study was done to elucidate the clinico-radiologic predictive factors for cancerous change detected by disease progression (PD) mainly defined by interval increase in cyst size and change of cyst morphology, for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) patients with relatively long-term follow-up.Retrospective analysis of medical records and imaging findings were performed on 107 patients with BD-IPMN enrolled from July 2005 to May 2013, in whom the communication between the cystic lesion and pancreatic duct was confirmed by either endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP).During the mean ± SD follow-up period of 51.5 ± 24.5 months, PD was noticed in 43 (40.2%) of 107 BD-IPMN patients. Among these 107 patients, 21 (19.6%) displayed cancerous change. By univariate analyses, septated/multilocular cyst morphology, cyst size larger than 30 mm, cyst wall thickening, mural nodules, and the presence of symptoms were significant predictive factors for cancerous changes in BD-IPMN patients. A Cox forward stepwise linear regression model revealed that cyst wall thickening (OR 9.187, 95% CI 1.883~44.820, P 0.01) and mural nodules (OR 6.224, 95% CI 1.311~29.549, P = 0.021) were significant and independent predictive factors for cancerous change in BD-IPMN patients.A significant proportion of patients with BD-IPMN showed PD and cancerous change during the long-term follow-up. Cyst wall thickening and mural nodules were significant and independent predictive factors of cancerous change in patients with BD-IPMN.

This study aimed to investigate the relationship between serum zinc level and hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). A cross-sectional study was conducted using nationally representative samples from the Korea National Health and Nutrition Examination Survey 2010. Significant hepatic fibrosis was defined as Fibrosis-4 (FIB-4) index>1.3. Zinc level was measured using inductively coupled plasma mass spectrometry. Univariable and multivariable logistic regression analyses were performed to assess risk factors for significant hepatic fibrosis in patients with NAFLD. A total of 300 patients with NAFLD were analyzed in this study. The mean serum zinc level was 139.8±29.9 μg/dL. FIB-4 index was significantly increased as the serum zinc level decreased (Adjusted correlation coefficient = -0.177, p = 0.003). Significant liver fibrosis was observed in 62 patients (21%). The multivariable analysis showed that significant liver fibrosis in NAFLD was associated with diabetes mellitus (odds ratio [OR], 3.25; 95% confidence interval [CI], 1.71–6.19; p

Diabetes and dyslipidemia have been linked to an increased risk of colorectal neoplasm (CRN). However, previous studies evaluating these associations have shown inconsistent results, and large-scale studies are few in number. To investigate the associations between the parameters of glucose and lipid metabolism and the presence of CRN. A cross-sectional study was performed on 38,490 Korean adults aged ≥30 years undergoing their first colonoscopy as part of routine preventive health care between 2010 and 2011. The prevalence of overall CRN increased with increasing levels of glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) and with decreasing level of apolipoprotein A1 (ApoA1). The adjusted prevalence ratios for overall CRN comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, triglycerides, total cholesterol, LDL-C, ApoB, and ApoA-1 were 1.83 (95 % CI 1.62–2.06), 1.17 (95 % CI 1.03–1.33), 1.09 (95 % CI 0.97–1.23), 1.22 (95 % CI 1.08–1.37), 1.31 (95 % CI 1.16–1.48), 1.19 (95 % CI 1.07–1.33), 1.38 (95 % CI 1.23–1.54), 1.30 (95 % CI 1.14–1.47), and 0.85 (95 % CI 0.76–0.95), respectively. There was also a significant association between higher levels of glucose, LDL-C, and ApoB with a higher prevalence of advanced CRN. Moreover, the risk of CRN increased further in cases in which the parameters of glucose metabolism and lipid metabolism worsened simultaneously. The levels of parameters of glucose and lipid metabolism are significantly associated with the prevalence of CRN. Altered glucose and lipid metabolism may contribute to the development of CRN.

Background: The incidence of rectal neuroendocrine tumors (NET) has been increasing since the implementation of the screening colonoscopy. However, very little is known about risk factors associated with rectal NETs. We examined the prevalence of and the risk factors for rectal NETs in a Korean population. Methods: A cross-sectional study was performed on 62,171 Koreans who underwent screening colonoscopy. The clinical characteristics and serum biochemical parameters of subjects with rectal NET were compared with those of subjects without rectal NET using multivariate logistic regression. Results: Of a total of 57,819 participants, 101 [OR, 0.17%; 95% confidence interval (CI), 0.14–0.20] had a rectal NET. Young age ( Conclusions: Young age ( Impact: The findings of this study contribute to a better understanding of the influence of gender, behavioral factors, and dyslipidemia in developing rectal NETs. Cancer Epidemiol Biomarkers Prev; 23(7); 1406–13. ©2014 AACR.

Background/Aims: There is an increased risk for inflam-matory bowel disease (IBD) patients to develop infections due to the use of immunomodulators and biologics. Several infections are preventable by immunizations. This study investigated the knowledge and awareness of Korean gastro-enterologists regarding the vaccination of patients with IBD. Methods: A self-reported questionnaire was sent by e-mail to the faculty members of tertiary hospitals. Gastroenterologists were asked ten questions regarding the immunization of pa-tients with IBD. A total of 56 gastroenterologists completed the questionnaire. Results: A majority of gastroenterologists (>60%) had rarely or never recorded an immunization history from their patients with IBD. Moreover, 50% to 70% of the gastroenterologists did not know that live vaccines should be avoided in immunosuppressed patients. The most com-monly mentioned resistance to vaccinations was “the lack of concern and knowledge regarding vaccination.” Gastroenter-ologists more frequently asked about the immunization his-tory of influenza, pneumococcal, hepatitis A, and hepatitis B vaccines and recommended these vaccines more often than others. Conclusions: Korean gastroenterologists` awareness and knowledge regarding the vaccination of patients with IBD were very poor. Intensive educational programs on im-munization guidelines directed toward gastroenterologists who care for patients with IBD are required to ensure that these patients receive the necessary vaccinations.(Gut Liver 2014;8:242-247)

BACKGROUND/AIMS: The red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores. METHODS: This study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively. RESULTS: After adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61±0.41% (mean±SD), 12.70±0.70%, 12.77±0.62%, 12.87±0.82%, and 13.25±0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71±0.72%, 12.79±0.66%, and 13.23±1.52% for those with FIB-4 scores of

Background/Aims Although mucosal mast cell tryptase is known to significantly increase intestinal permeability, the relationship between mucosal mast cells and intestinal permeability remains unclear. The objective of this study was to evaluate the correlation among intestinal permeability, tryptase activity and mucosal mast cell count. Methods Rectal biopsies from 16 patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and 7 normal subjects were assessed for tryptase activity and macromolecular permeability using horseradish peroxidase in Ussing chambers. In addition, mucosal mast cell levels were immunohistochemically quantified via image analysis. Results Rectal biopsy of tissues from IBS-D patients showed significantly increased permeability compared with those from normal controls (0.644 ± 0.08 and 0.06 ± 0.00 ng/2 hr/mm2, P < 0.01). Tryptase activity was also substantially higher in rectal biopsy samples from IBS-D patients than those from normal controls (0.86 ± 0.18 and 0.28 ± 0.04 mU/mg protein, P < 0.05). Mucosal mast cell counts were not significantly different between the 2 groups (P > 0.05). However, correlation analysis revealed that only mucosal mast cell count was significantly correlated with intestinal permeability in IBS-D patients (r = 0.558, P < 0.05). Conclusions This study demonstrated a positive correlation between the number of mucosal mast cells and intestinal permeability, suggesting that mucosal mast cells play an important role for increased intestinal permeability in patients with IBS-D.

Background and Aims The apolipoprotein B/AI (ApoB/AI) ratio is a strong new risk factor for cardiovascular (CV) disease. Although recent reports have shown the effects of non-alcoholic fatty liver disease (NAFLD) on CV disease, NAFLD is under-recognized as a predictable risk factor for CV disease. This study was performed to assess the independent association between ApoB/AI ratio and NAFLD. Methods This cross-sectional study was performed in 9162 subjects who participated in a health checkup program in South Korea in 2009. The presence of NAFLD was defined by ultrasonographic examination. Logistic regression analysis was applied to estimate the association between ApoB/AI ratio and NAFLD. The odds ratio (OR) and P were estimated according to the categorized level of the ApoB/AI ratio. Results The overall prevalence of NAFLD was 27.9% (n = 2554, 41.7% of the men, 10.8% of the women). Men had a 5.91-fold (95% CI 5.28–6.62) greater risk for NAFLD than women. After adjusting for confounding factors, the ApoB/AI ratio was more closely associated with the prevalence of NAFLD than with any other lipid profiles (OR 8.537 in men, 16.6 in women). NAFLD risk increased as the quartiles of the ApoB/AI ratio increased from the first to the fourth quartile (OR 1.359, 2.173 and 3.124, P for trend

Clinical outcomes associated with Gram-negative bacterial isolates with extended spectrum beta-lactamase (ESBL) in patients with biliary tract infection are largely unknown. The objective of the present study was to compare the demographics, risk factors, and clinical outcomes between patients with biliary tract infection caused by ESBL-producing and non-producing Klebsiella pneumoniae and Escherichia coli. Between February 2005 and August 2010, we collected 159 cases with biliary tract infection caused by K. pneumoniae and E. coli identified by blood or bile cultures obtained before endoscopic or surgical treatment performed at our institution. We also retrospectively collected the data of patients’ demographic characteristics, co-morbid conditions, antimicrobial therapy, and clinical outcomes. Among the 159 strains isolated, 21 strains (13.2 %) were positive for phenotypical ESBL-test. Sepsis was more common in ESBL-positive strains, but did not reach statistical significance (23.8 % for ESBL-positive strains and 9.4 % for ESBL-negative strains, P = 0.066). Thirty-day mortality was significantly higher in ESBL-positive strains (3/21, 14.3 %) compared to ESBL-negative strains (4/138, 2.9 %, P = 0.049). However, there were no significant differences in overall survival between ESBL-positive and ESBL-negative strains. By multivariate analysis, inadequate antimicrobial therapy (HR 4.06, 95 % CI 1.08–16.46, P = 0.049) and sepsis (HR 6.54, 95 % CI 1.26–33.85, P = 0.025) were independent and significant predictors of 30-day mortality. ESBL status of bacterial isolates for patients with biliary tract infection caused by K. pneumoniae and E. coli has clinical impact, especially on the short-term outcomes of those patients.

Background/Aims: The aim of this study was to assess the effects of endoscopy nurse participation on polyp detection rate (PDR) and adenoma detection rate (ADR) of second-year fellows during screening colonoscopies. Methods: This was a single-center, prospective, randomized study comparing a fellow alone and a fellow plus an endoscopy nurse as an additional observer during afternoon outpatient screening colonoscopies. The primary end points were PDR and ADR. Results: One hundred ninety-one colonoscopies performed by a fellow alone and 192 colonoscopies performed by a fel-low plus an endoscopy nurse were analyzed. The PDR was significantly higher when the nurse was involved (53.1% vs. 41.3%, p

Background/aims Nonselective β-blockers (NSBBs), such as propranolol, reportedly exert a pleiotropic effect in liver cirrhosis. A previous report suggested that survival was higher in patients receiving adjusted doses of NSBBs than in ligation patients. This study investigated whether low-dose NSBB medication has beneficial effects in patients with liver cirrhosis, especially in terms of overall survival. Methods We retrospectively studied 273 cirrhotic patients (199 males; age 53.6±10.2 years, mean±SD) who visited our institution between March 2003 and December 2007; follow-up data were collected until June 2011. Among them, 138 patients were given a low-dose NSBB (BB group: propranolol, 20-60 mg/day), and the remaining 135 patients were not given an NSBB (NBB group). Both groups were stratified randomly according to Child-Turcotte-Pugh (CTP) classification and age. Results The causes of liver cirrhosis were alcohol (n=109, 39.9%), hepatitis B virus (n=125, 45.8%), hepatitis C virus (n=20, 7.3%), and cryptogenic (n=19, 7.0%). The CTP classes were distributed as follows: A, n=116, 42.5%; B, n=126, 46.2%; and C, n=31, 11.4%. Neither the overall survival (P=0.133) nor the hepatocellular carcinoma (HCC)-free survival (P=0.910) differed significantly between the BB and NBB groups [probability of overall survival at 4 years: 75.1% (95% CI=67.7-82.5%) and 81.2% (95% CI=74.4-88.0%), respectively; P=0.236]. In addition, the delta CTP score did not differ significantly between the two groups. Conclusions Use of low-dose NSBB medication in patients with liver cirrhosis is not indicated in terms of overall and HCC-free survival.

Recent studies have suggested that a higher red blood cell distribution width (RDW) is associated with disease activity in patients with inflammatory bowel disease (IBD). However, the RDW in IBD patients without anemia has not been investigated. This study aimed to determine whether or not RDW could be used for the assessment of disease activity in IBD patients with and without anemia. The serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), hemoglobin concentration, platelet and white blood cell counts, and RDW were assessed in 221 IBD patients, comprised of 120 patients with ulcerative colitis (UC) and 101 patients with Crohn’s disease (CD). Disease activity was determined for UC and CD with the Mayo score and the Crohn’s disease activity index, respectively. The CRP level, ESR, hemoglobin concentration, hematocrit, and RDW increased according to disease activity in patients with and without anemia (all P

Background and Aim: There have been no trials comparing the prophylactic effect of oral quinolone and intravenous cephalosporin antibiotics and elucidating the predictive factors for the occurrence of bacterial infections in cirrhotic patients with gastrointestinal bleeding in Asian-Pacific region. Methods: One hundred and thirteen patients with advanced liver cirrhosis and active gastrointestinal hemorrhage were enrolled in our study. The patients were randomly allocated into either the oral ciprofloxacin group (n = 50, 500 mg every 12 h) or the intravenous ceftriaxone group (n = 63, 2.0 g per day for 7 days). Results: Proven or possible infections were significantly more frequent in the patients in the oral ciprofloxacin group (34.0%) than the intravenous ceftriaxone group (14.3%, P = 0.002). The intestinal permeability index (IPI, mean [SD]) measured the day after admission was significantly higher in the patients with proven or possible infections (1.45 [0.96]) compared with the no infection group (0.46 [0.48], P

Background/Aims: Recent studies have found that probiotics have anti-Helicobacter pylori (HP) properties. We evaluated the additive effects of (i) Saccharomyces boulardii combined with proton pump inhibitor (PPI)-based triple therapy and (ii) S. boulardii and a mucoprotective agent (DA-9601) coupled with PPI-based triple therapy for HP eradication. Methods: We recruited 991 HP infected patients and randomized them into one of three groups, (A) PPI-based 7-day triple therapy, (B) the same triple therapy plus S. boulardii for 4 weeks, and (C) the same 7-day triple therapy plus S. boulardii and mucoprotective agent for 4 weeks. All patients in the three groups were tested via 13C-urea breath test 4 weeks after the completion of the therapy. Results: According to the results of an intention-to-treat analysis, HP eradication rates for the groups A, B, and C were 71.6% (237/331), 80.0% (264/330), and 82.1% (271/330), respectively (p = .003). According to the results of a per protocol analysis, the eradication rates were 80.0% (237/296), 85.4% (264/309) and, 84.9% (271/319), respectively (p = .144). The frequency of side effects in group B (48/330) and C (30/330) was lower than that in group A (63/331) (p

Background and Aims: The purpose of the present study was to determine the clinical characteristics of subjects with gallbladder polyps and cholelithiasis compared with those with gallbladder polyps only. Methods: Between August 1999 and December 2005, 176 subjects with gallbladder polyps and cholelithiasis (study group) by transabdominal ultrasonography performed during a medical check-up at our institution were recruited and compared with a control group of 185 subjects who had gallbladder polyps only. Results: No significant difference in the mean interval change (delta) of polyp size during the follow-up period between the study and control groups (0.85 ± 1.39 mm vs 0.84 ± 1.58 mm, respectively, P = 0.927) was noted. A significantly higher proportion (9/176 [5.1%]) of examinees in the study group had attacks of acute cholecystitis compared with the control group (1/185 [0.5%], P

Background and Aims: Metabolic syndrome and insulin resistance are associated with a higher risk of colon cancer. Non-alcoholic fatty liver disease (NAFLD) is regarded as a manifestation of metabolic syndrome in the liver. This investigation was initiated to determine whether NAFLD has a relationship to colorectal adenomatous polyps. Methods: We examined the 2917 participants who underwent a routine colonoscopy at Kangbuk Samsung Hospital in 2007. We divided the 2917 subjects into the adenomatous polyp group (n = 556) and the normal group (n = 2361). Anthropometric measurements, biochemical tests for liver and metabolic function, and abdominal ultrasonographs were assessed. Results: The prevalence of NAFLD was 41.5% in the adenomatous polyp group and 30.2% in the control group. By multiple logistic regression analysis, NAFLD was found to be associated with an increased risk of colorectal adenomatous polyps (odds ratio, 1.28; 95% confidence interval, 1.03–1.60). An increased risk for NAFLD was more evident in patients with a greater number of adenomatous polyps. Conclusion: NAFLD was associated with colorectal adenomatous polyps. Further studies are needed to confirm whether NAFLD is a predictor for the development of colorectal adenomatous polyps and cancer.

Background and Aim: There have been no reports comparing the therapeutic results of adefovir (ADV) and entecavir (ETV) rescue therapy for patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). We aimed to compare the cumulative efficacy and resistance of ETV 1.0 mg monotherapy, ADV monotherapy and ADV add-on LAM combination therapy in LAM-refractory patients. Methods: One hundred and four patients were included in the following three treatment groups; group 1 (n = 24), LAM was switched to ETV (1.0 mg once a day); group 2 (n = 44), LAM was switched to ADV (10 mg once a day); and group 3 (n = 36), ADV was added to LAM (10 mg once a day). Results: After 6 months of rescue treatment, alanine aminotransferase normalization was observed in 75.0%, 65.9% and 74.3% of patients receiving ETV monotherapy, ADV monotherapy and ADV add-on therapy, respectively. A significantly higher log10HBV-DNA drop at 6 months occurred in the ADV add-on group compared with the ETV group. The rate of HBV-DNA polymerase chain reaction undetectability (

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) appear to have increased intestinal permeability; it has been suggested that activation of protease-activated receptor-2 (PAR-2) receptors is responsible for this alteration. The aims of this study are to evaluate (1) if rectal (large bowel) permeability is increased in IBS-D and (2) if tryptase plays a critical role in the altered permeability. Rectal biopsies from 20 patients with IBS-D and 30 subjects without the condition (normal controls) were assessed for macromolecular permeability using horseradish peroxidase in Ussing chambers in the basal state and after addition of drugs to the basolateral side. Reverse-transcription polymerase chain reaction (RT-PCR) was performed using colonic biopsy tissues from patients with IBS-D and normal subjects. When tryptase was added to the basolateral (not mucosal) side of normal rectal biopsy tissues, permeability appeared to be proportional to the increase in tryptase concentration (P

Background: We aimed to explore the predictive ability of preoperative carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels for assessing tumor resectability (R0 resection) in patients with pancreatic adenocarcinoma. Methods: The present study included 72 patients who had been treated surgically for potentially resectable pancreatic adenocarcinoma and 42 patients who had been treated surgically for palliation (bypass surgery) at our institution. Pancreatic adenocarcinoma was histologically confirmed by pathological examination of the resected specimen or, if unresected, by intraoperative biopsy. Results: For resectable disease, the mean and median values of CA19-9 were significantly lower than for R1/2 or unresectable disease. The best cut-off points for CEA, CA19-9, and tumor size to predict resectability were 2.47 ng/mL, 92.77 U/mL and 11.85 cm3, respectively. A CA19-9 ≥ 92.77 U/mL and both tumor markers no less than the cut-off levels predicted the possibility of R1/2 or unresectability with 90.6% and 88.6% accuracy, respectively. However, either tumor marker or both tumor markers less than the cut-off levels predicted the probability of R0 resection only with 27.1% and 40.6% accuracy, respectively. The independent contributing factors to resectability (R0 resection) by multivariate regression analysis were a CA 19-9

Background and Aims: There has been no study comparing the clinical efficacy of clevudine and entecavir in antiviral-naive patients with chronic hepatitis B (CHB). Methods: A total of 128 antiviral-naive CHB patients were included to receive clevudine 30 mg (n=55) or entecavir 0.5 mg (n=73) once daily for a mean follow-up period of 18.4 months. Results: Thirty-three (60.0%) in the clevudine group and 40 (54.8%) in the entecavir group were HBeAg positive (P>0.05). At 6 months from the baseline, the mean decreases in HBV-DNA were 4.86 and 4.72 log10 copies/ml in the clevudine and entecavir groups respectively (P>0.05). The proportion of patients with undetectable serum HBV-DNA ( 0.05). The proportion of patients with normal alanine aminotransferase levels at 6 months was 74.5 and 84.9% in the clevudine and entecavir groups respectively. During the mean follow-up of 18.4 months, genotypic resistance was noted in three patients (5.5%) in the clevudine group and no cases in the entecavir group. Eight patients (14.6%) in the clevudine group experienced symptoms, signs and laboratory abnormalities relevant to clevudine-induced myopathy. Conclusions: Clevudine and entecavir treatment effectively suppresses HBV replication in most antiviral-naive patients with CHB. During a mean follow-up of 18.9 months, a small proportion (5.5%) of patients in the clevudine group developed genotypic resistance. However, a substantial proportion (14.6%) of patients in the clevudine group had an adverse effect of clevudine-induced myopathy.

Background: Hepatitis C virus (HCV) infection is associated with a high prevalence of diabetes mellitus (DM). Insulin resistance (IR) is known to play a crucial role in the development of DM in chronic hepatitis C (CHC) patients. We prospectively investigated changes of insulin sensitivity in CHC patients during a 5-year period and analysed the factors significantly associated with IR. Methods: Sixty-two CHC patients with normal insulin sensitivity (CHC group), and a healthy control group of 172 subjects matched by age, gender, body mass index and lifestyles were studied. We compared the initial baseline insulin sensitivity, metabolic parameters and incidence of IR at the end of the follow-up period between the two groups. The changes in insulin sensitivity, metabolic parameters and the development of IR were analysed as well as factors associated with the development of IR. Results: IR developed in 22.5% of 62 CHC patients and 5.2% of 172 normal individuals (P < 0.001). HCV infection per se and the genotype 1 were independent risk factors for the development of IR. The duration of infection ≥120 months, initial fasting glucose 90–100 mg/dL, fasting insulin ≥10 µIU/mL and the homeostasis model assessment (HOMA-IR) 2.3–2.7 were significantly associated with the development of IR in the CHC group. Conclusion: HCV infection was an independent risk factor for the development of IR. All CHC patients, even those with normal insulin sensitivity, require careful monitoring for the development of IR.

Aims Defects in intrahepatic nitric oxide (NO) are attributed to reduced blood flow due to portal hypertension caused by diminished endothelial NO synthase (eNOS) activity. The aim of this study is to identify the therapeutic effects of silymarin on eNOS/NO-related enzymes and hepatic enzymes in carbon tetrachloride (CCl4)-induced cirrhotic rats. Main methods CCl4 treated for 12 weeks was discontinued and then administrated with silymarin daily for 4 weeks. Collagen concentrations were determined by measuring hydroxyproline content. Serum was assayed for hepatic enzymes like alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities. NOS activities were measured by oxyhemoglobin oxidation assay, and levels of enzyme expression and phosphorylation were detected by Western-blot analyses. Key findings Silymarin treatment restored the values for collagen content and ALT and ALP activities when compared to the values with spontaneous resolution following discontinuation of CCl4. CCl4 treatment highly increased eNOS expression and NOS activity in livers, but the phosphorylation was markedly decreased. Silymarin decreased significantly eNOS expression and activity. Expression and/or phosphorylation of enzymes activating eNOS were unchanged (Akt and AMPK) or decreased (PKA) by silymarin. Especially, the expression of caveolin-1, an inhibitor of eNOS was unchanged by CCl4, but its phosphorylation was significantly increased. However, silymarin markedly increased caveolin-1 expression but decreased its phosphorylation to expression. Significance These results suggest that chronic silymarin treatment can improve cirrhosis-induced liver enzyme activities and fibrosis, but may aggravate the hemodynamic eNOS activity, particularly by decreasing eNOS expression and increasing caveolin-1 expression.

Objectives: The clinical significance of liver steatosis has been studied because steatosis plays a role in the progression of liver fibrosis. Nevertheless, the impact of steatosis in the early stage of fibrosis in non-obese young men with chronic hepatitis B (CHB) is poorly understood. Thus, the purpose of this study was to investigate the prevalence of hepatic steatosis, assess the relationship between hepatic steatosis and fibrosis and to assess the laboratory parameters for predicting clinically significant liver fibrosis in non-obese young men with CHB. Methods: We prospectively evaluated liver biopsies in young male patients with CHBwith a serum alanine aminotransferase level of more than two times the upper limit of normal for at least 3 months before enrollment. Patients were excluded when they had co-infection with another virus and prior antiviral treatment. Demographical, anthropometric and laboratory parameters were analysed. Liver steatosis, necroinflammation and fibrosis were also assessed. Results: A total of 86 young male patients with CHB were included in this study. The median age was 21 years (range, 20–26 years) and the median body mass index was 23.0 kg/m2 (range, 18.0–28.3 kg/m2). Steatosis was present in 44 patients (51.2%). Significant fibrosis (beyond periportal fibrosis) was present in 50 patients (58.1%). Steatosis was associated with insulin, homeostasis model for insulin resistance (HOMA-IR), total cholesterol and triglycerides. On multiple regression analysis, steatosis was independently associated with triglyceride and HOMA-IR. Significant fibrosis was independently associated with γ-glutamyltransferase (GGT) and necroinflammation activity. However, there was no significant association between significant fibrosis and the presence of steatosis. Conclusions: The prevalence of hepatic steatosis is a common finding in young male patients with CHB. Hepatic steatosis in CHB patients seems to be associated with insulin resistance, but it is not associated with hepatic fibrosis. GGT levels can provide useful information on the stage of CHB.

Background/Aims Chronic hepatitis C virus (HCV) infection is associated with a higher risk of the development of insulin resistance. If HCV is a causal factor for insulin resistance, then clearance of HCV might decrease insulin resistance. The aim of this study was to elucidate the effects of clearance of HCV on insulin resistance. Methods We analyzed 28 patients with HCV infection who received combination treatment of 180 µg of pegylated interferon α-2a and ribavirin at our institution from May 2004 to November 2006. Insulin resistance was calculated according to the homeostasis model assessment of insulin resistance (HOMA-IR) method. Results Twenty-two patients (78.6%) achieved sustained virologic response (SVR), where the fasting plasma glucose level significantly decreased after antiviral treatment. Fasting serum insulin and HOMA-IR also significantly decreased after antiviral treatment, whereas the BMI value was not significantly affected. For the nonresponders (n=6), no significant changes were evident in BMI, fasting plasma glucose, fasting serum insulin, and HOMA-IR at 6 months after the end of antiviral treatment. Logistic regression analysis indicated that the only independent factor contributing to the reduction of insulin resistance was the complete disappearance of HCV RNA at 6 months after the end of antiviral treatment (SVR). Conclusions The clearance of HCV by the combination therapy of pegylated interferon α-2a and ribavirin improves insulin resistance by reducing fasting serum insulin and glucose levels.

BACKGROUND It is unknown whether microalbuminuria is associated with non-alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes. METHODS We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed. RESULTS The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P = 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin-to-creatinine ratio (14.6 +/- 52.0 microg/mg Cr vs 27.7 +/- 63.9 microg/mg Cr; P = 0.051 in prediabetes, 11.4 +/- 21.4 microg/mg Cr vs 44.7 +/- 76.4 microg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95%confidence interval (CI) 1.31-10.20, P = 0.013 in prediabetes, odds ratio 5.47;95% CI 1.01-29.61, P = 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension,smoking status and the metabolic syndrome. CONCLUSIONS The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.

Background/Aims: There has been no report concerning the predictive capability of each scoring system in determining the development of complications of liver cirrhosis such as variceal bleeding and/or hepatic encephalopathy. Methods: We retrospectively studied 128 patients with liver cirrhosis [92 males; mean (standard deviation) 54.2 (11.2) years] admitted to our institution from March 2004 to April 2006. Seventy-three patients (57.0%, group 1) were admitted because of complications of cirrhosis and 55 patients (43.0%, group 2) were admitted for causes unrelated to complications of cirrhosis. We calculated values for model for end-stage liver disease (MELD), MELD-sodium (MELD-Na) and Child–Turcotte–Pugh (CTP) scores on admission and at 3 and 6 months before admission. Each delta score was defined as the difference in the scores of 3 and 6 months before admission. Results: The relative risk for complications in the patients with ΔMELD/3 months ≥1.35, ΔMELD-Na/3 months ≥1.35 and ΔCTP/3 months ≥1 was 2.05 [95% confidence intervals (CI) 1.47–2.85, P

Our aim was to investigate whether the dynamic and static compliances differ between patients with irritable bowel syndrome (IBS) and normal subjects.Fifty-five IBS patients (age range 20-65 years, mean age 39.0 years, 28 women and 27 men; 36 diarrhea-predominant IBS (IBS-D) patients and 19 constipation-predominant IBS (IBS-C) patients) with symptoms that fulfilled the Rome-II criteria and 21 healthy controls (age range 25-58 years, mean age 37.8 years; 11 women and ten men) were recruited. The anorectal functions, including dynamic compliance, were evaluated via barostat tests. A power exponential model was used for the evaluation of static compliance.There was no significant difference in dynamic compliance between the normal subjects and the IBS patients (10.3+/-3.1 and 8.9+/-2.9 mmHg, respectively, P0.05). However, even though no significant difference was detected in the overall shape of the curve (beta; P0.05), there were significant differences in the kappa and P (half) between the normal subjects and the IBS patients (P0.05), respectively. When we compared the dynamic and static compliances between the IBS-C and IBS-D patients, there were no significant differences found (P0.05).An exponential model provided good fit to the actual data, and there were significant differences in static compliance between the normal subjects and the IBS patients. This result can reveal the altered biomechanical properties of the gut wall in IBS patients.

Background: Up to present, omeprazole plus two antibiotics are used for Helicobacter pylori eradication therapy . Few studies have compared double-dose new-generation, proton pump inhibitors (PPI) with omeprazole. Therefore, we conducted a randomized, prospective study to evaluate differences in H. pylori eradication rates by PPI type. Material and Methods: Between January 2006 and December 2006, 576 consecutive patients with proven H. pylori infection were enrolled prospectively. Four different PPIs [omeprazole 20 mg b.i.d. (old generation), or pantoprazole 40 mg b.i.d., rabeprazole 20 mg b.i.d., or esomeprazole 40 mg b.i.d. (new generation)] were added to clarithromycin (500 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week. Results: By intention-to-treat analysis, no difference was found between the eradication rates of these four PPIs: 64.9% (omeprazole, n = 148), 69.3% (pantoprazole, n = 140), 69.3% (rabeprazole, n = 140), and 72.9% (esomoprazole, n = 148). When eradication rates were analyzed according to whether patients had an ulcer or not on a per-protocol basis, no difference was found between the eradication rates of the four PPIs. However, side-effects were more common in the esomeprazole-based triple therapy group than in the other groups (p

Summary Background & aims : Systemic chemotherapy may damage gastrointestinal epithelium. Mucositis is associated with increased intestinal permeability (IP). It is known that IP test with chromium 51-ethylene diaminetetra-acetate ( 51 Cr-EDTA) is a useful tool to assess the mucositis. Oral glutamine supplements (OGS) may have a role in the prevention of chemotherapy-induced mucositis/stomatitis. The aim of this study was to characterize the relationship between the urinary excretion of 51 Cr-EDTA and the severity of mucositis, and the effect of OGS on 5-fluorouracil/leucovorin (FU/LV)-induced mucositis/stomatitis. Methods : Fifty-one patients with advanced or metastatic cancer received FU/LV chemotherapy. The control group included 18 healthy volunteers. IP was assessed via the measurement of 51 Cr-EDTA urinary excretion after oral challenge, on days 7 after the discontinuation of chemotherapy. Of the 51 patients, 22 patients received OGS (30 g/day) and 29 received only best supportive care (BSC). Glutamine supplementation continued for 15 days. It was initiated at least 3 days before the beginning of chemotherapy. Mucositis/stomatitis was graded according to version 3.0 of the Common Terminology Criteria for Adverse Events. Results : In the chemotherapy group, the median (25 percentile, 75 percentile) IP test score was significantly higher than those of the control group [6.78% (4.63, 10.66) vs. 2.17% (1.38, 2.40), P 0.001 ]. The severity of stomatitis was significantly correlated with IP test scores ( r = 0.898 , P 0.001 ). In the OGS group, the median IP test score was significantly lower than that of the BSC group [4.69% (3.10, 6.48) vs. 8.54% (6.48, 15.31), P 0.001 ]. A mucositis/stomatitis of grade 2–4 was observed in two patients of the OGS group (9%), and in 11 patients (38%) in the BSC group ( P 0.001 ). Conclusions : The IP test may be a useful tool in the evaluation of mucositis/stomatitis. OGS may exert a protective effect on FU/LV-induced mucositis/stomatitis. Further studies, however, will be necessary to define the role of glutamine supplementation in FU/LV-induced mucositis/stomatitis.

BackgroundThere is an increasing need for the early detection of emerging mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of hepatitis B virus (HBV) DNA polymerase with using sensitive molecular methods.MethodsWe evaluated the usefulness of monitoring lamivudine resistance using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based assay (the restriction fragment mass polymorphism; RFMP) in comparison with the direct sequencing assay, the TRUGENE™ HBV genotyping kit. We also investigated the treatment responses in relation to the presence of YMDD mutants. The sera from 50 chronic HBVs patients were analysed for the presence of YMDD mutants by performing RFMP and TRUGENE. The results at codons 180 and 204 were compared for 46 patients.ResultsThe concordance rate between the two assays was 65.2% (30/46). All the discordance corresponded to the detection of additional virus populations by RFMP. Early detection of mutants before viral breakthrough was accomplished by RFMP in two patients. Persistence of very low viraemia was observed in five patients who harboured mutant virus populations. Additional information was provided by TRUGENE in eight patients.ConclusionsRFMP showed a superior ability for detecting minor mutant virus populations compared with TRUGENE. However, the results of highly sensitive RFMP should be interpreted carefully because lamivudine could be effective despite the presence of mutants. RFMP could be a practical tool in conjuction with regular measurements of the HBV viral load for the early detection of lamivudine resistance and the timely introduction of new antiviral drugs.

In many centers, rapid on-site evaluation (ROSE) for the specimens obtained from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is not available. The aim of this study was to compare the diagnostic yields of EUS-FNAB in the presence or absence of ROSE. Seventy-five patients who underwent EUS-FNAB for the pancreatic, gastric subepithelial, and mesenteric mass lesions at our institution from November 2013 to August 2014 were included. For 20 patients in the pilot cohort, EUS-FNAB was performed with ROSE, and simultaneously, training of the staff endosonographer for tissue adequacy by an on-site cytopathologist was also performed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EUS-FNAB in the pilot cohort were 91.7, 100.0, 100.0, 88.9, and 95.0 %, respectively. The 3.2 ± 0.8 [mean ± standard deviation (SD)] needle passes were needed in this cohort. Fifty-five patients were enrolled as a validation cohort from April 2014 to August 2014, and tissue adequacies were assessed by an experienced endosonographer without ROSE in this cohort. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNAB in this validation cohort were 92.1, 100.0, 100.0, 85.0, and 94.6 %, respectively. The 4.5 ± 0.6 (mean ± SD) needle passes were needed in this cohort (p

Nonalcoholic fatty liver disease (NAFLD) has been associated with metabolic disorders, including central obesity, dyslipidema, hypertension, and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of NAFLD. The aim of this study was to identify the relative contribution of the metabolic syndrome, obesity, and insulin resistance to alanine aminotransferase (ALT) activity in NAFLD. A total of 3091 subjects diagnosed with fatty liver by ultrasonography were enrolled. All components of metabolic syndrome criteria, anthropometric parameters, fasting insulin levels, high-sensitivity C-reactive protein (hs-CRP) as an inflammation marker, and ALT were measured in each subject. Homeostasis model assessment--insulin resistance (HOMA-IR) as a measure of insulin resistance and body mass index (BMI) as a measure of obesity were calculated. The prevalence of increased ALT levels (>40 IU/L) was 26.7%. Increased ALT activity was significantly associated with the following characteristics: male sex, young age, increased triglycerides, fasting glucose, fasting insulin, HOMA-IR, hs-CRP, waist circumference, BMI and diastolic blood pressure, and decreased high-density lipoprotein cholesterol (HDL-C). According to the increase in the number of metabolic syndrome components, BMI, HOMA-IR, and hs-CRP, the prevalence and odds ratio for having increased ALT activity were significantly increased. Central obesity, raised triglycerides, reduced HDL-C, and raised fasting glucose were strongly associated with increased ALT activity. In conclusion, a number of metabolic syndrome components, obesity, insulin resistance, and hs-CRP, are strong predictors of increased ALT activity in NAFLD. Central obesity, raised triglycerides, reduced HDL-C, and raised fasting glucose are metabolic syndrome components that contributed to increased ALT activity.

There is, currently, no consensus with regard to the role of endoscopy in the etiologic investigation of asymptomatic pemenopausal women suffering from iron deficiency anemia (IDA). We conducted a retrospective case-control study to evaluate the contribution of esophagogastroduodenoscopy (EGD) and colonoscopy to the etiologic diagnosis of a group of asymptomatic premenopausal women suffering from IDA. One hundred eight consecutive asymptomatic premenopausal women who fulfilled our entry criteria were included in our patient group between January 1998 and December 2004. One hundred thirty-five age-matched asymptomatic premenopausal women without anemia who had undergone EGD and colonoscopy for medical checkups were included in the control group. Clinically relevant lesions were detected in 7 of 108 (6.5%) of the patients and in 8 of 135 (5.9%) of the controls. There were no differences with regard to the frequency of clinically relevant lesions between the two groups (P > 0.05). Concomitant upper and lower GI lesions were not detected in any patients. In the upper GI tract, the only lesion found to be potentially causative of IDA anemia was a severe erosive gastritis, which was found in both the patient and the control groups. A source consistent with chronic bleeding was detected in the lower GI tract in 6 (5.6%) of the patients and 7 (5.2%) of the controls. Bleeding hemorrhoids represented the most frequently detected lesions in both the patient and control groups. Only one case of colon cancer was detected in the patient group. As IDA in the premenopausal women could not be attributed consistently to GI blood loss in this study, prospective studies should be conducted to validate our findings and to identify which subgroup of asymptomatic premenopausal women would benefit from a diagnostic endoscopic evaluation.