Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead

Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris Maria Buti – Advisory Committees or Review Panels: Gilead,

Janssen, Vertex, MSD; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead, Janssen, Vertex, Novartis The following people have nothing to disclose: Iskren A. Kotzev Introduction: In patients with chronic hepatitis B (CHB) who failed on prior nucleos(t)ide (NUC) therapy, beta-catenin assay rescue therapy should involve an effective antiviral regimen that is active against any existing drug-resistant hepatitis B virus (HBV) variants. Combination therapy with entecavir (ETV) and tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single regimen suitable for all patients who failed on other NUC regimens. Here we present Week 96 results of the ENTEBE study assessing ETV+TDF for patients with prior failure on NUC therapy. Methods: In this single-arm, open-label, multicenter study, CHB patients with prior non-response, partial response, or virologic breakthrough on NUC therapy were treated with ETV (1 mg) plus TDF (300 mg) for 96 weeks. The primary endpoint was the proportion of patients with HBV DNA <50 IU/mL (Roche

COBAS TaqMan-HPS Assay) at Week 48 (non-completer=-failure). Secondary endpoints included proportions of patients

with antiviral responses at https://www.selleckchem.com/products/Deforolimus.html Week 96, safety, and resistance to ETV or adefovir (ADV). Results: Overall, 92 patients were treated; 6 patients discontinued prior to Week 96. At baseline, 65% of patients were HBeAg(+), median HBV DNA was 3.7 log10 IU/mL. Prior NUC treatment included monotherapy with ETV (53%), lamivudine (LVD; 22%), TDF (12%), (ADV; 4%), or telbivudine (LdT; 2%), or combinations of these agents (7%); 58% of patients had evidence of single- or multidrug resistance mutations (LVD: 52%, ETV: 26%; ADV: 7%). At Week 48, 76% (70/92) of patients achieved C-X-C chemokine receptor type 7 (CXCR-7) the primary endpoint (HBV DNA <50 IU/mL). By Week 96, 85% (78/92) of patients had HBV DNA <50 IU/mL, including 80% (16/20) with prior failure on LVD, 100% (4/4) on ADV, 88% (42/48) on ETV, 82% (9/11) on TDF, 100% (2/2) on LdT, and 83% (5/6) on combination therapy. No treatment-emergent resistance to ETV or ADV was observed. Six patients had on-treatment serious adverse events, none of which were considered related to study treatment. One patient died from hepatocellular carcinoma. Conclusions: In patients who failed prior NUC therapy, 96 weeks of ETV+TDF combination therapy was well tolerated and achieved virologic suppression in the majority (85%) of patients, irrespective of the type of prior NUC, with no new resistance development. All data shown as % (n/N). *Primary endpoint.

The polymorphism is more common in those of Southern European anc

The polymorphism is more common in those of Southern European ancestry.15 It is not associated with higher frequency of obesity or insulin resistance, but among the overweight it correlates closely with central obesity (waist circumference) and hepatic steatosis (mass resonance spectrometry).13 In Dallas, TX, rs738409G accounts for virtually all the ethnic differences in NAFLD frequency, from ∼40% in Hispanics, through ∼30% in Europeans, to ∼20% for African Americans.13 The PNPLA3 polymorphism NSC 683864 also correlates with raised serum alanine aminotransferase,15–17 indicating predilection to liver injury in subjects with NAFLD,

and it has now been linked to higher rates of NASH,18 and fibrosis

with NAFLD and alcoholic liver disease.18, 19 One might anticipate that knowing how PNPLA3 mutation is related to hepatic lipid distribution and liver injury would give profound insights into the pathogenesis of NASH. Unfortunately, information about the location (adipose or liver) and regulated roles of PNPLA3 in TG synthesis and lipolysis remains fragmentary and ambiguous.7, 15, 20 Although predominantly expressed in adipose, it is also present in liver, more so in humans than mice.20 PNPLA3 was discovered in the search for more complete understanding FK506 supplier of TG turnover. Earlier attention had focused on hormone-suppressible lipase which catalyzes hydrolysis of diacylglycerol, the second step in TG lipolysis, and mono-acylglyceride lipase, which with its coregulator, comparative gene identification-58, catalyzes the third step.7 The first step is catalyzed by acyltriglyceride lipase (ATGL) (adiponutrin 2).7 The adiponutrins seem to play cooperative roles in both lipolysis and its opposite

process of transacylation during TG synthesis.7, 15, 20 PNPLA3 expression is suppressed by fasting and induced by a carbohydrate-rich diet; it may therefore be involved with TG synthesis and storage during times of energy excess. Its strong regulation below by insulin (via SREBP1) accords with that function.15, 20 In the early stages of NAFLD pathogenesis, when partial IR activates SREBP1,1 PNPLA3, acting as a transacylation pathway in lipogenesis, could play a role in expanding adipose TG stores, but it is unclear whether this differs between SAT and VAT, or whether defective PNPLA3 would liberate more FFA to be taken up by the liver (Fig. 1). Conversely, if the main function of PNPLA3 is to regulate lipolysis, its inactivity would favor TG accumulation, which is desirable in adipose, but potentially increases TG storage in liver.

A number of agents in other classes are in human trials as well

A number of agents in other classes are in human trials as well. Polymerase inhibitors have somewhat lower efficacy than protease inhibitors,

but appear to have a higher intrinsic barrier to emergence of drug resistance [28]. Cyclophilin inhibitors target host proteins that the virus utilizes and appear quite potent as well with a good resistance profile, but need better characterization in terms of side-effect profiles [29]. NS5a inhibitors Metformin datasheet have also shown promising results in early trials. The opportunity to cure more patients with chronic HCV infection is now a reality, as multiple new agents become available. The next decade will see a rapid evolution of treatment modalities that will provide greater efficacy, less toxicity and shorter treatment duration. This will usher in the beginning of the end for chronic HCV infection. Human parvovirus B19 (B19) circulates worldwide. In temperate climates, epidemic manifestations occur more commonly in late winter, spring or early summer. B19 infection is commonly associated with rash-like illness in children [30]. B19 seroprevalence increases with age so that by the time one reaches adulthood, 50% of individuals have circulating B19-specific IgG. B19 infects, selleckchem replicates in and destroys the precursor cells that are responsible for

producing mature red blood cells. In an infected individual, destroying the source of mature red blood Ergoloid cells will result in dramatically lower haematocrit levels and a temporary anaemic state [31,32]. For those individuals who have disorders that shorten their red cell half-life, B19 infection worsens the presentation producing a more severe transient aplastic crisis. Symptoms in a B19 infected individual will vary considerably from one person to the next. An individual

can be infected and yet be completely asymptomatic, or have a mild flu-like illness, or a life-threatening illness. Despite the infected individual’s presentation, the viral load present within their bloodstream can be extremely high, at ∼1012 genome equivalents mL−1 (geq mL−1). This poses the risk that virus can be transmitted by transfusion of blood components obtained from asymptomatic viremic donors [33,34]. The incidence of B19 in the blood of healthy donors ranges from 1 in 20 000 to 1 in 50 000 donors [34,35]. The risk of transmission is greater when the blood components are made from pooled units compared with those made from single units. This fact places those individuals requiring repeated doses of any of these blood products at risk of becoming infected with B19 over time, including individuals living with haemophilia, who require life-long administration of clotting factor concentrate [34,36]. B19 DNA has also been detected in numerous batches of albumin, factor VIII, factor IX, clotting factor concentrates and immunoglobulin [37,38].

, 2007) Additionally, avoidance of an encroaching competitor/pre

, 2007). Additionally, avoidance of an encroaching competitor/predator (the coyote) has resulted in increased road mortality in red foxes because they are utilizing habitat that brings them closer to human habitation (Gosselink et al., 2007). Waves of disease have also resulted in significant mortality in carnivores. In dense urban populations, where individuals live in closer proximity to each other, it is intuitive that the likelihood of an infectious disease spreading may be increased (but see also White, Harris & Smith, 1995, who predicted Cobimetinib cell line that heterogeneity of urban habitats meant lower frequency of contact between rabies infected and uninfected British foxes than in rural

populations of a similar density). We summarized 29 studies that included cause of death statistics

for red fox, coyote, badgers, Doxorubicin price bobcats and raccoon to investigate whether the causes of death differed between urban and rural areas (Fig. 2). We identified the absolute numbers of animals where cause of death was identified as due to motor vehicles (‘cars’ or ‘road-kill’), hunting/euthanasia, toxicity, predation/aggression, disease, starvation/emaciation and unknown/other. Road accident has been listed as a major cause of mortality in carnivores, killing a large proportion of badgers (57%), red foxes (40%), coyotes (31%), bobcats (38%) and skunks (30%), with little difference evident between urban and rural habitats where these data are available (Fig. 2). Road death is likely to be biased towards individuals that disperse further, for example, males and juveniles (Baker et al., 2007). Of the 151 recorded deaths of black bears in urban environments (over a 10-year period), all were due to humans, and 89 of 151 (59%) were killed by vehicles (Beckmann & Lackey, 2008). In urban areas, deaths exceeded recruitment meaning urban areas

were sinks for this species (Beckmann & Lackey, 2008). Notably, an estimated 50 000 badgers are believed to die on British roads each year (Harris et al., 1992, 1995), which equates about to 49% of all adult and post-emergence cub fatalities. We could not find published mortality statistics specifically for urban badgers for comparison. Road accident is a major cause of death in urban raccoons (31%), but less so for rural animals (8%). Roads can act as barriers to dispersing wildlife (e.g. pumas Beier, 1995; bobcats and coyotes; Riley et al., 2003), although this can be mitigated by culverts and underpasses (Grilo, Bissonette & Santos-Reis, 2008; Harris et al., 2010a), while Bristol red foxes change their activity patterns, avoiding roads prior to midnight when traffic volume is higher (Baker et al., 2007). Hunting and destruction (i.e. euthanasia) are the next most common causes of death among carnivores (Fig. 2).

Winters, Jay H Hoofnagle, Theo Heller “
“Liver cirrhosis is

Winters, Jay H. Hoofnagle, Theo Heller “
“Liver cirrhosis is invariably associated with hemodynamic disturbances manifested as portal hypertension (PH) and concomitant splanchnic vasodilation. PH is the main cause of complications in patients with chronic liver disease. Its consequences are bleeding from gastroesophageal varices, ascites, hepatopulmonary syndrome, and hepatic encephalopathy.[1]

Understanding of the pathophysiology of PH may be important both for the introduction of effective pharmacological therapy and possibly also for the prediction of the development of esophageal varices. Ohm’s law (ΔPA = Q × R) explains why PH occurs. The meanings are ΔPA = intrahepatic pressure, Q = blood flow from systemic circulation, and R = intrahepatic GS-1101 cell line vascular resistance. Obviously, increasing either or both results in

an elevation of portal pressure. Current knowledge about the mechanisms of increased resistance to portal blood flow and of the formation of portal-systemic collaterals indicates that hepatic vascular resistance is modulated by adjustment to the increased hepatic vascular tone; the latter is attributable to hepatic endothelial dysfunction, and the abnormal angiogenesis resulting from liver inflammation and fibrogenesis,

while flow increases as a result of the hyperkinetic splanchnic circulation, contributing to the formation of varices.[2] Gastroesophageal Angiogenesis inhibitor varices are present in more than 50% of patients with PH and are more likely as liver disease progresses.[1, 3] Bleeding from esophageal varices occurs at a rate of 5–15% per year Telomerase in untreated patients. The risk factors for bleeding are variceal size, decompensated cirrhosis, and the presence of stigmata at endoscopy (red wale marks).[1] Currently, the American Association for the Study of the Liver recommends that all patients undergo endoscopy to assess the presence, the size, and the aspect of varices at the time of the diagnosis of cirrhosis. If no varices are present at index endoscopy, this procedure should be repeated at 2–3 years in compensated cirrhosis and annually in decompensated cirrhosis.[4] Therefore, there is considerable interest in developing models to predict the presence of large varices by nonendoscopic methods. Several studies have evaluated the noninvasive markers of esophageal varices in patients with cirrhosis, such as the platelet count, FibroTest, spleen size, portal vein diameter, transient elastography of the liver, and more recently, transient elastography of the spleen.

In total, 43% of the patients were smokers Patients with postope

In total, 43% of the patients were smokers. Patients with postoperative strictures were less frequently on anti-TNF therapy (17%, p = 0.023), thiopurines (34%, p = 0.001), and combination therapy (24%, p = 0.001) before surgery, and only 61% were on thiopurines at the time of postoperative colonoscopy (p = 0.040). In CD patients

with postoperative strictures, U0126 price 32% were symptomatic, 68% had an anastomotic stricture, and 18% had an ileal stricture. Endoscopic balloon dilatation was performed in 75% of patients (n = 30) with postoperative strictures, without any procedure complication, with a mean of two dilatations per patient, and mean time between dilatations of 7 ± 4 months. There were no differences between patients with postoperative strictures that were dilatated (n = 30) or not (n = 10), concerning hospital admission and new surgery. CD patients without anti-TNF therapy (OR 5.2 p = 0.033) or thiopurines (OR 5.3, p = 0.002) before surgery and without thiopurines (OR 2.21, p = 0.042) after surgery were at risk for postoperative strictures. Combination therapy before surgery was protective (OR 0.08, p = 0.001). There were no statistically significant differences for sex, Montreal classification, smoking, disease onset time until surgery and time until colonoscopy. Conclusion: Anti-TNF and/or thiopurines therapy before surgery

and thiopurines after surgery Stem Cell Compound Library purchase Phosphoribosylglycinamide formyltransferase are protective factors for postoperative stricture development in patients with Crohn’s disease. Key Word(s): 1. Crohn disease; 2. stricture; 3. surgery; 4. balloon dilatation;

Presenting Author: DUMINDA SUBASINGHE Additional Authors: NAVARATHNA MUDIYANSELAGEMETHTHANANDA NAVARATHNA, DHARMABANDUNANDADEVA SAMARASEKERA Corresponding Author: DUMINDA SUBASINGHE Affiliations: Department of Surgery, The National Hospital of Sri Lanaka Objective: Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory conditions related to the gastrointestinal tract. Faecal incontinence (FI) impairs quality of life (QOL), causing embarrassment and limiting daily activities. FI can have a negative impact on the QOL of patients with inflammatory bowel disease (IBD). There is limited published data on FI amongst people with IBD in South Asia. This study looks at the frequency and severity of FI, and its effect on the QOL in IBD patients who presented to a tertiary care center. Methods: Patients with an established diagnosis of IBD were identified and demographics, disease characteristics, FI (Vaizey score), quality of life (IBD-Q) were collected. Data were analyzed using SPSS version 15. Results: A total of 184 patients (women = 101, 54.9%; UC = 153, 83.2%) were included. Female preponderance was observed for UC (male/female ratio = 1 : 1.5) and male for CD (male/female = 2 : 1). Forty eight (26%) reported symptoms of FI.

None of the patients had complications Conclusion: The majority

None of the patients had complications. Conclusion: The majority of very elderly FOBT-positive patients without visible blood in the stool had no abnormalities or low-grade adenoma when the polyp was small, showing that advanced colon cancer was relatively rare. Considering their advanced age, colon polyps are unlikely to Sirolimus cost progress rapidly to cancer in very elderly patients. Thus, instead of offering colonoscopy to all very elderly FOBT-positive patients, non-invasive

abdominal computed tomography may be useful to select those with suspected advanced colon cancer for further examination by colonoscopy. Key Word(s): 1. very elderly patient; 2. FOBT-positive; 3. colonoscopy Presenting Author: HONGJIE ZHANG Additional Authors: XIUFANG CUI Corresponding Author: HONGJIE ZHANG Affiliations: Jiangsu People Hospital Objective: The present study was designed to investigate the effect of GLP-1 analogue exendin-4 on visceral hypersensitivity in rat model, and its possible regulation on SERT expression and 5-HT reuptake. Methods: Neonatal male Sprague-Dawley rats received intra-colonic injection of 0.5% acetic acid. Visceral sensation was determined

by assessing Trichostatin A datasheet abdominal withdrawal reflex (AWR) and electromyography (EMG) activity. Exendin-4 with doses of (1, 5, and 10 μg/kg) was administered by intra-peritoneal injection. SERT expression was detected by quantitative PCR (qRT-PCR)

and Western blotting. SERT function was determined by tritiated 5-HT reuptake experiment in IEC-6 cells. Forskolin, protein kinase A (PKA) inhibitors (H89) or adenylyl cyclase inhibitor (SQ22536) was used to investigate the GLP-1/ cAMP/PKA signaling pathway. Results: Neonatal acetic acid (AA) Cyclin-dependent kinase 3 intra-colonic treatment presented hypersensitivity to CRD in adult rats compared with controls. High levels of 5-HT were detected in plasma and colonic tissues in AA-treated rats (P < 0.05). Stimulated with exendin-4 at 10 μg/kg could reduce visceral sensation. The expressions of SERT reduced in colon of the AA-treated rats, and increased after treatment with exendin-4. The expressions of SERT up-regulated and 5-HT reuptake function enhanced in IEC-6 cells after treatment with exendin-4 in dose- and time-dependently manner. The former effect was abolished by pre-treatment with exendin-9, SQ22536 and H89. Exendin-4 and forskolin increased PKA activity in IEC-6 cells. Conclusion: Exendin-4, a GLP-1 analogue, can attenuate hyperalgesia in rats with neonatal colon sensitivity by up-regulating SERT expression and 5-HT reuptake, and its effect may involve in cAMP/PKA signaling pathway. Key Word(s): 1. irritable bowel syndrome; 2. glucagon-like peptide-1; 3. serotonin transporter Presenting Author: MURDANI ABDULLAH Additional Authors: D. MAKMUN, U.MAIMUNAH, ARLES, KUSNANTO, S.MIRO, SUYATA, NENENG, MARCELLUS S.

To this end, we exposed CXCR3−/− hepatocytes to CXCL10 or vehicle

To this end, we exposed CXCR3−/− hepatocytes to CXCL10 or vehicle. Interestingly, CXCL10 also induced this website apoptosis in these cells, as evidenced by increased levels of active caspase-3

and caspase-8 (Fig. 6A,B) as well as by prolonged Akt phosphorylation (Fig. 6C and Supporting Fig. 3B). To exclude a contamination of the recombinant CXCL10 by lipopolysaccharide, we preincubated CXCR3−/− hepatocytes with polymyxin B. In fact, this preparation did not change caspase-3 and Akt activation (Supporting Fig. 3C,D), demonstrating a CXCL10-specific effect on hepatocyte apoptosis. Importantly, in contrast to CXCL10, the related chemokine (CXCL9) did not affect hepatocyte apoptosis, as evidenced by measurement of caspase-3 activity (data not shown). Because CXCR3 is not involved in hepatocyte apoptosis, we became interested whether

see more an alternative receptor could trigger CXCL10-induced apoptosis in hepatocytes. Recently, Schulthess et al.24 identified TLR4 as a receptor for CXCL10 in pancreatic β-cells. First, we confirmed the expression of TLR4 on hepatocytes by PCR analysis (Supporting Fig. 4A). Next, we stimulated TLR4−/− hepatocytes with CXCL10 or vehicle. Indeed, we found no caspase-3 and caspase-8 activation (Fig. 6D,E). These results were confirmed by lack of Akt phosphorylation (Fig. 6F and Supporting Fig. 4B) subsequent to CXCL10 stimulation of these cells. Thus, activation of TLR4 signaling appears essential to trigger CXCL10-induced hepatocyte apoptosis. In light of these in vitro data, we hypothesized that systemic administration of CXCL10 might also induce liver cell apoptosis

in vivo. Indeed, a single injection of CXCL10 led to a low, but increased, number of TUNEL-positive liver cells, compared to vehicle treatment (Fig. 7A). The apoptotic response in CXCL10-treated animals was also reflected by increased caspase-3 and caspase-8 activity within livers of these animals (Fig. 7B and Supporting Fig. 4C). Moreover, treatment with CXCL10 increased AST serum levels (Fig. 7C) and reduced intrahepatic mRNA expression of the antiapoptotic factor, BCL-2 PAK5 (Fig. 7D). Importantly, in this experimental setting, TLR4−/− mice were almost completely protected from the proapoptotic effects of CXCL10. In contrast to WT mice, treatment of TLR4−/− mice with CXCL10 neither resulted in augmented cell death (Fig. 7A) nor in caspase-3 or caspase-8 activation (Fig. 7B and Supporting Fig. 4C). In line with these results, lack of TLR4 also triggered no changes in AST and BCL-2 levels after CXCL10 challenge, compared to their vehicle-treated counterparts (Fig. 7C,D), identifying the CXCL10/TLR4 axis as an important chemokine-based apoptotic pathway within the murine liver in vivo. Here, we provide in vitro and in vivo evidence that CXCL10 exerts proapoptotic effects in hepatocytes through its noncognate receptor (TLR4).

However, a significant heterogeneity in survival among RCTs remai

However, a significant heterogeneity in survival among RCTs remained even after stratifying patients and study features, and heterogeneity in the survival rates persisted even in the stratum of high-quality studies, implying that this was not explained by study validity alone. Therefore, the evaluation of the methodological quality did not seem to influence the variability of the assessed outcome, because of the mean high quality of the studies (75% of these RCTs were high-quality studies). Heterogeneity of these rates among RCTs may reflect

both inclusion of patients with different stages of disease and variability in the molecular Palbociclib nmr characteristics and biological behavior of the tumor, which are not included in any of the currently available staging systems. In our analysis, when studies were separated according to the BCLC stage, the 1-year survival was much higher in RCTs including only BCLC B or C patients (34%) than in those also including BCLC D patients (11%). This provides further evidence that the BCLC staging system has a good discriminative capacity for prognosticating survival not only in patients with early HCC41 but also in those with intermediate/advanced HCC. However, data on direct selleck BCLC stage were

lacking in several trials, and caution must be exercised when interpreting results from subgroup exploratory analyses. We found by meta-regression analysis that ECOG performance status and portal vein thrombosis are robust predictors of death in untreated patients as reported by Tandon and Garcia-Tsao42 in a recent systematic review of 72 studies on prognostic indicators in HCC. These

CHIR-99021 purchase two individual parameters, both included in the BCLC classification, may explain in large part why this staging system provides accurate information on prognosis in the setting of HCC. A remarkable difference in survival was found between occidental (North American and European) and oriental (Asia-Pacific) studies. The high prevalence of HBV-related liver disease found in Asia-Pacific countries may account for the different survival observed between oriental and occidental studies in which a high prevalence of HCV-related liver disease was observed. However, the potential role of HBV as a prognostic factor disappears when Asian-Pacific location of the studies and HBV-related disease were both included in a multivariate model. The survival differences between occidental and Asian studies may be explained by differences in the distribution of other risk and prognostic factors. In fact, the worse survival observed in the Asia-Pacific study36 could be explained by the higher prevalence of patients in advanced stage than in the SHARP study.

In conclusion, the author reported a projected FNH The DR of the

In conclusion, the author reported a projected FNH. The DR of the FNH showed atypical features such as small cells and hyperchromatic nuclei. The DR assumed features of ductal plate-like structures. KIT was positive in the DR in the FNH, suggesting that the cells of DR are liver stem cells, and proliferation of these cells take features of ductal plate-like structures, similar to embryonic biliary development. MUC apomucins are negative in the DR. “
“Background and Aim:  With the rising incidence of digestive cancers in the Asia Pacific region and the advancement in diagnosis, management

and palliation in these conditions, the clinical burden on oncologists is ever increasing. This Summit meeting was called to discuss the optimal management of digestive cancers

and the role of Gastroenterologists Method:  Experts from Asia Pacific countries in the fields of medical, oncologic, surgical and endoscopic management of cancers in selleck products the esophagus, stomach, colon/rectum and the liver reviewed the literature and their practice. 18 position statements were drafted, debated and voted. Results:  It was agreed that the burden on GI cancer is increasing. More research will be warranted on chemotherapy, chemoprevention, cost-effectiveness of treatment and nutrition. Cancer management guidelines should be developed in this region when more clinical data are available. In order to improve care to patients, a multi-disciplinary team coordinated by a “cancer therapist” is proposed. This cancer therapist can be a gastroenterologist, a surgeon Selleck JNK inhibitor or any related discipline who have acquired core competence the training. This training should include an attachment in a center-of-excellence in cancer management for no less than 12 months. Conclusion:  The management of GI cancer should be an integrated multi-disciplinary approach and training for GI cancer therapists

should be provided for. “
“Emerging therapies for chronic hepatitis C viral (HCV) infection involve inhibition of viral enzymes with drug combinations. Natural, or treatment-induced, enzyme polymorphisms reduce efficacy. We developed a phenotyping assay to aid drug selection based on viral transfer from monocytes to hepatocytes. We studied HCV in monocytes from infected patients and developed a model in which patient-derived HCV is “captured” by the cell line THP-1 and replication assessed after fusion to hepatoma cells. We found that monocytes from HCV-infected patients harbour virus that replicates when cells are fused to hepatocytes. THP-1 cells incubated with infected sera ‘capture’ HCV which replicates when fused to hepatocytes. Inhibitable replication of all HCV genotypes was achieved (42 of 52 isolates). We measured sensitivity of telaprevir and alisporivir in different genotypes and showed differences in IC50 correlating with clinical response (telaprevir IC50 for genotype (G)1 was 0.042 ± 0.003 µM, versus 0.