Animal models suggested that delayed clearance of LPS from the circulation occurred in chronic liver diseases because of the impaired phagocytosis of KC [15,16,17]. The persistence of endotoxinemia not only activated the liver immune cells with participating inflammatory process but also caused dysfunction of liver parenchymal cells and apoptosis [18]. Another theory on hepatic injury implied that LPS in the circulation interacted with toll like receptor 4 (TLR4) and mediated a signal transduction pathway, which included the formation of LPS-LBP-CD14secreted protein MD-2-TLR4 receptor complex [19,20,21]. The complex combined with myeloid differentiation factor 88, then phosphorylated and activated a series of cell kinases [21]. The activated kinases collectively further activated the transcription factor, mainly nuclear factor kB (NF-kB) [19,22], which resulted in increased production of pro-inflammatory cytokines, and 1326631 led to hepatic necrosis [19,20,21,22,23]. Lastly, LPS may also activate hepatic stellate cells (HSCs) to up-regulate gene expression of chemokines and adhesion molecules to induce liver injury [24,25,26]. Although the above theories on liver injury from LPS have been supported by animal models or a few in vivo studies, therelationship between the circulating LPS levels and 
liver disease activity or severity has not been fully explored in patients with ACHBLF. Previous published studies 
have focused on compensated liver disease or acute liver failure, which showed a significant correlation between elevated serum levels of LPS and liver disease severity [11,14,27]. In animal models for ACLF, Han et al suggested that LPS circulating in the blood may reach a certain level and then triggered the secondary liver injury on top of primary chronic liver disease. However, this theory has not been fully explored in patients with ACHBLF [10]. We sought to investigate LPS levels in different disease stages 15755315 of ACHBLF and the dynamic changes of LPS levels associated with the disease severity measured by clinical parameters in ACHBLF patients.Study 79831-76-8 web Design and MethodsThis was a 12 week prospective, observational study with healthy controls that enrolled ACHBLF patients and healthy volunteers from a single tertiary care center, the Third Affiliated Hospital of Sun Yet-Sen University in China from October 2008 through April 2010. The study protocol and the inform MedChemExpress Ebselen consent form were both approved (IRB approval N0:2008-321) by the Ethical Committee Board of Sun Yet-Sen University. All subjects were (or their designated health care proxy holders) consented prior to the screening.Study Population and Data CollectionAdult patients with ACHBLF who were willing to participate and consented to the study were screened for the following eligibility criteria: (1) age of 18?0 years; (2) meeting the diagnostic criteria of ACHBLF which included jaundice (serum bilirubin >5 mg/dl [85 umol/l]) and coagulopathy (INR = 1.5 or pro> = thrombin activity,40 ), ascites and/or encephalopathy as determined by physical examination within 4 weeks of the disease onset, and previously diagnosed chronic hepatitis B. (3) exacerbation of CHB for the first time. Key exclusion criteria were the followings: the time point of acute onset of ACHBLF was more than 14 days prior to the enrollment date; clinical evidence of cirrhosis or documented stage IV fibrosis on liver biopsy (if available); co-infection with hepatitis A, C, D, E or HIV virus; pregnant woman; diagnosis of oth.Animal models suggested that delayed clearance of LPS from the circulation occurred in chronic liver diseases because of the impaired phagocytosis of KC [15,16,17]. The persistence of endotoxinemia not only activated the liver immune cells with participating inflammatory process but also caused dysfunction of liver parenchymal cells and apoptosis [18]. Another theory on hepatic injury implied that LPS in the circulation interacted with toll like receptor 4 (TLR4) and mediated a signal transduction pathway, which included the formation of LPS-LBP-CD14secreted protein MD-2-TLR4 receptor complex [19,20,21]. The complex combined with myeloid differentiation factor 88, then phosphorylated and activated a series of cell kinases [21]. The activated kinases collectively further activated the transcription factor, mainly nuclear factor kB (NF-kB) [19,22], which resulted in increased production of pro-inflammatory cytokines, and 1326631 led to hepatic necrosis [19,20,21,22,23]. Lastly, LPS may also activate hepatic stellate cells (HSCs) to up-regulate gene expression of chemokines and adhesion molecules to induce liver injury [24,25,26]. Although the above theories on liver injury from LPS have been supported by animal models or a few in vivo studies, therelationship between the circulating LPS levels and liver disease activity or severity has not been fully explored in patients with ACHBLF. Previous published studies have focused on compensated liver disease or acute liver failure, which showed a significant correlation between elevated serum levels of LPS and liver disease severity [11,14,27]. In animal models for ACLF, Han et al suggested that LPS circulating in the blood may reach a certain level and then triggered the secondary liver injury on top of primary chronic liver disease. However, this theory has not been fully explored in patients with ACHBLF [10]. We sought to investigate LPS levels in different disease stages 15755315 of ACHBLF and the dynamic changes of LPS levels associated with the disease severity measured by clinical parameters in ACHBLF patients.Study Design and MethodsThis was a 12 week prospective, observational study with healthy controls that enrolled ACHBLF patients and healthy volunteers from a single tertiary care center, the Third Affiliated Hospital of Sun Yet-Sen University in China from October 2008 through April 2010. The study protocol and the inform consent form were both approved (IRB approval N0:2008-321) by the Ethical Committee Board of Sun Yet-Sen University. All subjects were (or their designated health care proxy holders) consented prior to the screening.Study Population and Data CollectionAdult patients with ACHBLF who were willing to participate and consented to the study were screened for the following eligibility criteria: (1) age of 18?0 years; (2) meeting the diagnostic criteria of ACHBLF which included jaundice (serum bilirubin >5 mg/dl [85 umol/l]) and coagulopathy (INR = 1.5 or pro> = thrombin activity,40 ), ascites and/or encephalopathy as determined by physical examination within 4 weeks of the disease onset, and previously diagnosed chronic hepatitis B. (3) exacerbation of CHB for the first time. Key exclusion criteria were the followings: the time point of acute onset of ACHBLF was more than 14 days prior to the enrollment date; clinical evidence of cirrhosis or documented stage IV fibrosis on liver biopsy (if available); co-infection with hepatitis A, C, D, E or HIV virus; pregnant woman; diagnosis of oth.