01 for both, as compared with the control and the intranasal group). Figure 1b shows serum anti-urease B IgA antibodies, and in this case, only rUreB adjuvanted by Freund’s resulted in significant levels of antibodies (P=0.01, as compared with the other three groups). Similar testing of stool pellets failed to show any measurable IgG or IgA (data not shown). Protection is shown on Fig. 1c and expressed as the number of H. pylori copies detected in the stomach of challenged mice. Except for one that was negative, control mice SCH727965 cell line had high levels of H. pylori infection (defined as >1000 copies μg−1 DNA), with an overall geometric mean of 1627 copies μg−1

DNA. Intranasal inoculation resulted in no protection, with all mice having high levels of infection and a geometric mean of 14 256 copies μg−1 DNA. Administration of rUreB with aluminum hydroxide had a modest effect, with one mouse being negative, two being positive at low levels of infection (defined as <1000 copies μg−1 DNA) and two at high levels, and a geometric mean of 309 copies μg−1 DNA (P=0.01 as compared with intranasal inoculation). rUreB adjuvanted with Freund's had a more marked effect, with three mice testing negative, one showing a low level of infection and

only one with a high level of infection, for a geometric mean of 22 copies μg−1 DNA (P=0.01 as compared with intranasal inoculation). There was no statistically significant difference in Vildagliptin Z-VAD-FMK chemical structure the level of infection between

the group that received rUreB and aluminum hydroxide and the group that received rUreB and Freund’s adjuvant (P=0.55). Similar to what others have described, we found that rUreB had a partial efficacy against H. pylori infection, with one animal protected and two partially protected. What is original about our study is the use of aluminum hydroxide as adjuvant. We elected to test aluminum hydroxide because it is the only adjuvant approved for the routine immunization of humans in the United States. Few other groups have evaluated aluminum hydroxide as an adjuvant to either natural (Lee et al., 1999; Weltzin et al., 2000; Londoño-Arcila et al., 2002) or recombinant (Moschos et al., 2006; Wu et al., 2008) urease. Similar to our findings, the immunogenicity has been good but the protective efficacy is unclear. The better protection that we found with Freund’s adjuvant indicates that rUreB is potentially a good antigen that can be made even more protective, provided better adjuvants are used or the antigen is presented in a more immunogenic manner. Other adjuvants such as MF59, approved in Europe for use with influenza vaccine in humans, can also be tested in the future. Serum IgG and IgA levels were very similar among mice in specific vaccination groups. The resulting protection, however, had a much wider distribution. Most variability was given by uninfected mice, i.e.

The unique receptor repertoire of dNK cells further includes the expression of several Ly49 receptors, the expression of activation markers such as CD69 and KLRG1 (which is considered as a marker for active NK cell proliferation37) and the expression of CD117 (the c-kit receptor). Another study, by Mallidi et al.17 described the phenotype of NK1.1+ dNK cells as DX5+ NKp46+ CD27+ CD11b+ CD11c+ CD69+. Interestingly, the NK1.1+ dNK cells expressed more B220 and CD69 than NK1.1+ eNK cells and also expressed ICOS (which is expressed on activated NK cells38), whereas eNK cells did not express ICOS at all. In the fetal-maternal interface, the maternal uterine tissue is

in close contact with the fetal-derived trophoblast cells. This interface contains immune cells, which constitute Silmitasertib 40% of the cells in the human decidua.39 Analysis of this immune population has revealed that, unlike any other tissues or mucosal surfaces, 50–70% of the human decidual lymphocytes are NK cells, while the remainder are CD14+ macrophages, dendritic cells,

CD4+ T cells, a few CD8+ T cells, γδ T cells, and NKT cells.35 dNK cell numbers are the highest in the first trimester of pregnancy and their numbers decline during the second trimester. As in mice, only few dNK cells are present in the human decidua at term.36 The majority of dNK cells are CD56bright CD16− (as opposed to mouse dNK cells which express high levels of CD1618). Indeed, dNK cells A769662 resemble peripheral blood CD56bright CD16− NK cells also in the high expression levels of CD94/NKG2.40 However, similar to eNK cells, dNK cells resemble CD56dim CD16+ NK cells in the expression of KIRs41 and in their granules cell content. In fact, dNK cells differ from peripheral Bupivacaine blood NK cells both in phenotype and in function. Comparison analysis of the gene expression in dNK cells versus peripheral blood NK cells showed that dNK cells

should be considered as a unique NK subset.27 dNK cells over-expressed several genes, compared with the two peripheral blood NK subsets and several genes were exclusively expressed in dNK cells. For example, granzyme A was significantly over-expressed in dNK cells, as were the C-type lectin-like receptors NKG2C and NKG2E. dNK cells have been shown to express several activating receptors, including NKp46, NKp30, NKp44 (in contrast to human eNK cells which lack NKp30 and NKp44 expression, as discussed above), NKG2D, and 2B4.42–44 The expression of NKp44 (which is not expressed on non-activated peripheral blood NK cells) and the expression of the activation marker CD6945 (which is also expressed on mouse dNK cells) suggest that dNK cells might already be activated in the local environment of the decidua.

In general, it is thought that bats and many potential pathogens have co-evolved and circulated for thousands of years, with a recent increased spillover of zoonotic pathogens to humans. Human encroachment into previously uninhabited areas is a contributing factor [48, 49]. Eidolon helvum is a straw-colored migratory fruit bat, its primary habitat being in equatorial Africa. It is found in large colonies in Angola, Cote d’Ivoire, Malawi, Mauritania, Nigeria, Uganda and Zambia [50], often roosting in trees within towns as well as on islands

in rivers or lakes [51]. Between mid-October and late December each year, major E. helvum colonies, comprising 5–10 million bats in all, congregate in Fulvestrant datasheet the Central Province of Zambia [50]. Some bat colonies have been shown to migrate more than 2500 km [52]. While ebolavirus has BEZ235 nmr never been isolated from these bats, ebolavirus-specific antibodies have been detected in blood samples from one bat [53]. If these bats shed infectious virus, they could potentially transmit ebolavirus infection between their primary habitats and their migratory sites, putting a large part of sub-Saharan Africa at risk of infection. Filovirus ecology is not yet well understood.

Although bats appear to play an important role in filovirus transmission [46], other animal species, including pigs [54], dogs [33], duikers [10] and nonhuman primates, may be involved [10, 32]. Although the effects of climate change on

infectious diseases are poorly understood, it likely affects wildlife habitats and densities, which has the potential to increase the frequency of disease outbreaks by increasing risk of exposure of humans to reservoir hosts and/or because of increased viral loads in these reservoir hosts [55]. An increasing population with an increasing demand for resources has forced people to intrude into previously uninhabited land for agricultural and mining activities, potentially bringing humans into contact with unknown pathogens, reservoir hosts and/or amplifying hosts [15, 56]. Wildlife trade, much of which is conducted informally and/or illegally, can also increase the risk of outbreaks. Contact between hunters, middle-men and consumers and wildlife could increase the possibility of disease transmission from Anidulafungin (LY303366) infected animals [57]. Associations between hunting/butchering/eating of infected carcasses and outbreaks of EVD have been reported [10, 38]. The only recorded human case of TAFV was in a researcher who contracted the infection by performing autopsies on chimpanzees [58]. The source of infection in the 2007 outbreak of EVD in the DRC was reportedly traced back to freshly killed bats bought for consumption [59]. Index cases in the 2001 EVD outbreaks in Gabon and the RC acquired the infection from handling animal carcasses [10].

It has

been suggested that CD127− Treg and foxp3+ Treg possibly represent different populations [9]. In our study, a correlation between these two Treg subsets was found only in the control group. In a study of HIV infection, the positive correlation between foxp3+CD127− and CD25+CD127− CD4+ T cells found in healthy HIV-negative subjects was not present in the early chronic stage of HIV infection [23]. Together these data indicate that different Treg may contribute in various stages of chronic infections. It has been shown that depletion of CD4+CD25high and CD4+CD25+foxp3+ cells from PBMCs from patients with TB, results in increased production of IFN-γ upon TB stimulation [10, 11, 24], indicating that there is an inverse correlation between Treg and immune Inhibitor Library activation. In contrast, although the immunosuppressive function of Treg was not characterized in our study, we found a positive correlation between the fractions of Treg and activated CD4+ T cells. DC can initiate immune responses and stimulate induction and expansion

of Treg [14]. Absolute numbers of DC have been shown to decrease in patients with Neratinib purchase TB compared to healthy controls [17]. Still, although the numbers of pDC and mDC were not estimated, in our study, we did not find any differences in the fraction of DC subsets among the various groups or any correlation between DC and Treg subsets. Altogether, these data suggest that different Treg subsets may have different capability to regulate immune activation and that modulation may be induced by different signals in the various stages of TB infection. As we found gradually higher fractions of CD127− Treg throughout the various stages of TB infection correlating to immune activation, a possible theory is that higher bacterial burden and inflammation

stimulate to increased levels of Treg to balance between anti-TB T cell responses and immune-mediated pathology. In support of this, in a study of macaques, there were increased frequencies of Treg cells in blood as the animals developed disease [25]. An alternative explanation may be that Treg inhibit protective Pregnenolone Th1 responses facilitating mycobacterial replication and act as a causative factor in the progression to active disease [12]. We found an increase in foxp3+ Treg after preventive anti-TB treatment. Our very limited data demonstrate that this was most dominant in patients converting to QFT negative and with reduced CD8+ T cell activation after treatment, possibly indicating that expansion of this Treg subset contributes to suppression or eradication of TB. Apoptosis of TB reactive T cells may account for the depression of TB-induced T cell responses seen in active TB, but data are conflicting [3, 26]. CD95 (Fas receptor), which upon ligation with Fas ligand induces an apoptotic death signal, was expressed by a higher proportion of CD8+ T cells and a lower proportion of CD4+ T cells in patients with pulmonary TB [3].

The incubation period was significantly increased by 40% for the +Si treatment. The area under spot blotch progress curve, number of lesions per cm2 of leaf area, and real disease severity significantly decreased by 62, 36 and 43.5% in +Si treatment. There was no significant PF-02341066 mouse effect of Si on lesion size. The role played by total soluble phenolics in the increased resistance to spot blotch of plants from both cultivars supplied with Si was not clear. Plants from cultivar BR-18 supplied with Si showed the highest values for concentration of lignin-thioglycolic acid derivatives during the most advanced stages

of fungus infection. Chitinase activity was high at the most advanced stages of fungus infection on leaves from both cultivars supplied with Si and may have had an effect on fungus growth based on the reduction of the components of resistance evaluated. Peroxidase activity was found to be high only at 96 h after inoculation of both cultivars supplied with Si. Polyphenoloxidase activity had no apparent effect on resistance regardless

of Si treatments. Results revealed that supplying Si to wheat plants can increase resistance against spot blotch. “
“Three hundred and forty-one isolates of Verticillium Opaganib clinical trial dahliae from upland cotton collected from 2007 to 2009 in central China (Hubei, Hunan, Jiangxi, Anhui and Jiangsu provinces) were tested for vegetative compatibility Dichloromethane dehalogenase groups (VCGs) and PCR-based genotyping. Approximately 332 (97%) isolates belonged to VCG1A, whereas the remaining 9 (3%) isolates belonged to VCG2. PCR-based genotyping also divided the isolates into two groups, namely PCR patterns A and C. There is a complete correspondence

between the VCGs and genotypes (VCG1A to PCR pattern A and VCG2 to PCR pattern C). Representative isolates (10 VCG1A isolates, nine VCG2 isolates) were tested for virulence on seedlings of upland cotton (Gossypium hirsutum cultivars E Mian 24 and Yin Rui 361). The VCG1A isolates caused cotton defoliation with the values of the disease severity index and the plant mortality being significantly (P < 0.05) higher than those caused by the VCG2 isolates, which did not cause any defoliation. Two isolates (one of each VCG) were also tested for virulence on 12 popular commercial upland cotton cultivars adapted in central China. Results showed that both isolates, particularly the defoliating pathotype (D pathotype) VCG1A isolate, were virulent on all the tested cotton cultivars. These results suggest that the D pathotype of V. dahliae is widely distributed and has become prevalent in central China. "
“Sheath blight disease of rice caused by Rhizoctonia solani is one of the most dreaded plant diseases faced by the rice farmers all over the world.

[1, 2] The effectiveness of antiviral treatment has historically been evaluated by the surrogate endpoint of sustained virologic response (SVR) 24 weeks after cessation of antiviral medication. In numerous studies, SVR has been associated with a reduced occurrence of liver failure, hepatocellular carcinoma (HCC), and liver-related deaths in patients with HCV.[3, 4] Whether the beneficial effects of SVR also result in reduced all-cause mortality, however, is the click here more essential

question to answer. Because all-cause mortality is the most definite clinical endpoint with clear interpretation, demonstrating direct clinical benefits of SVR on all-cause mortality would better justify the use of intensive and costly antiviral therapy. Knowing the effect of HCV antiviral treatment on all-cause mortality is also important for considering broader clinical questions such as the utility of birth cohort screening for HCV. In the largest prior effort, a study of 16,864 U.S. Veterans analyzed separately Omipalisib supplier by genotype found reduced

all-cause mortality among patients with HCV genotypes 1, 2, and 3 who were treated in routine medical practice.[5] Because the majority of these patients were treated without liver biopsy, there was limited information about the impact of SVR on all-cause mortality in patients with severe fibrosis or cirrhosis. The current article by van der Meer et al.[6] seeks to add to the information about the impact of SVR on all-cause mortality, Cyclin-dependent kinase 3 particularly in patients with severe fibrosis or cirrhosis. Van der Meer et al. report on long-term outcomes from 530 patients from five large tertiary care hospitals in Europe and Canada. The patients started an interferon-based regimen between 1990 and 2003 following histologic proof of advanced hepatic fibrosis or cirrhosis (Ishak

score of 4 in 27% of patients, Ishak score of 5 in 19% and Ishak score of 6 in 54%). In all, 175 patients started interferon monotherapy, 148 patients started interferon/ribavirin, and 176 patients started pegylated interferon/ribavirin with resulting SVR rates of 5.1%, 23.6%, and 42.1%, respectively. An additional 14 patients started pegylated interferon monotherapy and 17 patients started consensus interferon with or without ribavirin. A total of 204 patients with initial non-SVR were retreated, of whom 67 subsequently achieved SVR. Ultimately, 192 of 530 patients (36%) achieved SVR. The patients with successful retreatment were considered as patients without SVR in the analysis until after successful treatment, at which point they were treated as patients with SVR for the remainder of the follow-up. Thirteen patients with SVR and 100 patients without SVR died (10-year cumulative all-cause mortality rate 8.9% [95% confidence interval (CI) 3.3%-14.5%] with SVR and 26.0% [95% CI 20.2%-28.

We investigated

whether the genotype of the HCV strain leads to differences in the DNA profile of HCC. Methods: DNA was extracted from formalin fixed paraffin embedded blocks of surgically removed HCC associated with different strains of HCV. HCV genotype 1 (group 1 n=19), 3 (group 3 n=1 1) and 4 (group 4 n=14). HCV genotype 4 samples were recruited from Ain Shams University, Egypt. DNA was tagged using home designed primer tags and multiplexed on a single flow cell of Illumina’s Hiseq next generation sequencing platform. Between 5 to 8 million mapping reads were generated per genome. Each genome was divided into a series of continuous non-overlapping and PARP inhibitor equally sized windows. The number of reads per HCC windows was compared against selleck chemical number of reads in corresponding windows of a pool of normal genomes sequenced using the same platform and downloaded from the 1000 genome project. The data was normalized for GC content, smoothed and segmented. GISTIC 2.0 was used to identify areas

of significant copy number aberrations within each of the 3 groups of HCC. Results: Variations were found between the 3 groups of HCC. Group 1 had 43 significant copy number aberrations (CNAs), 24 of which were deletions. Group 3 had 29 significant CNAs, 12 of which were deletions while group 4 had 19 significant CNAs of which 5 were deletions. Seven amplification peaks were shared between the 3 groups (1q21.2, 2p11.2, 2p11.1, 14q11.2, 14q32.33, 16p11.2, 22q11.1). Three amplification peaks were shared between groups 1 and 4 (4p11, 9p13.1, 9p11.2) and three amplification peaks were shared between groups 1 and 3 (5q13.2, 8q24.3, 15q1 1.2). A single amplification peak was shared between groups 3 and 4 (9p12). There were 6 unique amplification peaks to group 1, 6 to group 3 and 3 to group 4. No deletion peaks were shared between all 3 groups. Two deletion peaks were shared between groups 1 and 4 (8p23.1, 9p12) and five deletion peaks were shared between groups 1 and 3 (2p11.2, 16p13.3, 16q24.3, 17q25.3, 19p13.3). No deletion peaks was shared between groups 3 and 4. There were 17 unique deletion peaks to group 1, 7 to group

3 and 3 to group very 4. Conclusions: Low coverage sequencing revealed differences in the DNA profiles of HCC according to the causative HCV strain. Increasing the number of cases is needed to confirm these variations. Targeted, deeper sequencing of the altered areas described above is needed understand the biology of these changes. Disclosures: Stefano Berri – Employment: Illumina UK Ltd The following people have nothing to disclose: Waleed Fateen, Henry Wood, Judy Wyatt, Mahmoud El-meteini, Charles Millson, Philip Quirke Background: The purpose of this study is to determine the effect of drug combination therapy in liver cancer stem cells (LCSC) and HCC cell lines targeting wtn-β-catenin and RAS/RAF/MAPK signaling pathways.

3% vs 92.6% (gain: 3.3%) or multiplied

by 3: 84.9% vs 91.2% (gain: 6.3%). Conclusion. Thanks to reliability assessment and correction of unreliable results, the present combination of blood markers and elastometry improves accuracy, and guaranties a high accuracy in clinical practice conditions exposed to CAL 101 numerous unreliability causes, especially comorbidities. Disclosures: Paul Cales – Consulting: BioLiveScale Frederic Oberti – Speaking and Teaching: LFB, gore Isabelle Fouchard-Hubert – Speaking and Teaching: JANSSEN Jean-Pierre H. Zarski – Advisory Committees or Review Panels: BMS, Gilead, Janssen Cilag, BMS, Gilead, Janssen Cilag; Consulting: Roche, Scherring Plough, Novartis, Roche, Scherring Plough, Novartis; Speaking and Teaching: Siemens The following people have nothing to disclose: Gilles Hunault, Jerome Boursier BACKGROUND; Liver stiffness, measured click here by Transient Elastography (TE) or by Acoustic Radiation Force Impulse ARFI, correlates to the stage of fibrosis at biopsy, but is also affected by necroinflammation. Since Collagen

Proportionate Area (CPA) is a continuous histological variable measuring collagen but not necroinflammation, it could represent a better reference to assess the performance of TE and ARFI in the setting of noninvasive staging of fibrosis. METHODS: Ninety-three consecutive Palbociclib patients with chronic hepatitis C (CHC) were evaluated for histological fibrosis (METAVIR score), CPA measurement and biochemical features, and underwent TE

and ARFI. RESULTS: TE was unreliable in six patients (6.4%), while ARFI measurement was recorded in all patients. By linear regression analysis both TE and ARFI significantly correlated with CPA (CPA-ARFI: R2 = 0.522 p < 0.001; CPA-TE: R2 = 0.454 p < 0.001). By univariate analysis AST, PLT, TE, ARFI, inflammation grade and CPA were related to MetAvIR stage > 2. At multivariate logistic regression analysis, only CPA (OR: 1.47, CI95%: 1.07-2.01, p=0.01 8), inflammation grade (OR: 5.42, CI95%1.06-27.70, p = 0.042) and ARFI (Oade and CPA were related to cirrhosis (METAVIR stage F4), but by multivariate analysis, only CPA (OR: 1.66, CI95%: 1.23-2.23, p=0.001) and ARFI (OR: 29.87, CI95%: 2.25-397.45, p=0.010) were independently associated with cirrhosis. Liver stiffness by TE was not independently associated with METAVIR stage ≥ F2 (OR: 1.14, CI95%: 0.83-1.57, p=0.416) but was marginally associated with cirrhosis (OR:.2.60, CI95%: 0.86-7.85, p=0.091). CONCLUSIONS: In patients with CHC, liver stiffness evaluations by TE and ARFI are related to CPA. However, ARFI imaging is more accurate than TE for the non-invasive staging of both significant and severe stages of liver fibrosis.

o. in combination with tolvaptan throughout the trial period. Patients were randomized to four groups receiving tolvaptan at 7.5, 15, 30 mg or placebo once daily for 7 consecutive days (defined as the 7.5-mg group, the 15-mg group, the 30-mg group and the placebo group). The registration center allocated the eligible patients

to the treatment groups by stratifying them according to the presence/absence of lower limb edema. Random allocation was performed by a trial drug allocation manager from an independent contact research organization after confirmation that the packages containing tolvaptan tablets and matching placebo tablets were indistinguishable in appearance. The primary end-point was change in bodyweight from baseline at the final dosing day in patients

receiving trial drugs as a surrogate marker for PLX4032 purchase improvement of hepatic edema.[3, 4] The relationship of change in bodyweight and dose of tolvaptan was evaluated by using s linear regression model. Secondary end-points were change in abdominal circumference and increase in daily urine volume.[20] Bodyweight was measured before breakfast following urination each day through the treatment period. Abdominal circumference was also measured before breakfast following urination on days 2–3 and on day 7. Changes in bodyweight and abdominal circumference from baseline to the final dosing day in the tolvaptan groups were compared with those in the placebo group. Cumulative 24-h urine samples were collected after patients had urinated completely before drug administration (after breakfast) each day from the day before the start of trial drug administration until the end of the post-treatment period. Urinary

sodium Maraviroc cell line concentration was measured. Fluid intake was not restricted and measured values were recorded Farnesyltransferase during the trial period. Mean differences between daily fluid intake and daily urine volume were calculated by the treatment groups. Serum sodium concentration was measured before breakfast (baseline), 4–8 h and 22–24 h post-dose on day 1, and before breakfast on days 2–3, on days 7 and 9, and on days 14–17. If patients discontinued, these values were measured at an appropriate time. Change in serum sodium concentration from baseline to the final dosing day was assessed. Plasma concentration of tolvaptan was measured at baseline, on day 1 (22–24 h) and on day 7 (2–4, 8–16 and 22–24 h). Safety assessment was performed throughout the trial period. Safety variables included adverse events, adverse events that occurred before the start of trial drug administration, clinical laboratory tests, vital signs and electrocardiograms. For the change from baseline to the final dosing day, anova was performed for pair-wise comparison between each of the tolvaptan groups and the placebo group. The other continuous data were analyzed by anova. The category data were analyzed by Fisher’s exact test or Kruskal–Wallis test. None of the analyses were adjusted for multiple comparison.

HBeAg reverted to positive in 25 patients

and seven patients progressed to HBeAg-negative CHB. Differences between the 40 patients with relapse and 138 patients with SVR in terms of age, baseline ALT, and baseline HBV DNA were investigated. In univariate analysis, significant predictive factors for SVR were age (years; mean, 41.8 ± 11.1 vs. 38.1 ± 10.0; P = 0.048), baseline serum ALT (IU/L; mean, 215.5 ± 155.1 vs. 279.5 ± 240.4; P = 0.048), additional PCI-32765 mw treatment duration after HBeAg clearance (months; mean, 7.9 ± 7.0 vs. 17.9 ± 12.4; P < 0.001), and additional treatment duration after HBeAg seroconversion (months; mean, 7.1 ± 5.9 vs. 14.1 ± 11.6; P < 0.001). In particular, when the duration of additional lamivudine treatment after HBeAg clearance or seroconversion was stratified ATR inhibitor into 6- and 12-month intervals, the cumulative relapse rates were significantly lower in patients with an additional treatment duration of ≥12 months (P < 0.001). Gender, baseline HBV DNA, family history, and

previous INF-α treatment were not significantly different between patients with relapse and SVR (Table 2). Multivariate Cox regression analysis revealed that patients with age ≤40 years (odds ratio [OR], 1.950; 95% confidence interval [CI], 1.031-3.689; P = 0.040), additional treatment duration after HBeAg clearance ≥12 months (OR, 9.259; 95% CI, 4.184-20.408; P < 0.001), and additional treatment duration after HBeAg seroconversion ≥12 months Erythromycin (OR,

14.292; 95% CI, 6.791-34.285; P < 0.001) were independent determinants of SVR (Table 3). At 5 years the cumulative relapse rates were higher in patients >40 years (≤40 vs. >40 years, 24.6% vs. 36.9%; P = 0.039; Fig. 3A) and those with additional treatment duration after HBeAg clearance of <12 months (<12 vs. ≥12 months, 61.9% vs. 8.7%; P < 0.001; Fig. 3B). Among 287 patients with CR, 109 patients received prolonged lamivudine therapy after CR (Fig. 1). Sixty-five (59.6%) patients maintained undetectable HBV DNA by polymerase chain reaction (PCR) (<300 copies/mL) at the time of last follow-up (mean total follow-up duration, 51.8 months), whereas 44 (40.4%) patients had detectable HBV DNA after CR. Among 44 patients, 21 patients developed virologic breakthrough along with lamivudine-resistant mutations during an additional treatment for a median duration of 33 months (range, 5-83). Of the 21 patients with a lamivudine-resistant mutation, 12 patients had both rtM204I and rtL180M mutations, six patients had both rtM204V and rtL180M mutations, and three patients had the rtM204I mutation only. Spontaneous HBeAg clearance and seroconversion predict long-lasting suppression of HBV, reduced infectivity, and improved clinical prognosis. Thus, lamivudine-induced HBeAg clearance and seroconversion have been considered a potential endpoint for stopping antiviral treatment.