18 On the other hand, if bacterial overgrowth is induced experimentally in the small intestine, this causes liver inflammation and injury.40 We speculate that activation of the mucosal innate immune system, as demonstrated by increased levels of Reg3b and Reg3g, contributes to reduced intestinal bacterial overgrowth in Muc2−/− mice. Prebiotics restore Reg3b and Reg3g expression, limit bacterial overgrowth and ameliorate alcohol-induced steatohepatitis.28 However, other antimicrobial molecules or components of

the mucosal innate immune system might work in concert with Reg3b and Reg3g, and future studies are required for further investigations. Thus, based on our study, we propose a concept in which Selleckchem Ruxolitinib suppression of intestinal bacterial overgrowth by host antimicrobial molecules results in a decreased availability Sorafenib solubility dmso of intraluminal bacterial products. Less of these products are able to cross the intestinal barrier into the portal circulation, which eventually limits alcoholic liver disease. We have also recently demonstrated qualitative changes in the enteric microbiome (dysbiosis) using a model of intragastric

alcohol feeding in mice. Alcohol-associated dysbiosis is characterized by a profound suppression of commensal probiotic bacteria, including Lactobacillus.28 Several studies have shown that a restoration of eubiosis using supplemental probiotic Lactobacillus ameliorates alcoholic steatohepatitis in rodents.41, 42 Interestingly, Muc2−/− mice are protected from alcohol-associated changes in the microbial composition, including a suppression of Lactobacillus. In addition, Muc2 deficiency limits the proliferation of bacteria (such as

gram-negative A. muciniphila) that use mucins as carbon source. Thus, the absence of Muc2 prevents alcohol-associated dysbiosis, restores intestinal homeostasis, and inhibits experimental alcoholic liver disease. selleck The mucus layer has a very important role in the intestine. It largely prevents the translocation of viable bacteria from the gut lumen to extraintestinal organs such as lymph nodes and the systemic circulation.43 The absence of Muc2 as a major component of the intestinal mucus layer has no obvious adverse effect for the gut-liver axis at baseline without challenge. The thickness of the mucus layer increases in alcoholics as shown in our study and by others in rodents,27 which could be interpreted as a defense against alcohol or more likely against intestinal epithelial cell injury. And indeed, enteric infections also increase the Muc2 production and the mucus layer.43 A downside of this obvious good reaction of the intestine of increasing the mucus layer is that the vigorous immune defense system of enterocytes against bacteria is impaired.

Moreover, long-term studies of dieting indicate that the majority of individuals who dieted regain virtually all of the weight that was lost after dieting, regardless of whether they maintain their diet or exercise program.[8-10] Therefore, the maintenance of weight loss is still one of the biggest challenges of dietary interventions in patients with NAFLD. Provide 200–800 calories Crizotinib in vivo per day, maintaining protein intake but limiting calories from both fat and carbohydrates. Must be undertaken with medical supervision to prevent adverse side-effects, such as loss

of lean muscle mass, increased risks of gout, gallbladder stone, and electrolyte imbalances. Aside from the possibility of achieving weight loss through caloric restriction (either low in carbohydrates or low in fats) as JAK drugs a treatment for NAFLD, many dietary factors (especially macronutrients) can directly influence the development of NAFLD (Table 2).[3-7, 12-27] Manipulation of dietary composition might affect the outcomes of NAFLD and associated metabolic disorders independent of weight loss.[4-6] The dietary carbohydrates are often divided into complex carbohydrate (refer to any sort of digestible saccharide present in a whole food, where fiber, vitamins, and minerals are also found), or simple carbohydrates such as monosaccharides and disaccharides

(refer to sugar, provide calories but few other nutrients, and raise blood glucose rapidly especially if processed). Dietary carbohydrate

especially sugars contribute to increased circulating insulin and triglyceride concentrations and lead to increased hepatic de novo lipogenesis and decreased hepatic insulin sensitivity check details because of the lipogenic potential of fructose during liver metabolism.[12-16] In addition, recent genome-wide studies have identified several polymorphisms that contribute to increased liver fat accumulation, with some of these genes relating to dietary carbohydrate and sugar consumption.[7, 33] Dietary fructose consumption primarily in the form of soft drinks worldwide has increased in parallel with the increase in obesity, diabetes, and NAFLD, and some studies have suggested a direct association.[1-6] The role of fructose and sucrose in NAFLD and metabolic disorders has been thoroughly reviewed elsewhere. Low-carbohydrate diets are increasingly employed for treatment of obesity and NAFLD; they have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity.[4-6, 9, 34] However, the relationship between long-term maintenance on low-carbohydrate diets and systemic insulin resistance in humans remains to be elucidated. In addition, low glycemic index (GI ≤ 55) foods such as oats have been shown to increase appetite, reduce calories intake, and decrease plasma glucose and total cholesterol levels.

Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (MBL2), the ficolin-2 gene (FCN2), and the MBL-associated serine protease gene (MASP2) of recipients and donors were determined. Recipients

receiving a donor liver in the principal cohort with polymorphisms in all three components i.e., MBL2 (XA/O; O/O), FCN2+6359T, and MASP2+371A, had a cumulative risk of an infection Wnt inhibitor of 75% as compared to 18% with wild-type donor livers (P = 0.002), an observation confirmed in the second cohort (P = 0.04). In addition, a genetic (mis)match between donor and

recipient Rucaparib clinical trial conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52; P = 8.1 × 10−6) and the donor-recipient (mis)match genotype (hazard ratio = 6.41; P = 1.9 × 10−7), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and P < 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality selleck inhibitor (P = 0.9 × 10−8), of which 80% was infection-related. Conclusion: Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT. (HEPATOLOGY 2010;) The occurrence of infectious complications is a major clinical problem after orthotopic liver transplantation (OLT).1 Immunosuppressive agents that prevent graft rejection interfere with the adaptive immune response and thereby increase the susceptibility to infections. These drugs do not affect, however,

the innate immune system that is crucial for the first line of immunological defense. Lectins, humoral pattern recognition molecules of the innate immune system, recognize pathogen-associated carbohydrate motifs on microorganisms and elicit activation of multiple processes of innate immunity. In order to execute the elimination of microorganisms, these lectins, such as mannose-binding lectin (MBL) and ficolins, cooperate with phagocytes and other humoral factors, including complement. Upon pathogen binding, both lectins activate the complement system via MBL-associated serine proteases (MASPs), leading to C3b-mediated opsonization of the microorganism followed by phagocytosis and the formation of a complement membrane attack complex that directly kills the pathogen.

Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (MBL2), the ficolin-2 gene (FCN2), and the MBL-associated serine protease gene (MASP2) of recipients and donors were determined. Recipients

receiving a donor liver in the principal cohort with polymorphisms in all three components i.e., MBL2 (XA/O; O/O), FCN2+6359T, and MASP2+371A, had a cumulative risk of an infection PARP inhibitor of 75% as compared to 18% with wild-type donor livers (P = 0.002), an observation confirmed in the second cohort (P = 0.04). In addition, a genetic (mis)match between donor and

recipient R788 research buy conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52; P = 8.1 × 10−6) and the donor-recipient (mis)match genotype (hazard ratio = 6.41; P = 1.9 × 10−7), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and P < 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality selleck screening library (P = 0.9 × 10−8), of which 80% was infection-related. Conclusion: Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT. (HEPATOLOGY 2010;) The occurrence of infectious complications is a major clinical problem after orthotopic liver transplantation (OLT).1 Immunosuppressive agents that prevent graft rejection interfere with the adaptive immune response and thereby increase the susceptibility to infections. These drugs do not affect, however,

the innate immune system that is crucial for the first line of immunological defense. Lectins, humoral pattern recognition molecules of the innate immune system, recognize pathogen-associated carbohydrate motifs on microorganisms and elicit activation of multiple processes of innate immunity. In order to execute the elimination of microorganisms, these lectins, such as mannose-binding lectin (MBL) and ficolins, cooperate with phagocytes and other humoral factors, including complement. Upon pathogen binding, both lectins activate the complement system via MBL-associated serine proteases (MASPs), leading to C3b-mediated opsonization of the microorganism followed by phagocytosis and the formation of a complement membrane attack complex that directly kills the pathogen.

Approval for experiments related to the study of liver carcinogenesis in experimental animal models was obtained from the General Direction of Environment and Biodiversity, Government buy Enzalutamide of Catalonia, #4589, 2011. All animals received humane care and study protocols comply with the institution’s guidelines. Human tissues were collected with the required approvals from the Institutional Review Board (Comité Ético de Investigación Clínica del Hospital Universitario

de Bellvitge) and patient’s written consent conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Cell lines used in this study were from commercial sources. Hep3B, HepG2, and PLC/PRF/5 were obtained from the European Collection of Cell Cultures (ECACC). SNU449 were obtained from

the American Tissue Culture Collection (ATCC). Huh7 and HLF cells were from the Japanese Collection of Research see more Bioresources (JCRB Cell Bank) and were kindly provided by Dr. Perales (University of Barcelona, Spain) and Dr. Giannelli (University of Bari, Italy), respectively. Cell lines were never used in the laboratory for longer than 4 months after receipt or resuscitation. HepG2 and Hep3B were maintained in modified Eagle’s medium (MEM) medium, PLC/PRF/5 and Huh7 in Dulbecco’s modified Eagle’s medium (DMEM) medium, SNU449 and HLF in RPMI medium. Neonatal mice hepatocytes were immortalized selleck products as described[17] and cultured in DMEM. All media (Lonza, Basel, Switzerland) were supplemented with 10% fetal bovine serum (FBS; Sera Laboratories International, Cinder Hill, UK) and cells maintained in a humidified atmosphere of 37°C, 5% CO2. Analysis of cell viability was performed by Crystal violet staining.[3] Fluorescence microscopy studies were performed as described[3] (further details in the Supporting Materials and Methods). Cells were visualized with a Nikon eclipse 80i microscope with the appropriate filters. Representative images were taken with a Nikon DS-Ri1 digital camera. ImageJ software (National Institutes of Health

[NIH], Bethesda, MD) was used to analyze fluorescence from TIFF images captured using the same exposure conditions. Human HCC tissues were obtained from the Pathological Anatomy Service, University Hospital of Bellvitge, Barcelona. Paraffin-embedded tissues were cut into 4-μm-thick sections, incubated with the specific primary antibody overnight at 4°C, and binding developed with the Vectastain ABC kit (Vector Laboratories, Burlingame, CA). Further information is supplied in the Supporting Materials and Methods. Total protein extracts and western blotting procedures were carried out as described.[3] Source of antibodies are detailed in the Supporting Materials and Methods. RNeasy Mini Kit (Qiagen, Valencia, CA) was used for total RNA isolation.

The distribution of the relative rostral lengths (RL) of individuals followed a cline with no subgrouping. Both δ13C and δ15N showed high variability, which suggests that individuals use habitat heterogeneously. δ15N correlated with RL, indicating that longer beaked individuals either feed at a higher trophic

level and/or inhabit waters located further offshore than shorter beaked animals. Although δ13C and δ15N were correlated, RL and δ13C failed to show any correlation, possibly because the incremental effect of trophic level on δ13C has selleck been offset by the potential allopatric distribution of the morphotypes. We conclude that both the long-beaked and short-beaked forms of common dolphin do occur off Mauritania but,

in contrast to other areas, the existence of more than one species in the region is questioned because both stable isotopes and skull morphometric FK506 purchase appear to reflect differential use of habitat rather than taxonomy. Even though proposed previously by some authors, this is the first time that skull differentiation in common dolphins has been demonstrated to be likely due to niche segregation and not to speciation. This reveals that caution is needed when considering that long-beaked and short-beaked common dolphins from outside the eastern North Pacific fall into the taxonomic model described for this region. “
“We studied the density of a Geoffroy’s cat Leopardus geoffroyi population in a semiarid scrubland of Argentina, by comparing density estimates obtained during camera-trapping surveys in a national park and in nearby cattle ranches in 2006 and 2007–2008. Overall, we obtained 247 pictures of Geoffroy’s cats. The density (mean ±se) of the species at the park ranged from 1.2 ± 0.3 to 2.9 ± 1.4 individuals km−2, depending on the buffer applied, whereas density estimates at ranches were on average 32% lower. Only 11% of the Geoffroy’s cats identified in 2006 could still be detected in the area 2 years later, indicating that there was a high turnover of individuals in this population. The sex ratio (M:F) estimated during both surveys at the

park was 1:1.4, whereas at the ranches it was 1:0.8. The capture success of sympatric pampas cats Leopardus colocolo and jaguarundis Puma yagouaroundi was <0.3 records per selleck products 100 trap-days, and no evidence of these species was found in the ranches. Geoffroy’s cats seem to be tolerant to some degree of habitat alteration produced by livestock management, and the numerical response of this species in ranches could be largely the result of human persecution and the effects of livestock management on the habitat structure and prey base. “
“The feeding systems of durophagous vertebrates are well suited for studying how the performance of feeding structures is affected by growth. For these animals, feeding structures that deviate from isometric growth (i.e.

36 The proportion of responders increased from 8% to 16% and the proportion AG-014699 price of symptom-free days increased from 21% to 36% after 4 weeks of treatment in the lesogaberan versus placebo group. Overall, lesogaberan was safe and well tolerated. While lesogaberan

appear to be a promising future treatment for PPI failure, the aforementioned studies demonstrated only modest effect. Last year, AstraZeneca terminated further development of this compound. Glutamate is the primary neurotransmitter involved in signaling from visceral primary afferents to the CNS. Peripherally located mGluR5 receptors have been associated with control of TLESRs, making it a potential target for the treatment http://www.selleckchem.com/ferroptosis.htmll of GERD.26 The only mGluR5 antagonist that reached clinical assessment was ADX10059, a potent, selective, negative allosteric modulator. ADX10059 significantly decreased TLESRs and reduced esophageal acid exposure and improved symptomatic reflux episodes.37,38 However, the drug was associated with a predictable rise in liver function tests,

cases of hepatic failure, and CNS-related adverse events. Consequently, ADX10059 drug development was recently halted. Thus far, there are no studies that specifically evaluated the value of visceral pain modulators in refractory GERD patients. However, given the fact that most of the patients who fail PPI treatment originate from the NERD group and more than 50% of the PPI failure (twice daily) subjects demonstrate lack of either weakly or acidic reflux, the usage of these agents is highly attractive.39,40 Additionally, it could be argued that even for weakly acidic reflux that has not been shown to be associated with esophageal

mucosal damage, visceral pain modulators check details could be helpful. Pain modulators such as tricyclic antidepressants, trazodone (a tetracyclic antidepressants), and selective serotonin reuptake inhibitors have all been shown to improve esophageal pain in patients with non-cardiac chest pain.40–42 It is believed that these agents confer their visceral analgesic effect by acting at the CNS and/or peripherally at the sensory afferent level. The pain modulators are used in non-mood-altering doses, and they presently provide a therapeutic alternative until more novel esophageal-specific compounds are available. In addition, side-effects are relatively common, and may limit their usage in certain patient populations, like the elderly or those with multiple comorbidities. The addition of antacids, alginate-based formulations, such as Gavison, and sucralfate to once daily PPI in patients with refractory GERD has yet to be studied.5,6 Similarly, the value of cholestyramine, a bile-acid binder, in improving symptoms of refractory GERD patients has never been assessed.

Diabetic nephropathy and retinopathy are two well-established manifestations of small vessel hyaline arteriosclerosis in diabetes. Based on our observation NU7441 solubility dmso of isolated cases of patients with diabetes and liver enzyme abnormalities in whom the only finding on liver biopsy was hyaline arteriosclerosis, we decided to undertake a crosssectional

blinded study assessing this and other histological findings in diabetics. While nonalcoholic steatohepatitis is a well-recognized hepatic complication of diabetes, microangiopathy of the liver has never previously been reported in diabetic patients. The aim of this study was to evaluate the association between hyaline arteriosclerosis and diabetes. Methods: Liver biopsy findings from 62 patients with diabetes that met inclusion criteria between January 2006 and December 2009 were compared to those of 62 patients without diabetes matched by age and gender. Patients with cirrhosis, liver mass, right heart failure, significant alcohol use,

or insufficient available clinical information were excluded. Medical records were reviewed for the presence of diabetes, BMI, diabetes treatment, and comorbidities at time of biopsy (e. g. underlying liver disease, hypertension, dyslipidemia). An experienced pathologist (DJ) blinded to all clinical data (including presence or absence of diabetes) reviewed all biopsies. Results: Diabetic check details and control groups had the same average age (50y) and proportion of females (42%). Prevalence of hepatitis C was not different between the groups (68% vs.53%, p=0.12). Diabetics had a higher average BMI (35m/kg2 vs.29m/kg2, p=0.001), prevalence of hypertension (76% vs.34%, p <0.001) and learn more prevalence of dyslipidemia (47% vs.23%, p=0.0025). Among diabetics, 87% had type 2 diabetes and 48% used insulin. Histologically, prevalence of steatosis (23% vs.15%, p=0.25) and steatohepatitis (34% vs.29%, p=0.52) were not different between diabetics and controls. Hyaline arteriosclerosis was significantly more prevalent among diabetics compared

with controls: 47% vs.26% (p=0.012). A subgroup analysis among diabetics showed that age was significantly greater in patients with hyaline arteriosclerosis (54y vs.46y, p=0.021). Sex, BMI, insulin use, hypertension, and dyslipidemia were not associated with hyaline arteriosclerosis among diabetics. Conclusions: Hyaline arteriosclerosis of hepatic arterioles is a small vessel hepatic complication of diabetes described for the first time. The clinical and prognostic implications of this finding, particularly regarding liver injury, remain to be investigated. Disclosures: The following people have nothing to disclose: Maya Balakrishnan, Guadalupe Garcia-Tsao, Yanhong Deng, Maria Ciarleglio, Dhanpat Jain Background and aims.

Diabetic nephropathy and retinopathy are two well-established manifestations of small vessel hyaline arteriosclerosis in diabetes. Based on our observation selleck screening library of isolated cases of patients with diabetes and liver enzyme abnormalities in whom the only finding on liver biopsy was hyaline arteriosclerosis, we decided to undertake a crosssectional

blinded study assessing this and other histological findings in diabetics. While nonalcoholic steatohepatitis is a well-recognized hepatic complication of diabetes, microangiopathy of the liver has never previously been reported in diabetic patients. The aim of this study was to evaluate the association between hyaline arteriosclerosis and diabetes. Methods: Liver biopsy findings from 62 patients with diabetes that met inclusion criteria between January 2006 and December 2009 were compared to those of 62 patients without diabetes matched by age and gender. Patients with cirrhosis, liver mass, right heart failure, significant alcohol use,

or insufficient available clinical information were excluded. Medical records were reviewed for the presence of diabetes, BMI, diabetes treatment, and comorbidities at time of biopsy (e. g. underlying liver disease, hypertension, dyslipidemia). An experienced pathologist (DJ) blinded to all clinical data (including presence or absence of diabetes) reviewed all biopsies. Results: Diabetic Selleck Daporinad and control groups had the same average age (50y) and proportion of females (42%). Prevalence of hepatitis C was not different between the groups (68% vs.53%, p=0.12). Diabetics had a higher average BMI (35m/kg2 vs.29m/kg2, p=0.001), prevalence of hypertension (76% vs.34%, p <0.001) and see more prevalence of dyslipidemia (47% vs.23%, p=0.0025). Among diabetics, 87% had type 2 diabetes and 48% used insulin. Histologically, prevalence of steatosis (23% vs.15%, p=0.25) and steatohepatitis (34% vs.29%, p=0.52) were not different between diabetics and controls. Hyaline arteriosclerosis was significantly more prevalent among diabetics compared

with controls: 47% vs.26% (p=0.012). A subgroup analysis among diabetics showed that age was significantly greater in patients with hyaline arteriosclerosis (54y vs.46y, p=0.021). Sex, BMI, insulin use, hypertension, and dyslipidemia were not associated with hyaline arteriosclerosis among diabetics. Conclusions: Hyaline arteriosclerosis of hepatic arterioles is a small vessel hepatic complication of diabetes described for the first time. The clinical and prognostic implications of this finding, particularly regarding liver injury, remain to be investigated. Disclosures: The following people have nothing to disclose: Maya Balakrishnan, Guadalupe Garcia-Tsao, Yanhong Deng, Maria Ciarleglio, Dhanpat Jain Background and aims.

Methods: Adult patients enrolled in one of the NASH CRN studies with 2 or more biopsies (excluding active treatment arms of the PIVENS study) at least a year apart were included. Laboratory and anthropometric data was included if available within 6 months of biopsy. All biopsies underwent blinded consensus review. Fibrosis progression/regression was defined as any worsening/improvement in fibrosis stage. Univariate and multivariate logistic regression models were used to assess association with fibrosis progression. Results: 359 patients (mean age 47 years,

64% female) had at least 2 biopsies, with a mean time between biopsies of 4.4 years (range 1 to 17.3).128 showed fibrosis progression and 103 showed regression.181 patients had laboratory data available Alpelisib chemical structure at baseline. Using any degree of fibrosis progression as the outcome, only ballooning (O. R.0.67), Mallory-Denk bodies (O. R.2.4), and Caucasian race (O. R.3.4) showed significant associations (p<0.05) in multivariate models. We therefore examined the changes in laboratory data and BMI from first to last biopsy (Table) adjusting for baseline values in 169 patients with paired clinical data. While changes in BMI and transaminases were significant in the univariate model, only worsening transaminase levels were associated with fibrosis progression in the multivariate model. Conclusion: The natural history of NAFLD is complex, with both improvement and worsening observed in

a mean four year interval. Baseline histologic, demographic, anthropometric and laboratory

this website data were of little value in predicting fibrosis progression, but increased transaminases and BMI from first to last biopsy were associated with fibrosis progression. Univariate Multivariate Characteristic O. R. 95% CI P O. R. 95% CI P A BMI (kg/m2) 1.19 1.03-1.36 0.02 1.14 0.97-1.34 0.11 AALT(U/L/10) 1.18 1.05-1.33 0.004 1.20 1.04-1.38 0.01 A AST (U/L/10) 1.35 1.14-1.59 <0.001 A Aik phos (U/L/10) 1.17 0.98-1.40 0.08 1.09 0.89-1.33 0.43 A Triglycerides (mg/dL/10) 1.01 0.99-1.04 0.38 1.01 0.99-1.04 0.27 A Glucose (mg/dL/10) 1.08 0.98-1.18 0.10 A Insulin click here (μU/mL/10) 1.04 0.91-1.19 0.54 A HOMA-IR (log) 1.02 0.98-1.06 0.36 1.00 0.96-1.05 0.86 Disclosures: Elizabeth M. Brunt – Speaking and Teaching: Geneva Foundation Kris V. Kowdley – Advisory Committees or Review Panels: Abbott, Gilead, Merck, Novartis, Vertex; Grant/Research Support: Abbott, Beckman, Boeringer Ingelheim, BMS, Gilead Sciences, Ikaria, Janssen, Merck, Mochida, Vertex Arun J. Sanyal – Advisory Committees or Review Panels: Gore, Gilead, Abbott, Ikaria; Consulting: Salix, Immuron, Exhalenz, Bayer-Onyx, Genentech, Norgine, GalMed, Novartis, Echosens, Takeda; Grant/Research Support: Salix, Genentech, Genfit, Intercept, Ikaria, Takeda, Gilead; Independent Contractor: UpToDate Brent A. Neuschwander-Tetri – Advisory Committees or Review Panels: Genentech, Nimbus Discovery The following people have nothing to disclose: David E.