Mean follow-up was 64 months (16-158). Follow-up was at least of 1 year in all patients, 2 years in 96% of patients, 3 years in 86.7% and 4 years in 68% of patients. FibroTest was applicable in 74/75 patients (98.6%) and FibroScan in 68/75 patients (90.7%). Three patients (4%) declared an excessive alcohol consumption, whereas 27 (36%) had a CDT>1.8%. Overall, 36% of patients developed significant fibrosis (F>2). Independent factors associated with the development of significant fibrosis were weight at evaluation (p=0.003), cold ischemia (p=0.05), STA-9090 in vivo and alcohol abuse (p=0.04), but not the development of metabolic syndrome after LT. Conclusion

Alcohol consumption is underestimated after LT for pure alcoholic cirrhosis and should be evaluated with objective biomarkers such as CDT. Abusive drinking after LT is associated with significant progression of fibrosis that should be regularly assessed with noninvasive methods. Disclosures: Marika Rudler – Speaking and Teaching: Gilead Pascal Lebray – Grant/Research Support: Merck, astellas; Speaking and Teaching: Janssen, MSD, Gilead

Thierry Poynard – Advisory Committees GSK-3 inhibition or Review Panels: Merck; Grant/Research Support: BMS, Gilead; Stock Shareholder: Biopredictive The following people have nothing to disclose: Geraldine Rousseau, Corinne Vezinet, Daniel Eyraud, Jean-Christophe Vaillant, Dominique Thabut Background: Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the one of the main indication for liver transplantation (LT). However, 80% of transplanted patients present an accelerated recurrence of the disease. This study aim was to assess regulatory T-cell subsets, and T helper 1, 2 and 17 cells involvement in recurrent hepatitis C after liver transplantation. Patients and Methods: Peripheral blood mononuclear cells, obtained before and one month after

LT, from 22 liver transplant recipients have been analysed. Forty four key molecules, related to Treg, T helper 1, 2 and 17 responses, were evaluated by using qRT-PCR analysis. Liver transplant recipients have been classified on two groups in function of fibrosis evaluation observed on the one year follow-up biopsy. The severity 上海皓元 of hepatitis C recurrence was evaluated by the results METAVIR analysis on one year liver biopsy (mild: F<1, severe F≥ 1). The results of patients that will develop a severe hepatitis C recurrence (n=9) were compared to those obtained in patients will develop a mild recurrence (n=13). Results: Our results demonstrated a significant increase in mRNA levels of Treg markers (CD4,CD25,TGFf>,CTLA-4, GATA-3, and IL-10Ra/p) early after liver transplantation (one month) in patients with a severe evolution of HCV recurrence. Th1 markers (IL-2, IFNg, IL-23, T-bet), which could be implicated in antiviral response, were also elevated in same group of patients.

In addition, the ALT activity in PD-1-/- mice co-treated with anti-CTLA4 antibody and AQ did not return ABT-737 molecular weight to normal as it had in other mice. Conclusion: We report here the first animal model of IDILI that is similar to the IDILI that

occurs in humans, and it was accomplished by inhibiting immune tolerance. (Hepatology 2014) “
“We read with great interest the article by Xu et al.1 The authors used lentiviral vectors to overexpress microRNA 122 (miR-122). They constructed three different vectors carrying one, four, or eight copies of the miR-122 precursor. Finally, the authors generated stable cells possessing eight copies of the miR-122 precursor. This is an ingenious method for further improving the expression level of miR-122. However, we think that some problems need to be discussed. First, how do we determine that the stable HepG2 cells possess eight copies of the miR-122 precursor when the cells are infected with lentiviral vectors carrying multiple copies?

Why do we not use lentiviral vectors carrying 10 or more copies to further improve the level of miR-122? Are there data from the experiment using a gradually http://www.selleckchem.com/products/cx-5461.html increasing number of miR-122 copies in vectors to construct miR-122–overexpressed stable cells? Recently, in our experimentation, HepG2 cells were transfected with vectors carrying a single copy of the miR-122 precursor. By screening different single clones, we obtained several HepG2 cell clones that had large differences in the expression level of miR-122. We deduced that the miR-122 precursor sequence could be integrated into several sites of the genome simultaneously. Information about the copy number can help us to choose optimal stable cell lines because MCE of the existence of copy loss in the genome.

We think that a stable cell line with a high copy number should be chosen when there are similar expression levels in different cell lines. Second, primary microRNA must be cleaved into precursor microRNA (pre-miRNA) by the nuclear RNase III endonuclease Drosha. Then, the pre-miRNA is actively transported from the nucleus to the cytoplasm by ras-related nuclear protein–guanosine triphosphate and the export receptor exportin 5.2, 3 The processes of enzyme digestion and export depend on not only the transcript sequences but also their space structure.4 We suppose that when eight or more copies of the miR-122 hairpin were chained to express in one primary transcript, the processing or export of pre-miRNA was likely influenced by the changes in the conformational construct of the primary transcript or pre-miRNA. Therefore, we want to know how to determine the optimal copy number of a microRNA precursor in a vector. In many studies, microRNA-overexpressed stable cell lines have been obtained by the integration of the microRNA precursor sequence into the cell genome.5, 6 In most cases, a vector carrying a single-copy precursor sequence has been chosen.

We conclude that Yap induces metabolic reprogramming in the liver, resulting in decreased ammonia detoxification (Urea cycle) and increased check details ammonia assimilation into glutamine, prior to tumor formation. We hypothesize that the Yap-driven accumulation of glutamine may provide essential components for rapid cell proliferation that may contribute to hepatic growth in liver development and tumorigenesis. Disclosures: Wolfram Goessling – Consulting: Fate Therapeutics,

Fate Therapeutics; Patent Held/Filed: Fate Therapeutics, Fate Therapeutics The following people have nothing to disclose: Andrew G. Cox, Katie L. Hwang, Sebastian Beltz, Kimberley Evason, Keelin O’Connor, Kristin Brown, Evan C. Lien, Sagar selleck chemical Chhangawala, Yariv Houvras, Didier Y. Stainier Introduction: Acute liver failure leads to a variety of complications with one of the most difficult to manage clinically being the neurological complications, collectively called hepatic enceph-alopathy (HE). Following liver damage, the liver upregulates a variety of factors in response to injury. Transforming

growth factor beta 1 (TGF 1) is involved in the promotion of liver fibro-sis and is elevated in the serum following liver injury. Insulin-like growth factor 1 (IGF-1) is a neuroprotective peptide that is anti-inflammatory and can be suppressed by TGF 1 signaling in other organs. Therefore, we hypothesize that circulating hepatic-derived TGF 1 suppresses neural IGF-1 during

HE and subsequently exacerbates the neurological decline associated with HE. Methods: Male C57Bl/6 mice were injected with the hepatotoxin azoxymethane (AOM; 100 mg/kg). In parallel, mice were pretreated with an anti-TGF neutralizing antibody (1 mg/kg) 1 hour prior to AOM, or were infused ICV with recombinant mouse IGF-1 (120 ng/mouse/day) for 3 days prior to AOM injection. Cognitive impairment was monitored and at coma, livers, serum and whole brains were collected. Liver histology was assessed by H&E stains and liver function was determined via ALT and bilirubin measurement. TGF 1, IGF-1, and the microglia marker IBA-1 were assessed by immu-noblotting, immunohistochemistry and/or RT-PCR. Results: Mice injected with AOM had elevations of hepatic and circulating MCE公司 TGF 1 as well as a suppression of cortical IGF-1. Treatment of AOM mice with anti-TGF neutralizing antibodies or IGF-1 ICV prior to AOM significantly reduced the rate of neurological decline without causing significant changes in liver damage or function when compared to mice only treated with AOM. Mice treated with anti-TGF observed an increase of IGF-1 mRNA in the cortex. Treatment with both anti-TGF and IGF-1 ICV was found to reduce microglia activation and proliferation as measured by IBA1 staining. Conclusion: Elevated TGF 1 following liver failure leads to decreased IGF-1 expression, increased inflammation, and worse outcomes for HE mice.

05), the expression of the IL-4 in mucosa and IL-9 in serum were lower than that in model group (p < 0.05). Conclusion: Chinese herbal formula TongXieYaoFang may improve the visceral hypersensitivity in rats by regulating IL-4 /IL-9 and the number of MCs. Key Word(s): 1. hypersensitivity; 2. Dendritic cell; 3. mast cell; 4. TongXieYaoFang; Presenting Author: WANG HUAN Additional Authors: ZHANGXIU JING, HOUXIAO HUA Corresponding Author: HOUXIAO HUA Affiliations: astrazeneca Objective: Recently, research has increasingly suggested that synaptic plasticity plays an important role of the induction

and progression of PI-IBS. In a previous study from our laboratory, Synaptic plasticity contributes to the formation of visceral hypersensitivity in PI-IBS rat model FK506 cell line induced by Trichinella spiralis infection. In central nervous system, EphrinB2 signal pathway has been emphasized recently in the development of synaptic plasticity. The aim of this study was to

determine whether EphrinB2 signal pathway can contribute to development of PI-IBS. Methods: Visceral hypersensitivity was induced by Trichinella Acalabrutinib concentration spiralis infection in mice. Visceral sensitivity is assessed by abdominal withdrawal reflex (AWR) at 8 weeks post infection (PI). Preparation of submucosal plexus was microdissected as described by Wood and Mayer. Expression of EphrinB2, TrkB, NMDAR1, NMDARB2 and CaMK II in submucosal plexus of ileum, as major proteins of EphrinB2 signal pathway, was determined by Western blotting. Results: 1) At 40, 60 mmH g, the AWR scores of 8 weeks PI groups were higher than that in the control group (P < 0.05); 2) EphrinB2 in 8 weeks PI (1.17 ± 0.25) were higher than that of control group (0.88 ± 0.10, p < 0.05). Similarly, TrkB, NMDAR1, NMDARB2 and CaMK II were increased in the comparison of control group; 3) There were significant positive correlations between AWR scores of 60 mmHg and expression of EphrinB2 (r2 = 0.526, P < 0.05). 上海皓元 Conclusion: The close correlation between EphrinB2 signal pathway and visceral sensitivity supports the hypothesis that EphrinB2 signal pathway can contribute to development of synaptic plasticity

in PI-IBS. Key Word(s): 1. PI-IBS; 2. EphrinB2; 3. Visceral sensitivity; Presenting Author: PATRICIASUN TE Additional Authors: EDWARDLORENZO LIM Corresponding Author: PATRICIASUN TE Affiliations: Chinese General Hospital Objective: BACKGROUND: Most colonic diverticulosis in the West are reported as left sided. However, Asian studies have proven otherwise. AIM: The aim of this study was to determine the 1.) Incidence of diverticulosis among patients undergoing colonoscopy in Chinese General Hospital; 2.) Distributional pattern of colonic diverticula; 3.) Incidence of colonic polyps with diverticular disease. Methods: 8715 patients (4370 females, 4345 males) who underwent total colonoscopy at Chinese General Medical Center from 2008 to 2012 were retrospectively analysed.

Coronary artery calcium score (CACS), which was not appraised in LTR, is considered the most sensitive method for assessing CV risk. Our aim was to evaluate a cohort of LTR 4 years after transplant regarding MS, CV risk and CV disease. PATIENTS AND METHODS:

Forty consecutive LTR outpatients, admitted between 2009 and 2010, were fol-lowed-up by 1 and 4-year period, and consecutively enrolled. The anthropometric data, liver enzymes, metabolic syndrome features, glucose and lipid profiles, and insulin resistance data were collected. Framingham risk score (FRS) was calculated in both 1 and 4-year evaluation, and CACS was assessed in the end of the follow-up period. Comparisons between 1 and 4 years were done. RESULTS: The study population comprised 62.5% males, mean age 53.8 years and body mass index (BMI) 26.9 kg/m2. Regarding the components YAP-TEAD Inhibitor 1 order of MS, 65% patients had hypertension, 55% diabetes, 60% dyslipidemia and mean waist circumference was 96.7 cm. One year after liver transplantation, 22.4% had MS and after 4 years, this AZD0530 solubility dmso percentage increased to 47.5%. Besides, 20% of the patients developed CV disease after 4 years LT. The median FRS also increased from 2% to 15.5% between the 1st and 4th year, which ranks the cardiovascular risk in 10 years, as an intermediary. Medium CACS values were 166.03, which is moderately altered. Patients with MS had higher values of CACS than others (p =0.018).

When MS components were evaluated separately, we found higher values of CACS for dyslipidemic patients when compared to non-dyslipidemic (p =0.011); and for hypertensive

than non-hypertensive patients (p=0.004). There was no difference in the values of CACS, when we assessed BMI and waist circumference. There was a statistically significant correlation between FRS, CACS and GGT 4 years after medchemexpress transplantation. Individuals who never drank or smoked had values of CACS significantly lower compared to patients who drank/smoked. We sought a correlation between smoking burden and values of CACS moderately or severely altered (> or =100) and concluded that the former was significantly higher in these patients than in those with CACS lower value (28.95 × 17.29 pack-years; p=0.0015). CONCLUSIONS: MS and CV risk significantly increased from 1 to 4 years after LT. CACS is useful in evaluating CV risk in this population, and correlated well with FRS, GGT and alcohol/tobacco consumptions. Disclosures: The following people have nothing to disclose: Livia M. Linhares, Mario R. Alva-res-da-Silva, Claudia P. Oliveira, José Tadeu Stefano, Eloisa M. Gebrim, Flair J. Carrilho, Luiz C. D’Albuquerque BACKGROUND: Diabetes is a common complication after liver transplantation (LT) that has shown to negatively impact transplant outcome. There is however scarce information on the quality of diabetes care in LT patients. AIM: To investigate the rate and quality of diabetes care in LT patients.

Its use for the follow up and management of these complications could be of great interest and should be evaluated further Key Word(s): 1. Fibroscan; 2. Liver Stiffness; 3. Portal Hypertension; 4. Cirrhosis; Presenting Author: HONG-LING FENG Corresponding Author: HONG-LING

FENG Affiliations: Tianjin Second People’s Hospital Objective: To investigate the efficacy of colon dialysis therapy with integrated traditional Chinese and Western medicine and artificial liver support system in treating patients with acute-on-chronic liver failure Methods: Fifty-four patients with acute-on-chronic liver failure were divided into two groups (trial grou[ and control group) randomly and treated with comprehensive management and artificial liver treatment. The patients in treatment group were treated with colon dialysis therapy on the base of routine treatment three times every day for four weeks. Torin 1 research buy The changes check details of symptom, liver function, PTA, serum endotoxin, TNF and

IL-βwere observed before and after the treatment. Results: The incidences of dry mouth, abdominal distention, constipation and endotoxemia in pretreated patients were 86.84%, 86.84%, 60.53% and 100%. After treatment, these symptoms were improved and the levels of bilirubin, prothrombin activity (PTA), endotoxin (ET), and tumor necrosis factor (TNF) decreased in all patients. The efficacy achieved in the treatment group was superior to that in the control group (all p < 0.05 or 0.01). Conclusion: Colon dialysis therapy with integrated traditional Chinese and Western medicine can promote defecation, decrease the levels of serum endotoxin, proinflammatory cytokines and bilirubin, shorten medchemexpress prothrombin time and improve the symptoms. Key Word(s): 1. colon dialysis; 2. artificial liver; 3. ACLF; 4. endotoxin; Presenting Author: YONGJUN ZHU Additional Authors: RUOTING MEN, MAOYAO WEN, XIAOLIN HU, XIAOJING LIU,

LI YANG Corresponding Author: XIAOJING LIU, LI YANG Affiliations: West China Hospital, SCU; Hospital of Southwest University Objective: Proliferation is a ‘multiplier’ for extracellular matrix production and contraction of activated hepatic stellate cells (HSC) in fibrotic liver. Transient receptor potential melastatin-like 7 channels (TRPM7) were implicated in survival and proliferation of various kinds of cells. The aim of this study was to investigate the effect of TRPM7 inhibitor 2-APB on survival and proliferation of HSC and the underlying mechanisms. Methods: Rat HSC were stimulated by 2-APB for 24 h and then collected for further use. Cell viability was detected by MTT test, and apoptosis was determined by AnnexinV/PI staining and TUNEL assay. Gene expressions of apoptosis related factors bcl-2 and bax, and endoplasmic reticulum (ER) stress key members CHOP, caspase-12, ATF4, ATF6, Xbp1, GRP78 and calnexin were evaluated with quantitative RT-PCR.

“
“Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary selleck screening library liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to

comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell–like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation,

we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell–like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition find more (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell–like traits and TGF-β/EMT molecules may play a pivotal role in the aggressive phenotyping Protirelin of S-HCC. (HEPATOLOGY 2012;55:1776–1786) Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. Most HCCs and CCs are derived from hepatocytes and cholangiocytes, respectively. Both hepatocytes and cholangiocytes

originate from common liver stem cells with the potential to differentiate into both types of cells.1, 2 Thus, the primary liver cancers that arise from different developmental stages of liver stem cells are thought to harbor common genomic traits between HCC and CC. The existence of combined hepatocellular-cholangiocarcinoma (CHC) also supports the phenotypic overlap between HCC and CC.3, 4 In previous histological studies, a rare variant of HCC, characterized by abundant fibrous stroma between tumor nests, was reported in the absence of any preoperative treatment.5-8 These HCCs, namely scirrhous HCC (S-HCC), comprise up to 4.6% of the total cases of HCC.6 S-HCC has been known to express several liver stem/progenitor cell (SPC) markers, such as keratins (K) 7 and K19 and epithelial cell adhesion molecule (EpCAM).7, 9 This suggests that S-HCC may harbor intermediate traits between HCC and CC, including stem-cell traits.

Patients and methods. 12 studies including 2132 cirrhotic admitted in ICU were analyzed after selection of original articles and response to a standardized questionnaire by the corresponding authors. The prognostic performance of 177 variables (including reason for admission, organ check details replacement therapy, and composite prognostic scores)were analyzed for each period according to the method

of Der Simonian and Laird (708 pooled analysis). Results. In-ICU, in-hospital, 3 and 6 month-survival were 55% (range 28-66%), 45% (27-61%), 23% (13-37%) and 20% (13-35%), respectively. In-ICU survival was better in recent studies (>yr2000) (OR=1.36,p=0.036), in centers containing a liver transplant program (OR=1.82,p<0.0001) in patients admitted for variceal bleeding (OR=1.80, p<0.0001, PPV=0.67), with MELD<13 (OR=4.31, p<0.0001, PPV=0.86), albumin>35g/L (OR=3.97, p<0.0001, PPV=0.77), INCB024360 clinical trial <2 organ failures (OR=4.81, p<0.0001, VPP=0.70). In-ICU mortality was significantly associated with

23 variables and better predicted by: a CLIF-SOFA>22 (OR=5.94, p=0.005, PPV=1); >5 organ failures (OR=10.87, p<0.0001, PPV=0.98); SOFA>19 (OR=14.46, p<0.0001, PPV=0.97), a fungemia (OR=4.61, p=0.0005,PPV=0.87), ARDS (OR=4.48,p<0.0001,PPV=0.81), refractory oli- guria (OR=9.17, p<0.0001, VPP=0.79), a MELD>35 (OR=5.43, p<0.0001,PPV=0.77), this website sepsis-induced hypotension (OR=5.75, p<0.0001, PPV=0.77), an increased SOFA at d3 (OR=4.57,p<0.0001,PPV=0.72), positive

blood cultures (OR=2.15, p=0.004, PPV=0.73), infection with GN Bacilii (OR=2.24,p<0.0001,PPV=0.70),and the use of MARS (OR=2.04,p=0.0081,PPV=0.64). The mSOFA, APACHE, alcohol consumption, direct admission in ICU, HRS, nosocomial infection or infection with GP cocci had no impact. The results were heterogeneous for the Pugh, creatinine, the use of intubation or norepinephrine. SBP was associated only with in-hospital mortality. Patients who received TIPS had better in-hospital, 3 and 6 month survival. The Pugh, MELD, SOFA, the presence of SIRS, bacterial infection or ARDS, the need for haemodi-alysis kept an impact on 3 and 6 month survival. Conclusion The prognostic performance of general ICU scores decreases over the long-term, unlike the Pugh and MELD scores. Some events can be considered alone and have an excellent predictive value for short-term and long-term prognosis, as well as composite scores. Disclosures: Constantine J.

Co-occurrence of these disorders appears to potentiate greater liver injury than either alone; the underlying mechanisms are poorly understood. In this study we have investigated the regulation of hepatic microRNA (miRNA) expression in a mouse model of iron

and fat co-mediated liver injury. Methods: Hfe-knockout Barasertib concentration mice were fed either control or high calorie diets. Mice were sacrificed after 20 weeks of treatment. Small RNA was extracted from liver tissue and profiled using next-generation miRNA-sequencing and differentially expressed miRNAs identified. mRNA-seq was available from these same mice, and was utilized to perform combination analysis (which identifies which differentially expressed mRNAs are potential targets of differentially expressed miRNAs) and correlation analysis (which compares the level of expression of all identified miRNAs with the levels of expression of all of their potential target mRNAs) to identify miRNA-mRNA pairs of interest. Results: 39 differentially

expressed miRNAs were identified. Of these 10 have published links to relevant Lonafarnib cost pathologies including miRNAs-190 and -199 which have

both been linked to hepatic fibrosis, selleckchem miRNA-223 which has been linked to hepatocellular carcinoma and obesity-associated adipose tissue inflammation, and miRNA-103 which has been linked to glucose homeostasis and insulin sensitivity. Combination analysis identified 49 miRNA-mRNA pairs in which both the miRNA and its target mRNA were differentially expressed including miRNA-199a-3p for which nine of its target mRNAs are differentially expressed. Correlation analysis identified 424 miRNA-mRNA pairs with a Pearson correlation coefficient > ±0.8 and p < 0.05. Conclusions: This study demonstrates a dysregulation in hepatic miRNA expression in the setting of combined iron overload and steatosis. Ten miRNAs are identified which are linked to relevant pathologies supporting the validity of this study, and a further 29 miRNAs which have not previously been liked to either hepatic or lipid pathology where also identified. Further, the integration of mRNA data has identified potential mechanisms of action for several of the differentially expressed miRNAs.

23 This new division of acid reflux exposure underscores the important effect of sleep physiology on gastroesophageal reflux.

As was previously mentioned, sleep deprivation per se can also affect GERD. In a recent study by Schey et al., the authors exposed 10 healthy subjects and 10 GERD patients to sleep deprivation (<3 h) and normal sleep (≥7 h).7 The authors were able to demonstrate that after sleep deprivation, subjects were significantly more sensitive to esophageal acid perfusion than after a good night's sleep. This study clearly showed that sleep deprivation is likely an important central factor that can exacerbate GERD symptoms by enhancing perception of intra-esophageal stimuli. The two pivotal underlying mechanisms for reduced quality of sleep and sleep disturbances in patients with Crizotinib GERD are heartburn that awakens patients from sleep during the night and short, amnestic arousals that lead to sleep deprivation. Between 47% and 57% of the GERD patients reported having heartburn that awakens them from sleep during the night.1,9,10 In the general population, approximately a quarter of the subjects reported Small molecule library heartburn that awakened them from sleep. Whilst night-time heartburn

has been perceived by many investigators as the most important underlying mechanism for sleep deprivation in GERD patients, recent studies have shown that acid reflux events are more commonly encountered and often associated with short, amnestic arousals.24 In one study, 90% of acid reflux events were associated with short arousals during sleep.24 These arousals usually last 30 s and tend to occur during an acid reflux event. Most of the arousals occurred during stage 2 of sleep and rarely during the rapid eye movement (REM) period. While early studies

in normal subjects suggested that reflux associated with transient lower esophageal sphincter relaxations can occur only during periods of arousals from sleep, further studies in GERD patients produced conflicting results.25 When assessing the risks for injury to the esophagus in patients who awake with heartburn versus those with short arousals in response to an acid reflux event, the former appears to have an important defensive effect. Patients who awake with heartburn can initiate swallows and thus primary peristalsis, deliver alkalinized saliva to the distal portion Fossariinae of the esophagus and consume anti-reflux treatment with an acute ameliorating effect [e.g. antacids, Gaviscon, (GlaxoSmithKlein, Middlesex, UK) over-the-counter H2RA]. In contrast, patients who respond to a reflux agent with only short arousal will be unable to activate these vital esophageal defense mechanisms leading to prolonged esophageal acid contact time and possibly esophageal mucosal injury (Table 1). Surprisingly, there is no difference in relation to the effect on sleep quality between patients with non-erosive reflux disease and those with erosive esophagitis.26 Dickman et al.