Objective: Linaclotide is a novel guanylate cyclase-C (GC-C) agonist approved for treatment in adult patients with irritable bowel syndrome with constipation (IBS-C). Linaclotide effects on bowel movements are mediated by intracellular

cGMP produced upon activation of GC-C. It is hypothesized that the effects of linaclotide on abdominal pain are mediated by extracellular cGMP, which has been shown to decrease the activity of pain-sensing nerves. This study investigated the effects of linaclotide on cGMP secretion from mouse Cyclopamine colonic epithelium, following linaclotide stimulation. Methods: An ex vivo Ussing chamber assay was used to measure cGMP secretion from the mouse colonic mucosa in response to linaclotide treatment. Linaclotide-induced ion transport and epithelial barrier function were monitored by measuring short-circuit current (Isc) and trans-epithelial electrical resistance (TEER). Results: Stimulation

with linaclotide (1 μM) elicited a robust Isc across mouse colonic epithelium. Isc reached a maximum within ten minutes following stimulation with linaclotide and remained steady throughout the duration of the study (60 minutes). Treatment of colonic mucosa with linaclotide induced release of cGMP from the basolateral as well as the apical side of the epithelium. The time course of cGMP accumulation in the basolateral bath of the Ussing chamber was linear with an estimated cGMP secretion rate equal to AG-014699 clinical trial 23 fmol/min×cm2. The TEER of the colonic mucosa did not change over the course of the study indicating that the cGMP measured in the basolateral

compartment after linaclotide stimulation is not diffusing from the apical compartment. Conclusion: These findings demonstrate that linaclotide-stimulated mouse colonic epithelium secretes cGMP from both the apical and basolateral sides and that cGMP is present in the submucosal space to inhibit colonic nociceptors. Key Word(s): 1. cGMP; 2. GI pain; 3. guanylate cyclase-C; 4. linaclotide; Presenting Author: GERHARD HANNIG Additional Authors: JOEL CASTRO, ANDREA HARRINGTON, PEI GE, HONG JIN, MARCOM. KESSLER, L. ASHLEY BLACKSHAW, CAROLINEB. KURTZ, MARKG. CURRIE, STUARTM. Protein kinase N1 BRIERLEY, INMACULADA SILOS-SANTIAGO Corresponding Author: GERHARD HANNIG Affiliations: Ironwood Pharmaceuticals, Inc.; University of Adelaide; Queen Mary University of London Objective: The 14-amino acid peptide linaclotide is a guanylate cyclase-C (GC-C) agonist related to the hormones guanylin and uroguanylin. In animal models, linaclotide reduced colonic hypersensitivity in a GC-C dependent manner, a mechanism not previously linked to the GC-C/cGMP pathway. It has been hypothesized that the analgesic effects of linaclotide are mediated by extracellular cGMP, following GC-C activation.

Mild inflammation has been documented in human HH studies during the development of fibrosis and cirrhosis.38 Deugnier et al. reported inflammatory infiltrates in approximately 50% of liver biopsies from HH patients.39 Inflammation was predominantly present in portal and periportal regions and correlated with histological iron scores, sideronecrotic changes in hepatocytes, and hepatic fibrosis. Another study showed that approximately 25% of liver biopsies from untreated HH patients displayed moderate inflammatory infiltration.40 Bridle et al. also reported that 60% of liver biopsies from HH patients showed mild inflammation consisting of scattered inflammatory foci. Furthermore, patients with

PD98059 research buy hepatic inflammation had a higher incidence of hepatic fibrosis.41 Iron-loaded and apoptotic/necrotic hepatocytes are purported to induce the activation of HSCs by various signaling mechanisms, resulting in enhanced production of proinflammatory and -fibrogenic cytokines as well as the recruitment of inflammatory cells.8 Our study provides further support for the direct hepatotoxic effects of iron overload, which results from the disruption of Hfe and Tfr2, manifesting as inflammation and increased collagen

deposition, suggesting the activation of HSCs. Iron plays ABT-263 nmr an important part in the progression of hepatic injury, and it does this through its ability to catalyze the formation of highly reactive, damaging ROS. ROS induce tissue injury by promoting LPO as well as protein and DNA modification, leading, ultimately, to apoptosis and necrosis.

Further investigation into the molecular mechanisms of iron toxicity and how it causes liver injury will provide a better understanding of the role iron plays in the progression of liver disease. The Hfe−/−×Tfr2mut mouse represents a model of the genetic iron overload disorder, HH, that mimics Carbachol both iron overload and consequent liver injury observed in humans with HH. Additional Supporting Information may be found in the online version of this article. “
“At what age and risk level may warrant hepatocellular-carcinoma (HCC) screening remains to be defined. To develop risk score for stratifying average-risk population for mass HCC screening, we conducted a pooled analysis using data from three cohorts involving 12377 Taiwanese adults aged 20-80 years. During 191240.3 person-years of follow-up, 387 HCCs occurred. We derived risk scores from Cox model in two-thirds of the participants, and used another one-third for model validation. Besides assessing discrimination and calibration, we performed decision curve analysis to translate findings into public health policy. A risk score according to age, sex, alanine aminotransferase, prior chronic liver disease, family history of HCC, and cumulative smoking had good discriminatory accuracy in both model derivation and validation sets (c-statistics for 3-, 5-, and 10-year risk prediction: 0.76-0.83).

We devised 10 mm sized ring type magnet (outdiameter:10 mm, indiameter:4 mm, thickness:3 mm, maximal magnetic force:2660 G) which was coated with silicon, and we tied loop using 3-0 nylon. We inserted the marking magnet near lesion with biopsy forcep, and then clipped magnet on target through loop of magnet. A magnetic marking clip was applied on the distal find more side of lesion during preoperative colonoscopy. During surgery, another magnetic body hanged with long thread which was inserted through laparoscopic trocar, was used to find out the lesion that was marked by magnetic clipping. We analyzed detection rate, detection time, resection margin length from lesion and complication. Results: 7 of 12 patients’ tumor

locations were on the rectum, 5 were on sigmoid colon. Tumor size ranged from 10 to 18 mm. Magnetic marking clips were successfully detected in all 12 patients. selleck products The time required for detection ranged from 10 to 35 sec. The resection margin from lesion ranged from 40 to 50 mm. None of our patients experienced complication s from this marking technique. Conclusion: Magnetic marking technique was simple and convenient for surgeon,

and showed good result for accuracy of tumor localization without complication. Therefore, the magnetic marking clip method may be useful for colorectal tumor detection during laparoscopic surgery. And we expect that correct and simple method results in minimizing extent of colon resection. Key Word(s): 1. endoclip; 2. magnet; 3. laparoscopic surgery; Presenting Author: GERALD FILEU ROLLUQUI, MDVILLANUEVA ROLLUQUI Additional Authors: SANDEEP SHRESTHA, MDCHANDRA SHRESTHA, HIGINIO MAPPALA, MD, FPCP, FPSG, FPSDETIU MAPPALA Corresponding Author: SANDEEP SHRESTHA, G protein-coupled receptor kinase MDCHANDRA SHRESTHA, HIGINIO MAPPALA, MD, FPCP, FPSG, FPSDETIU MAPPALA Affiliations: Philippine Society of Gastroenterology Objective: Several

studies within the last decade have shown a progressive decline in eradication rates for Helicobacter Pylori (HP), particularly in our country, which may be due to the increasing antimicrobial drug resistance to clarithromycin (12%) and metronidazole (46%). Amoxicillin resistance remains to be very low (<1%). Thus, this study was done to evaluate the cure rates of triple regimens containing either clarithromycin or levofloxacin in our local patient population. This is to further determine whether the combination of Omeprazole + Amoxicillin + Clarithromycin (group 1) is as effective as the standard treatment regimen of Omeprazole + Amoxicillin + Levofloxacin (Group 2) in patients with HP infection and may be considered as a first-line HP eradication regimen. Methods: The study involved a systematic search of randomized control trials using either Clarithromycin or Levofloxacin as part of the triple regimen for the eradication of H. Pylori on local subjects. A comparative meta-analysis was done.

However whether these cells also interact with hepatic stellate cells (HSCs) and contribute to liver fibrosis remains unknown. In the current study, we evaluated the effect of EPC-secreted angiogenic factors on the functions of HSCs under in vitro conditions and also the effect of EPC transplantation on liver fibrosis in bile duct ligated (BDL) cirrhotic rat models in vivo. Methodology: For the in vitro studies, HSCs were isolated from normal rats after liver perfusion, cultured and characterized by alpha-SMA staining. Circulating human EPCs were isolated from blood and characterized by CD34 and

vegfr2 staining. HSCs were then co-cultured with conditioned learn more media (CM) obtained from EPCs. The

proliferation of HSCs was analyzed by MTT assay and the level of an important angiogenic factor secreted by HSCs, vascular endothelial growth factor (VEGF) was evaluated by ELISA in presence of EPC-CM. For in vivo studies, rat models (n= 1 0) were SCH772984 prepared by identifying and ligating the bile duct. EPCs isolated from human blood, were cultured ex vivo and transplanted in treated group of BDL rats (n=5) via the tail vein, three weeks after bile duct ligation. The untreated group of rats (n= 5) received only saline. Rats were sacrificed one week after the transplantation of cells. Fibrosis was evaluated by histopathology of the liver tissues from untreated and EPC-treated rats. The expression of an important fibrogenic marker, alpha-SMA was analyzed in EPC-treated and untreated animals by western blotting. Results: HSCs co-cultured with EPC-CM showed significantly increased proliferation in comparison to that observed in HSCs alone (P< 0.05).

However, VEGF levels in HSCs didn’t show a significant change in presence of EPC-CM. The in vivo histopathology studies revealed an increase of fibrosis from stage 2 to stage 3 (bridging fibrosis) in EPC-treated rats as compared to the untreated rats. Also, the expression of the fibrosis marker, alpha-SMA present on activated HSCs was about 1.2 fold higher in EPC-treated rats as compared to the untreated rats (p<0.05). Conclusion: The study suggests that EPCs may contribute to liver fibrosis by enhancing the proliferation of HSCs. Further HAS1 studies are underway to evaluate the association of EPC-mediated angiogenesis with liver fibrosis. Disclosures: The following people have nothing to disclose: Skand Gupt, Mohsin Hasan, Neha Sharma, Vaibhav Dixit, Deepti Vyas, Dinesh M. Tripathi, Savneet Kaur, Nirupma Trehanpati, Shiv K. Sarin Background and aims: 1,25(OH)2D3, the active form of vitamin D has anti-proliferative and anti-fibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo.

[9, 16] Many approaches have not been evaluated in placebo-controlled studies, and the relative usefulness of the various treatment options remains to be established.[9] Dietary measures entail adjustment to meal composition and frequency.[1, Opaganib order 9] Eating small

meals is recommended as patients often have early satiety, that is, feeling full when eating a normal size meal, In addition, larger meals may alter gastric emptying times.[17, 18] Consuming mainly liquids such as soups and stews can be useful as gastric emptying of liquids is often preserved in patients with gastroparesis.[1] Avoidance of fats and indigestible fibers is recommended because they delay gastric emptying.[1, 9] When small meals are used in the gastroparesis diet, more frequent meals, ∼4-5 meals per day, are often needed to maintain caloric intake. Medications with gastric prokinetic properties, which

are the mainstay of treatment for gastroparesis, include metoclopramide, erythromycin, and domperidone.[16, 19] Metoclopramide is the only medication click here licensed in the United States for the treatment of gastroparesis.[1] Anti-emetics include the phenothiazine derivatives (eg, prochlorperazine), the serotonin-3 receptor antagonists (eg, ondansetron), the dopamine receptor antagonists (eg, metoclopramide), the histamine receptor antagonists (eg, diphenhydramine), and benzodiazepines (eg, lorazepam).[1, 19] Surgical and endoscopic approaches are considered in patients in whom drug therapy is ineffective and who cannot meet their nutritional requirements.[1]

Endoscopic treatment entails injection of botulinum Pyruvate dehydrogenase toxin (Botox; Allergan, Inc., Irvine, CA, USA) into the pyloric sphincter. Botox injections reduce pyloric muscle spasms that are thought to contribute to delayed gastric emptying. Although this may help in some patients, controlled clinical trials have not shown efficacy of this treatment. Surgical treatments include placement of jejunostomy tubes and gastric electrical stimulation.[1] These options are typically considered only in patients with severe, refractory gastroparesis. Evidence suggests that migraine attacks are associated with delayed gastric emptying.[20] Nausea, a symptom of gastric stasis, is also a defining feature of migraine headaches. Episodic migraine, according to International Classification of Headache Disorders, 2nd edition criteria, is manifested by headache that is not attributed to another disorder and that lasts 4 to 72 hours (untreated or unsuccessfully treated) with at least 2 of the characteristics of (1) unilateral location; (2) pulsating quality; (3) moderate or severe pain intensity; and (4) aggravation by or causing avoidance of routine physical activity with (1) nausea and/or vomiting and/or (2) photophobia and phonophobia.[21] The nature of the relationship between gastric stasis and migraine-associated nausea is unknown.

1% vs 68.2%, Satisfaction with Side Effects 48.6% vs 67.3%). The percentage of patients who were confident or very confident in treating repeated migraine attacks also increased (baseline: 41.0%, 90% confidence interval

[CI] 35.4, 46.9 vs end of treatment: this website 66.5%, 90% CI 58.9, 70.1). The efficacy results (pain relief, pain-free response, sustained 24-hour pain relief and pain-free response) were consistent with those previously observed with needle-based sumatriptan. Conclusion.— Patients currently treated with triptans and less than very satisfied with their acute migraine therapy experienced a statistically significant and clinically relevant increase in satisfaction with therapy and enhanced confidence in treatment after use of Sumavel DosePro for up to 4 migraine attacks. “
“Objective.— To prospectively evaluate the diagnosis of menstrual migraine (MM) by comparing 2 diagnostic systems. Methods.— Female migraineurs self-reporting a substantial relationship between migraine and

menses were evaluated with 3 consecutive months of daily headache recording diaries. A relationship between menses Dabrafenib research buy and migraine was evaluated using International Classification of Headache Disorders (ICHD-II) criteria and a probability model called Probability MM. Results.— Three months of pretreatment prospective diaries were completed by 126 women. ICHD-II menstrually related migraine was diagnosed in 73.8% with pure MM in 7.1%. ICHD-II and Probability diagnoses agreed for all cases of ICHD-II non-MM and pure MM, with disagreement among women diagnosed with ICHD-II menstrually related migraine, only half of whom were identified as having a relationship

with menses greater than chance alone using the Probability model. Interestingly, 20% of those women self-reporting a substantial relationship between migraine and menses were not prospectively diagnosed with MM using either diagnostic system. Differences in menstrual vs nonmenstrual headaches were greater when using the Probability Chlormezanone model. Conclusions.— Prospective headache diaries are needed to diagnose MM. A probability-based method, which considers the chance occurrence of headaches during the menstrual cycle, identifies fewer women as having menstrually related migraine compared with the diary-based methods recommended by the current ICHD-II candidate criteria. (Headache 2010;50:539-550) “
“Background.— Primary exertional headache (PEH) is a long-known phenomenon. Divergent prevalences of between 0.2 and 12.3% are reported among the general population. The aim of this study was to establish the prevalence among an athletic population. Method.— A link to an online questionnaire was sent to all participants of a tough cycling event held in The Netherlands. Results.— Four thousand participants filled out the questionnaire. One thousand eight hundred and ten (45%) stated that they had suffered, at least once in their lives, from exercise-related headaches (EHs).

The underlying pathological process leading to these changes most probably includes demyelination. “
“The purpose of this study was to identify imaging markers and clinical risk factors that significantly predict the evolution of computed tomography (CT) imaging features of carotid artery atherosclerotic disease over a 1-year period. Our prospective study involved 120 consecutive patients undergoing emergent CT evaluation for symptoms of acute stroke. These patients were asked to consent to a follow-up CT exam in 1 year. To evaluate for atherosclerotic plaque, both at baseline and on

follow-up, we employed a comprehensive computed tomography angiography (CTA) protocol that captured the carotid, vertebral, aortic, and coronary arteries. To further evaluate carotid artery plaque components, we used an automated classifier computer algorithm that distinguishes among the histological components of the carotid artery wall (lipids, calcium, PI3K inhibitor fibrous tissue) based on appropriate thresholds of CT density. Baseline values of carotid imaging features and clinical variables were assessed for their ability to significantly predict changes in these imaging features over 1 year. Of these 120 consecutive patients, 17 received both a baseline and a follow-up CTA

exam. Wall volume increased more when the largest lipid cluster was located close to the lumen (coefficient buy Palbociclib −7.61, −13.83 to −1.40, P = .016). The volume of lipid increased with age (coefficient .36, .21 to .50, P = .000), in smokers (coefficient 8.89, 6.82 to 10.95, P = .000) and when fewer lipid clusters were present at baseline (coefficient −0.11, −0.17 to −.04, P = .001). The volume of calcium increased with greater volume of lipid at baseline (coefficient .35, .02 to .68, P = .035) and in patients on statins (coefficient 4.79, 1.73 to 7.86, P = .002). There are a number of imaging markers and risk factors that significantly predict the C59 mw evolution of CT imaging features of carotid artery atherosclerotic

disease over a 1-year period. Stroke is the third leading cause of death and the leading cause of disability in the United States. It is important to identify those patients who are at risk for future stroke or transient ischemic attack (TIA) in order to prevent such death and disability. A major cause of ischemic stroke is embolism from carotid artery atherosclerotic plaque. Therefore, identifying carotid plaque that is more likely to embolize, or “vulnerable plaque,” is one approach to identify patients at risk for future stroke. The concept of a “vulnerable plaque” emerged in the literature a number of years ago, first with regards to coronary artery disease.[1] Vulnerable plaques are believed to be at greater risk of rupture, leading to thrombosis or embolic phenomena. The vulnerability of coronary plaques was ascribed to thin fibrous caps and lipid-rich cores of individual plaques, rather than to the severity of the resulting stenosis.

Dr De Paepe acknowledges that this work was supported by a grant nr.# G.0171.05N from the Fund for Scientific Research, Flanders to ADP and a Methusalem grant # BOF08/01M01108 from the Flemish Government and the Ghent University to ADP. FM is a postdoctoral research fellow from the Fund for Scientific Research, Flanders. Dr Shovlin acknowledges funding support from the British Heart Foundation, donations from British HHT patients and the NIHR Biomedical Research Centre Funding Scheme. “
“Summary.  An antibody response to therapeutically administered factor VIII (FVIII) can occur in up to 30% of patients with haemophilia,

resulting in the production of inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction (ITI) therapy can be used to eradicate inhibitors U0126 chemical structure in these this website patients, allowing them to continue with factor replacement therapy. Patients with inhibitors (prior to initiation

of ITI, while on ITI or those who fail ITI) experience more difficulty in treating bleeds than those patients who do not develop inhibitors. Increasingly, prophylaxis with bypassing therapy is being employed in patients who develop inhibitors. Two bypassing agents, a plasma-derived activated prothrombin complex concentrate [aPCC (FEIBA®; Baxter AG, Vienna, Austria)] and NovoSeven® [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are potentially available for prophylaxis in patients with haemophilia who have developed inhibitors. Results from recent retrospective studies demonstrate the efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of bleeding episodes in patients with haemophilia and inhibitors. In this article, we highlight of a number of ongoing studies that aim to identify patients who should be placed on prophylaxis with bypassing agents. The development of neutralizing antibodies (inhibitors) to replacement factors [factor VIII (FVIII) or factor IX (FIX)] [1] can be devastating

for patients with haemophilia [2]. The burden of orthopaedic complications and the impact on quality of life (QoL) are more severe in haemophilic patients who have developed inhibitors than in those without inhibitors [3]. Incidence estimates suggest that inhibitors develop in 20–30% of patients with haemophilia A and in 5% of patients with haemophilia B [4], and although these patients do not experience more bleeding episodes than those without inhibitors, haemostasis is more difficult to control when bleeding does occur [2]. Inhibitors may be transient or resolve with immune tolerance induction (ITI) therapy [5], the initiation of which aims to eradicate inhibitors with the purpose of permitting a return to prophylaxis with FVIII or FIX replacement. Since the introduction of ITI, the success rate achieved with various regimens has typically been between 60% and 80% [6].

Dr De Paepe acknowledges that this work was supported by a grant nr.# G.0171.05N from the Fund for Scientific Research, Flanders to ADP and a Methusalem grant # BOF08/01M01108 from the Flemish Government and the Ghent University to ADP. FM is a postdoctoral research fellow from the Fund for Scientific Research, Flanders. Dr Shovlin acknowledges funding support from the British Heart Foundation, donations from British HHT patients and the NIHR Biomedical Research Centre Funding Scheme. “
“Summary.  An antibody response to therapeutically administered factor VIII (FVIII) can occur in up to 30% of patients with haemophilia,

resulting in the production of inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction (ITI) therapy can be used to eradicate inhibitors DAPT mw in these Carfilzomib patients, allowing them to continue with factor replacement therapy. Patients with inhibitors (prior to initiation

of ITI, while on ITI or those who fail ITI) experience more difficulty in treating bleeds than those patients who do not develop inhibitors. Increasingly, prophylaxis with bypassing therapy is being employed in patients who develop inhibitors. Two bypassing agents, a plasma-derived activated prothrombin complex concentrate [aPCC (FEIBA®; Baxter AG, Vienna, Austria)] and NovoSeven® [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are potentially available for prophylaxis in patients with haemophilia who have developed inhibitors. Results from recent retrospective studies demonstrate the efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of bleeding episodes in patients with haemophilia and inhibitors. In this article, we highlight Methamphetamine a number of ongoing studies that aim to identify patients who should be placed on prophylaxis with bypassing agents. The development of neutralizing antibodies (inhibitors) to replacement factors [factor VIII (FVIII) or factor IX (FIX)] [1] can be devastating

for patients with haemophilia [2]. The burden of orthopaedic complications and the impact on quality of life (QoL) are more severe in haemophilic patients who have developed inhibitors than in those without inhibitors [3]. Incidence estimates suggest that inhibitors develop in 20–30% of patients with haemophilia A and in 5% of patients with haemophilia B [4], and although these patients do not experience more bleeding episodes than those without inhibitors, haemostasis is more difficult to control when bleeding does occur [2]. Inhibitors may be transient or resolve with immune tolerance induction (ITI) therapy [5], the initiation of which aims to eradicate inhibitors with the purpose of permitting a return to prophylaxis with FVIII or FIX replacement. Since the introduction of ITI, the success rate achieved with various regimens has typically been between 60% and 80% [6].

We assumed treatment of 80 %of F3-4 and 50 %of F2 during the 1st year, 100 %of F3-4 and 80 %of F2 during the 2nd year, and 100 %of F2-4 during the 3rd year. An alternative scenario considered that the cost of treatment of 24 weeks is equal to 12 weeks. Based on these two scenarios, the total costs of treating

HCV would be 2.43.9 billion €: 1.5-2.5 the 1st year (20,000 treated patients), 0.7-1.1 the 2nd year (9,300 treated patients) and 0.2-0.3 the 3rd year (2,500 treated patients) (Table). When we decreased sofosbuvir and ledipasvir costs in sensitivity analysis, total costs decreased to 1.2-2.4 billion €. In France, even if we consider that no F0-1 patients are treated and no additional HCV patients are screened, based on Selinexor cost sofosbuvir cost in early access program, IFN-free DAA-based regimens would add 2 to 4 billion € to an already overburdened medical care system. Fair prices for these drugs are needed. Disclosures: Sylvie Deuffic-Burban – Consulting:

MSD, GSK, Gilead, Abbott; Grant/Research Support: Roche, Janssen Pharmaceuticals, Schering-Plough; Speaking and Teaching: Cellestis Stanislas Pol – Board Membership: Sanofi, Bristol-Myers-Squibb, Boehringer Ingel-heim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Tyrosine Kinase Inhibitor Library Grant/Research Support: Glaxo Smith Kline, Gilead, Roche, MSD; Speaking and Teaching: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis Francoise Roudot-Thoraval – Advisory Committees or Review Panels: Roche, Roche; Consulting: LFB; Speaking and Teaching: Gilead, Gilead, Roche, Janssen, BMS Yazdan

Yazdanpanah – Board Membership: BMS, Gilead, Abott, ViiV healthcare, MSD, Tibotec The following people have nothing to disclose: Dorothee Obach, Valerie Can-va-Delcambre, Daniel Dhumeaux Purpose: LDV/SOF has shown excellent efficacy in CHC, including difficult-to-treat patients Fossariinae with liver cirrhosis. A decision-analytic model evaluated the health outcomes of LDV/ SOF compared with current recommended options in cir-rhotic patients across GT 1-4. Methods:The analysis modeled cohorts of 10,000 cirrhotic GT 1-4 (treatment-na’fve (TN) or treatment-experienced (TE)) patients with an average age of 52 and varying level of fibrosis from a US third-party payer perspective for a lifetime horizon. In GT1 patients, LDV/SOF for 12 weeks was compared with SOF+pegylated interferon alfa and ribavirin (PR) for 12 weeks, simeprevir (SMV)+ PR for 12 per prescribing information), and no treatment (NT). In GT2 patients, SOF+R for 12 weeks was compared with PR for 24 weeks and NT. In GT3 patients, SOF+R for 24 weeks was compared with PR for 24 weeks and NT. In GT4 patients, SOF+PR for 12 weeks was compared with PR for 48 weeks and NT.