Ared to those in the progression or remission phase. The abnormal distributions of LPS levels among different phases were statistically significant in ACHBLF. In addition, the changes in LPS levels were correlated with MELD-Na scores in the progression and the peak phase. To our knowledge, this is by far the first study in which detailed the ASP015K web dynamic changes of LPSDynamic Changes of LPS in ACLF with HBVTable 1. Baseline assessments of AN-3199 ACHBLF patients and healthy subjects.Mean ?SD Male (M) Age (year)* HBeAg ( ) HBV-DNA (log10 IU/mL)* Serum bilirubin (umol/l)* ALT (IU/l)* AST (IU/l)* Creatinine(mmol/l)* Prothrobin time (Sec.)* MELD-Na score Serum LPS (EU/mL)Control group(n = 10) 8 32.3064.ACHBLF group(n = 5) 5 34.268.23 (80 ) 6.2762.case 1 M 28 + 3.44 237.1 423 293 57.8 23.3 15.13 0.case 2 M 37 + 6.22 321.7 921 1466 76.0 33.2 25.00 0.case 3 M 25 + 8.39 215.8 2579 2071 70.1 23.7 17.67 0.case 4 M 35 4.71 389.8 337 144 71.1 24.5 20.14 0.case 5 M 46 + 8.56 373.3 75 173 107.2 27.3 17.55 0.12.3362.06 20.7065.33 19.4063.37 47.6963.63 12.5460.307.54678.53 86761004.88 829.46885.32 76.44618.46 26.464.11 19.2263.0.020160.0.018360.Test of normality is done by Kolmogorov-Smirnov Test. *P.0.05. doi:10.1371/journal.pone.0049460.tlevels in different phases of ACHBLF, and provided the evidence of acute liver injury in ACHBLF associated with increased LPS levels. Since MELD-Na scores were correlated with LPS levels in the progression and the peak phase, our data pointed to the direction of the secondary injury from LPS in chronic liver disease leading to liver failure, which was proposed by Han et al. in the study from animal model. Further studies with histology correlation to LPS are needed to confirm if the severity of liver injury actually is directly correlated with LPS levels in ACHBLF patients.The findings in this study also implied a possible therapeutic intervention for ACHBLF by removing LPS from the serum. Several studies done by Adachi et al observed that there was a positive correlation between the occurrence of bacterial translocation from the gut to portal system and liver dysfunction in alcoholic hepatitis [34,35]. Li et al demonstrated that elevation of endotoxin levels in the circulation from translocation of gut flora occurred during acute flares in patients with chronic hepatitis [27]. It is possible that the elevation of LPS level in CHB patients was due to bacterial translocations from the gut to portal circulation resulting in endotoxemia in the early phase (or progressive phase ) of ACHBLF. On the other hand, the liver dysfunction in the early stage of ACHBLF probably further induced bacterial translocation from the gut leading to higher level of endotoxemia. In addition, in patients with liver dysfunction, the uptake of endotoxin by hepatic and Kupffer cells were compromised as compared to normal physical conditions, resulting in higher circulating levels of LPS [9,13,36]. High levels of LPS then induced the aggravations of liver injury through the LPS-MD-2/TLR4/NF-kb signal pathway and further negatively impacted on KC and hepatic clearance of endotoxin [33]. Thus, it is expected that the peak level of LPS was observed during the peak phase of ACHBLF. In our study, the dynamic changes of LPS were paralleled with the changes of TBil and MELD-Na in different phases of ACHBLF. The changes in LPS levels were correlated with MELD-Na scores in the progression and the peak phase, further indicated that the worsen disease severity was the.Ared to those in the progression or remission phase. The abnormal distributions of LPS levels among different phases were statistically significant in ACHBLF. In addition, the changes in LPS levels were correlated with MELD-Na scores in the progression and the peak phase. To our knowledge, this is by far the first study in which detailed the dynamic changes of LPSDynamic Changes of LPS in ACLF with HBVTable 1. Baseline assessments of ACHBLF patients and healthy subjects.Mean ?SD Male (M) Age (year)* HBeAg ( ) HBV-DNA (log10 IU/mL)* Serum bilirubin (umol/l)* ALT (IU/l)* AST (IU/l)* Creatinine(mmol/l)* Prothrobin time (Sec.)* MELD-Na score Serum LPS (EU/mL)Control group(n = 10) 8 32.3064.ACHBLF group(n = 5) 5 34.268.23 (80 ) 6.2762.case 1 M 28 + 3.44 237.1 423 293 57.8 23.3 15.13 0.case 2 M 37 + 6.22 321.7 921 1466 76.0 33.2 25.00 0.case 3 M 25 + 8.39 215.8 2579 2071 70.1 23.7 17.67 0.case 4 M 35 4.71 389.8 337 144 71.1 24.5 20.14 0.case 5 M 46 + 8.56 373.3 75 173 107.2 27.3 17.55 0.12.3362.06 20.7065.33 19.4063.37 47.6963.63 12.5460.307.54678.53 86761004.88 829.46885.32 76.44618.46 26.464.11 19.2263.0.020160.0.018360.Test of normality is done by Kolmogorov-Smirnov Test. *P.0.05. doi:10.1371/journal.pone.0049460.tlevels in different phases of ACHBLF, and provided the evidence of acute liver injury in ACHBLF associated with increased LPS levels. Since MELD-Na scores were correlated with LPS levels in the progression and the peak phase, our data pointed to the direction of the secondary injury from LPS in chronic liver disease leading to liver failure, which was proposed by Han et al. in the study from animal model. Further studies with histology correlation to LPS are needed to confirm if the severity of liver injury actually is directly correlated with LPS levels in ACHBLF patients.The findings in this study also implied a possible therapeutic intervention for ACHBLF by removing LPS from the serum. Several studies done by Adachi et al observed that there was a positive correlation between the occurrence of bacterial translocation from the gut to portal system and liver dysfunction in alcoholic hepatitis [34,35]. Li et al demonstrated that elevation of endotoxin levels in the circulation from translocation of gut flora occurred during acute flares in patients with chronic hepatitis [27]. It is possible that the elevation of LPS level in CHB patients was due to bacterial translocations from the gut to portal circulation resulting in endotoxemia in the early phase (or progressive phase ) of ACHBLF. On the other hand, the liver dysfunction in the early stage of ACHBLF probably further induced bacterial translocation from the gut leading to higher level of endotoxemia. In addition, in patients with liver dysfunction, the uptake of endotoxin by hepatic and Kupffer cells were compromised as compared to normal physical conditions, resulting in higher circulating levels of LPS [9,13,36]. High levels of LPS then induced the aggravations of liver injury through the LPS-MD-2/TLR4/NF-kb signal pathway and further negatively impacted on KC and hepatic clearance of endotoxin [33]. Thus, it is expected that the peak level of LPS was observed during the peak phase of ACHBLF. In our study, the dynamic changes of LPS were paralleled with the changes of TBil and MELD-Na in different phases of ACHBLF. The changes in LPS levels were correlated with MELD-Na scores in the progression and the peak phase, further indicated that the worsen disease severity was the.