, MD (General Hepatology Update) Speaking and Teaching: SALIX Llovet, Josep M., MD (Early Morning Workshops) Consulting: Selleckchem Lumacaftor Bayer Pharmaceutical,

Bristol Myers Squibb, Imclone, Biocompatibles, Novartis Grant/Research Support: Bayer Pharmaceutical, Bristol Myers Squibb, Boehringer-Ingelheim Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Lo, Chung-Mau, MD (AASLD/ILTS Transplant Course) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Loomba, Rohit, MD (SIG Program) Consulting: Gilead Inc, Corgenix Inc Grant/Research Support: Daiichi Sankyo Inc, AGA Content of the presentation does not include discussion of off-label/investigative

use of medicine(s), medical devices or procedure(s) Lucey, Michael R., MD (AASLD Postgraduate Course) Grant/Research Ensartinib nmr Support: Vertex, Abbvie, Gilead, Salix Speaking and Teaching: Roche Luxon, Bruce A., MD, PhD (Career Development Workshop, Competency Training Workshop, Meet-the-Professor Luncheon) Consulting: Vertex Speaking and Teaching: Merck Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices

or procedure(s) Machicao, Victor I., MD (ABIM Maintenance of Certification) Advisory Committees or Review Panels: Gilead Sciences Inc, Vertex Pharmaceuticals Mack, Cara, MD (Parallel Session) Nothing to disclose Magee, John C., MD (AASLD/NASPGHAN Pediatric Symposium) Grant/Research Support: Novartis Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Mandrekar, Pranoti, PhD (Parallel Session) Nothing to disclose 上海皓元 Marrero, Jorge A., MD (Advances for Practitioners, Early Morning Workshops, General Hepatology Update) Advisory Committees or Review Panels: Bayer, Onyx Grant/Research Support: Bayer, BMS Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Martin, Paul, MD (AASLD Postgraduate Course) Consulting: Roche, BMS, Gilead, Vertex, Roche, BMS, Gilead, Vertex, Roche, BMS, Gilead, Vertex, Roche, BMS, Gilead, Vertex Speaking and Teaching: Roche, BMS, Roche, BMS, Roche, BMS, Roche, BMS Marzioni, Marco (Early Morning Workshops) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Mason, Andrew L.

Our data suggest that overweight or obese patients with NASH can successfully achieve a weight reduction of 7% to 10% of initial body weight and maintain it through 1 year of study participation. In the current study, participants in the lifestyle this website intervention group lost an average of 9.3% from baseline weight as compared with 0.2% in the control group. Importantly, the results from this study suggest that lifestyle modifications focusing on diet, exercise, and behavioral changes can successfully

lead to improvements in overall NASH histological activity, degree of steatosis, and liver chemistry. Published studies on weight reduction as a treatment for NASH have several major limitations.30, 31 Most notably, there has yet to be a rigorously conducted randomized controlled trial to address the efficacy of weight reduction in adult patients with NASH. Most published studies have been either small retrospective or prospective case series without inclusion of a comparison group.32, 33 Many studies did not stratify patients according to histological criteria34 and thus may have included not only patients with NASH but also patients with simple steatosis who have a different natural history and clinical outcomes. In addition, these studies used primary outcomes that are not well accepted, such as serum aminotransferases

or sonographic findings.35–38 Another important shortcoming of earlier studies is that they used weight reduction strategies such as prolonged fasting39 or very-low-calorie anti-EGFR antibody inhibitor dieting40 that cannot be sustained over a long period. Several recent pharmaceutical trials for NASH have included dietary intervention for comparison.8, 41 Although the effects medchemexpress of nutritional counseling in these studies appeared to be inferior to the investigational drugs, these dietary interventions produced minimal or no weight loss and thus cannot address the question of whether weight loss leads to improvements in NASH. This study had a number of strengths, including

the selection of patients with well-characterized NASH both clinically and histologically, the randomized design, the high completion rate (97%, only one dropout), and the use of the current histological scoring criteria by NASH Clinical Research Network. In addition, our study used a standardized, protocol-based lifestyle intervention similar to the programs implemented in the Diabetes Prevention Program15 and Look AHEAD, an ongoing study with overweight individuals with type 2 diabetes.18 The effect sizes for overall NASH disease activity (Cohen’s d = .82) and steatosis (Cohen’s d = .97) were large, and thus differences between lifestyle and control were statistically significant even with the relatively small sample size.

2 In this oxidative stress theory, the role of free intracellular copper in initiating generation of reactive oxygen species and consequent oxidative hepatic injury has been proposed.

Indeed, several studies in patients with WD and in appropriate animal models indicated that oxidative damage to mitochondria might be involved in hepatic copper toxicity.3, 4 However, how can copper cause uncontrolled redox reactions, although there is good evidence that copper is at all times bound to proteins and small molecules and thus is not freely available?5-8 Zischka and colleagues addressed the question whether there might exist an alternative mechanism of how copper overload causes mitochondrial dysfunction in WD and ventured a step beyond this website current disease concepts. They questioned if oxidative stress is perhaps not the cause, but the consequence of mitochondrial damage in WD. The findings of Zischka and colleagues,9 recently reported in the Journal of Clinical Investigation, indicate that copper overload can directly induce intramitochondrial membrane crosslinking that culminates in mitochondrial destruction and liver failure. With this finding, an important step in the pathogenesis of WD can now be explained in a new way. Zischka and colleagues impressively show in a WD rat model, by use of electron microscopy, that major structural alterations of the mitochondria

occur early and parallel to increasing mitochondrial copper content. cancer metabolism inhibitor The alterations clearly precede major functional deficits of the mitochondria and can be reversed by copper-chelating therapy in this early phase. This observation and the fact that signs of oxidative damage were absent in this early phase argues strongly against

copper-related oxidative stress as a causative mechanism. In the rat model that was analyzed, clinically evident liver failure occurred late after excessive mitochondrial destruction and subsequent oxidative damage had taken 上海皓元 place. After establishing an in vitro cell-free system, the investigators were able to reproduce the observed mitochondrial alterations with isolated control mitochondria exposed to copper under conditions mimicking the physiological intramitochondrial milieu. In this cell-free system, Zischka and colleagues could show that complete mitochondrial destruction occurred only at late stages with massive mitochondrial copper overload and was then paralleled by oxidative damage. As an attempt to explain the observed copper-overload–related structural alterations of mitochondria, Zischka and colleagues used a redox proteomics approach and were able to identify three abundant mitochondrial membrane proteins that might form intermolecular thiol bridges between proteins anchored in the outer and the inner mitochondrial membrane under copper-overload conditions.

Skin prick tests were negative to all food allergens tested, i.e. cow’s milk, soy, egg white, wheat, peanut, several tree nuts, cod fish, shrimp, beef, chicken, lamb, pork, oats, corn and rice. House AZD5363 dust mite tested positive (8 mm), and rye grass was borderline positive (2 mm). A broad-based elimination diet (cow’s milk, soy, eggs, nuts, wheat, fish, shellfish, rye, barley, oats, chicken, lamb and beef) was instituted after dietetics review and maintained for 8 weeks. A calcium supplement of 1000 mg daily was prescribed. A follow-up gastroscopy demonstrated histological remission of EoE (four eosinophils/HPF in the upper, and three eosinophils/HPF in the middle and lower esophagus). Soy and oats were then

introduced, and a repeat gastroscopy 3 months later revealed no histological relapse. Liberation of the diet to egg, tuna, and other fish then followed, with a fourth gastroscopy at 10 years of age demonstrating ongoing histological remission. Nuts and meats were then introduced, with a further normal endoscopy 6 months later. At 11 years of age the patient was only avoiding cow’s milk and wheat. A repeat gastroscopy after re-introduction of cow’s milk demonstrated a recurrence of esophageal inflammation (45 eosinophils/HPF in upper,

this website 68/HPF in middle and 34/HPF in the lower esophagus). Cow’s milk was subsequently eliminated, and normal histology demonstrated on a repeat gastroscopy 6 months later. The dietary trial for the reintroduction of wheat is pending. The patient was instructed to avoid cow’s milk in the long-term. Learning points: Despite negative skin prick tests, the patient responded to dietary restriction of food allergens. While the single elimination of cow’s milk failed initially, the patient responded to a more broad-based elimination diet. Over the following 3 years, most avoided food allergens could step-wise be reintroduced, followed by a normal gastroscopy. A relapse of EoE was demonstrated after the reintroduction

of cow’s milk, confirming ongoing cow’s milk sensitivity. Subsequent elimination MCE of cow’s milk was followed by remission of EoE. This case illustrates the need for gradual liberalization of diet after formal elimination periods and step-wise food challenges, followed by gastroscopy and biopsy. This process is complex, resource consuming and sometimes not conclusive. Confounding factors include the unrecognized aggravation of EoE during the pollen season or use of inhaled steroids for treatment of asthma. Non-invasive markers to assess the effects of oral food challenges on EoE are urgently needed. Case study 3 A 12-year-old boy presented to the emergency department with an acute food bolus obstruction after eating chicken. In the weeks leading up to the episode he had experienced occasional episodes of retrosternal pain, acid regurgitation and food sticking during meals. On the morning of the bolus obstruction he had been moving hay bales.

High-abundance proteins proteins in the serum were removed by immune-chromatography assay, Isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography/tandem PXD101 concentration mass spectrometry (2D-LC-MS/MS) were used to analyze and identify the proteins expression of between four groups. The samples of intestinal metaplasia group, dysplasia group, gastric cancer group and normal control group were labeled with

iTRAQ reagent 117, 119, 116, and 118, respectively. The samples were detected by cation exchange chromatography (SCX) and reversed phase chromatography (RP), Protein Pilot 4.2 were used to deal with the results of peptides mass spectrometry, and qualitative

and quantitative identified various protein. Serum differential proteins involving in the genesis and development of gastric cancer were screened, ratio >1.6 or ratio <0.625 and P-Value < 0.05 as an approximate benchmark for variation in protein expression. Bioinformatics was used to analysed the serum differential proteins. Results: This iTRAQ coupled with 2D-LC-MS/MS proteomics analysis led to the identification of a total of 10540 unique peptides, which correspond to a set of 199 RG7420 research buy proteins. ratio >1.6 or ratio <0.625 and P-Value < 0.05 as an approximate benchmark for variation in protein expression. Compared with normal control population, seventeen serum differential proteins, including twelve proteins expression were up- regulated and five proteins expression medchemexpress were expression were down-regulated in gastric cancer patients were screened; two serum differential proteins were up- regulated in dysplasia patients were screened; eight serum differential proteins, including seven proteins expression were up-regulated and one proteins expression were expression were down-regulated in intestinal metaplasia

patients; one serum differential proteins was up-regulated both in gastric cancer patients and dysplasia patients; one serum differential proteins was up- regulated and one serum differential proteins was down-regulated both in gastric cancer patients and intestinal metaplasia patients; one serum differential proteins was up- regulated both in dysplasia patients and intestinal metaplasia patients, whereas there was any serum differential proteins was screened between this there types of patients. According to the biological function, all of the differential proteins were comprised immune related protein, lipid transport and metabolism protein, transportation and storage protein, cell adhesion and movement protein, energy metabolism and coagulation-related protein.

5E) could be important not only for development of HCCs but also for other tumor types. The inverse correlation between selenium levels and tumor size described here in HCC patients is consistent with several epidemiologic studies. An inverse relation between plasma selenium levels and HCC risk was observed in Taiwan.18 Based on previous animal experiments60 an intervention trial was performed in Quidong/China, a region with low selenium intake. Daily doses of 200 μg selenium decreased HCC rates by 35% and cessation of selenium supplementation brought tumor rates back to initial values.17,

60-62 Consistently, an intervention study in the USA demonstrated protection by selenium against prostate cancer.63 In contrast, selleck inhibitor the more recent SELECT study did not show any benefit of selenium

supplementation.64 This might, however, be due to the high baseline selleck products plasma levels of selenium observed in this study that could conceal potentially beneficial effects of selenium supplementation. Although comparison of selenium levels between different studies is difficult because of inconsistent methodologies, conclusions can be drawn from environmental parameters. In particular, low selenium concentrations in the serum have been documented for the Austrian population that are due to low selenium in the soil.65 In conclusion, the mechanistic data in the present study support the notion that the inverse correlation between selenium levels and the risk to develop HCC may have a causal MCE公司 basis. Therefore, selenium supplementation could be considered a strategy for chemoprevention or additional therapy for HCC patients

with low selenium levels. We thank M. Seif, E. Hangelmann, M. Eisenbauer, and N. Kandler for excellent technical assistance, M. Vidali for help in optimization of LOOH-Ab detection, M. Jakupec for help in selenium quantification, B. Marian for critical reading of the article, and A. Kaider for statistical evaluation of the data. Additional Supporting Information may be found in the online version of this article. “
“Aim:  The aim of this study was to evaluate the feasibility of gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd-EOB-DTPA) in magnetic resonance imaging (MRI) to assess the ablative margin of radiofrequency (RF) ablation to hepatocellular carcinoma (HCC). Methods:  RF ablation was performed in the livers of six pigs after the i.v. administration of Gd-EOB-DTPA 20 min before ablation. Three pigs were killed 2 h after administration (group A), and the other pigs were killed 7 days after ablation (group B). Thereafter, correlation between pathological findings and MRI was investigated. Moreover, the Gd concentrations were examined in ablated and non-ablated regions. An initial clinical evaluation was conducted for 28 HCC nodules.

Adiponectin levels were comparable, showing no differences among

the groups; however, LFD+VDD, WD and WD+VDD animals had higher leptin than LFD animals (Table 3). There were no significant differences in plasma IL-1β serum levels (LFD 14.0 ± 6.6 pg/mL, LFD+VDD 21.6 ± 11.1, WD 34.7 ± 26.2, WD+VDD 61.9 ± 47 pg/mL). IL-6 plasma levels were below the detection click here level of the assay (<5 pg/mL) in LFD groups but were detectable in WD (143 ± 138 pg/mL) and WD+VDD (90 ± 54 pg/mL) (t test, NS). Serum LBP levels were significantly higher in WD than in LFD groups (LFD: 878 ± 31, LFD+VDD 936 ± 21, WD: 1,373 ± 209, WD+VDD 1,493 ± 242 ng/mL, P < 0.05 WD versus LFD groups). Hepatic steatosis and lobular inflammation were lower in LFD animals and this was unaffected by VDD. There was no significant difference in hepatic steatosis and lobular inflammation between LFD and WD animals, in part due to variability in responses. In WD+VDD animals, we found increased hepatic steatosis and lobular inflammation. Lobular inflammation and NAS were significantly higher in WD+VDD relative to all other groups. Moreover, there was a trend for higher ballooning score in WD+VDD rats compared to the other groups (Table 4, Fig. 1A-D). After the 10 weeks of dietary exposures, there was no significant fibrosis that fulfilled the NASH CRN criteria in zones 1 or 3 (Fig. 1E); however, incipient this website perivenular/pericellular

fibrosis was seen in 3 WD+VDD rats (Fig. 1F). Gene expression studies were executed to determine whether increased NASH was accompanied by increased inflammation. VDD had a greater effect on inflammatory genes in the liver compared to adipose tissue. Specifically, liver resistin mRNA levels were higher in VDD groups compared to VitD replete animals (Fig. 2A), but no differences between groups were seen in adipose tissue (data not shown). IL-4 mRNA levels were higher

in VDD than in VitD replete groups, with greater effect exhibited in liver than adipose tissue (Fig. 2B; Supporting Fig. 2A). IL-6 mRNA levels were higher in VDD than in VitD replete groups in the liver (Fig. 2C), and higher in WD+VDD compared to all other groups MCE in adipose tissue (Supporting Fig. 2B). Further examination of hepatic signaling pathways involved in inflammation and oxidative stress in liver revealed activation of IL-1β in both WD and VDD independently (Fig. 2D), and activation of IL-10 by WD (Fig. 2E), whereas in adipose tissue IL-1β did not differ significantly between the groups (data not shown). Liver mRNA levels for HO-1, a marker for oxidative stress, were significantly higher in WD+VDD versus WD rats (Fig. 2F). Analysis of the TLR signaling pathways showed activation of TLR4 and LBP in both WD and VDD independently (Fig. 3A,B), activation of CD14, TLR2, TIRAP, and TLR9 by WD with further increment by VDD (Fig.

Adiponectin levels were comparable, showing no differences among

the groups; however, LFD+VDD, WD and WD+VDD animals had higher leptin than LFD animals (Table 3). There were no significant differences in plasma IL-1β serum levels (LFD 14.0 ± 6.6 pg/mL, LFD+VDD 21.6 ± 11.1, WD 34.7 ± 26.2, WD+VDD 61.9 ± 47 pg/mL). IL-6 plasma levels were below the detection Dabrafenib concentration level of the assay (<5 pg/mL) in LFD groups but were detectable in WD (143 ± 138 pg/mL) and WD+VDD (90 ± 54 pg/mL) (t test, NS). Serum LBP levels were significantly higher in WD than in LFD groups (LFD: 878 ± 31, LFD+VDD 936 ± 21, WD: 1,373 ± 209, WD+VDD 1,493 ± 242 ng/mL, P < 0.05 WD versus LFD groups). Hepatic steatosis and lobular inflammation were lower in LFD animals and this was unaffected by VDD. There was no significant difference in hepatic steatosis and lobular inflammation between LFD and WD animals, in part due to variability in responses. In WD+VDD animals, we found increased hepatic steatosis and lobular inflammation. Lobular inflammation and NAS were significantly higher in WD+VDD relative to all other groups. Moreover, there was a trend for higher ballooning score in WD+VDD rats compared to the other groups (Table 4, Fig. 1A-D). After the 10 weeks of dietary exposures, there was no significant fibrosis that fulfilled the NASH CRN criteria in zones 1 or 3 (Fig. 1E); however, incipient click here perivenular/pericellular

fibrosis was seen in 3 WD+VDD rats (Fig. 1F). Gene expression studies were executed to determine whether increased NASH was accompanied by increased inflammation. VDD had a greater effect on inflammatory genes in the liver compared to adipose tissue. Specifically, liver resistin mRNA levels were higher in VDD groups compared to VitD replete animals (Fig. 2A), but no differences between groups were seen in adipose tissue (data not shown). IL-4 mRNA levels were higher

in VDD than in VitD replete groups, with greater effect exhibited in liver than adipose tissue (Fig. 2B; Supporting Fig. 2A). IL-6 mRNA levels were higher in VDD than in VitD replete groups in the liver (Fig. 2C), and higher in WD+VDD compared to all other groups MCE公司 in adipose tissue (Supporting Fig. 2B). Further examination of hepatic signaling pathways involved in inflammation and oxidative stress in liver revealed activation of IL-1β in both WD and VDD independently (Fig. 2D), and activation of IL-10 by WD (Fig. 2E), whereas in adipose tissue IL-1β did not differ significantly between the groups (data not shown). Liver mRNA levels for HO-1, a marker for oxidative stress, were significantly higher in WD+VDD versus WD rats (Fig. 2F). Analysis of the TLR signaling pathways showed activation of TLR4 and LBP in both WD and VDD independently (Fig. 3A,B), activation of CD14, TLR2, TIRAP, and TLR9 by WD with further increment by VDD (Fig.

Adiponectin levels were comparable, showing no differences among

the groups; however, LFD+VDD, WD and WD+VDD animals had higher leptin than LFD animals (Table 3). There were no significant differences in plasma IL-1β serum levels (LFD 14.0 ± 6.6 pg/mL, LFD+VDD 21.6 ± 11.1, WD 34.7 ± 26.2, WD+VDD 61.9 ± 47 pg/mL). IL-6 plasma levels were below the detection Ibrutinib clinical trial level of the assay (<5 pg/mL) in LFD groups but were detectable in WD (143 ± 138 pg/mL) and WD+VDD (90 ± 54 pg/mL) (t test, NS). Serum LBP levels were significantly higher in WD than in LFD groups (LFD: 878 ± 31, LFD+VDD 936 ± 21, WD: 1,373 ± 209, WD+VDD 1,493 ± 242 ng/mL, P < 0.05 WD versus LFD groups). Hepatic steatosis and lobular inflammation were lower in LFD animals and this was unaffected by VDD. There was no significant difference in hepatic steatosis and lobular inflammation between LFD and WD animals, in part due to variability in responses. In WD+VDD animals, we found increased hepatic steatosis and lobular inflammation. Lobular inflammation and NAS were significantly higher in WD+VDD relative to all other groups. Moreover, there was a trend for higher ballooning score in WD+VDD rats compared to the other groups (Table 4, Fig. 1A-D). After the 10 weeks of dietary exposures, there was no significant fibrosis that fulfilled the NASH CRN criteria in zones 1 or 3 (Fig. 1E); however, incipient www.selleckchem.com/products/icg-001.html perivenular/pericellular

fibrosis was seen in 3 WD+VDD rats (Fig. 1F). Gene expression studies were executed to determine whether increased NASH was accompanied by increased inflammation. VDD had a greater effect on inflammatory genes in the liver compared to adipose tissue. Specifically, liver resistin mRNA levels were higher in VDD groups compared to VitD replete animals (Fig. 2A), but no differences between groups were seen in adipose tissue (data not shown). IL-4 mRNA levels were higher

in VDD than in VitD replete groups, with greater effect exhibited in liver than adipose tissue (Fig. 2B; Supporting Fig. 2A). IL-6 mRNA levels were higher in VDD than in VitD replete groups in the liver (Fig. 2C), and higher in WD+VDD compared to all other groups 上海皓元医药股份有限公司 in adipose tissue (Supporting Fig. 2B). Further examination of hepatic signaling pathways involved in inflammation and oxidative stress in liver revealed activation of IL-1β in both WD and VDD independently (Fig. 2D), and activation of IL-10 by WD (Fig. 2E), whereas in adipose tissue IL-1β did not differ significantly between the groups (data not shown). Liver mRNA levels for HO-1, a marker for oxidative stress, were significantly higher in WD+VDD versus WD rats (Fig. 2F). Analysis of the TLR signaling pathways showed activation of TLR4 and LBP in both WD and VDD independently (Fig. 3A,B), activation of CD14, TLR2, TIRAP, and TLR9 by WD with further increment by VDD (Fig.

Adolescents aged 12 to <18 years with chronic HBV infection, defined as documented positive serum HBsAg for at least 6 months prior to enrollment, were included. They Tamoxifen molecular weight could be either positive or negative

for HBeAg. Key inclusion criteria at screening included HBV DNA ≥105 copies/mL (measured by polymerase chain reaction [PCR; COBAS TaqMan HBV test]) and either ALT ≥2 times the upper limit of normal (ULN) or any history of ALT ≥2 times the ULN within the past 24 months. The ULN was defined as 43 U/L for males and 34 U/L for females. Patients also had to weigh at least 35 kg and be able to swallow oral tablets. Patients must have discontinued any oral anti-HBV nucleoside/nucleotide therapy ≥16 weeks prior to screening and any interferon therapy ≥6 months prior to screening. Investigational sites in Poland required patients to have had a history of treatment for HBV or a contraindication for treatment with existing drugs. Exclusion criteria included previous therapy with tenofovir DF; serological evidence of coinfection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus; history of significant bone disease, decompensated liver disease, or renal disease; or evidence of hepatocellular carcinoma. Randomization was centralized EGFR assay and stratified by age (12-14 years or 15-17 years) and geographical region

(North America or Europe). Patients were randomized in a 1:1 ratio to receive oral tenofovir DF 300 mg

上海皓元 or a matching placebo once daily for 72 weeks. Randomization was accomplished via an interactive voice or web response system, using an allocation sequence generated with SAS software by an independent party. Patients were also required to take a daily multivitamin containing 100% of the recommended daily allowance for vitamin D. All investigators, patients, and clinical research personnel remained blinded to treatment and HBV efficacy outcomes. Unblinding was possible if there was concern about the patient’s welfare or if any patient had a sustained ALT elevation of grade 4 for ≥16 weeks or an ALT flare. An ALT flare was defined as either an ALT measurement >2 times the baseline level and >10 times the ULN (with or without associated symptoms) or an ALT elevation of one grade or to twice a previous value that was associated with abnormalities in other laboratory parameters suggestive of worsening hepatic function. If breaking the blind for an ALT flare revealed that the patient was in the placebo group, the patient could be offered open-label treatment with tenofovir DF. Patients were evaluated at baseline, weeks 4 and 8, and every 8 weeks thereafter through week 72. The primary efficacy measure was the percentage of patients with HBV DNA <400 copies/mL (virologic response) at week 72.