We see an opportunity to improve the care of UC patients. Establishing an early diagnosis of PSC in children with UC is controversial. There is no proven therapy to halt the progression to cirrhosis; however, many complications of end-stage liver disease can be effectively managed. The potential impact of an early diagnosis selleck screening library of PSC on the clinical care of children with IBD must be further investigated. We speculate that patients could benefit from an earlier diagnosis of PSC in a number of ways, including counseling on potential liver disease outcomes, avoidance of hepatotoxic medications, earlier recognition and management of the complications

of cirrhosis, and, potentially, focused screening strategies for cholangiocarcinoma. The strengths of our study include its population-based, multicenter nature. We maximized case Selleck BAY 80-6946 ascertainment with multiple, overlapping search strategies and with careful reviews of the medical records of all potential patients. In no case did we rely exclusively on the use of

administrative data or ICD-9 codes to include or exclude patients. There were several imitations to our study. First was the retrospective design, which did not allow access to patients or a uniform diagnostic workup. Thus, we cannot exclude the possibility of misclassification bias: the prevalence of ASC may have been higher and the prevalence of PSC and AIH may have been lower had all PSC patients undergone liver biopsy and all AIH patients undergone cholangiography. learn more Second, although our results reflect nearly universal ascertainment of IMLD, we cannot exclude the idea that a small proportion of the true burden of IBD was missed. The general local practice pattern of the minority of gastroenterologists outside the two large hospital systems is to refer all pediatric-aged patients to a pediatric subspecialist, so we believe that almost all of these patients were sampled. Finally, these data are almost exclusively from Caucasian patients of Northern and Western European descent. Utah is not a genetic isolate, and these results are likely generalizable to

populations of similar ancestry,[45] but they may not entirely reflect disease epidemiology or behavior in other racial and ethnic groups. In conclusion, we identified all patients with the major IMLDs of childhood in a population-based manner. We described the epidemiology and natural history of PSC, ASC, and AIH. We identified complications of IMLD as a major source of morbidity and mortality in pediatric UC patients, and we suggested further exploration of the role of an early diagnosis of PSC and ASC in UC patients. Our data suggest the need for improved diagnostic definitions of the spectrum of IMLDs. The authors thank Luana Micallef, M.S., and Peter Rodgers, Ph.D. (University of Kent, Kent, United Kingdom), for the use of their proportional-area Venn diagram creator, EulerAPE (http://www.eulerdiagrams.org/eulerAPE). They also thank Dr. Greg Stoddard, Dr.

We developed a multi-stage microfluidic technology to derive mature cells from pluripotent cells. This technology was implemented with generation

of 1 mm (diameter of hepatic lobule) stable oxygen gradient. Obtained cells have been characterized both with hepatic markers (AFP, CK 18 −19, ALB, CYP3A) and functional tests (proliferation, glycogen storage, indocyanine green uptake, albumin secretion). Results: We developed a microfluidic technology to generate a stable 〇2 gradient and culture and differentiate human pluripotent cells. We efficiently differentiated both hESCs and hiPSCs. Two hepatic lineages were obtained: hepatocyte- and cholangiocyte-like KU-60019 solubility dmso Aloxistatin chemical structure cells showing high CYP3A expression, ICG uptake, glycogen storage and albumin secretion over a 14-day period. This

technology allowed to accurately control hPSC expansion and fate toward early endoderm commitment, hepatic development and functional maturation on a chip. Compared to conventional culture, microfluidic oxygen-defined platform allowed shortening of the time reguired for differentiation and enhanced functional activity. The proportion between hepatocyte- and cholangiocyte-like cells was 3: 1. In particular, we obtained 75% of cells with glycogen storage capacity, whereas the number of CYP3A-positive cells resulted

in 60% of the total, with 20% increase compared to standard hepatocytes differentiation. Albumin production was about 40% higher than standard conditions. Conclusions: The engineerization of hPSC differentiation into hepatic lineages under defined oxygen gradient will allow us to further understand the mechanisms involved in tissue development. Moreover, mature hepatic cells fully integrated selleck inhibitor on a chip could be directly used for temporaldefined toxicological assays and drug screening. Disclosures: The following people have nothing to disclose: Giovanni G. Giobbe, Federica Tonon, Alessandro Zambon, Federica Michielin, Nicola Elvassore, Annarosa Floreani We have identified the TLR4-NANOG oncogenic pathway in the genesis of CD133+CD49f+ tumor initiating stem cell-like cells (TICs) and liver tumor in alcohol-fed HCV Ns5aTg mice and our most recent finding extends this notion to other HCC models including DEN/Pb-treated or Spnb2+/- mice. Although ectopic TLR4 expression is presumed to have occurred primarily in hepatocytes in these models, the evidence also suggests liver progenitor cells (LPCs) may be the source of TLR4+ TICs. [Aim] The present study investigated whether and why hepatocytes (HC) vs. liver progenitor cells (LPCs) are the primary target of the oncogenic TLR4 pathway.

In this study we evaluate whether LDV/SOF together with either Cisplatin supplier ribavirin (RBV) or the non-nucleotide NS5B inhibitor GS-9669 would allow patients to achieve high rates of SVR when administered for a shorter duration of 8 weeks in patients

with cirrhosis. Methods: 100 compensated cirrhotic patients with chronic HCV genotype 1 infection were randomized in equal proportions to receive LDV/SOF+RBV, LDV/SOF+GS-9669 250 mg, or LDV/SOF+GS-9669 500 mg daily for 8 weeks. Results: 100 patients were randomized and treated. The majority were male (65%), Caucasian (92%), treatment-experienced (74%), and had HCV genotype 1a (62%), and IL28B non-CC genotype (82%). 25 had previously Akt inhibitor been treated with a protease inhibitor+PEG+RBV regimen. The median BMI was 28.9 kg/m2 and the median HCV RNA was 6.1 log10 IU/ml. SVR12 rates are shown in the table. LDV/SOF+RBV or +GS-9669 was safe and well tolerated. There were two SAEs. One patient discontinued study

treatment due to an exacerbation of preexisting CHF. Adverse events were generally mild, and Grade 3/4 laboratory abnormalities were infrequent. The most frequent adverse events were headache, diarrhea, and nausea; both headache and nausea were most frequent in the LDV/SOF+500 mg GS-9669 group. Conclusions: Ledipasvir/sofosbuvir together with RBV or GS-9669 was effective in treating HCV. Overall 87% of patients achieved SVR12. Coadministration of GS-9669 did not appear to provide additional efficacy compared to RBV. To shorten therapy further or achieve higher selleckchem rates of SVR a more

potent agent or one with a complimentary mechanism of action may be required. All regimens were safe and well tolerated. Disclosures: Eric Lawitz – Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals, BioCryst, Biotica, Enanta, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Santaris Pharmaceuticals, Theravance, Vertex Pharmaceuticals; Grant/Research Support: AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co, Novartis, Presidio, Roche, Santaris Pharmaceuticals, Vertex Pharmaceuticals ; Speaking and Teaching: Gilead, Kadmon, Merck, Vertex Fred Poordad – Advisory Committees or Review Panels: Abbott, Achillion, BMS, Inhibitex, Boeheringer Ingelheim, Pfizer, Genentech, Idenix, Gilead, Merck, Vertex, Salix, Janssen, Novartis; Grant/Research Support: Abbott, Anadys, Achillion, BMS, Boehringer Ingelheim, Genentech, Idenix, Gilead, Merck, Phar-massett, Vertex, Salix, Tibotec/Janssen, Novartis Robert H. Hyland – Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc Jing Wang – Employment: Gilead Science Phillip S.

In the study, we aim to detail anti-metastatic effects and molecular mechanisms of baicalein on HCC cells. Methods: The anti-metastatic effect of baicalein was determined using wound healing assay and transwell invasive model. find more The expression of MMP-2, MMP-9 and u-PA mRNA and protein in MHCC97H cells was determined by quantitative RT-PCR and western blot. The activity of MMP-2, MMP-9 and u-PA was determined by zymography.

The expression of TIMP-1 and TIMP-2 was determined by Western blot. The expression of MEK1 and ERK1/2 was measured by Western blot. Expression Plasmids (pcDNA3.1(+)-MEK1)were constructed and transfected Results: The migration and invasion of MHCC97H cells were markedly suppressed by baicalein in a dose-dependent manner. MMP-2, -9 and u-PA have been considered to be important in cancer cell invasion and metastasis because they play important Opaganib nmr roles in the degradation of the ECM. In our study, we found that treatment with baicalein on MHCC97H for 24h resulted in a decrease in MMP-2, -9 and u-PA expression, as well as proteinase activity. Meanwhile, the expression

of TIMP-1 and TIMP-2 were increased in a dose-dependent fashion. Thus, the anti-metastatic effect of baicalein on MHCC97H cells is correlated to proteinases and their inhibitors. Moreover, ERK pathway is closely correlated with synthesis of proteinases and their inhibitors. In our study, we found that

baicalein treatment decreased the levels of phosphorylation of MEK1 and ERK1/2. Overexpression of MEK1 partially blocked anti-metastatic effects of baicalein. Conclusion: Baicalein preferentially inhibits HCC invasion through inhibition of ERK pathway and by regulating synthesis of proteinases and their inhibitors. Acknowledgements: this website Supported by a grant from Program for changjiang Scholars and Innovative Research Team in University (PCSIRT: 1171). Key Word(s): 1. Baicalein; 2. HCC; 3. ERK pathway; 4. ECM; Presenting Author: WEILI HUANG Additional Authors: XIAOHUI GUAN Corresponding Author: WEILI HUANG Affiliations: Department of Digestion, Affiliated Hospital of Beihua University Objective: To investigate the relationship between the contents of β-catenin in cell nucleus of gastric cancer tissue and sFas in blood plasma and the degree of hyperplasia and infiltration of gastric cancer cells.

In the study, we aim to detail anti-metastatic effects and molecular mechanisms of baicalein on HCC cells. Methods: The anti-metastatic effect of baicalein was determined using wound healing assay and transwell invasive model. Selleck Compound Library The expression of MMP-2, MMP-9 and u-PA mRNA and protein in MHCC97H cells was determined by quantitative RT-PCR and western blot. The activity of MMP-2, MMP-9 and u-PA was determined by zymography.

The expression of TIMP-1 and TIMP-2 was determined by Western blot. The expression of MEK1 and ERK1/2 was measured by Western blot. Expression Plasmids (pcDNA3.1(+)-MEK1)were constructed and transfected Results: The migration and invasion of MHCC97H cells were markedly suppressed by baicalein in a dose-dependent manner. MMP-2, -9 and u-PA have been considered to be important in cancer cell invasion and metastasis because they play important Birinapant chemical structure roles in the degradation of the ECM. In our study, we found that treatment with baicalein on MHCC97H for 24h resulted in a decrease in MMP-2, -9 and u-PA expression, as well as proteinase activity. Meanwhile, the expression

of TIMP-1 and TIMP-2 were increased in a dose-dependent fashion. Thus, the anti-metastatic effect of baicalein on MHCC97H cells is correlated to proteinases and their inhibitors. Moreover, ERK pathway is closely correlated with synthesis of proteinases and their inhibitors. In our study, we found that

baicalein treatment decreased the levels of phosphorylation of MEK1 and ERK1/2. Overexpression of MEK1 partially blocked anti-metastatic effects of baicalein. Conclusion: Baicalein preferentially inhibits HCC invasion through inhibition of ERK pathway and by regulating synthesis of proteinases and their inhibitors. Acknowledgements: selleck chemicals llc Supported by a grant from Program for changjiang Scholars and Innovative Research Team in University (PCSIRT: 1171). Key Word(s): 1. Baicalein; 2. HCC; 3. ERK pathway; 4. ECM; Presenting Author: WEILI HUANG Additional Authors: XIAOHUI GUAN Corresponding Author: WEILI HUANG Affiliations: Department of Digestion, Affiliated Hospital of Beihua University Objective: To investigate the relationship between the contents of β-catenin in cell nucleus of gastric cancer tissue and sFas in blood plasma and the degree of hyperplasia and infiltration of gastric cancer cells.

Of those, 800,000 to 1.4 million have chronic HBV infections and 2.7 to 3.9 million have chronic HCV infections. About 65% and 75% of the infected population are unaware that they are infected with HBV and HCV, respectively.2, 3 Although the incidence of acute HBV infection is declining in the U.S., due to the availability of HBV vaccines,

about 43,000 new acute HBV infections still occur each year.4 Of those new infections, about 1,000 infants acquire the infection from their HBV-positive mothers.5 HBV is also transmitted by sexual contact with an infected person, sharing injection drug equipment, and needlestick injuries. The number of people in the U.S. who are living with chronic HBV infection may be increasing as a result of legal immigration from highly endemic countries (especially countries in the western Pacific region, Asia, and sub-Saharan Africa). HCV buy Lenvatinib is efficiently transmitted this website by direct percutaneous exposure to

infectious blood. Persons likely to have chronic HCV infection include those who received a blood transfusion before 1992 and past or current injection-drug users (IDUs). Most IDUs in the United States have serologic evidence of HCV infection.6, 7 While HCV incidence appears to have declined over the last decade, a large portion of IDUs, who often do not have access to healthcare services, are not identified by current surveillance systems making interpretation of that trend complicated. Despite federal, state, and local public health efforts to prevent and control HBV and HCV, these diseases remain serious health problems in the U.S. Therefore, the Centers for Disease Control and Prevention (CDC), the Department of Health and Human Services’ Office of Minority Health, the Department of Veterans Affairs,

and the National Viral Hepatitis Roundtable sought guidance from the Institute of Medicine (IOM) in identifying missed opportunities related to the prevention and control of HBV and HCV infections. The IOM assembled an expert committee to address that task; its findings click here and recommendations are published in a report. This article summarizes the IOM’s report Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C.8 Abbreviations: CDC, Centers for Disease Control and Prevention; HBV, hepatitis B virus; HCV, hepatitis C virus; IDU, injection drug user; IOM, Institute of Medicine. The IOM committee’s overall approach to its task is presented in Fig. 1. Major factors that impede efforts to prevent and control hepatitis B and C are the lack of knowledge and awareness on the part of healthcare providers, at-risk populations, the public, and policy makers. Insufficient understanding about the seriousness of this public health problem has led to inadequate allocation of public resources for viral hepatitis prevention, control, and surveillance programs.

Methods: A retrospective analysis of 23561 cases with endoscopic screening for esophageal carcinoma in high-risk area in Hebei Province during 2005 and 2010 was performed. Results: The incidence of SMPECs was 6.24% (188/3012) in patients

with early esophageal and gastric cardia carcinomas and precancerous lesions. The detection rate of SMPECs in 2008–2010 was significantly higher than that in 2005–2007 (7.02% vs 5.09%, p < 0.05). In this study the distribution of SMPECs in male and female was 1.00% (115/11471) and 0.6% (73/12090), the difference had statistical significance (p < 0.01). Among 40 to 69 years group, the SMPECs with increasing trend, and the R428 supplier detection rate of aged under 55 and over 55 was 0.40% (61/15393) and 0.55% (127/8168) respectively. Additionally, with upper gastrointestinal carcinoma family history was a significant risk for SMPECs (OR = 3.84, 95% CI: 2.41–5.01, p = 0.00). The results indicate the occurrence of precancerous lesions at middle esophagus (64.9%, 122/188) and 12 to 3 o’clock position (85.6%, 161/188) in gastric cardia were more common. Esophageal mucosal congestion-roughness (61.1%, 113/185) and gastric selleck chemicals llc cardia mucosal congestion-edema (73.7%, 132/179) were the most common endoscopic features of precancerous lesions of SMPECs. There were 178 cases low grade dysplasia in esophageal precancerous

lesion of SMPECs, which was more common than that in gastric cardia (137 cases) (p = 0.00). Conclusion: This learn more study show that synchronous multiple

primary early esophageal and gastric cardia carcinomas and precancerous lesions are not rare in high-risk areas. Male, aged over 55 and family history of upper gastrointestinal carcinoma does seem to increase the risk of SMPECs, they should be regarded as a high-risk groups during clinical examination and endoscopic screening. The endoscopic mucosal abnormality of precancerous lesion in esophagus and gastric cardia is slight and less visible, and the detection of low grade dysplasia in gastric cardia precancerous lesion of SMPECs needs to be improved. Key Word(s): 1. Multiple primary; 2. Esophageal; 3. Gastric cardia; 4. Early carcinoma; Presenting Author: DEXIN ZHANG Additional Authors: GUOHONG ZHAO, JIANQIN KANG, GUOHUI XU, YONGZHAN NIE, KAICHUN WU, DAIMING FAN, HONGBO ZHANG Corresponding Author: DEXIN ZHANG Affiliations: Xijing Hospital, The Fourth Military Medical University Objective: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to its high frequency of metastasis and invasion. Recent studies have suggested that Grp78 may play important roles in the progression and development of malignant tumors. However, the mechanisms of invasion and metastasis of ESCC in relation to Grp78 still remain unknown.

1 ± 6.44 versus 38.1 ± 18.64 (P < 0.05) and 40.8 ± 12.91 cells per HPF (P < 0.005); Fig. 6C]. The adaptor protein ASC contributes to immune responses through activation of cysteine protease caspase-1–dependent IL-1β.26 Although under normal conditions ASC-associated inflammasomes

are autorepressed, they become activated by a wide range of pathogen stimuli, including oxidative stress, ischemia, and damage signals. As an endogenous danger signal or alarmin, HMGB1, BIBW2992 mouse released from activated macrophages/necrotic cells, may bind immune receptors, including TLRs and RAGE, to trigger immune responses.21 This study has identified the essential role of HMGB1 in ASC/caspase-1/IL-1β–dependent inflammatory ASC KO responses in hepatic IRI. Indeed, global decreased sALT levels, depressed local macrophage/neutrophil sequestration, reduced hepatocellular apoptosis, and mitigated proinflammatory cytokine/chemokine

programs in IR-stressed livers. Moreover, ASC deficiency diminished Palbociclib chemical structure the induction of HMGB1 and alleviated IR-triggered liver damage through negative regulation of TLR4. The molecular mechanisms of ASC/caspase-1/IL-1β signaling for programming an inflammatory phenotype might involve the activation of multiple intercellular pathways. We found that disruption of ASC inhibited HMGB1/TLR4 expression and led to decreased induction of inflammatory mediators; this suggests that ASC/caspase-1/IL-1β plays an important role in triggering local inflammation. In fact, the adaptor ASC was initially believed to exert its effects by bridging the interaction between NLRs and caspase-1 in inflammasome complexes.27 The activation of ASC within inflammasomes leads to the maturation of caspase-1 and the processing of its IL-1β and IL-18

selleck chemical substrates. Our in vitro data demonstrate that ASC deficiency decreased caspase-1 activity and IL-1β/IL-18 production in LPS-stimulated BMMs, and this implies a role for ASC in caspase-1/IL-1β–mediated inflammation. Although the ASC/caspase-1/IL-1β axis is essential for the initiation of an inflammatory response, the molecular pathways involved in crosstalk with HMGB1 have not been elucidated. Our data demonstrate that the treatment of ASC KO mice with rHMGB1 increased IR-induced hepatocellular damage, whereas the disruption of ASC without exogenous rHMGB1 prevented hepatic inflammatory development. These results are consistent with the ability of endogenous HMGB1 to promote liver IR damage19 and suggest that HMGB1 might have a distinct role during ASC/IL-1β–mediated inflammation in hepatic IRI. As an intracellular protein, HMGB1 translocates to the nucleus, where it binds DNA to regulate gene transcription.28 However, extracellular HMGB1 has been shown to act as a cytokine mediator in response to inflammatory stimuli due to infection,15 whereas HMGB1 promotes TLR4-mediated inflammation in hepatic IRI.

1 ± 6.44 versus 38.1 ± 18.64 (P < 0.05) and 40.8 ± 12.91 cells per HPF (P < 0.005); Fig. 6C]. The adaptor protein ASC contributes to immune responses through activation of cysteine protease caspase-1–dependent IL-1β.26 Although under normal conditions ASC-associated inflammasomes

are autorepressed, they become activated by a wide range of pathogen stimuli, including oxidative stress, ischemia, and damage signals. As an endogenous danger signal or alarmin, HMGB1, check details released from activated macrophages/necrotic cells, may bind immune receptors, including TLRs and RAGE, to trigger immune responses.21 This study has identified the essential role of HMGB1 in ASC/caspase-1/IL-1β–dependent inflammatory ASC KO responses in hepatic IRI. Indeed, global decreased sALT levels, depressed local macrophage/neutrophil sequestration, reduced hepatocellular apoptosis, and mitigated proinflammatory cytokine/chemokine

programs in IR-stressed livers. Moreover, ASC deficiency diminished Selleck RAD001 the induction of HMGB1 and alleviated IR-triggered liver damage through negative regulation of TLR4. The molecular mechanisms of ASC/caspase-1/IL-1β signaling for programming an inflammatory phenotype might involve the activation of multiple intercellular pathways. We found that disruption of ASC inhibited HMGB1/TLR4 expression and led to decreased induction of inflammatory mediators; this suggests that ASC/caspase-1/IL-1β plays an important role in triggering local inflammation. In fact, the adaptor ASC was initially believed to exert its effects by bridging the interaction between NLRs and caspase-1 in inflammasome complexes.27 The activation of ASC within inflammasomes leads to the maturation of caspase-1 and the processing of its IL-1β and IL-18

selleck inhibitor substrates. Our in vitro data demonstrate that ASC deficiency decreased caspase-1 activity and IL-1β/IL-18 production in LPS-stimulated BMMs, and this implies a role for ASC in caspase-1/IL-1β–mediated inflammation. Although the ASC/caspase-1/IL-1β axis is essential for the initiation of an inflammatory response, the molecular pathways involved in crosstalk with HMGB1 have not been elucidated. Our data demonstrate that the treatment of ASC KO mice with rHMGB1 increased IR-induced hepatocellular damage, whereas the disruption of ASC without exogenous rHMGB1 prevented hepatic inflammatory development. These results are consistent with the ability of endogenous HMGB1 to promote liver IR damage19 and suggest that HMGB1 might have a distinct role during ASC/IL-1β–mediated inflammation in hepatic IRI. As an intracellular protein, HMGB1 translocates to the nucleus, where it binds DNA to regulate gene transcription.28 However, extracellular HMGB1 has been shown to act as a cytokine mediator in response to inflammatory stimuli due to infection,15 whereas HMGB1 promotes TLR4-mediated inflammation in hepatic IRI.

Interestingly, the recent report that mice lacking the negative regulator of TLR signaling IRAK-M exhibit increased alcohol-induced TLR4 signaling and microbiota alteration indicate that microbiota composition alteration and inflammation are likely highly intertwined Selleckchem RAD001 coregulating events.[34] Together, these data support the concept that microbiota products, especially endotoxin, play a central role in alcohol-induced liver disease,

and suggest that antagonizing TLR4-mediate recognition of endotoxin might be a means of treating/preventing alcohol-induced liver injury.[21] Following alcoholism, the most well-established classic cause of liver disease is infection, especially with hepatitis viruses.

Although less well studied, similar paradigms may be relevant to mechanisms by which alcoholism and viral infection cause chronic inflammatory disease of the liver. For example, hepatitis B virus (HBV), which is thought to be responsible for a considerable portion of the worldwide liver disease burden, is Selleckchem FK866 associated with both altered gut permeability and alterations in the gut microbiota composition, either of which can be envisaged to result in increased activation of liver TLR/NLR.[35, 36] In a mouse model of viral-induced liver disease, germfree mice are protected from disease and conventional mice can be protected by the antibiotic/TLR4 antagonist polymixin B.[37] Thus, although the myriad of ways in which microbiota and viruses interact have only begun

to be deciphered, it seems likely that mechanisms by which HBV and perhaps hepatitis C virus (HCV) promote liver disease are mediated, in part, by way of the gut microbiota. While alcoholism and infection remain major causes of liver disease, perhaps the most alarming increase in liver disease click here is occurring in the form NAFLD. Twenty percent of NAFLD individuals develop chronic hepatic inflammation, i.e., nonalcoholic steatohepatitis (NASH) associated with cirrhosis, portal hypertension, and/or hepatocellular carcinoma (HCC). The rapidity of increased incidence of NAFLD over the last half-century, amidst relatively constant human genetics, indicates that environmental and/or lifestyle factors are driving this alarming trend. This is, of course, not occurring in isolation but rather is associated with the constellation of metabolic abnormalities including obesity, insulin resistance/type 2 diabetes, hyperlipidemia, and hypertension collectively referred to as metabolic syndrome. Like NAFLD and other chronic liver diseases, metabolic syndrome is increasingly appreciated to be a chronic inflammatory disease in which gut microbial products are prime suspects to be drivers of inflammation. Thus, it is possible that NAFLD and other aspects of metabolic syndrome are promoting each other and/or that both have related underlying causes.