Mucosal PGE2 contents were also increased by luminal perfusion of ATP, reduced by P2Y receptor antagonists, NADPH oxidase inhibitors, or cPLA2 inhibitors, further supporting our hypothesis that ATP-P2Y signal-induced H2O2 production increases PGE2 synthesis, augmenting HCO3− secretion. H2O2 increases electrogenic Cl− secretion via PGE2 synthesis in rat colon[32] and in primary inner medullary collecting duct cells,[33] consistent with

our results. Luminal acid exposure increases HCO3− secretion accompanied by increased H2O2 output into the perfusate, inhibited by co-perfusion of P2Y receptor antagonists or NADPH oxidase inhibitors. Furthermore, acid-induced HCO3− secretion was reduced by inhibition CH5424802 mouse of cPLA2 without affecting H2O2 output. Acid-augmented mucosal PGE2 content was also reduced by these inhibitors, suggesting that the duodenal mucosa exposed to luminal ATP or acid generates H2O2 and PGE2 via the same pathway. Therefore, acid exposure triggers ATP-P2Y signals, which activate see more Duox2 to generate extracellular H2O2, which activates epithelial cPLA2, which increases PGE2 synthesis via COX, followed by EP4 receptor activation, intracellular cAMP increase, and cystic

fibrosis transmembrane conductance regulator (CFTR) activation, augmenting the rate of luminal HCO3− secretion (Fig. 2). This sequential pathway may explain the fundamental question of how luminal acid augments PG synthesis. Duodenal epithelial cells possess high catalase activity,[34-36] which may protect them from self-generated H2O2. Luminal exposure to H2O2 ≤ 0.3 mmol/L dose-dependently increased HCO3− secretion without epithelial injury or increasing mucosal permeability,[18] consistent with the effect of H2O2 on rat colonic Cl− secretion.[32] In contrast, 0.5 mmol/L H2O2 inhibits cAMP-induced or Ca2+-dependent Cl− secretion in colonic T84 cells.[37, 38] H2O2 also increases epithelial permeability

and cellular toxicity at higher concentration (≥ 0.5 mmol/L),[39, 40] suggesting that the effect of luminal H2O2 is dependent on whether its concentration is in the physiological or pathological ranges. Since generation of H2O2 by Duox2 requires sufficient luminal O2, and since activation of HCO3− secretion 上海皓元 consumes intracellular ATP, epithelial O2 consumption may be increased during acid exposure. We reported that post-prandial epithelial hypoxia was present in duodenal villous cells, induced by acid exposure, and inhibited by pretreatment with proton pump inhibitor (PPI) or oral catalase.[41] Since duodenal hypoxia increases hypoxia-inducible factor-2α signaling, enhancing iron absorption,[42, 43] and since PPI treatment decreased COX expression in the duodenal mucosa,[41] acid exposure may maintain mucosal integrity by inducing villous hypoxia. This mechanism may be implicated in the clinical observation of PPI-induced iron deficiency.

In addition, because immersion in water may interfere with iontophoresis, it is recommended that patients avoid bathing or swimming during the 4 hours of patch operation. Patch PCI 32765 placement may also be an issue, as it is unknown to what extent, if at all, the presence of scars, lesions, tattoos, and other dermal irregularities may alter

drug delivery or tolerability. Finally, although the incidence of allergic contact dermatitis in the 12-month assessment was relatively low and within the accepted range for currently marketed transdermal systems,[39] a small proportion of patients will be affected. Multiple clinical trials indicate that sumatriptan TDS provides rapid relief of migraine pain and MRN, as well as the constellation of symptoms associated with migraine, with consistent drug delivery and low interpatient variability and efficacy demonstrated over 12 months. Sumatriptan TDS also has an excellent safety profile, Acalabrutinib mouse with a low incidence of the triptan-sensation AEs commonly associated with triptans. Sumatriptan TDS will allow patients who experience

MRN and vomiting to receive the benefits of migraine-specific therapy. “
“Pain has been considered as part of a defensive strategy whose specific role is to signal an immediate active danger to the organism. This definition fits well for acute pain. It does not work well, however, for chronic pain that is maintained even

in absence of an ongoing, active threat. Currently, acute and chronic pain are considered medchemexpress to be separate conditions. What follows is a review of the different theories about pain and its history. Different hypotheses regarding pain mechanisms are illustrated. New data emerging from scientific research on chronic pain (migraine in particular) involving innovative imaging techniques are reported and discussed. “
“Background.— Many migraineurs report attack “triggers,” but relatively few published data exist regarding the relative prevalences of individual triggers, variations related to gender, duration of migraine or migraine subtype, or the existence of any regional variations in the prevalences and distributions of triggers. Objective.— We sought to determine the prevalence and types of migraine triggers in our clinic population, to determine what influence gender, migraine subtype, or duration of migraine might have on the prevalences and types of triggers reported and to compare our findings with data derived from surveys we previously had conducted involving 2 clinic-based populations and 1 general population sample from other regions of the USA. Methods.— We evaluated 200 consecutive new migraine patients referred to our clinic.

I felt xxx listened to me more than the other healthcare professionals I have seen and took into account the effects the pain was having on my life in general,

rather than just treating me as a diagnosis.[104] In addition to the standard pain history, psychiatric RG-7388 clinical trial comorbidities must be identified and addressed early in the therapeutic relationship, as they may have been present before the onset of the pain.[15] It is also essential to elicit detailed information regarding social history, major life events, psychosocial stressors, and the impact of pain on the patient’s ability to participate in the activities of daily living. Many patients with facial pain who present to secondary care or pain clinics have attended consultations with a large number of primary and secondary care providers, and VX-770 cost may have had multiple investigations or interventions for their pain.[7, 102, 105] This is illustrated by the following patient quotation: “A lot of people would think [that consulting a] dentist, max facs [maxillo-facial surgery], neurologist was already over the top but I wanted to be certain that

I’d tried everything. These patients often have a significant level of psychological distress, and this can impact negatively on the therapeutic relationship and management strategies. Understanding the patient’s expectations and illness beliefs, and assessing negative prognostic factors such as catastrophizing or low self-efficacy levels is essential in order to formulate an appropriate treatment plan using the biopsychosocial model

that will then require a multidisciplinary team approach.[106] Psychological screening tools such as the National Institutes of Clinical Excellence medchemexpress depression screening questions, the Hospital Anxiety and Depression Scale, Patient Health Questionnaire, and the Beck Depression Inventory are useful for quantifying the degree of psychological comorbidity.[107] The inclusion of an objective measure of pain impact on quality of life is essential in every facial pain consultation; the Graded Chronic Pain Scale, Brief Pain Inventory (including the extended version),[108] the Pain Catastrophizing Scale, and the EuroQoL scale are useful tools. However, these measures need to be carefully interpreted in the context of the patient’s comorbidities. As 1 patient commented: “And if you’re very depressed and it’s hard to verbalize how you feel about things, or whether you can’t just mark on a scale between nought and ten what your pain is like, you know, what’s your pain, is it nought or is it ten?”[31] There is also the propensity for clinicians to “label” patients with a diagnosis, with the expectation that this will enable the patient to accept the condition and progress with treatment. This approach may be helpful for some patients – 1 patient stated: “I was quite relieved to have a diagnosis … although I had hoped I would come away with a solution for a cure, I am happy now that I know the cause and that it is not serious.

I felt xxx listened to me more than the other healthcare professionals I have seen and took into account the effects the pain was having on my life in general,

rather than just treating me as a diagnosis.[104] In addition to the standard pain history, psychiatric CCI-779 concentration comorbidities must be identified and addressed early in the therapeutic relationship, as they may have been present before the onset of the pain.[15] It is also essential to elicit detailed information regarding social history, major life events, psychosocial stressors, and the impact of pain on the patient’s ability to participate in the activities of daily living. Many patients with facial pain who present to secondary care or pain clinics have attended consultations with a large number of primary and secondary care providers, and selleck chemical may have had multiple investigations or interventions for their pain.[7, 102, 105] This is illustrated by the following patient quotation: “A lot of people would think [that consulting a] dentist, max facs [maxillo-facial surgery], neurologist was already over the top but I wanted to be certain that

I’d tried everything. These patients often have a significant level of psychological distress, and this can impact negatively on the therapeutic relationship and management strategies. Understanding the patient’s expectations and illness beliefs, and assessing negative prognostic factors such as catastrophizing or low self-efficacy levels is essential in order to formulate an appropriate treatment plan using the biopsychosocial model

that will then require a multidisciplinary team approach.[106] Psychological screening tools such as the National Institutes of Clinical Excellence MCE公司 depression screening questions, the Hospital Anxiety and Depression Scale, Patient Health Questionnaire, and the Beck Depression Inventory are useful for quantifying the degree of psychological comorbidity.[107] The inclusion of an objective measure of pain impact on quality of life is essential in every facial pain consultation; the Graded Chronic Pain Scale, Brief Pain Inventory (including the extended version),[108] the Pain Catastrophizing Scale, and the EuroQoL scale are useful tools. However, these measures need to be carefully interpreted in the context of the patient’s comorbidities. As 1 patient commented: “And if you’re very depressed and it’s hard to verbalize how you feel about things, or whether you can’t just mark on a scale between nought and ten what your pain is like, you know, what’s your pain, is it nought or is it ten?”[31] There is also the propensity for clinicians to “label” patients with a diagnosis, with the expectation that this will enable the patient to accept the condition and progress with treatment. This approach may be helpful for some patients – 1 patient stated: “I was quite relieved to have a diagnosis … although I had hoped I would come away with a solution for a cure, I am happy now that I know the cause and that it is not serious.

15, 16 Differentiating muscle cells15, 17 and transfected HeLa,16 HEK293,17-20 Cos-7,21 Hep3B,21, 22 and HepG216, 23, 24 cells release soluble ≈50 and ≈40 kDa isoforms (sHjv) in extracellular media; sHjv has also been detected in human,22, 25 rat,17 and mouse21 serum. Hjv interacts with neogenin, which may modulate the secretion of sHjv in a positive24 or a negative20 manner. sHjv can be generated by proteolytic cleavage with either furin and other pro-protein convertases,19, 21, 26 or matriptase-2.27 The latter, a protease encoded by

the TMPRSS6 gene,28 HM781-36B inactivates cellular Hjv27 and inhibits hepcidin expression by attenuating BMP signaling.29 Furin cleaves cellular Hjv at R332 and matriptase-2 at R288.30 Cleavage of the GPI anchor, possibly by phospholipase A, may yield full-length buy Everolimus sHjv, consisting of the entire ectodomain.19 In vitro experiments with purified recombinant sHjv and with conditioned media from Hjv-transfected cells suggested that this protein functions as a decoy receptor and inhibits BMP

signaling to hepcidin.19, 20, 22 Moreover, a sHjv.Fc fusion construct was shown to directly interact with BMP610 and to decrease hepcidin expression in vivo.31 Nevertheless, sHjv generated by matriptase cleavage did not compete BMP signaling to hepcidin.30 To elucidate the tissue-specific function of Hjv in the control of body iron homeostasis, we generated mice with targeted disruption of the Hfe2 gene in liver hepatocytes or in muscles. We show that only hepatic Hjv is essential for an appropriate hepcidin MCE response, whereas muscle Hjv does not exert any apparent iron-regulatory function. BMP, bone morphogenetic protein; GPI, glycosylphosphatidylinositol; Hjv, hemojuvelin; RGM, repulsive guidance molecule; sHjv, soluble hemojuvelin; TfR2, transferrin receptor 2; TIBC, total iron binding capacity. For conditional disruption of Hfe2, a targeting vector32 (kindly provided by Dr. Stephane Richard, McGill University) was employed to “flox” a 3.4 kb region spanning exons

2-4, with loxP sites. A neo-PGK cassette was also introduced for antibiotic selection of homologous recombination events. The targeting construct was transfected into 129S6/SvEvTac embryonic stem cells and two (out of 500) positive clones were identified. The clones were expanded and microinjected into C57BL/6J blastocysts; this procedure was performed at the McIntyre Cancer Centre Transgenic Core Facility of McGill University. The resulting chimeras were crossed with female C57/BL6 mice to produce agouti mice, which were polymerase chain reaction (PCR)-genotyped for germline transmission of the floxed Hfe2 allele. Heterozygotes (Hfe2wt/f) were crossed to obtain Hfe2f/f mice. PCR genotyping from tail genomic DNA was performed by using the RedExtract kit (Sigma) with primers shown in Table 1A. Alb-Cre mice (B6.Cg-Tg(Alb-cre)21Mgn/J strain) were purchased from the Charles River Laboratories (Cambridge, MA).

15, 16 Differentiating muscle cells15, 17 and transfected HeLa,16 HEK293,17-20 Cos-7,21 Hep3B,21, 22 and HepG216, 23, 24 cells release soluble ≈50 and ≈40 kDa isoforms (sHjv) in extracellular media; sHjv has also been detected in human,22, 25 rat,17 and mouse21 serum. Hjv interacts with neogenin, which may modulate the secretion of sHjv in a positive24 or a negative20 manner. sHjv can be generated by proteolytic cleavage with either furin and other pro-protein convertases,19, 21, 26 or matriptase-2.27 The latter, a protease encoded by

the TMPRSS6 gene,28 see more inactivates cellular Hjv27 and inhibits hepcidin expression by attenuating BMP signaling.29 Furin cleaves cellular Hjv at R332 and matriptase-2 at R288.30 Cleavage of the GPI anchor, possibly by phospholipase A, may yield full-length Selleckchem Stem Cell Compound Library sHjv, consisting of the entire ectodomain.19 In vitro experiments with purified recombinant sHjv and with conditioned media from Hjv-transfected cells suggested that this protein functions as a decoy receptor and inhibits BMP

signaling to hepcidin.19, 20, 22 Moreover, a sHjv.Fc fusion construct was shown to directly interact with BMP610 and to decrease hepcidin expression in vivo.31 Nevertheless, sHjv generated by matriptase cleavage did not compete BMP signaling to hepcidin.30 To elucidate the tissue-specific function of Hjv in the control of body iron homeostasis, we generated mice with targeted disruption of the Hfe2 gene in liver hepatocytes or in muscles. We show that only hepatic Hjv is essential for an appropriate hepcidin 上海皓元医药股份有限公司 response, whereas muscle Hjv does not exert any apparent iron-regulatory function. BMP, bone morphogenetic protein; GPI, glycosylphosphatidylinositol; Hjv, hemojuvelin; RGM, repulsive guidance molecule; sHjv, soluble hemojuvelin; TfR2, transferrin receptor 2; TIBC, total iron binding capacity. For conditional disruption of Hfe2, a targeting vector32 (kindly provided by Dr. Stephane Richard, McGill University) was employed to “flox” a 3.4 kb region spanning exons

2-4, with loxP sites. A neo-PGK cassette was also introduced for antibiotic selection of homologous recombination events. The targeting construct was transfected into 129S6/SvEvTac embryonic stem cells and two (out of 500) positive clones were identified. The clones were expanded and microinjected into C57BL/6J blastocysts; this procedure was performed at the McIntyre Cancer Centre Transgenic Core Facility of McGill University. The resulting chimeras were crossed with female C57/BL6 mice to produce agouti mice, which were polymerase chain reaction (PCR)-genotyped for germline transmission of the floxed Hfe2 allele. Heterozygotes (Hfe2wt/f) were crossed to obtain Hfe2f/f mice. PCR genotyping from tail genomic DNA was performed by using the RedExtract kit (Sigma) with primers shown in Table 1A. Alb-Cre mice (B6.Cg-Tg(Alb-cre)21Mgn/J strain) were purchased from the Charles River Laboratories (Cambridge, MA).

Aim: To describe our centers click here experience with NTZ in post LT HCV recurrence.

Methods: When used at our center, NTZ was prescribed off-label in prior non-responders or in patients with aggressive disease, such as early cholestatic HCV recurrence. NTZ was mainly used as lead in therapy for PEG-IFN/RBV. Demographics, clinical, immunosuppression and virologic data in LT recipients treated with NTZ/PEG-IFN/RBV were collected for descriptive analysis. The primary endpoint was sustained virologic response (SVR). Results: Nineteen patients were treated with NTZ, 2 were excluded for introduction of telaprivir to the course of treatment. The study group included 17 patients, mean age 50±4 years, including 13 (76%) males (13 (76% ) Caucasian, 2 (12%) Black, and 2 (12%) Hispanic), all had HCV genotype 1. NTZ was used in 13 (76%) prior non-responders and in 4 (23%) patients as part of their first course of HCV treatment post LT. Of the 13 non-responders, 9 (69%) were converted from tacrolimus to cyclosporine due to severity of HCV recurrence and 6 (46%) had advanced fibrosis prior to NTZ therapy. NTZ was introduced at 4.9±3.4 years post LT, as 4 week lead-in 10 (77%) and extended a further 4-16 weeks in 3 (23%) cases. Five (38%) patients previously had a <1 log and 4 (31%) had a >2log drop in viral

GS-1101 mw load, none had cleared virus on prior PEG-IFN/RBV, and 5 (38%). With NTZ/PEG-IFN/RBV 1 (8%) patient had <1 log and 5 (38%) had >2 log drop in viral load, with the latter 5 clearing HCV on treatment and 4 achieving SVR (31%), 2 with advanced fibrosis. Of the 4 treatment naive patients post-LT

receiving 4 week lead-in NTZ and PEG-IFN/RBV, 2 (cyclosporine) were treated for cholestatic HCV infection with <2 log response. Two patients (on tacrolimus) were treated 4-5 years post LT, without advanced fibrosis. Both cleared HCV on therapy, but 1 died before completing therapy (due to de novo malignancy) and 1 died after completing therapy but before SVR was established (due to pulmonary hemorrhage). Conclusion: LT recipients with HCV genotype 1 recurrence but without access to or success of direct acting agents, who are being considered for PEG-IN/ RBV may benefit from NTZ lead-in therapy. Disclosures: Paul Y. Kwo - Advisory Committees or Review Panels: Abbott, Novartis, Merck, Gilead, BMS, Janssen; Consulting: medchemexpress Vertex; Grant/Research Support: Roche, Vertex, GlaxoSmithKline, Merck, BMS, Abbott, Idenix, Vital Therapeutics, Gilead, Vertex, Merck, Idenix; Speaking and Teaching: Merck, Merck Marwan Ghabril – Grant/Research Support: Salix The following people have nothing to disclose: Marshall E. McCabe, Saurabh Agrawal, Marco A. Lacerda, A. Joseph Tector Introduction: Treatment (Tx) of Hepatitis C Virus (HCV) infection in kidney transplant (KT) recipients with interferon (IFN)-based regimens has been contra-indicated. IFN-free therapies with good safety profiles offer the opportunity of HCV Tx after KT for the first time.

However, it is not possible to exclude the idea that difficulties in daily urine collection in this age group may have played a role, even if in our population the parents underwent

appropriate training and the daily urine volume was consistent with the age and weight. Current recommendations by the AASLD conclude that PCT may be performed in symptomatic children if a diagnosis of WD is suspected NVP-BGJ398 order but basal urinary copper excretion is normal.2 Data about PCT sensitivity at the cutoff value of 1575 μg/24 hours are very heterogeneous; the sensitivity ranges from 69% to 88% in children with active liver disease and from 46% to 56% in asymptomatic siblings.3, 9 There is only one report showing a specificity of 93% at the proposed cutoff of 1575 μg/24 hours.9 In this study, however, the group of asymptomatic children was small (only 13 patients) and was not well characterized with respect to

liver enzymes. Our study provides further and stronger evidence that PCT should not be performed in children without symptomatic liver disease regardless of the presence of neurological symptoms. In our series, only patients with more severe liver damage according to a histological examination had a positive PCT in both the WD and control groups, and this suggests that copper excretion is influenced by the severity of the liver injury. Moreover, the suggestion of applying to children with basal urinary copper levels < 100 μg/24 hours a test with a cutoff value established in Rapamycin chemical structure a population of children with basal urinary copper levels > 100 μg/24 hours9, 13 is controversial. The present MCE study has shown that CDG can mimic WD-related liver disease because patients

with this disorder may present low serum levels of ceruloplasmin. A correct differential diagnosis of WD versus CDG may be challenging if we consider that the CDG patients included in our control group presented with an isolated liver disease in the absence of the typical CDG phenotype characterized by severe neurological involvement, dysmorphisms, and multiorgan impairment. In these patients, further investigations for CDG were triggered only by the presence of a mild coagulopathy not explained by the liver disease. It is noteworthy that this novel CDG phenotype with prevalent liver involvement has been recently recognized and characterized in asymptomatic children and young adults with cryptogenic elevated aminotransferases and/or liver steatosis with fibrosis.23, 29 The CDG patients, who were included in the control group and were diagnosed as being affected by a new phenotype called CDG-X, shared with the WD patients low levels of ceruloplasmin and high levels of liver copper, but in all of them, WD was ruled out because of negative ATP7B gene sequencing and spread haplotype analysis, low urinary copper excretion (both at the baseline and after PCT), and the absence of typical mitochondrial changes according to an electron microscopy examination.

However, it is not possible to exclude the idea that difficulties in daily urine collection in this age group may have played a role, even if in our population the parents underwent

appropriate training and the daily urine volume was consistent with the age and weight. Current recommendations by the AASLD conclude that PCT may be performed in symptomatic children if a diagnosis of WD is suspected PD0325901 mouse but basal urinary copper excretion is normal.2 Data about PCT sensitivity at the cutoff value of 1575 μg/24 hours are very heterogeneous; the sensitivity ranges from 69% to 88% in children with active liver disease and from 46% to 56% in asymptomatic siblings.3, 9 There is only one report showing a specificity of 93% at the proposed cutoff of 1575 μg/24 hours.9 In this study, however, the group of asymptomatic children was small (only 13 patients) and was not well characterized with respect to

liver enzymes. Our study provides further and stronger evidence that PCT should not be performed in children without symptomatic liver disease regardless of the presence of neurological symptoms. In our series, only patients with more severe liver damage according to a histological examination had a positive PCT in both the WD and control groups, and this suggests that copper excretion is influenced by the severity of the liver injury. Moreover, the suggestion of applying to children with basal urinary copper levels < 100 μg/24 hours a test with a cutoff value established in ACP-196 a population of children with basal urinary copper levels > 100 μg/24 hours9, 13 is controversial. The present MCE study has shown that CDG can mimic WD-related liver disease because patients

with this disorder may present low serum levels of ceruloplasmin. A correct differential diagnosis of WD versus CDG may be challenging if we consider that the CDG patients included in our control group presented with an isolated liver disease in the absence of the typical CDG phenotype characterized by severe neurological involvement, dysmorphisms, and multiorgan impairment. In these patients, further investigations for CDG were triggered only by the presence of a mild coagulopathy not explained by the liver disease. It is noteworthy that this novel CDG phenotype with prevalent liver involvement has been recently recognized and characterized in asymptomatic children and young adults with cryptogenic elevated aminotransferases and/or liver steatosis with fibrosis.23, 29 The CDG patients, who were included in the control group and were diagnosed as being affected by a new phenotype called CDG-X, shared with the WD patients low levels of ceruloplasmin and high levels of liver copper, but in all of them, WD was ruled out because of negative ATP7B gene sequencing and spread haplotype analysis, low urinary copper excretion (both at the baseline and after PCT), and the absence of typical mitochondrial changes according to an electron microscopy examination.

It has become the most common cause of chronic liver disease, and yet there continues to be a lack of effective therapeutic options. This article reviews current concepts underlying the pathophysiological basis of nonalcoholic steatohepatitis from development of insulin resistance to the establishment of fibrosis. Then using a physiology-based approach, specific targeted therapeutics are reviewed along with their drawbacks. The evidence behind current therapies is based predominantly on small trials and, thus, no recommendations can be made until larger randomized trials are

conducted. “
“Hepatitis B virus (HBV) resistance to nucleoside/nucleotide analogs is frequent. Ultra-deep pyrosequencing (UDPS) is a powerful new tool that can detect minor viral variants and characterize complex quasispecies mixtures. We used UDPS Proteases inhibitor to analyze the dynamics of adefovir-resistant HBV variants in patients with chronic HBV infection in whom adefovir resistance occurred during treatment. Amino acid substitutions known to confer resistance to adefovir were detected at baseline in most patients. The dynamics of adefovir-resistant variants were complex and differed among patients as a result of evolving differences in variant fitness.

UDPS analysis revealed successive selleckchem waves of selection of HBV populations with single and multiple amino acid substitutions. Adefovir-resistant variants were partially inhibited by lamivudine, but remained fit in its presence. Conclusion: Substitutions conferring HBV resistance to nucleoside/nucleotide analogs exist before treatment, and that the dynamics of adefovir-resistant populations are much more complex and heterogeneous MCE公司 than previously thought and involve thus far unknown amino acid substitutions. The UDPS-based approach described here is likely to have important implications for the assessment

of antiviral drug resistance in research and clinical practice. (Hepatology 2013;53:890–901) Approximately 240 million individuals worldwide are chronically infected with hepatitis B virus (HBV).[1] Chronic HBV infection is the leading cause of chronic liver disease and accounts for nearly 1 million deaths every year.[2-4] Chronic hepatitis B (CHB) can be treated with either pegylated interferon alpha or nucleoside/nucleotide analogs. The latter drugs act by directly inhibiting the enzymatic function of HBV reverse transcriptase, the enzyme responsible for viral replication. Five such drugs have been approved for HBV therapy, namely, three nucleoside analogs (lamivudine, telbivudine, and entecavir) and two nucleotide analogs administered as prodrugs (adefovir dipivoxil and tenofovir disoproxil fumarate). The vast majority of HBV-infected patients have an indication for therapy with nucleoside/nucleotide analogs.