20 In hepatocytes of fructose-fed animals, PTP1B expression levels and activities were higher.21 Our results shown here confirmed an alteration in hepatic PTP1B level in mice fed an HFD, being consistent with the observation that the protein was up-regulated in patients with nonalcoholic steatohepatitis.22 Mature miRNAs work as posttranscriptional regulators by hybridizing to complementary binding sites in the 3′UTR of target mRNAs.23 This property allows a single miRNA sequence to have

multiple binding sites on various mRNAs. The discovery of posttranscriptional gene check details silencing as an additional regulatory principle to control protein levels suggests that dysregulation of miRNAs may affect the development of hepatic insulin resistance.24 Dicer-deficient mice showed markedly increased apoptosis, proliferation, and lipid accumulation in hepatocytes, showing steatosis; a deficiency in dicer down-regulated the levels of miRNAs highly enriched in the liver,11 highlighting the role of miRNAs in regulating glucose and lipid metabolism. MiR-122 is the most abundantly (accounting for 52%) expressed miRNA in the liver,25 and may be involved in lipid and cholesterol metabolism.26 Transfection of miR-122 inhibitor significantly increased the mRNA levels of lipogenic genes such as FAS, HMG-CoA reductase, SREBP-1c, and SREBP-2.9 selleck chemicals Thus, miR-122

down-regulation may alter lipid metabolism, potentially facilitating the pathogenesis of nonalcoholic steatohepatitis. Our results provide evidence that miR-122 has an inhibitory effect on PTP1B levels. Luciferase assays using plasmids harboring the PTP1B 3′UTR confirmed this regulatory effect. Moreover, bioinformatic analyses of the miRNA array data obtained from human nonalcoholic steatohepatitis samples (Supporting Table S1)9 and our in vivo and in vitro results enabled us to identify miR-122 as an miRNA that critically controls PTP1B-associated insulin resistance in the liver. Moreover, miR-122 levels were consistently decreased in the liver of several different in vivo models with insulin resistance selleckchem (i.e., HFD-fed rats, ob/ob mice,

and streptozotocin-induced diabetic mice) (Supporting Table S2).27, 28 The conditions responsible for increased PTP1B gene transcription are not well defined except the finding that D-glucose enhanced transcription of the PTP1B gene in a human hepatocyte cell line by way of protein kinase C (PKC).29 Macrophage activation enhanced PTP1B induction by palmitate in myotubes.30 TNF-α induces PTP1B by nuclear factor kappa B (NF-κB) activation.31 So, TNF-α from macrophages increases insulin resistance. The target scan results shown in the present study raised the proposal that the miRNAs including miR-203, 135, 29, 124, 506, and 206 might also interact with the binding sites within the 3′UTR of human PTP1B mRNA. Although the levels of these miRNAs were also decreased in HepG2 cells exposed to TNF-α, they were not changed in the in vivo model.

20 In hepatocytes of fructose-fed animals, PTP1B expression levels and activities were higher.21 Our results shown here confirmed an alteration in hepatic PTP1B level in mice fed an HFD, being consistent with the observation that the protein was up-regulated in patients with nonalcoholic steatohepatitis.22 Mature miRNAs work as posttranscriptional regulators by hybridizing to complementary binding sites in the 3′UTR of target mRNAs.23 This property allows a single miRNA sequence to have

multiple binding sites on various mRNAs. The discovery of posttranscriptional gene selleck silencing as an additional regulatory principle to control protein levels suggests that dysregulation of miRNAs may affect the development of hepatic insulin resistance.24 Dicer-deficient mice showed markedly increased apoptosis, proliferation, and lipid accumulation in hepatocytes, showing steatosis; a deficiency in dicer down-regulated the levels of miRNAs highly enriched in the liver,11 highlighting the role of miRNAs in regulating glucose and lipid metabolism. MiR-122 is the most abundantly (accounting for 52%) expressed miRNA in the liver,25 and may be involved in lipid and cholesterol metabolism.26 Transfection of miR-122 inhibitor significantly increased the mRNA levels of lipogenic genes such as FAS, HMG-CoA reductase, SREBP-1c, and SREBP-2.9 AZD4547 ic50 Thus, miR-122

down-regulation may alter lipid metabolism, potentially facilitating the pathogenesis of nonalcoholic steatohepatitis. Our results provide evidence that miR-122 has an inhibitory effect on PTP1B levels. Luciferase assays using plasmids harboring the PTP1B 3′UTR confirmed this regulatory effect. Moreover, bioinformatic analyses of the miRNA array data obtained from human nonalcoholic steatohepatitis samples (Supporting Table S1)9 and our in vivo and in vitro results enabled us to identify miR-122 as an miRNA that critically controls PTP1B-associated insulin resistance in the liver. Moreover, miR-122 levels were consistently decreased in the liver of several different in vivo models with insulin resistance selleck compound (i.e., HFD-fed rats, ob/ob mice,

and streptozotocin-induced diabetic mice) (Supporting Table S2).27, 28 The conditions responsible for increased PTP1B gene transcription are not well defined except the finding that D-glucose enhanced transcription of the PTP1B gene in a human hepatocyte cell line by way of protein kinase C (PKC).29 Macrophage activation enhanced PTP1B induction by palmitate in myotubes.30 TNF-α induces PTP1B by nuclear factor kappa B (NF-κB) activation.31 So, TNF-α from macrophages increases insulin resistance. The target scan results shown in the present study raised the proposal that the miRNAs including miR-203, 135, 29, 124, 506, and 206 might also interact with the binding sites within the 3′UTR of human PTP1B mRNA. Although the levels of these miRNAs were also decreased in HepG2 cells exposed to TNF-α, they were not changed in the in vivo model.

Cylindrospermum badium Johansen et Hrčková sp. nov.

(Fig 5, aa-aj) Thallus gelatinous to leathery, spreading, blue-green in young cultures, becoming olive-green to brown with age, with nacreous, shiny surface. Filaments motile. Trichomes short or long, straight or flexuous, constricted at the cross walls, isopolar to heteropolar, motile, 3.0–4.8 μm wide. Vegetative cells cylindrical, isodiametric to longer than wide, with pale blue-green, finely granulated content, 3.5–7.5 μm long. Heterocytes forming terminally after trichome fragmentation, solitary, unipored, almost spherical, elongated or slightly conical, tan colored, 5–10(13) μm long, 3–5 μm wide. Akinetes forming paraheterocytically, solitary, broadly oval, flattened at both ends, 17–30 μm long, 10.0–14.4 μm wide. Exospore usually 1–3 μm wide, initially Adriamycin supplier colorless, later chestnut-brown, smooth, internally structured, sometimes not firmly

delimited. Holotype: BRY37721, Monte L. Bean Museum, Provo, Utah. Reference strain: CCALA 1000. Partial 16S and complete 16S-23S ITS sequences for operons containing tRNAAla and tRNAIle (operon 1) and lacking tRNA genes (operon2) in the ITS portion are X-396 chemical structure available under GenBank accession numbers KF052616 and KF142524 respectively. Type locality: recultivated top soil after coal mining with sweet gum, Pyramid State Recreational Area, Illinois, USA. Etymology: badius = chestnut brown, referring to the chestnut-brown exospore. Taxonomic Notes: Morphologically and phylogenetically similar to C. moravicum, but differing in the more darkly colored and flattened exospore. Secondary structures of conserved ITS domains very similar to those in the C. catenatum group, but

MCE differing from those in C. moravicum. Cylindrospermum catenatum Ralfs ex Bornet et Flahault (Fig. 4, u-ai) Thallus gelatinous, shapeless, blue-green in young cultures, becoming yellowish with age, becoming brownish after akinete formation. Trichomes short or long, dispersed in a wide mucilage, flexuous, constricted at the cross walls, isopolar to heteropolar, 3.7–4.4 μm wide. Vegetative cells slightly barrel-shaped or almost cylindrical, mainly isodiametric, pale blue-green to green, finely granulated content, 3.5–5.0 μm long. Heterocytes forming terminally after trichome fragmentation, solitary, unipored, spherical to elongated, sometimes bluntly conical, with greenish smooth content, 5.0–7.2 μm long, 4.0–5.0 μm wide. Akinetes forming paraheterocytically, solitary or more commonly in rows of up to six cells, elongated oval to cylindrical, with smooth, thin (up to 1 μm), golden to dirty brown exospores, 14–22 μm long, 8–12 μm wide. Isolated from diverse damp soils in Czech and Slovak Republics. Reference strains CCALA 990, CCALA 991, CCALA 996, CCALA 997, and CCALA 999. Herbarium vouchers BRY37711, BRY37712, BRY37717, BRY37718, BRY37720. Sequences KF052601 – KF052604, KF052611 – KF052613, KF052615.

Cylindrospermum badium Johansen et Hrčková sp. nov.

(Fig 5, aa-aj) Thallus gelatinous to leathery, spreading, blue-green in young cultures, becoming olive-green to brown with age, with nacreous, shiny surface. Filaments motile. Trichomes short or long, straight or flexuous, constricted at the cross walls, isopolar to heteropolar, motile, 3.0–4.8 μm wide. Vegetative cells cylindrical, isodiametric to longer than wide, with pale blue-green, finely granulated content, 3.5–7.5 μm long. Heterocytes forming terminally after trichome fragmentation, solitary, unipored, almost spherical, elongated or slightly conical, tan colored, 5–10(13) μm long, 3–5 μm wide. Akinetes forming paraheterocytically, solitary, broadly oval, flattened at both ends, 17–30 μm long, 10.0–14.4 μm wide. Exospore usually 1–3 μm wide, initially U0126 ic50 colorless, later chestnut-brown, smooth, internally structured, sometimes not firmly

delimited. Holotype: BRY37721, Monte L. Bean Museum, Provo, Utah. Reference strain: CCALA 1000. Partial 16S and complete 16S-23S ITS sequences for operons containing tRNAAla and tRNAIle (operon 1) and lacking tRNA genes (operon2) in the ITS portion are Belnacasan concentration available under GenBank accession numbers KF052616 and KF142524 respectively. Type locality: recultivated top soil after coal mining with sweet gum, Pyramid State Recreational Area, Illinois, USA. Etymology: badius = chestnut brown, referring to the chestnut-brown exospore. Taxonomic Notes: Morphologically and phylogenetically similar to C. moravicum, but differing in the more darkly colored and flattened exospore. Secondary structures of conserved ITS domains very similar to those in the C. catenatum group, but

MCE公司 differing from those in C. moravicum. Cylindrospermum catenatum Ralfs ex Bornet et Flahault (Fig. 4, u-ai) Thallus gelatinous, shapeless, blue-green in young cultures, becoming yellowish with age, becoming brownish after akinete formation. Trichomes short or long, dispersed in a wide mucilage, flexuous, constricted at the cross walls, isopolar to heteropolar, 3.7–4.4 μm wide. Vegetative cells slightly barrel-shaped or almost cylindrical, mainly isodiametric, pale blue-green to green, finely granulated content, 3.5–5.0 μm long. Heterocytes forming terminally after trichome fragmentation, solitary, unipored, spherical to elongated, sometimes bluntly conical, with greenish smooth content, 5.0–7.2 μm long, 4.0–5.0 μm wide. Akinetes forming paraheterocytically, solitary or more commonly in rows of up to six cells, elongated oval to cylindrical, with smooth, thin (up to 1 μm), golden to dirty brown exospores, 14–22 μm long, 8–12 μm wide. Isolated from diverse damp soils in Czech and Slovak Republics. Reference strains CCALA 990, CCALA 991, CCALA 996, CCALA 997, and CCALA 999. Herbarium vouchers BRY37711, BRY37712, BRY37717, BRY37718, BRY37720. Sequences KF052601 – KF052604, KF052611 – KF052613, KF052615.

Our data also suggest that the inflammatory pathway is not involved in hepcidin regulation by iron. In summary, our results demonstrate that circulating iron and tissue iron differentially activate the BMP-SMAD signaling pathway to modulate hepcidin expression. The liver is the predominant source of

the BMP6 that regulates hepcidin in response to iron in vivo, and increases in LIC induce hepatic expression of BMP6 ligand, whereas increases in Tf sat activate SMAD1/5/8 phosphorylation downstream of BMP6. Inhibitory SMAD7 is significantly modulated by both acute and chronic iron administration, mirroring the overall activation of the SMAD1/5/8 signaling cascade, and may play a role Fulvestrant supplier in feedback inhibition of hepcidin expression. Hepatic Erk1/2 phosphorylation is not stimulated by either acute or chronic buy MI-503 iron administration in mice, suggesting that these MAP kinases are not involved in hepcidin regulation by iron in vivo. Future studies will be needed to further delineate the

precise molecular mechanisms involved in iron sensing and BMP6-SMAD pathway activation in hepcidin regulation and iron homeostasis. Additional Supporting Information may be found in the online version of this article. “
“Acute-on-chronic liver failure (ACLF) is a clinical entity where there is a potential for reversibility of hepatic dysfunction once the acute hepatic insult resolves. The portal and systemic hemodynamics medchemexpress in ACLF patients to study its relevance in determining the clinical outcomes was studied. Clinical, laboratory, portal, and systemic hemodynamic assessments were done at admission and after 3 months. Standard medical care was given to all the patients. Fifty-seven patients with ACLF were enrolled, and they underwent baseline hepatic venous pressure gradient (HVPG) measurement. Twenty-six (46%) patients died during the 3-month follow-up.

Presence of high HVPG and hepatic encephalopathy were found to be independent baseline predictors of mortality. Of the 31 surviving patients, 24 consented for a repeat HVPG. The baseline HVPG reduced from 16 (range 12–30) to 13 (range 6–21) mmHg; (P < 0.05). The reduction in HVPG correlated with clinical and biochemical recovery, and reduction in Child–Turcotte–Pugh score score (P < 0.05), while the aortic mean arterial pressure, cardiac index and systemic vascular resistance index improved significantly (< 0.05). Six (25%) patients developed upper gastrointestinal bleed; the median HVPG between bleeders and non-bleeders was not different possibly because of early onset of bleed (median 20 [15–45 days]). Baseline HVPG is an independent predictor of mortality in ACLF patients. The portal and systemic circulatory anomalies regress substantially by 90 days and correlate with clinical recovery.

Our data also suggest that the inflammatory pathway is not involved in hepcidin regulation by iron. In summary, our results demonstrate that circulating iron and tissue iron differentially activate the BMP-SMAD signaling pathway to modulate hepcidin expression. The liver is the predominant source of

the BMP6 that regulates hepcidin in response to iron in vivo, and increases in LIC induce hepatic expression of BMP6 ligand, whereas increases in Tf sat activate SMAD1/5/8 phosphorylation downstream of BMP6. Inhibitory SMAD7 is significantly modulated by both acute and chronic iron administration, mirroring the overall activation of the SMAD1/5/8 signaling cascade, and may play a role Talazoparib cell line in feedback inhibition of hepcidin expression. Hepatic Erk1/2 phosphorylation is not stimulated by either acute or chronic Osimertinib iron administration in mice, suggesting that these MAP kinases are not involved in hepcidin regulation by iron in vivo. Future studies will be needed to further delineate the

precise molecular mechanisms involved in iron sensing and BMP6-SMAD pathway activation in hepcidin regulation and iron homeostasis. Additional Supporting Information may be found in the online version of this article. “
“Acute-on-chronic liver failure (ACLF) is a clinical entity where there is a potential for reversibility of hepatic dysfunction once the acute hepatic insult resolves. The portal and systemic hemodynamics 上海皓元 in ACLF patients to study its relevance in determining the clinical outcomes was studied. Clinical, laboratory, portal, and systemic hemodynamic assessments were done at admission and after 3 months. Standard medical care was given to all the patients. Fifty-seven patients with ACLF were enrolled, and they underwent baseline hepatic venous pressure gradient (HVPG) measurement. Twenty-six (46%) patients died during the 3-month follow-up.

Presence of high HVPG and hepatic encephalopathy were found to be independent baseline predictors of mortality. Of the 31 surviving patients, 24 consented for a repeat HVPG. The baseline HVPG reduced from 16 (range 12–30) to 13 (range 6–21) mmHg; (P < 0.05). The reduction in HVPG correlated with clinical and biochemical recovery, and reduction in Child–Turcotte–Pugh score score (P < 0.05), while the aortic mean arterial pressure, cardiac index and systemic vascular resistance index improved significantly (< 0.05). Six (25%) patients developed upper gastrointestinal bleed; the median HVPG between bleeders and non-bleeders was not different possibly because of early onset of bleed (median 20 [15–45 days]). Baseline HVPG is an independent predictor of mortality in ACLF patients. The portal and systemic circulatory anomalies regress substantially by 90 days and correlate with clinical recovery.

Delgado, Lucía Bonet, Juan I. Arenas, Conrado M. Fernandez Rodriguez, Luisa Gonzalez-Diéguez, selleck Óscar Núñez, Manuel Praga, Javier del Pino, Moisés Diago Background. Hepatitis B core related antigen (HBcrAg) is a new marker which is a combined measure of the core proteins HBeAg, HBcAg and p22cr, and correlates with intrahe-patic covalently closed circular DNA. Serum HBcrAg levels may therefore be associated with response to antiviral therapy. Methods. We studied HBeAg-positive patients treated within an international randomized trial (ARES), in which all

patients were treated with ETV (0.5mg/day) from w0-24, and randomized to either PEG-IFN add-on from w24-48 (n=85), or to ETV-monotherapy continuation (n=90). Response was defined as HBeAg-loss with HBV DNA<200IU/ml. Only responders at w48 stopped ETV at w72. All patients were followed until learn more w96. Serum HBcrAg was measured using the Lumipulse® G HBcrAg (Fujirebio Europe). Results. At w96, response was achieved in 31% vs. 20% of patients assigned PEG-IFN add-on vs. monotherapy respectively. Lower HBcrAg levels at w0 were associated with response to ETV (OR 0.5, 95%CI:0.3-0.8, p<0.001), but not to PEG-IFN add-on

(OR 0.9, 95%CI:0.5-1.6, p=0.678). At w96 more HBcrAg decline was observed among responders (−2.6 vs -2.0 log U/mL for monotherapy and −3.5 vs −2.0 log U/mL for add-on, both p<0.001), with more decline for responders to add-on vs. monotherapy (p=0.010; figure). Lower HBcrAg levels at w48 were associated with HBsAg levels <1000IU/mL at w96 (OR 0.5, 95%CI:0.3-0.8, p=0.002). By Bland-Altman analysis, agreement between HBeAg and

HBcrAg measurements at w0 was close (mean difference -3.1×10-6 Log U/mL, 95%CI:-0.9 – 0.9), with comparable on-treatment results obtained for w12-96. Conclusion. On-treatment HBcrAg decline is associated with response to both ETV monotherapy and ETV+PEG-IFN add-on therapy, with most prominent declines observed during PEG-IFN. HBcrAg and HBeAg measurements seemed to follow similar medchemexpress on-treatment dynamics. Disclosures: Milan J. Sonneveld – Advisory Committees or Review Panels: Roche; Speaking and Teaching: Roche, BMS Suzan D. Pas – Grant/Research Support: the Virgo consortium, funded by the Dutch government (FES0908), the Netherlands Genomics Initiative (NGI) project number 050-060-452, the European Community Seventh Framework Programme (FP7/2007-2013) under project EMPERIE (grant agreement no. 223498] Robert J. de Knegt – Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag Andre Boonstra – Grant/Research Support: BMS, Janssen Pharmaceutics, Merck, Roche Harry L.

Delgado, Lucía Bonet, Juan I. Arenas, Conrado M. Fernandez Rodriguez, Luisa Gonzalez-Diéguez, http://www.selleckchem.com/products/BIBW2992.html Óscar Núñez, Manuel Praga, Javier del Pino, Moisés Diago Background. Hepatitis B core related antigen (HBcrAg) is a new marker which is a combined measure of the core proteins HBeAg, HBcAg and p22cr, and correlates with intrahe-patic covalently closed circular DNA. Serum HBcrAg levels may therefore be associated with response to antiviral therapy. Methods. We studied HBeAg-positive patients treated within an international randomized trial (ARES), in which all

patients were treated with ETV (0.5mg/day) from w0-24, and randomized to either PEG-IFN add-on from w24-48 (n=85), or to ETV-monotherapy continuation (n=90). Response was defined as HBeAg-loss with HBV DNA<200IU/ml. Only responders at w48 stopped ETV at w72. All patients were followed until check details w96. Serum HBcrAg was measured using the Lumipulse® G HBcrAg (Fujirebio Europe). Results. At w96, response was achieved in 31% vs. 20% of patients assigned PEG-IFN add-on vs. monotherapy respectively. Lower HBcrAg levels at w0 were associated with response to ETV (OR 0.5, 95%CI:0.3-0.8, p<0.001), but not to PEG-IFN add-on

(OR 0.9, 95%CI:0.5-1.6, p=0.678). At w96 more HBcrAg decline was observed among responders (−2.6 vs -2.0 log U/mL for monotherapy and −3.5 vs −2.0 log U/mL for add-on, both p<0.001), with more decline for responders to add-on vs. monotherapy (p=0.010; figure). Lower HBcrAg levels at w48 were associated with HBsAg levels <1000IU/mL at w96 (OR 0.5, 95%CI:0.3-0.8, p=0.002). By Bland-Altman analysis, agreement between HBeAg and

HBcrAg measurements at w0 was close (mean difference -3.1×10-6 Log U/mL, 95%CI:-0.9 – 0.9), with comparable on-treatment results obtained for w12-96. Conclusion. On-treatment HBcrAg decline is associated with response to both ETV monotherapy and ETV+PEG-IFN add-on therapy, with most prominent declines observed during PEG-IFN. HBcrAg and HBeAg measurements seemed to follow similar MCE公司 on-treatment dynamics. Disclosures: Milan J. Sonneveld – Advisory Committees or Review Panels: Roche; Speaking and Teaching: Roche, BMS Suzan D. Pas – Grant/Research Support: the Virgo consortium, funded by the Dutch government (FES0908), the Netherlands Genomics Initiative (NGI) project number 050-060-452, the European Community Seventh Framework Programme (FP7/2007-2013) under project EMPERIE (grant agreement no. 223498] Robert J. de Knegt – Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag Andre Boonstra – Grant/Research Support: BMS, Janssen Pharmaceutics, Merck, Roche Harry L.

Brunetto – Speaking and Teaching: Roche, Gilead, Schering-Plough, Bristol-Myers Squibb, Abbott, Roche, Gilead, MSD, Novartis Markus Cornberg – Advisory Committees or Review Panels: Merck (MSD Ger-mamny), Roche, Gilead, Novartis; Grant/Research Support: Merck (MSD Ger-mamny), Roche; Speaking and Teaching: Merck (MSD Germamny), Roche, Gilead, BMS, Novartis, Falk Harry L. Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research

Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris The following people have nothing to disclose: Bettina E. Hansen, Pauline SCH 900776 Arends, Steffen B. Wiegand Purpose: To compare the efficacy of 1 04-week treatment of telbivudine and entecavir in Hepatitis B e Antigen (HBeAg)-posi-tive chronic hepatitis B (CHB) patients in a head-to-head trial.

Methods: In this randomized, controlled study, we randomly assigned 1 80 HBeAg-positive CHB patients in a ratio of 1:1 to receive oral telbivudine 600 mg once daily (n=90) or oral entecavir 0.5 mg once daily (n=90) for 1 04 weeks. At 52 weeks, if Cilomilast in vivo virological rebound and HBV DNA>103 copies/mL were observed, adefovir dipivoxil 1 0 mg QD was added to ongoing therapy. At 1 04 weeks, we evaluated the efficacy of telbivudine and entecavir treatment, and analyzed the predicators of HBeAg seroconversion. Results: At 104 weeks, the HBV DNA undetectable rate was 96.25% in the entecavir group and 94% in the telbivudine group, the rate of ALT normalization was 97.5% with

MCE公司 entecavir and 95.23% with telbivudine (P>0.05). The HBeAg loss rate in the telbivudine group was significantly higher than that in the entecavir group (47.62% vs. 27.5%), telbivudine also demonstrated a higher rate of HBeAg seroconversion rate than entecavir (45.24% vs. 22.5%) (P<0.01). The overall rate of virological rebound in the telbivudine and entecavir groups were 8.3% and 1.25%, respectively (P<0.05). After adjustment for ongoing treatment at week 52, the new virological breakthrough rate at week 104 was 3.75% in the telbivudine group versus 1.25% in the entecavir group (P>0.05). No correlation was found between HBeAg seroconversion rate at week 104 and HBV DNA levels at baseline (P>0.05).

Brunetto – Speaking and Teaching: Roche, Gilead, Schering-Plough, Bristol-Myers Squibb, Abbott, Roche, Gilead, MSD, Novartis Markus Cornberg – Advisory Committees or Review Panels: Merck (MSD Ger-mamny), Roche, Gilead, Novartis; Grant/Research Support: Merck (MSD Ger-mamny), Roche; Speaking and Teaching: Merck (MSD Germamny), Roche, Gilead, BMS, Novartis, Falk Harry L. Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research

Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris The following people have nothing to disclose: Bettina E. Hansen, Pauline GSI-IX purchase Arends, Steffen B. Wiegand Purpose: To compare the efficacy of 1 04-week treatment of telbivudine and entecavir in Hepatitis B e Antigen (HBeAg)-posi-tive chronic hepatitis B (CHB) patients in a head-to-head trial.

Methods: In this randomized, controlled study, we randomly assigned 1 80 HBeAg-positive CHB patients in a ratio of 1:1 to receive oral telbivudine 600 mg once daily (n=90) or oral entecavir 0.5 mg once daily (n=90) for 1 04 weeks. At 52 weeks, if Metformin virological rebound and HBV DNA>103 copies/mL were observed, adefovir dipivoxil 1 0 mg QD was added to ongoing therapy. At 1 04 weeks, we evaluated the efficacy of telbivudine and entecavir treatment, and analyzed the predicators of HBeAg seroconversion. Results: At 104 weeks, the HBV DNA undetectable rate was 96.25% in the entecavir group and 94% in the telbivudine group, the rate of ALT normalization was 97.5% with

上海皓元 entecavir and 95.23% with telbivudine (P>0.05). The HBeAg loss rate in the telbivudine group was significantly higher than that in the entecavir group (47.62% vs. 27.5%), telbivudine also demonstrated a higher rate of HBeAg seroconversion rate than entecavir (45.24% vs. 22.5%) (P<0.01). The overall rate of virological rebound in the telbivudine and entecavir groups were 8.3% and 1.25%, respectively (P<0.05). After adjustment for ongoing treatment at week 52, the new virological breakthrough rate at week 104 was 3.75% in the telbivudine group versus 1.25% in the entecavir group (P>0.05). No correlation was found between HBeAg seroconversion rate at week 104 and HBV DNA levels at baseline (P>0.05).