Change of insulin sensitivity in hepatitis C patients with normal insulin sensitivity: a 5-year prospective follow-up study variation of insulin sensitivity in HCV patients.

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 > or = 120 months, initial fasting glucose 90-100 mg/dL, fasting insulin > or = 10 microIU/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.

Impact of non-alcoholic fatty liver disease on microalbuminuria in patients with prediabetes and diabetes.

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.

Quality and effect of single dose versus split dose of polyethylene glycol bowel preparation for early-morning colonoscopy.

BACKGROUND AND STUDY AIMS: The conventional procedure of ingestion of an entire dose of polyethylene glycol solution on the day before early-morning colonoscopy may result in poor bowel preparation. The aim of this study was to evaluate the efficacy and effect of a split-dose ingestion of polyethylene glycol for early-morning colonoscopy. METHODS: A total of 303 age- and sex-matched consecutive individuals presenting for medical check-ups were randomly assigned to receive either 4 L of polyethylene glycol solution with a soft diet on the day before colonoscopy (n = 152; group A), or 3 L of polyethylene glycol solution with a soft diet on the preceding day and then 1 L of the solution on the day of colonoscopy (n = 151; group B). The quality of bowel preparation was evaluated using the Ottawa scale, and the time to cecal intubation and the technical difficulty during the procedure were also recorded. RESULTS: There was no difference in compliance between group A (single-dose) and group B (split-dose). The quality of bowel preparation was better in group B compared with group A. When the participants were categorized according to compliance (good compliance, 116 in group A, 119 in group B; poor compliance, 36 in group A, 32 in group B), the quality of the bowel preparation had a higher score in the good compliance compared with the poor compliance group, and in group B this difference was usually significant. CONCLUSIONS: Split-dose bowel preparation with polyethylene glycol solution provided a better quality preparation than the conventional method for patients undergoing early-morning colonoscopy.

Weight loss and waist reduction is associated with improvement in gastroesophageal disease reflux symptoms: A longitudinal study of 15 295 subjects undergoing health checkups.

BACKGROUND: General obesity and abdominal obesity is an established risk factor of gastroesophageal reflux disease (GERD). However, the influence of weight or waist change on improvement of GERD is unclear. Our aim was to investigate if weight loss or waist reduction improves GERD symptoms and esophagitis. METHODS: A retrospective longitudinal study of 15 295 subjects who underwent gastroscopy for a health checkup and reported GERD symptoms between 2011 and 2013, and repeated a checkup until 2014 was conducted. The improvement of GERD symptoms and esophagitis according to weight loss (≥-2, -0.5 to -2 kg/m2 in body mass index [BMI]), waist reduction (≥-5, -0.1 to -0.5 cm) and baseline BMI/waist circumference (WC) categories was assessed using logistic regression. KEY RESULTS: Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Among subjects with general obesity (BMI ≥25 kg/m2 ) and decreased ≥2 kg/m2 in BMI, the adjusted odds ratio (OR) of improvement in GERD symptoms was 2.34 (95% confidence interval [CI] 1.70-2.83). Among subjects with abdominal obesity (WC ≥90 cm) and decreased ≥5 cm in WC, the corresponding OR was 2.16 (95% CI 1.56-2.90). There was no association between weight loss or waist reduction and improvement in esophagitis. CONCLUSIONS & INFERENCES: Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Weight loss or waist reduction will be an important treatment option in obese patients.

Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double-blind, placebo-controlled, multicenter, phase II trial.

BACKGROUND: Probiotics can be beneficial in irritable bowel syndrome (IBS). Mosapride citrate, a selective 5-HT4 receptor agonist, stimulates gastrointestinal motility. We investigated the efficacy of combination therapy with probiotics and mosapride for non-diarrheal-type IBS. METHODS: Two hundred and eighty-five IBS patients were randomly assigned to either a combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at one of four different doses or a placebo for 4 weeks. The primary outcome was the proportion of patients experiencing adequate relief (AR) of global IBS symptoms at week 4. The secondary outcomes included subject's global assessment (SGA) of IBS symptom relief, individual symptoms, stool parameters, and IBS-quality of life. KEY RESULTS: The proportion of AR at week 4 was significantly higher in all treatment groups compared to the placebo group (53.7% in group 1, 55.0% in group 2, 55.2% in group 3, 53.6% in group 4 [the highest dose], and 35.1% in placebo group, respectively, p < 0.05). The proportion of patients reporting 'completely or considerably relieved' in the SGA was higher in the treatment groups than in the placebo group. The abdominal pain/discomfort score in the treatment group 4 was more prominently improved compared with that of the placebo group. In patients with constipation-predominant IBS, the improvements in stool frequency and consistency were significantly higher in the treatment groups 4 and 1, respectively, than those in the placebo group. CONCLUSIONS & INFERENCES: Combination therapy with probiotics and mosapride is effective for relief of symptoms in patients with non-diarrheal-type IBS. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT01505777).

Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine.

BACKGROUND: The 5-HT(3) receptor antagonists are known to be effective for the treatment of diarrhea-predominant irritable bowel syndrome (IBS), but not widely used yet. The aim of this study was to compare the efficacy and safety of ramosetron, a 5-HT(3) receptor antagonist, and mebeverine in male patients with IBS with diarrhea (IBS-D). METHODS: This study was performed in a multicenter, randomized, open-label design. Data of 343 male patients with IBS-D who were randomized to either a 4-week treatment of ramosetron 5µg once daily or a 4-week treatment of mebeverine 135 mg three times daily were analyzed by the intent-to-treat analysis. The primary efficacy parameter was the proportion of patients with adequate relief of IBS symptoms at the last week of treatment. The secondary endpoints were changes in each symptom score and the safety profiles. KEY RESULTS: The responder rates for global IBS symptoms, abdominal pain/discomfort and abnormal bowel habits in the ramosetron and mebeverine groups significantly increased during the treatment period. The severity scores of abdominal pain/discomfort and urgency, the stool form score, and the stool frequency in both treatment arms were significantly reduced, compared with the baselines. There were no significant differences in the responder rates (37%vs 38% on ITT analysis) and adverse event profiles between the ramosetron and mebeverine groups. Neither severe constipation nor ischemic colitis was reported by ramosetron-treated patients. CONCLUSIONS & INFERENCES: Ramosetron 5µg once daily is as effective as mebeverine three times daily in male patients with IBS-D.

Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients.

BACKGROUND: In cholangiocarcinoma (CC), HER-2/neu protein overexpression has rarely been reported and the results are conflicting. The present study aimed to clarify the rates of HER-2/neu protein overexpression and gene amplification in human extrahepatic CC and to evaluate the correlation between HER-2/neu and several clinicopathologic features. PATIENTS AND METHODS: We investigated HER-2 gene amplification by chromogenic in situ hybridization (CISH) and HER-2/neu protein overexpression by immunohistochemistry in 55 extrahepatic CC patients who underwent curative surgery at our institution. RESULTS: Overexpression of HER-2/neu protein (staining intensity score > or = 2) was found in 16 out of 55 patients (29.1%). CISH revealed that HER-2 gene signals were increased in 10 out of 55 patients (18.1%). There was a positive and significant correlation between HER-2 gene amplification and HER-2/neu protein overexpression (Spearman's rho = 0.718, P < 0.01). In subgroup with lymph node metastases, HER-2 gene amplification by CISH was significant prognostic factor for survival (OR 43.6, 95% confidence interval 1.6-1219.6). CONCLUSIONS: HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases. In subgroup with lymph node metastases who exhibit HER-2/neu overexpression might constitute potential candidates for new adjuvant therapy, such as humanized monoclonal antibodies.

Clinical features associated with improvement of fatty liver disease.

BACKGROUND: We presumed that identification of the factors associated with improvement of fatty livers disease (FLD) would support the therapeutic options for FLD. The goal of this study was to clarify what clinical characteristics are associated with biochemical and sonographic improvements in the non-alcoholic population with fatty livers. METHODS: A total of 615 non-alcoholic men had elevated alanine aminotransferase (ALT) (> or = 40 IU/L) levels and sonographic evidence of a fatty liver, and their clinical characteristics were assessed at the beginning of the study and after 1 year of follow up. The improvement was defined as combination of normal ALT level and negative sonography for hepatic fat after 1 year. Programmed intervention or medications were not applied in this study population. RESULTS: The overall rate of improvement of FLD after a 1-year follow up was 37/615 (6.0%). The improvement was strongly associated with decrement of changes in bodyweight, body mass index, waist circumference, gamma-glutamyltransferase, fasting blood sugar, total cholesterol, triglycerides, low-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio and homeostasis model assessment. Multivariate analysis showed that decrement of changes in bodyweight (odds ratio (OR) = 1.56; 95% confidence interval (95%CI): 1.27-1.92) per 1 kg, body mass index (OR = 2.42; 95%CI: 1.58-3.71) per 1 SD (0.8 kg/m2), waist circumference (OR = 2.13; 95%CI: 1.02-4.54) per 1 cm, and low-density lipoprotein cholesterol (OR = 1.64; 95%CI: 1.05-2.56) per 1 SD (22 mg/dL) were all independent predictors for improvement of FLD. CONCLUSIONS: These results suggest that the reduction of bodyweight is a major key point for the improvement of FLD.

A case of ischemic colitis associated with pheochromocytoma.

A 40-year-old woman was admitted because of abdominal pain and diarrhea. She sometimes experienced paroxysmal hypertension, sweating, headache, and palpitation. Sigmoidoscopic findings showed well-demarcated diffuse mucosal edema, hyperemia, and easy touch bleeding from distal descending colon up to the splenic flexure area. Barium x-ray showed loss of haustral marking, thumb printing appearance, and diffuse luminal stenosis in the transverse, descending, and sigmoid colon. On the abdominal computed tomogram, a 3.8-cm sized well-enhanced right adrenal mass was incidentally found. Twenty-four hour urinary excretion of vanillyl mandelic acid, norepinephrine, and normetanephrine were increased. Iodine131 metaiodobenzylguanidine scan showed hot uptake on the right adrenal gland compatible with pheochromocytoma. Exploratory laparotomy was done under the impression of ischemic colitis associated with pheochromocytoma. Adrenalectomy and resection of the stenotic left colon were performed. After surgery, pain subsided, blood pressure fell gradually, blood sugar and catecholamine level became normal, and bowel habit returned to normal.