We have identified TSP-1 as a novel immediate early gene derived from ECs, showing that the expression level of TSP-1 was immediately BMN 673 cell line up-regulated and returned to basal levels by 24 hours in response to PH hepatectomy. Our findings and the previous report28 suggest that ECs may play two distinct roles in hepatocyte proliferation after PH hepatectomy: One is an antiproliferative role by activating the TSP-1/TGF-β1 axis within 24 hours, and the other is a proproliferative role by activating VEGFR-2 after 24 hours. This finding is consistent with the evidence that TSP-1 inhibits the activation of VEGFR-2

through its receptor, CD47, in ECs,23 and suggests that the reduction of TSP-1 expression may be required for the functional shift in ECs from an anti- to a proproliferative role in hepatocytes. Microvascular rearrangement is important for tissue remodeling, and the antiangiogenic action is one of the well-recognized functions of TSP-1.29 check details However, the expression of CD31 mRNA for monitoring angiogenesis did not show any significant difference between WT and TSP-1-null mice at 24, 48, and 72 hours after PH hepatectomy (Hayashi H, and Sakai T;

unpublished data), suggesting that TSP-1 does not affect vascularization during liver regeneration after PH hepatectomy. TGF-β1 is known to be a potent inhibitor of mitogen-stimulated DNA synthesis in cultured hepatocytes.3 p21 is important for inhibiting hepatocyte proliferation in vivo, especially at the G1/S transition of the cell cycle,20 and the expression of p21 is up-regulated by TGF-β1.30 There is evidence that TGF-β1 mRNA induction occurs within 4 hours and remains elevated until 72 hours after PH hepatectomy.5, 6 In contrast, we found the only limited activation of TGF-β signaling in an earlier phase (within 24 hours), with a peak at ∼12 hours. It is known that TGF-β is secreted as latent forms and

Glycogen branching enzyme they are converted into active TGF-β in response to injury. There are several mechanisms for activation, such as by proteases, integrins (e.g., αvβ6 and αvβ8), and TSP-1, all of which are likely to be tissue specific.31 Whereas the complete lack of TGF-β-mediated signal in hepatocyte-specific TGF-β type II receptor knockout mice accelerates hepatocyte proliferation in the later phase (∼36-48 hours) after hepatectomy,7 the role of TGF-β signaling in the earlier phase (within 24 hours) remains to be elucidated. Our present findings provide compelling evidence that locally activated TGF-β1 mediated by TSP-1 as an immediate early gene is critical in the early phase (within 24 hours) post PH posthepatectomy to initiate the inhibitory effect on hepatocyte proliferation, and this TGF-β signaling has a functional link to the G1/S-phase transition by modulating p21 protein expression. A major downstream target of TGF-β1, PAI-1,21 is a negative regulator of liver regeneration, and PAI-1-null mice show acceleration of liver regeneration after Fas-mediated massive hepatocyte death.

“
“A 27-year-old woman was referred to our Clinic because of a liver mass on a computed tomography (CT) scan. Over the preceding 6 months, she had noted intermittent

pain in the right upper quadrant of her abdomen. She had been taking an oral contraceptive pill for 6 years. Physical examination revealed mild hepatomegaly while routine blood tests showed minor elevations of liver enzymes. On a triphasic CT scan (Figure 1), she had occlusion (non-enhancement) of the left hepatic vein (white arrow), slit-like narrowing of the inferior vena cava (large black arrow) and multiple venovenous collateral vessels (small black arrows). A more PXD101 mw caudal CT section (Figure 2) showed massive hypertrophy of the caudate and deep right lobe of the liver, simulating a neoplastic mass. The peripheral segments of the liver were atrophic and heterogeneously BGJ398 solubility dmso enhancing (white arrow). Other CT sections showed a patent inferior vena cava and an enlarged patent vein draining the caudate lobe. An hepatic venogram showed extensive intrahepatic serpiginous collateral veins forming a ‘spiderweb’ while an inferior vena cavogram showed extrinsic compression of the retrohepatic inferior vena cava caused by the enlarged caudate

lobe. She was diagnosed with a Budd-Chiari syndrome and anticoagulated with warfarin. Various tests for a hypercoagulable state were negative. The majority of patients with a Budd-Chiari syndrome (70%) have manifestations that appear weeks or months after the development of hepatic vein thrombosis. The most common manifestation is ascites that is relatively resistant to treatment with diuretics. Other manifestations include gastrointestinal bleeding from esophageal varices and a progressive deterioration in general health, often associated with ascites. Approximately

70% of patients with the Budd-Chiari syndrome develop hypertrophy of the caudate lobe while 40% develop regenerative nodules, usually in areas of decreased portal perfusion. The reason for caudate lobe hypertrophy is the presence Erlotinib research buy of patent caudate lobe veins that enter the inferior vena cava just below the ostia of the main hepatic veins. In the patient described above, caudate lobe hypertrophy was prominent and mimicked the presence of a caudate lobe neoplasm. The use of oral contraceptive drugs appears to increase the risk of Budd-Chiari syndrome by a factor of 2 but most patients also have a coexisting thrombogenic disorder. “
“Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ-/- mice have increased lipid droplet (LD) size but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation.

5-Fluorouracil (5-FU) chemotherapy for cancer treatment is often accompanied by severe intestinal injury (mucositis). It is unknown whether ME Gefitinib cell line impacts on the processes of mucositis and neoplasia in normal and transformed epithelial cells. Aims: MEs from different host trees (Quercus: Oak,

Fraxini: Ash and Mali: Apple) in the presence or absence of 5-FU chemotherapy, were examined for their effects on viability of colon cancer and normal non-transformed intestinal cells in vitro. Methods: 3-(4,5-Dimethylthiazol-2 yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine Caco-2 (colonic cancer) and IEC-6 (non-transformed) cell viability after 48 hr incubation with MEs (Quercus: Oak, Fraxini: Ash and Mali: Apple) (1–100 μg/mL)

or MEs (1–100 μg/mL) combined with 5-FU (100 μM for Caco-2 and 5 μM for IEC-6). Statistical significance was assumed at p < 0.05. Results: Fraxini; with highest levels of lectin and viscotoxin, was the most potent ME followed by Quercus and Mali with IC50 values of 42.7, 65.5 and 84.4 μg/mL, respectively, Pictilisib chemical structure on Caco-2 cells. Fraxini (50 μg/mL) when combined with 5-FU (5 μM), significantly increased the toxicity of 5-FU on IEC-6 cells compared to Fraxini (50 μg/mL) alone (p < 0.05). None of the MEs, when combined with 5-FU, significantly increased 5-FU toxicity on Caco-2 cells compared to the corresponding MEs administered in the absence of 5-FU chemotherapy. Quercus and Mali did not alter the degree of 5-FU toxicity on IEC-6 cells, compared to the same concentrations

of Quercus and Fraxini without 5-FU. Conclusions: Of the ME species tested, the oak sourced ME (Quercus) demonstrated significant toxicity to colon cancer cells with lesser impact on normal intestinal epithelial cells. Future studies could investigate ME effects in models of colon cancer in vivo to determine whether ME (particularly Quercus) inhibits the development of colonic neoplasia without exacerbating the undesirable impact of 5-FU on the normal healthy intestine. SM ABIMOSLEH,1,2 CD TRAN,1,2 GS HOWARTH1,2,3 1Department of Gastroenterology, Women’s and Children’s Hospital, North Adelaide, CYTH4 South Australia, Australia, 2Discipline of Physiology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia, 3School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, Roseworthy, South Australia, Australia Introduction: Mucositis resulting from cancer chemotherapy is characterized by intestinal inflammation and ulceration. Treatment options are variably effective, highlighting the need to broaden therapeutic approaches. Previously, Emu Oil (EO) improved intestinal architecture (Br J Nutr, 2010) in a rat model of chemotherapy-induced mucositis.

Interestingly, 17-DMAG had a profound effect on TNFα promoter-driven reporter activity, pointing to the likely involvement of other repressive transcription factors in 17-DMAG-mediated proinflammatory cytokine reduction in the liver. Although inhibition of Hsp90 releases HSF1 from its inactive state to induce target

gene expression,29, 30 HSF1 also negatively regulates the induction of proinflammatory cytokine genes.49-51 Consistent with previous findings,31 no change in hsp90 protein levels was observed after 17-DMAG treatment in the liver. On the other hand, hsp90 inhibition resulted in a significant up-regulation of HSF1 DNA binding and induction of hsp70 mRNA and protein in the liver, confirming the inhibition of hsp90 chaperone function. The repressive function of HSF1 on the transcription of proinflammatory cytokine gene TNFα in macrophages during exposure to febrile temperatures has been shown.51-53 The TNFα GSK1120212 nmr promoter selleck kinase inhibitor is reported to have a binding site for HSF1.33 We postulated that activated HSF1 in the liver may serve as a repressor of TNFα gene induction during treatment with 17-DMAG. Using the ChIP assay, we showed the binding of HSF1 to the TNFα promoter in the presence of 17-DMAG treatment in macrophages. This observation correlates with elevated DNA-binding activity of HSF1

in response to hsp90 inhibition by 17-DMAG in the liver. Furthermore, whereas HSF1 bound to the hsp70 promoter, 17-DMAG treatment did not induce the binding of HSF1 to the IL-6 promoter, indicating an HSF1 indirect or independent down-regulation

of IL-6 during 17-DMAG treatment. Previous studies showed that HSF1 indirectly negatively regulates the IL-6 promoter through the induction of ATF3.37 Our studies exhibited an up-regulation of LPS-induced ATF3 mRNA and protein in the liver during 17-DMAG treatment, suggesting that HSF1 negatively regulates IL-6, likely through ATF3 induction. Future studies will determine the role of ATF3 in 17-DMAG-treated macrophages and liver inflammatory responses. Finally, using HSF1 siRNA, we also confirmed the direct repressive role for HSF1 in TNFα inhibition and an indirect regulation of IL-6 in 17-DMAG-treated macrophages. Thus, HSF1 appears to play a significant role in the down-regulation of proinflammatory cytokine responses in the liver on treatment with 17-DMAG, a specific hsp90 Farnesyltransferase inhibitor. The clinical significance of our study is related to the emerging function of hsp90 as a potential therapeutic target in different diseases.18, 28, 43, 44, 54 Compelling approaches using hsp90 inhibitors in hepatocellular carcinoma41 and hepatitis C virus replication54, 55 have been reported. Our results here, for the first time, suggest a novel application for hsp90 inhibitor 17-DMAG in alleviating LPS-mediated liver injury, providing a solid basis for clinical investigations using hsp90 inhibitors in acute and chronic liver diseases.

In contrast, <2-log and <3-log declines in the HCV RNA levels from baseline to week 8 accurately identified modest numbers of therapeutic failures with only 1 misclassification of a patient eventually achieving SVR, but this strategy would require testing at an additional time point. Figure 2 displays a scatter plot of HCV RNA levels in 300 evaluable boceprevir recipients at week 8 from RESPOND-2. The recipients

were divided into SVR and non-SVR groups. No robust futility rule was evident at week 8 that would have completely prevented missed SVRs (Table 2). However, a week 8 HCV RNA cutoff of ≥1000 IU/mL would have allowed appropriate early discontinuation in 27 patients at the Selleckchem CHIR99021 cost of 1 SVR. Per protocol, 72 patients were to be discontinued for futility because AZD2014 of detectable HCV RNA at week 12 (Table 3). In this group, 39 patients

had week 12 levels <100 IU/mL; these patients included 31 with HCV RNA levels between the LLQ (25 IU/mL) and the LLD (9.3 IU/mL). Six of these 31 patients completed the treatment despite the protocol stipulation that such patients discontinue therapy. All six patients had >5.5-log declines from the baseline HCV RNA levels by week 12. Five of the six patients (both patients with a previous partial response and three of the four patients with a previous relapse with P/R) were treated for 48 weeks (including 44 weeks of boceprevir) and achieved SVR; the other patient received 36 weeks of treatment and did not attain SVR. Although detectable HCV RNA levels (<100 IU/mL) at week 12 did not preclude SVR, only one of the eight patients with week 12 levels between 25 and 100 IU/mL continued therapy and achieved HCV RNA undetectability by the end of treatment; this patient relapsed during follow-up. Among the 33 Non-specific serine/threonine protein kinase patients with detectable HCV RNA levels (≥100 IU/mL) at week 12, therapy was continued in 1 patient who achieved SVR; the HCV RNA levels in this successfully treated patient were 14,813,507 IU/mL at baseline; detectable (<25 IU/mL) at week 10 (day 71); 103, 125,

and 148 IU/mL in a single specimen (run in triplicate) at week 12 (day 85); and undetectable by week 16 (day 113) and thereafter. Five of the 21 patients (24%) with a <0.5-log decline in the baseline HCV RNA levels at week 4 achieved SVR after the addition of boceprevir. At week 8, a <2-log decline was the only rule with which no SVR was missed, but therapy would have been discontinued in just three patients with this criterion. In all, 195 of the 277 evaluable patients (70%) with a ≥4-log decline at week 12 in their baseline HCV RNA levels achieved SVR; this number includes 6 patients with HCV RNA detectable at week 12 (as described previously). With conventional P/R therapy, generally accepted stopping rules include a <2-log viral load decline at week 12 and/or detectable HCV RNA at week 24.

In contrast, <2-log and <3-log declines in the HCV RNA levels from baseline to week 8 accurately identified modest numbers of therapeutic failures with only 1 misclassification of a patient eventually achieving SVR, but this strategy would require testing at an additional time point. Figure 2 displays a scatter plot of HCV RNA levels in 300 evaluable boceprevir recipients at week 8 from RESPOND-2. The recipients

were divided into SVR and non-SVR groups. No robust futility rule was evident at week 8 that would have completely prevented missed SVRs (Table 2). However, a week 8 HCV RNA cutoff of ≥1000 IU/mL would have allowed appropriate early discontinuation in 27 patients at the Topoisomerase inhibitor cost of 1 SVR. Per protocol, 72 patients were to be discontinued for futility because Opaganib concentration of detectable HCV RNA at week 12 (Table 3). In this group, 39 patients

had week 12 levels <100 IU/mL; these patients included 31 with HCV RNA levels between the LLQ (25 IU/mL) and the LLD (9.3 IU/mL). Six of these 31 patients completed the treatment despite the protocol stipulation that such patients discontinue therapy. All six patients had >5.5-log declines from the baseline HCV RNA levels by week 12. Five of the six patients (both patients with a previous partial response and three of the four patients with a previous relapse with P/R) were treated for 48 weeks (including 44 weeks of boceprevir) and achieved SVR; the other patient received 36 weeks of treatment and did not attain SVR. Although detectable HCV RNA levels (<100 IU/mL) at week 12 did not preclude SVR, only one of the eight patients with week 12 levels between 25 and 100 IU/mL continued therapy and achieved HCV RNA undetectability by the end of treatment; this patient relapsed during follow-up. Among the 33 ROS1 patients with detectable HCV RNA levels (≥100 IU/mL) at week 12, therapy was continued in 1 patient who achieved SVR; the HCV RNA levels in this successfully treated patient were 14,813,507 IU/mL at baseline; detectable (<25 IU/mL) at week 10 (day 71); 103, 125,

and 148 IU/mL in a single specimen (run in triplicate) at week 12 (day 85); and undetectable by week 16 (day 113) and thereafter. Five of the 21 patients (24%) with a <0.5-log decline in the baseline HCV RNA levels at week 4 achieved SVR after the addition of boceprevir. At week 8, a <2-log decline was the only rule with which no SVR was missed, but therapy would have been discontinued in just three patients with this criterion. In all, 195 of the 277 evaluable patients (70%) with a ≥4-log decline at week 12 in their baseline HCV RNA levels achieved SVR; this number includes 6 patients with HCV RNA detectable at week 12 (as described previously). With conventional P/R therapy, generally accepted stopping rules include a <2-log viral load decline at week 12 and/or detectable HCV RNA at week 24.

In contrast, <2-log and <3-log declines in the HCV RNA levels from baseline to week 8 accurately identified modest numbers of therapeutic failures with only 1 misclassification of a patient eventually achieving SVR, but this strategy would require testing at an additional time point. Figure 2 displays a scatter plot of HCV RNA levels in 300 evaluable boceprevir recipients at week 8 from RESPOND-2. The recipients

were divided into SVR and non-SVR groups. No robust futility rule was evident at week 8 that would have completely prevented missed SVRs (Table 2). However, a week 8 HCV RNA cutoff of ≥1000 IU/mL would have allowed appropriate early discontinuation in 27 patients at the Linsitinib cost of 1 SVR. Per protocol, 72 patients were to be discontinued for futility because Cisplatin of detectable HCV RNA at week 12 (Table 3). In this group, 39 patients

had week 12 levels <100 IU/mL; these patients included 31 with HCV RNA levels between the LLQ (25 IU/mL) and the LLD (9.3 IU/mL). Six of these 31 patients completed the treatment despite the protocol stipulation that such patients discontinue therapy. All six patients had >5.5-log declines from the baseline HCV RNA levels by week 12. Five of the six patients (both patients with a previous partial response and three of the four patients with a previous relapse with P/R) were treated for 48 weeks (including 44 weeks of boceprevir) and achieved SVR; the other patient received 36 weeks of treatment and did not attain SVR. Although detectable HCV RNA levels (<100 IU/mL) at week 12 did not preclude SVR, only one of the eight patients with week 12 levels between 25 and 100 IU/mL continued therapy and achieved HCV RNA undetectability by the end of treatment; this patient relapsed during follow-up. Among the 33 Phospholipase D1 patients with detectable HCV RNA levels (≥100 IU/mL) at week 12, therapy was continued in 1 patient who achieved SVR; the HCV RNA levels in this successfully treated patient were 14,813,507 IU/mL at baseline; detectable (<25 IU/mL) at week 10 (day 71); 103, 125,

and 148 IU/mL in a single specimen (run in triplicate) at week 12 (day 85); and undetectable by week 16 (day 113) and thereafter. Five of the 21 patients (24%) with a <0.5-log decline in the baseline HCV RNA levels at week 4 achieved SVR after the addition of boceprevir. At week 8, a <2-log decline was the only rule with which no SVR was missed, but therapy would have been discontinued in just three patients with this criterion. In all, 195 of the 277 evaluable patients (70%) with a ≥4-log decline at week 12 in their baseline HCV RNA levels achieved SVR; this number includes 6 patients with HCV RNA detectable at week 12 (as described previously). With conventional P/R therapy, generally accepted stopping rules include a <2-log viral load decline at week 12 and/or detectable HCV RNA at week 24.

Importantly, Axl knock-down severely impaired resistance to TGF-β-mediated growth inhibition. Tanespimycin Analysis of the Axl interactome revealed binding of Axl to 14-3-3ζ, which is essentially required for Axl-mediated cell invasion, transendothelial

migration and resistance against TGF-β. Axl/14-3-3ζ signaling caused phosphorylation of Smad3 linker region (Smad3L) at Ser213, resulting in the upregulation of tumor-progressive TGF-β target genes such as PAI1, MMP9 and Snail as well as augmented TGF-β1 secretion in mesenchymal HCC cells. Accordingly, high Axl expression in HCC patient samples correlated with elevated vessel invasion of HCC cells, higher risk of tumor recurrence after liver transplantation, strong phosphorylation of Smad3L and lower survival. In addition, elevated expression

of both Axl and 14-3-3ζ showed strongly reduced survival of HCC patients. Conclusion: Our data suggest that Axl/14-3-3ζ signaling is central for TGF-β-mediated HCC progression and a promising target for HCC therapy. (Hepatology 2014) “
“Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated selleck compound interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, cAMP and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half

were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ≤3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups. Conclusion: This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response.

Additionally, this disease is particularly difficult to treat because of the high recurrence rate, its chemotherapy-resistant nature and the premalignant nature of surrounding cirrhotic liver disease. In the past few years, compelling evidence has emerged in support of the hierarchic cancer stem cell (CSC)/tumor-initiating cell (T-IC) model for solid tumors, including HCC. Understanding the characteristics and

function of CSCs in the liver has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress in liver CSC research with regard to identification, regulation and therapeutic implications will be discussed. There are currently two conflicting views that attempt

to explain tumor formation. The classical stochastic model, also referred to as the clonal evolution model,1 proposes that a BTK inhibitor nmr single cell acquires random and additive genetic mutations, with subsequent clonal selection, to result in the formation of a group of clonal tumor cells. Every cell within the tumor is biologically homogeneous and has an equal potential to generate a tumor. The likelihood of each of these cells becoming a tumor-initiator is governed by a low probability of stochastic mutations. In contrast, the cancer stem cell (CSC) or tumor-initiating cell (T-IC) theory suggests that a tumor Erlotinib comprises a heterogeneous population of cells that form a distinct cellular hierarchy; only a subset of cells within this tumor hierarchy has the ability to self-renew, differentiate into defined progenies and, most importantly, initiate and sustain tumor growth.2 Contrary to the stochastic model, each of the small subset Ureohydrolase of CSCs in the tumor

has a significantly higher probability to become a tumor-founding cell, relative to the non-CSCs that make up the bulk of the tumor. According to this theory, it should be possible to identify and target the cells responsible for tumor initiation and progression because not all of the cells have the same phenotypic and functional characteristics. Although the idea of CSCs has been around for many years, the work by John Dick and colleagues over a decade ago was the first to demonstrate the critical role of stem cells in hematological malignancies3 and has, as a result, revolutionized the widely held belief of the clonal origin of carcinogenesis. Since then, substantial evidence has emerged to support the notions of tumor heterogeneity and cellular hierarchy within a tumor, not only in the field of hematological cancers but also in solid cancers. Indeed, several pivotal studies have recently provided convincing evidence that these cells do exist in solid tumors of many types, including breast, brain, colorectal, pancreas, liver, melanoma and prostate cancers.

Serum alphafetoprotein (AFP) level over 100 ng/mL during hepatitis flare usually represents more extensive hepatocytolysis or bridging hepatic necrosis (Liver 1986; 6:133-7). Whether higher AFP levels during hepatitis flare are associated with greater reduction in HBsAg level during Nuc therapy is unknown. Patients and methods: The study included 217 chronic hepatitis B patients who had adequate AFP measurement during hepatitis B flare (ALT ≥ 5X ULN). HBsAg level was measured at baseline, 6 month and 12 month of Nuc therapy using Elecsys HBsAg II (Roche Diagnostics, Indianapolis, IN, USA). The

click here results were analyzed according to AFP levels (<20, 20-50, 50-100 and ≥ 100 ng/mL) and ALT levels (5-10X, 10-20X, > 20XULN), respectively, and compared with that of 44 CHB patients with ALT < 5X ULN. Results: The results (Table 1) showed the higher the AFP level during hepatitis flare, the greater the reduction in HBsAg level during Nuc therapy. The reduction in HBsAg level was also greater in patients with higher ALT levels. Stepwise multiple linear regression analysis showed that AFP level, not ALT level, was significantly associated with greater reduction in 6th month and 1st year

HBsAg levels. Conclusion: The increase of AFP during hepatitis B flare, reflecting more extensive hepatocytolysis and subsequent regeneration, contributes to greater reduction in HBsAg level during Nuc therapy. Log10 reduction in HBsAg level in patients with this website different AFP and ALT levels Linear trend of HBsAg Log reduction at 6th month by ALT and AFP are P=0.000, respectively. Linear trend of HBsAg Log reduction at 12th month by ALT and AFP are P=0.000, respectively. AFP: alphafetoprotein; ALT: alanine transaminase; ULN: upper limit of normal; HBsAg: hepatitis B surface antigen. Disclosures: Yun -Fan Liaw -

Advisory Committees or Review Panels: Roche; Grant/Research Support: Roche The following people have nothing to disclose: Rachel Wen-Juei Fenbendazole Jeng, Yi-Cheng Chen, Ming-Ling Chang Background and Aim: Liver Stiffness (LS) measured by Fibros-can (transient elastography; TE) has been reported to correlate with fibrosis stages in various liver diseases. The purpose of antiviral treatment for chronic hepatitis B is a suppression of liver fibrosis progression and a reduction of the risk for hepato-cellular carcinoma (HCC). The aim of the present study was to evaluate the effect of antiviral treatment on LS and its correlation to hepatocarcinogenesis in chronic hepatitis B. Methods: LS (kPa) was measured by TE in 372 patients with chronic hepatitis B.