Oral isosorbide mononitrate was then started at 20 mg once at bedtime, followed by 20 mg twice a day for 1 day, and finally increased to 40 mg BD if tolerated. Once the maximal tolerated drug doses were achieved, a second hemodynamic study was scheduled 5-7 days later. According to the hemodynamic response observed, patients were classified in two groups: responders, when the HVPG was ≤12 mm Hg and/or had decreased ≥20% from baseline values; and nonresponders, when these hemodynamic find more targets were not achieved. According

to available recommendations, responders were maintained with the same pharmacological therapy (drugs only) until their first rebleeding episode or the end of follow-up (regardless of the results of follow-up HVPG measurements). Only if a first rebleeding episode occurred was ligation prophylaxis added to drug therapy in responders. Nonresponders were treated from the start with the combination of drugs and endoscopic ligation, except for a few Sotrastaurin ic50 patients at the beginning of the study period who received a transjugular portosystemic shunt (TIPS). Ligation was performed with commercial multiband devices at 2- to 3-week intervals until variceal obliteration had been achieved. Once eradicated, patients underwent a follow-up endoscopy

at 3 months and at 6-month intervals thereafter. Additional sessions of ligation were conducted if varices reappeared. None of the patients with hepatitis C in this cohort of decompensated patients with cirrhosis received antiviral therapy during follow-up, in line with available recommendations. Patients were followed at 3-month intervals at the outpatient liver clinic. History and examination evaluated alcohol abstinence, compliance to drug therapy and adverse effects. Alcohol abstinence was assessed by direct anamnesis with the patient, separated interview with close relatives and unexpected determinations of alcoholemia. Compliance to drug therapy was assessed in all patients by blood pressure and heart rate measurements at each follow-up visit, in addition to a specific anamnesis. Moreover, responders underwent

annual determinations of HVPG for see more 3 years. The study was continued for 6 months after the enrollment of the last patient. Diagnosis of cirrhosis was based on liver biopsy or the usual clinical and imaging criteria. Bleeding was considered from esophageal variceal origin when the emergency endoscopy performed within 12 hours after admission showed any of the accepted criteria defining variceal bleeding.14 The primary endpoints of the study were maintenance of long-term response, rebleeding and the composite of death and liver transplantation (LT). These endpoints were prespecified before the beginning of the study. An initial hemodynamic responder was considered to maintain long-term response if all follow-up HVPG measurements were ≤12 mm Hg and/or >20% of baseline value.

Oral isosorbide mononitrate was then started at 20 mg once at bedtime, followed by 20 mg twice a day for 1 day, and finally increased to 40 mg BD if tolerated. Once the maximal tolerated drug doses were achieved, a second hemodynamic study was scheduled 5-7 days later. According to the hemodynamic response observed, patients were classified in two groups: responders, when the HVPG was ≤12 mm Hg and/or had decreased ≥20% from baseline values; and nonresponders, when these hemodynamic click here targets were not achieved. According

to available recommendations, responders were maintained with the same pharmacological therapy (drugs only) until their first rebleeding episode or the end of follow-up (regardless of the results of follow-up HVPG measurements). Only if a first rebleeding episode occurred was ligation prophylaxis added to drug therapy in responders. Nonresponders were treated from the start with the combination of drugs and endoscopic ligation, except for a few buy LBH589 patients at the beginning of the study period who received a transjugular portosystemic shunt (TIPS). Ligation was performed with commercial multiband devices at 2- to 3-week intervals until variceal obliteration had been achieved. Once eradicated, patients underwent a follow-up endoscopy

at 3 months and at 6-month intervals thereafter. Additional sessions of ligation were conducted if varices reappeared. None of the patients with hepatitis C in this cohort of decompensated patients with cirrhosis received antiviral therapy during follow-up, in line with available recommendations. Patients were followed at 3-month intervals at the outpatient liver clinic. History and examination evaluated alcohol abstinence, compliance to drug therapy and adverse effects. Alcohol abstinence was assessed by direct anamnesis with the patient, separated interview with close relatives and unexpected determinations of alcoholemia. Compliance to drug therapy was assessed in all patients by blood pressure and heart rate measurements at each follow-up visit, in addition to a specific anamnesis. Moreover, responders underwent

annual determinations of HVPG for selleck chemicals llc 3 years. The study was continued for 6 months after the enrollment of the last patient. Diagnosis of cirrhosis was based on liver biopsy or the usual clinical and imaging criteria. Bleeding was considered from esophageal variceal origin when the emergency endoscopy performed within 12 hours after admission showed any of the accepted criteria defining variceal bleeding.14 The primary endpoints of the study were maintenance of long-term response, rebleeding and the composite of death and liver transplantation (LT). These endpoints were prespecified before the beginning of the study. An initial hemodynamic responder was considered to maintain long-term response if all follow-up HVPG measurements were ≤12 mm Hg and/or >20% of baseline value.

Our aims are: To assess for EPI pre and post-surgery by measuring FE To determine if the different surgical indications have an impact on EPI Methods: All patients undergoing pancreatic surgery had FE measured pre- and post-surgery. FE levels were measured using the ScheBo faecal elastase 1 (Glesson, Germany). FE levels were classified as severely low if < 100 μg/g stool, normal if >200 μg/g stool and mild to moderate if 100–200 μg/g stool. Results: Twenty-six patients were recruited (15 men, mean age 57.4 years). Indications for surgery were pancreas cancer involving the head (8 patients), cancer distal to the head (6), ampullary cancer (5), distal cystic neoplasms (4), distal neuroendocrine tumour (1),

chronic pancreatitis (1) and cholangiocarcinoma

(1). Pre-operative FE was measured in 24 patients – 7 had severely http://www.selleckchem.com/screening/epigenetics-compound-library.html low levels (4 pancreatic head cancer, 1 ampullary cancer, 1 chronic pancreatitis and 1 cystic LY2835219 molecular weight neoplasm) and 1 patient had moderately low levels (pancreatic head cancer). Fourteen patients had post-op FE results. Only 4 patients retained normal post-op pancreatic function. Nine patients with EPI had undergone Whipple’s surgery and 1 distal pancreatectomy. Twelve patients had paired pre and post-op FE results. Three had EPI prior to surgery (pancreatic head cancer), which persisted following Whipple’s operation. Six patients developed EPI post-surgery (5 Whipple’s and 1 distal pancreatectomy). Three patients retained see more exocrine pancreatic function (pancreatic surgery involving body and/or tail). Conclusion: Head of pancreas cancer or surgery involving the head is a significant risk factor for the development of EPI. Approximately a third of patients will have EPI prior to surgery which will rise to 70% following surgery. Key Word(s): 1. faecal elastase; 2. malnutrition; 3. exocrine function; 4. pancreas surgery; Presenting Author: MUHAMMAD OSAMATARIQ BUTT Additional Authors: ZAIGFHAM ABBAS, NASIR LUCK, MUJAHID HASSAN Corresponding Author: MUHAMMAD OSAMATARIQ BUTT Affiliations: SIUT Objective: Extrahepatic cholestasis associated with dilated bile ducts, is caused by bile duct stones

or strictures. This study was done out to evaluate common liver function tests (LFTs) in the differential diagnosis of extrahepatic cholestasis separating patients with bile duct strictures from those with stones. Methods: All consecutive patients with deranged LFTs and biliary dilatation on ultrasound were evaluated by endoscopic retrograde cholangiopancreatography (ERCP). Patients with biliary strictures were compared with bile duct stones. Complete blood counts, international normalization ratio, plasma alkaline phosphatase, gamma-glutamyltransferase, aminotransferases, and bilirubin values were determined in the same morning before doing ERCP. Total patients evaluated were 227. 24 patients on ERCP were found to have mild biliary dilation without stone or stricture while 15 had both stone and stricture.

Interestingly, we replicated the findings of Bruce et al., and observed in addition that maternal HFD feeding modified the sexual dimorphic effect of HFD on liver steatosis and abdominal fat content observed in offspring

of mothers fed an SCD. Female Wistar rats were randomly assigned to either ad libitum HFD solid diet2 or SCD. Dams were fed 15 days before conception and during gestation and lactation. The 17-week-old PLX-4720 ic50 offspring were assigned either ad libitum HFD or SCD for an 18-week period, generating eight experimental groups (Fig. 1). At the completion of the study, animals were sacrificed and abdominal fat tissue (intraperitoneal and retroperitoneal) was measured by direct weighing; the degree of liver steatosis was assessed as previously reported.3 In the group of HFD-fed offspring of SCD-fed dams, we observed a

clear sexually dimorphic effect of HFD check details feeding because female rats developed a significantly greater degree of fatty change than male rats; this finding was similar when we analyzed abdominal fat content (Fig. 1). However, in the group of HFD-fed offspring of HFD-fed dams, the sexual differences in both fatty liver degree and abdominal fat content were not observed, although the degree of liver steatosis was lower in female offspring of HFD-fed dams versus those of SCD-fed dams (Fig. 1). Interestingly, these effects were independent of dam body weight, which suggests a specific effect of the diet. In conclusion, the female-specific consequences of feeding HFD (a finding previously reported in other rat models of NAFLD4) deserves further investigations as the underlying mechanisms involved in the sex difference are not clear. Otherwise, our study provides additional evidence of the effect of maternal high-fat nutrition on the liver and abdominal fat accumulation in either male or female HFD-fed offspring, thus

suggesting the importance of the developmental programming that can induce the NAFLD phenotype completely independent of sex differences. This finding strongly supports the hypothesis selleckchem of Bruce et al. about the “priming” effect of maternal mitochondria on metabolic pathways associated with NAFLD, which is compatible with our recent findings of a decrease in mitochondrial DNA copy number in adolescents with insulin resistance5 and in newborns with abnormal birth weight,6 which are two well-known risk factors for metabolic syndrome in adults. This study was partially supported by grants UBACYT M055 (Universidad de Buenos Aires) and PICT 06-124 (Agencia Nacional de Promoción Científica y Tecnológica). Adriana L. Burgueño Ph.D.*, Julieta Carabelli M.Sc.*, Silvia Sookoian M.D., Ph.D.*, Carlos J. Pirola Ph.D., F.A.H.A.

Interestingly, we replicated the findings of Bruce et al., and observed in addition that maternal HFD feeding modified the sexual dimorphic effect of HFD on liver steatosis and abdominal fat content observed in offspring

of mothers fed an SCD. Female Wistar rats were randomly assigned to either ad libitum HFD solid diet2 or SCD. Dams were fed 15 days before conception and during gestation and lactation. The 17-week-old find more offspring were assigned either ad libitum HFD or SCD for an 18-week period, generating eight experimental groups (Fig. 1). At the completion of the study, animals were sacrificed and abdominal fat tissue (intraperitoneal and retroperitoneal) was measured by direct weighing; the degree of liver steatosis was assessed as previously reported.3 In the group of HFD-fed offspring of SCD-fed dams, we observed a

clear sexually dimorphic effect of HFD check details feeding because female rats developed a significantly greater degree of fatty change than male rats; this finding was similar when we analyzed abdominal fat content (Fig. 1). However, in the group of HFD-fed offspring of HFD-fed dams, the sexual differences in both fatty liver degree and abdominal fat content were not observed, although the degree of liver steatosis was lower in female offspring of HFD-fed dams versus those of SCD-fed dams (Fig. 1). Interestingly, these effects were independent of dam body weight, which suggests a specific effect of the diet. In conclusion, the female-specific consequences of feeding HFD (a finding previously reported in other rat models of NAFLD4) deserves further investigations as the underlying mechanisms involved in the sex difference are not clear. Otherwise, our study provides additional evidence of the effect of maternal high-fat nutrition on the liver and abdominal fat accumulation in either male or female HFD-fed offspring, thus

suggesting the importance of the developmental programming that can induce the NAFLD phenotype completely independent of sex differences. This finding strongly supports the hypothesis selleckchem of Bruce et al. about the “priming” effect of maternal mitochondria on metabolic pathways associated with NAFLD, which is compatible with our recent findings of a decrease in mitochondrial DNA copy number in adolescents with insulin resistance5 and in newborns with abnormal birth weight,6 which are two well-known risk factors for metabolic syndrome in adults. This study was partially supported by grants UBACYT M055 (Universidad de Buenos Aires) and PICT 06-124 (Agencia Nacional de Promoción Científica y Tecnológica). Adriana L. Burgueño Ph.D.*, Julieta Carabelli M.Sc.*, Silvia Sookoian M.D., Ph.D.*, Carlos J. Pirola Ph.D., F.A.H.A.

Regional differences between the metabolically labile trunk integument and the structural tailstock integument were also investigated.

Mean densities of both trunk and tailstock integument were similar across life history categories (trunk find more = 1,040.7 ± 14.1 kg/m3; tailstock = 1,077.1 ± 21.2 kg/m3) and were statistically similar to the density of seawater (1,026 kg/m3). The mean buoyant force of integument from the trunk (−1.01 ± 1.74 N) and tailstock (−0.30 ± 0.21 N) did not vary significantly across ontogeny. In contrast, pregnancy and emaciation did influence the integument’s buoyancy, which ranged between 9 N and −45 N in these categories. Although neutral during growth, the integument’s contribution to whole body buoyancy can be influenced by an individual’s reproductive and nutritional status. selleck products “
“The intestine of 52 (28 males and 24 females) striped dolphins (Stenella coeruleoalba) from western Mediterranean waters was examined for helminths. Animals were found stranded along the Spanish coasts during the morbillivirus epizootic in 1990. In accordance with observations from other pelagic tetrapods,

including cetaceans from other geographical regions, the intestinal helminth community was depauperate. Four helminth species were found: three tetrabothriid cestodes, Tetrabothrius forsteri (prevalence: 96.2%; mean intensity [95% CI]: 47.4 [34.4–68.2]), Trigonocotyle globicephalae (9.6%; 1.8 [1.0–2.2]), and Strobilocephalus triangularis (23.1%; 5.3 [2.9–10.2]), and immature individuals of the acanthocephalan Bolbosoma vasculosum (51.9%; 2.7 [2.0–3.4]). Schluter’s variance test indicated a weak, but statistically significant association of occurrence of helminth species in dolphins, suggesting that some tetrabothriid species might use the same intermediate or paratenic

hosts. Neither the abundance of helminth species nor infracommunity descriptors were significantly affected by sex, host body length or age. The absence of predictable effects of body size and age on the recruitment rate of helminths could be related to the fact that the host check details sample was largely composed of adults. This study provides quantitative evidence about helminth community structure of striped dolphins, based on a large sample size. “
“Florida manatees (Trichechus manatus latirostris) inhabit coastal regions because they feed on the aquatic vegetation that grows in shallow waters, which are the same areas where human activities are greatest. Noise produced from anthropogenic and natural sources has the potential to affect these animals by eliciting responses ranging from mild behavioral changes to extreme aversion. Sound levels were calculated from recordings made throughout behavioral observation periods. An information theoretic approach was used to investigate the relationship between behavior patterns and sound level. Results indicated that elevated sound levels affect manatee activity and are a function of behavioral state.

Regional differences between the metabolically labile trunk integument and the structural tailstock integument were also investigated.

Mean densities of both trunk and tailstock integument were similar across life history categories (trunk KU 57788 = 1,040.7 ± 14.1 kg/m3; tailstock = 1,077.1 ± 21.2 kg/m3) and were statistically similar to the density of seawater (1,026 kg/m3). The mean buoyant force of integument from the trunk (−1.01 ± 1.74 N) and tailstock (−0.30 ± 0.21 N) did not vary significantly across ontogeny. In contrast, pregnancy and emaciation did influence the integument’s buoyancy, which ranged between 9 N and −45 N in these categories. Although neutral during growth, the integument’s contribution to whole body buoyancy can be influenced by an individual’s reproductive and nutritional status. selleckchem “
“The intestine of 52 (28 males and 24 females) striped dolphins (Stenella coeruleoalba) from western Mediterranean waters was examined for helminths. Animals were found stranded along the Spanish coasts during the morbillivirus epizootic in 1990. In accordance with observations from other pelagic tetrapods,

including cetaceans from other geographical regions, the intestinal helminth community was depauperate. Four helminth species were found: three tetrabothriid cestodes, Tetrabothrius forsteri (prevalence: 96.2%; mean intensity [95% CI]: 47.4 [34.4–68.2]), Trigonocotyle globicephalae (9.6%; 1.8 [1.0–2.2]), and Strobilocephalus triangularis (23.1%; 5.3 [2.9–10.2]), and immature individuals of the acanthocephalan Bolbosoma vasculosum (51.9%; 2.7 [2.0–3.4]). Schluter’s variance test indicated a weak, but statistically significant association of occurrence of helminth species in dolphins, suggesting that some tetrabothriid species might use the same intermediate or paratenic

hosts. Neither the abundance of helminth species nor infracommunity descriptors were significantly affected by sex, host body length or age. The absence of predictable effects of body size and age on the recruitment rate of helminths could be related to the fact that the host selleck products sample was largely composed of adults. This study provides quantitative evidence about helminth community structure of striped dolphins, based on a large sample size. “
“Florida manatees (Trichechus manatus latirostris) inhabit coastal regions because they feed on the aquatic vegetation that grows in shallow waters, which are the same areas where human activities are greatest. Noise produced from anthropogenic and natural sources has the potential to affect these animals by eliciting responses ranging from mild behavioral changes to extreme aversion. Sound levels were calculated from recordings made throughout behavioral observation periods. An information theoretic approach was used to investigate the relationship between behavior patterns and sound level. Results indicated that elevated sound levels affect manatee activity and are a function of behavioral state.

Response to milk free diet Results: N = 26, M: F – 14:12. Median age: 16.88 months (SD +/− 10.27). Mean duration between presentation and introduction of cow milk: 8.18 months (0.5–29). Presentation: 15 (57.6%) – chronic diarrhea and blood in stool, 10 (38.4%) – chronic diarrhea and failure to thrive. Endoscopic rectal mucosal biopsies were performed in 20 (76.9%) and EGD with duodenal

biopsies in 6 (23%) – all were positive. Mean follow up: 7.23 PLX4032 molecular weight months (SD +/− 5.49). All patients responded to milk free diet. Peptide based chicken formula prescribed in 9 (34.6%) and extensively hydrolyzed amino acid formula given to 3 (11.5%). Remaining 14 (53%) were managed on home made diet. Re-challenge was undertaken in 7 after parental consent. Re – challenge was done at 2 years of age or one year after stopping milk. Only one patient presented with recurrence following re-challenge. Conclusion: Chronic diarrhea, blood in stool and failure to thrive are common presenting symptoms of CMPA. Mucosal biopsies help in establishing diagnosis. More than 50% patients can be managed with a home-modified diet. Key Word(s): 1. cow milk protein allergy;

2. milk protein allergy; 3. paediatric diarrhoea Presenting Author: ERIC CHEAH Additional Authors: KEVIN GASKIN, MICHAEL STORMON, SHOMA DUTT, ANNABEL MAGOFFIN, EDWARD O’LOUGHLIN Corresponding Author: ERIC CHEAH Affiliations: EPZ-6438 chemical structure The Children’s Hospital at Westmead, The Children’s this website Hospital at Westmead, The Children’s Hospital at Westmead, The Children’s Hospital at Westmead, The Children’s Hospital at Westmead

Objective: Eosinophilic oesophagitis (EO) is a chronic, immune/antigen-mediated oesophageal disease characterized by oesophageal dysfunction and histologically by eosinophil-predominant inflammation. This study will report on our 5 year experience in children diagnosed with EO at the Children’s Hospital at Westmead, a tertiary paediatric institution in Sydney, Australia. Methods: A retrospective audit was performed between January 1, 2008 and December 31, 2012 to evaluate all patients newly diagnosed with EO. The follow up period was included up to May 31, 2014. Demographic data, clinical symptoms, associated conditions, atopic history and treatment modalities were collated. Results: A total of 108 patients were diagnosed with EO: 71% male, median age 6.8 years (range 0.8–16.8 years); representing an average of 4% of total endoscopies performed per year. 41 patients had dysphagia symptoms, 34 patients had gastro-oesophageal reflux symptoms, 11 patients with abdominal pain and 23 patients with non-EO symptoms. Atopic history was elicited in 54% of patients whilst 36% had food allergy. Concomitant diagnosis included coeliac disease, Helicobacter pylori gastritis and proctitis/ulcerative colitis. Endoscopic appearance was normal in 8.3% of patients. Patients required a median of 2 (range 0–10) follow up endoscopies. Treatments are presented in Table 1.

Response to milk free diet Results: N = 26, M: F – 14:12. Median age: 16.88 months (SD +/− 10.27). Mean duration between presentation and introduction of cow milk: 8.18 months (0.5–29). Presentation: 15 (57.6%) – chronic diarrhea and blood in stool, 10 (38.4%) – chronic diarrhea and failure to thrive. Endoscopic rectal mucosal biopsies were performed in 20 (76.9%) and EGD with duodenal

biopsies in 6 (23%) – all were positive. Mean follow up: 7.23 learn more months (SD +/− 5.49). All patients responded to milk free diet. Peptide based chicken formula prescribed in 9 (34.6%) and extensively hydrolyzed amino acid formula given to 3 (11.5%). Remaining 14 (53%) were managed on home made diet. Re-challenge was undertaken in 7 after parental consent. Re – challenge was done at 2 years of age or one year after stopping milk. Only one patient presented with recurrence following re-challenge. Conclusion: Chronic diarrhea, blood in stool and failure to thrive are common presenting symptoms of CMPA. Mucosal biopsies help in establishing diagnosis. More than 50% patients can be managed with a home-modified diet. Key Word(s): 1. cow milk protein allergy;

2. milk protein allergy; 3. paediatric diarrhoea Presenting Author: ERIC CHEAH Additional Authors: KEVIN GASKIN, MICHAEL STORMON, SHOMA DUTT, ANNABEL MAGOFFIN, EDWARD O’LOUGHLIN Corresponding Author: ERIC CHEAH Affiliations: selleck chemicals The Children’s Hospital at Westmead, The Children’s this website Hospital at Westmead, The Children’s Hospital at Westmead, The Children’s Hospital at Westmead, The Children’s Hospital at Westmead

Objective: Eosinophilic oesophagitis (EO) is a chronic, immune/antigen-mediated oesophageal disease characterized by oesophageal dysfunction and histologically by eosinophil-predominant inflammation. This study will report on our 5 year experience in children diagnosed with EO at the Children’s Hospital at Westmead, a tertiary paediatric institution in Sydney, Australia. Methods: A retrospective audit was performed between January 1, 2008 and December 31, 2012 to evaluate all patients newly diagnosed with EO. The follow up period was included up to May 31, 2014. Demographic data, clinical symptoms, associated conditions, atopic history and treatment modalities were collated. Results: A total of 108 patients were diagnosed with EO: 71% male, median age 6.8 years (range 0.8–16.8 years); representing an average of 4% of total endoscopies performed per year. 41 patients had dysphagia symptoms, 34 patients had gastro-oesophageal reflux symptoms, 11 patients with abdominal pain and 23 patients with non-EO symptoms. Atopic history was elicited in 54% of patients whilst 36% had food allergy. Concomitant diagnosis included coeliac disease, Helicobacter pylori gastritis and proctitis/ulcerative colitis. Endoscopic appearance was normal in 8.3% of patients. Patients required a median of 2 (range 0–10) follow up endoscopies. Treatments are presented in Table 1.

RESULTS: The accuracy of the scores is described in the Table below. Based on the 95%CI, the NFS was equally accurate as the FIB-4 score, but significantly more accurate than the APRI, NIKEI and BARD scores. The FIB-4 was similar to the NIKEI and BARD scores, but significantly better than the APRI score. There was no a significant difference among the NIKEI, APRI and BARD scores. The NIKEI had the lowest indeterminate score value, but also the lowest NPV and PPV. CONCLUSIONS: This large independent validation analysis demonstrates the high accuracy of noninvasive scores to distinguish between patients with and without advanced fibrosis. Combining

the NPV and the PPV, the NFS seems the most accurate followed by the FIB-4, the APRI, the NIKEI and the BARD scores. Accuracy of the socre to distinguish between patients with

STA-9090 purchase and without advanced (stage 3/4) fibrosis AUROC (95%CI) Indeterminate score NPV (low GSK3 inhibitor cut-point) PPV (high cut-point) NFS •825 (.789,.861) 30% 89% 84% APRI .729 (.686,.771) 49% 86% 62% FIB-4 .814 (.777,.851) 29% 89% 76% NIKEI .749 (.711,.788) 1% 78% 55% BARD .744 (.702,.786) NA 78% 55% Disclosures: Charles D. Rice – Employment: Sanofi-Spouse; Management Position: SanofiSpouse; Stock Shareholder: Sanofi-Spouse Jacob George – Advisory Committees or Review Panels: Roche, BMS, MSD, Gilead, Janssen Christopher P. Day – Advisory Committees or Review Panels: Abbott; Board Membership: Abbott Paul Angulo – Grant/Research Support: NIDDK, Mochida, Genfit The following people have nothing to disclose: Elisabetta Bugianesi, Einar Bjornsson, Phunchai Charatcharoenwitthaya, Peter R. Mills Background: Recent evidence suggest that coffee consumption

could be of benefit for those In non-alcoholic fatty liver disease (NAFLD) patients at risk of developing hepatic fibrosis. The underlying mechanisms of hepatic benefits selleck kinase inhibitor of coffee intake remain unclear. Aims: a) to assess if coffee administration influences hepatic inflammation and fibrosis or mitochondrial respiration in a dietary model of non-alcoholic steatohepatitis (NASH), b) to test the effect of caffeine on hepatic stellate cells (HSC). Methods: C57bl6 mice were fed a choline-deficient amino acid-defined (CDAA) diet for 22 weeks to induce NASH. Unfiltered coffee was added to drinking water during diet administration (CDAA-C and CSAA-C groups). Hepatic steatosis, inflammation, and fibrosis were scored histologically (hematoxylin-eosin and Sirius red staining). Hepatic triglyceride content (HTG) and mRNA expression of inflammatory markers such as TNF-α and MCP-1 as well as mitochondrial respiration were assessed. In addition, primary rat HSC were culture-activated and treated with caffeine for 96h (5 to 20mM) or its main metabolite 1, 7-dimethylxanthine (1, 7-DMX) (for 72h, 1mM).