We assessed HFE mutations in a prospective cohort of 31,192 parti

We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants’ HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131

male, 160 female) with baseline and follow-up SF concentrations <1000 μg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types Mitomycin C mouse for both normal and moderately elevated SF concentrations. The maximum BIBW2992 supplier prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = −6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use,

95% confidence interval = −3%, 16%; P = 0.11). Conclusion: Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 μg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes. HEPATOLOGY 2010 Hereditary hemochromatosis (HH) refers to symptoms and signs of disease that result from an inherited predisposition to iron overload. Iron overload is preventable, but can lead to significant health problems, including arthritis, hepatic cirrhosis, hepatocellular carcinoma, fatigue, and diabetes mellitus, if it is left untreated.1 More than 80% of patients presenting with symptomatic iron overload2, 3 are homozygous for the 845GA mutation in the hemochromatosis (HFE) gene, which leads to the Cys282Tyr (C282Y) substitution in the HFE protein.4 The prevalence of C282Y homozygotes is at least 1 in 200 for people

of northern European descent.5, 6 The majority of C282Y homozygotes have elevated iron indices7, 8 but the serum click here ferritin (SF) concentration threshold at which there is an increased risk of developing HH-associated signs and symptoms other than cirrhosis is not known. We have recently shown that at least 28% of male C282Y homozygotes develop iron overload–related disease (as defined by both the presence of documented iron overload9 and one of the following five objective HH features: hepatocellular carcinoma, cirrhosis/fibrosis, physician-diagnosed symptomatic HH, elevated liver enzymes, or evidence of HH-associated arthritis),7 with onset in the majority by age 55 years. Other studies have shown that individuals with SF concentrations >1000 μg/L are at significantly increased risk of cirrhosis.

We assessed HFE mutations in a prospective cohort of 31,192 parti

We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants’ HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131

male, 160 female) with baseline and follow-up SF concentrations <1000 μg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types Maraviroc in vitro for both normal and moderately elevated SF concentrations. The maximum learn more prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = −6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use,

95% confidence interval = −3%, 16%; P = 0.11). Conclusion: Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 μg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes. HEPATOLOGY 2010 Hereditary hemochromatosis (HH) refers to symptoms and signs of disease that result from an inherited predisposition to iron overload. Iron overload is preventable, but can lead to significant health problems, including arthritis, hepatic cirrhosis, hepatocellular carcinoma, fatigue, and diabetes mellitus, if it is left untreated.1 More than 80% of patients presenting with symptomatic iron overload2, 3 are homozygous for the 845GA mutation in the hemochromatosis (HFE) gene, which leads to the Cys282Tyr (C282Y) substitution in the HFE protein.4 The prevalence of C282Y homozygotes is at least 1 in 200 for people

of northern European descent.5, 6 The majority of C282Y homozygotes have elevated iron indices7, 8 but the serum selleck ferritin (SF) concentration threshold at which there is an increased risk of developing HH-associated signs and symptoms other than cirrhosis is not known. We have recently shown that at least 28% of male C282Y homozygotes develop iron overload–related disease (as defined by both the presence of documented iron overload9 and one of the following five objective HH features: hepatocellular carcinoma, cirrhosis/fibrosis, physician-diagnosed symptomatic HH, elevated liver enzymes, or evidence of HH-associated arthritis),7 with onset in the majority by age 55 years. Other studies have shown that individuals with SF concentrations >1000 μg/L are at significantly increased risk of cirrhosis.

Methods:  A prospective database was used to identify those patie

Methods:  A prospective database was used to identify those patients who were treated with either locoregional therapy (n = 128) or supportive care (n = 92). Survival analysis was performed

for groups matched by CLIP score at presentation. Comparison of important prognostic factors was undertaken and univariate and multivariate analysis was performed to assess determinants of survival. Results:  Use of locoregional therapies was only associated with a survival benefit in patients with a CLIP score of 1 or 2. In this group, the median survival in patients who received locoregional therapies was 25.0 months (95% confidence interval 22.7–27.4) compared with 8.9 months (95% confidence interval 7.3–10.5) for supportive care (P = 0.001). For patients MK-8669 purchase with CLIP scores of 3 or greater, no survival benefit of locoregional therapies was observed. Multivariate analysis revealed locoregional intervention, CLIP score, tumor symptoms, α-fetoprotein level, bilirubin and alkaline phosphatase level as independent prognostic indicators. Conclusion:  Locoregional therapies should be targeted find more specifically to patients with non-advanced hepatocellular carcinoma as assessed

by validated scoring systems. Use of these therapies in patients with advanced disease does not appear to be associated with a survival benefit and may expose patients to unnecessary harm. “
“Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic

hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms. The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey. The patients with CHC have lower physical HRQOL see more status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman’s rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann–Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score ≤ 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045).

More specifically, of the eight cases with SHh+ ballooned hepatoc

More specifically, of the eight cases with SHh+ ballooned hepatocytes, only two showed SHh+ periportal hepatocytes and in these two cases, less than 25% of the portal tracts showed periportal hepatocellular SHh positivity. Conversely, most of the cases with SHh+ periportal hepatocytes

showed no SHh+ ballooned hepatocytes. Of the two cases with SHh+ periportal hepatocytes and SHh+ ballooned hepatocytes, three or fewer SHh+ ballooned hepatocytes were identified per ×100 magnification. On the other hand, SHh+ bile duct/ductular cells tended to be associated with SHh+ periportal hepatocytes, and (like SHh+ periportal hepatocytes) were rarely noted in livers with prevalent SHh+ ballooned hepatocytes. The intensity of SHh+ periportal hepatocellular staining was significantly positively associated with the percentage

of portal Selleck JNK inhibitor tracts showing SHh+ periportal hepatocytes (P < 0.0009) and negatively associated with numbers of SHh+ ballooned hepatocytes (Fig. 3F,G). Gli2+ staining in portal tracts cells was observed in all cases examined (n = 18). The distribution of the grades of Gli2+ portal tract staining was: Roscovitine chemical structure G1, 27.8%; G2, 38.9%; and G3, 33.3%. K7+ ductular cells (i.e., liver progenitor cells) were also identified in all cases evaluated (n = 25). The distribution of the grades of K7+ positivity was: G1, 27.8%; G2, 27.8%; and G3, 44.4%. Gli2+ staining and K7+ staining increased with fibrosis stage (Fig. 4A,B). There was a significant positive association between grades of Gli2 portal tract staining and grades of K7 staining (P < 0.017, Fig. 4C). Gli2+ cells were also located in the hepatic lobule in 13 out of the 18 cases,

showing either a zone 3-dominant pattern (Fig. 4D, n = 4), or a zone 1 dominant pattern (Fig. 4E, n = 1) or a combination of zone 1- and zone 3-positivity (n = 8). The pattern of Gli2 staining in the lobule did not show an association with any of the histologic features. In a small number of cases (n = 5), we costained for SHh ligand and the liver progenitor marker, K7. Interesting relationships between SHh positivity and K7 positivity were revealed. learn more All the cases with more than minimal K7 staining (n = 4) showed SHh+ bile duct cells and mild to moderate SHh+ periportal hepatocytes, while the one case with minimal K7 positivity did not show any SHh+ bile duct cells or periportal hepatocytes. The aggregate data, therefore, link portal/periportal production of Hh ligands with accumulation of immature liver cells in the portal/periportal progenitor niche (e.g., ductal plate remnant). Because it is difficult to acquire liver tissue from healthy children to map development-related changes in Hh pathway activity, we performed this analysis in liver sections harvested from healthy male mice at different timepoints during development.

More specifically, of the eight cases with SHh+ ballooned hepatoc

More specifically, of the eight cases with SHh+ ballooned hepatocytes, only two showed SHh+ periportal hepatocytes and in these two cases, less than 25% of the portal tracts showed periportal hepatocellular SHh positivity. Conversely, most of the cases with SHh+ periportal hepatocytes

showed no SHh+ ballooned hepatocytes. Of the two cases with SHh+ periportal hepatocytes and SHh+ ballooned hepatocytes, three or fewer SHh+ ballooned hepatocytes were identified per ×100 magnification. On the other hand, SHh+ bile duct/ductular cells tended to be associated with SHh+ periportal hepatocytes, and (like SHh+ periportal hepatocytes) were rarely noted in livers with prevalent SHh+ ballooned hepatocytes. The intensity of SHh+ periportal hepatocellular staining was significantly positively associated with the percentage

of portal NVP-LDE225 supplier tracts showing SHh+ periportal hepatocytes (P < 0.0009) and negatively associated with numbers of SHh+ ballooned hepatocytes (Fig. 3F,G). Gli2+ staining in portal tracts cells was observed in all cases examined (n = 18). The distribution of the grades of Gli2+ portal tract staining was: check details G1, 27.8%; G2, 38.9%; and G3, 33.3%. K7+ ductular cells (i.e., liver progenitor cells) were also identified in all cases evaluated (n = 25). The distribution of the grades of K7+ positivity was: G1, 27.8%; G2, 27.8%; and G3, 44.4%. Gli2+ staining and K7+ staining increased with fibrosis stage (Fig. 4A,B). There was a significant positive association between grades of Gli2 portal tract staining and grades of K7 staining (P < 0.017, Fig. 4C). Gli2+ cells were also located in the hepatic lobule in 13 out of the 18 cases,

showing either a zone 3-dominant pattern (Fig. 4D, n = 4), or a zone 1 dominant pattern (Fig. 4E, n = 1) or a combination of zone 1- and zone 3-positivity (n = 8). The pattern of Gli2 staining in the lobule did not show an association with any of the histologic features. In a small number of cases (n = 5), we costained for SHh ligand and the liver progenitor marker, K7. Interesting relationships between SHh positivity and K7 positivity were revealed. selleck chemicals llc All the cases with more than minimal K7 staining (n = 4) showed SHh+ bile duct cells and mild to moderate SHh+ periportal hepatocytes, while the one case with minimal K7 positivity did not show any SHh+ bile duct cells or periportal hepatocytes. The aggregate data, therefore, link portal/periportal production of Hh ligands with accumulation of immature liver cells in the portal/periportal progenitor niche (e.g., ductal plate remnant). Because it is difficult to acquire liver tissue from healthy children to map development-related changes in Hh pathway activity, we performed this analysis in liver sections harvested from healthy male mice at different timepoints during development.

24 Hyperinsulinemia induces hepatic SREBP-1c expression while hyp

24 Hyperinsulinemia induces hepatic SREBP-1c expression while hyperglycemia stimulates ChREBP activity. These events lead to transcriptional activation of all lipogenic genes including adenosine triphosphate selleck products citrate lyase, acetyl-CoA carboxylase, and FAS,25 effectively increasing FAS flux. Because citrate formed in the TCA cycle and shuttled to the cytosol is the primary metabolite required in the production of fatty acids, there is inevitably an increase in demand for this intermediate. Therefore, it is unsurprising that a recent 13C isotopomer

study found a 2-fold increase of hepatic TCA cycle flux in patients with nonalcoholic fatty liver disease.26 Because only pyruvate that enters the TCA cycle through PC produces a net increase in cycle intermediates, whereas pyruvate entering through PDH is restricted to energy production only,27 the elevated PC flux and OAA pool observed in diabetic mice must have also catered

to the increased FAS demand. This agrees with our recent observation in the hypertrophied heart, in which a larger 13C-citrate signal (from increased pyruvate anaplerosis) was recorded.28 Moreover, detection of citrate pool with hyperpolarized [2-13C]pyruvate substrate Luminespib manufacturer has recently been demonstrated to be feasible in the study of myocardial TCA flux29; therefore, similar measurements in the insulin-resistant liver will undoubtedly aid in validating the hypothesis that an enlarged citrate pool supports FAS. Metformin is used clinically to counter elevated FAS and gluconeogenesis in diabetes, primarily through its activation of adenosine-monophosphate–activated protein kinase.30 In this study, we demonstrated that metformin treatment

leads to reduced HGP by, at least check details in part, decreasing PC activity, as well as production of malate and aspartate from pyruvate. The advent of hyperpolarized 13C MRS has enabled visualization of real-time metabolism in the in vivo mouse liver, in particular, the anaplerosis of pyruvate into the TCA cycle. The distinct patterns in downstream metabolite progression suggest that hyperpolarized 13C MRS is sensitive to subtle differences in metabolic conversions. It is worth noting that LDH-, ALT-, MDH-, and AST-mediated conversions are reversible. Therefore, the appearance of lactate, alanine, malate, aspartate, and OAA peaks resulted from the enzyme-mediated exchange of the hyperpolarized 13C label, in which equilibrium is dependent on the concentrations of both substrate and product, as well as the redox potential. Hence, these metabolite signals reflect the concentration of each metabolite that already exists within the cellular environment and in the plasma, rather than net metabolite production.

24 Hyperinsulinemia induces hepatic SREBP-1c expression while hyp

24 Hyperinsulinemia induces hepatic SREBP-1c expression while hyperglycemia stimulates ChREBP activity. These events lead to transcriptional activation of all lipogenic genes including adenosine triphosphate Protease Inhibitor Library citrate lyase, acetyl-CoA carboxylase, and FAS,25 effectively increasing FAS flux. Because citrate formed in the TCA cycle and shuttled to the cytosol is the primary metabolite required in the production of fatty acids, there is inevitably an increase in demand for this intermediate. Therefore, it is unsurprising that a recent 13C isotopomer

study found a 2-fold increase of hepatic TCA cycle flux in patients with nonalcoholic fatty liver disease.26 Because only pyruvate that enters the TCA cycle through PC produces a net increase in cycle intermediates, whereas pyruvate entering through PDH is restricted to energy production only,27 the elevated PC flux and OAA pool observed in diabetic mice must have also catered

to the increased FAS demand. This agrees with our recent observation in the hypertrophied heart, in which a larger 13C-citrate signal (from increased pyruvate anaplerosis) was recorded.28 Moreover, detection of citrate pool with hyperpolarized [2-13C]pyruvate substrate DNA Damage inhibitor has recently been demonstrated to be feasible in the study of myocardial TCA flux29; therefore, similar measurements in the insulin-resistant liver will undoubtedly aid in validating the hypothesis that an enlarged citrate pool supports FAS. Metformin is used clinically to counter elevated FAS and gluconeogenesis in diabetes, primarily through its activation of adenosine-monophosphate–activated protein kinase.30 In this study, we demonstrated that metformin treatment

leads to reduced HGP by, at least see more in part, decreasing PC activity, as well as production of malate and aspartate from pyruvate. The advent of hyperpolarized 13C MRS has enabled visualization of real-time metabolism in the in vivo mouse liver, in particular, the anaplerosis of pyruvate into the TCA cycle. The distinct patterns in downstream metabolite progression suggest that hyperpolarized 13C MRS is sensitive to subtle differences in metabolic conversions. It is worth noting that LDH-, ALT-, MDH-, and AST-mediated conversions are reversible. Therefore, the appearance of lactate, alanine, malate, aspartate, and OAA peaks resulted from the enzyme-mediated exchange of the hyperpolarized 13C label, in which equilibrium is dependent on the concentrations of both substrate and product, as well as the redox potential. Hence, these metabolite signals reflect the concentration of each metabolite that already exists within the cellular environment and in the plasma, rather than net metabolite production.

24 Hyperinsulinemia induces hepatic SREBP-1c expression while hyp

24 Hyperinsulinemia induces hepatic SREBP-1c expression while hyperglycemia stimulates ChREBP activity. These events lead to transcriptional activation of all lipogenic genes including adenosine triphosphate Saracatinib chemical structure citrate lyase, acetyl-CoA carboxylase, and FAS,25 effectively increasing FAS flux. Because citrate formed in the TCA cycle and shuttled to the cytosol is the primary metabolite required in the production of fatty acids, there is inevitably an increase in demand for this intermediate. Therefore, it is unsurprising that a recent 13C isotopomer

study found a 2-fold increase of hepatic TCA cycle flux in patients with nonalcoholic fatty liver disease.26 Because only pyruvate that enters the TCA cycle through PC produces a net increase in cycle intermediates, whereas pyruvate entering through PDH is restricted to energy production only,27 the elevated PC flux and OAA pool observed in diabetic mice must have also catered

to the increased FAS demand. This agrees with our recent observation in the hypertrophied heart, in which a larger 13C-citrate signal (from increased pyruvate anaplerosis) was recorded.28 Moreover, detection of citrate pool with hyperpolarized [2-13C]pyruvate substrate LBH589 concentration has recently been demonstrated to be feasible in the study of myocardial TCA flux29; therefore, similar measurements in the insulin-resistant liver will undoubtedly aid in validating the hypothesis that an enlarged citrate pool supports FAS. Metformin is used clinically to counter elevated FAS and gluconeogenesis in diabetes, primarily through its activation of adenosine-monophosphate–activated protein kinase.30 In this study, we demonstrated that metformin treatment

leads to reduced HGP by, at least check details in part, decreasing PC activity, as well as production of malate and aspartate from pyruvate. The advent of hyperpolarized 13C MRS has enabled visualization of real-time metabolism in the in vivo mouse liver, in particular, the anaplerosis of pyruvate into the TCA cycle. The distinct patterns in downstream metabolite progression suggest that hyperpolarized 13C MRS is sensitive to subtle differences in metabolic conversions. It is worth noting that LDH-, ALT-, MDH-, and AST-mediated conversions are reversible. Therefore, the appearance of lactate, alanine, malate, aspartate, and OAA peaks resulted from the enzyme-mediated exchange of the hyperpolarized 13C label, in which equilibrium is dependent on the concentrations of both substrate and product, as well as the redox potential. Hence, these metabolite signals reflect the concentration of each metabolite that already exists within the cellular environment and in the plasma, rather than net metabolite production.

The only analysis performed and reported on from this surveillanc

The only analysis performed and reported on from this surveillance system concerned the development of inhibitors [7]. The problem with this national system is that the introduction of national contracting has meant that all patients will

be exposed to only a very limited number of concentrates and the value of the surveillance will thus be limited. The only other European country with a central AERS is the Netherlands, but no data from this system have been formally reported. No central haemophilia AERS is available in the other European Countries. Recently, a European AERS called European Haemophilia Surveillance System (EUHASS) has been learn more initiated. European Haemophilia Surveillance System is a prospective

this website adverse and serious event reporting system. A total of 56 haemophilia centres caring for 18 000 patients with inherited bleeding disorders in 27 European countries are taking part. The system is electronic, in English, and events are reported live as they occur or 3 monthly at the latest. The reported events are allergic/acute reactions, transfusion transmitted infections, inhibitors, thromboses, malignancies and deaths. As centres report data on the exposed population, incident rates can be calculated. In the first year of surveillance, 167 events have been reported. A total of 56 different clotting factor concentrates were used in the participating centres. EUHASS has the potential to find more provide pharmacovigilance information on large numbers of exposed persons with inherited bleeding

disorders. As this is a dynamic cohort, a new method has been developed to calculate the inhibitor risk in patients with <50 exposures. Further information on EUHASS can be found at the project website http://www.euhass.org. Mark Weinstein The World Health Organization (WHO) is interested in developing a global haemovigilance network. In December 2007, the WHO Global Collaboration for Blood Safety (GCBS) met and agreed on the need to support such a network. A global consortium consisting of WHO, Canada, International Society of Blood Transfusion, European Haemovigilance Network and the USPHS agreed to form a multilateral steering committee to support collaborative efforts and develop a work plan. The Global Steering Committee for Haemovigilance (GloSCH) will: ‘provide an ongoing, international forum to develop and promote global haemovigilance; function as a forum for dialogue, advice and information gathering; promote standardized global haemovigilance reporting tools and determine whether these tools are useful and relevant; and share information concerning haemovigilance data among member organizations.’ The GloSCH is currently working on two documents: ‘Development of WHO Recommendations on Establishment of National Haemovigilance Systems’; and a technical and/or guidance document to support standardization of haemovigilance reporting.

ETV is the most potent antiviral agent It can reduce serum HBV D

ETV is the most potent antiviral agent. It can reduce serum HBV DNA by 6.9 log10 in HBeAg-positive patients and by 5 log10 in HBeAg-negative patients. Although more powerful in its antiviral potency, the 1-year HBeAg seroconversion rate is not superior than other NA (21% at 1 year and 31% after 2 years of ETV treatment).26 A phase III clinical trial involving 648 patients randomized to receive

either ETV 0.5 mg/day or LAM 100 mg/day for 48 weeks was conducted to compare the safety and efficacy of ETV versus LAM in patients with HBeAg-negative chronic hepatitis B.27 Patients treated with ETV showed a significantly higher rate of histological improvement, HBV DNA reduction and undetectable HBV DNA (< 60 IU/mL), compared with patients treated with LAM. Of note is the very low resistance rate (1.2%) observed in the nucleoside-naïve Ruxolitinib molecular weight HBeAg-negative patients treated with ETV for up to 5 years. In a randomized LAM-controlled ETV trial in HBeAg-positive patients, the

HBV DNA levels (< 80 vs > 80 IU/mL) at week 24 were also useful in predicting the HBeAg seroconversion rates (30% vs 17%) and undetectable HBV DNA (96% vs 50%) at week 52 of ETV therapy.28 A large-scale phase III trial involving 921 HBeAg-positive and 466 HBeAg-negative patients showed that virological response to Ldt was superior to that for LAM after 1 and 2 years of treatment.17,18 In HBeAg-negative patients, a RG7204 clinical trial higher proportion treated with Ldt than LAM achieved undetectable HBV DNA levels (88% vs 71% at 1 year and 82% vs 57% at 2 years) with the polymerase chain reaction method (COBAS Amplicor HBV Monitor, Roche Molecular Systems) with a detection limit of 60 IU/mL. Ldt was associated with a lower rate of resistance than LAM was. The resistance rates at 1 and 2 years for Ldt were 2.3% and 11%, respectively. Notably, the resistance rate was quite low at 1 year in HBeAg-negative patients who had undetectable HBV DNA levels at week 24, compared with patients whose HBV DNA levels were ≧ 2000 IU/mL (0% vs 30%) (Table 2).17 Further analysis using a multivariate logistic regression model to evaluate baseline and/or early on-treatment

variables showed that: (i) HBeAg-positive selleck patients with baseline HBV DNA < 9 log10 copies/mL, ALT ≧ 2xULN and non-detectable HBV DNA at week 24 achieved undetectable HBV DNA in 89%, HBeAg seroconversion in 52% and Ldt resistance in 1.8% at 2 years; and (ii) HBeAg-negative patients with baseline HBV DNA < 7 log10 copies/mL and undetectable serum HBV DNA at week 24 achieved undetectable HBV DNA in 91% and Ldt resistance in 2.3% at 2 years.29 More recently, a phase III study was reported that involved 266 HBeAg-positive and 375 HBeAg-negative patients who were randomized in a 2:1 ratio to receive TDF 300 mg (n = 176 in HBeAg-positive and 250 in HBeAg-negative) or ADV 10 mg (n = 90 in HBeAg-positive and 125 in HBeAg-negative) for 48 weeks.