MicroRNAs consist selleckchem of short RNA molecules 21 base pairs in length that do not withhold the sequential information to transcribe for proteins, but instead control the transcriptional levels of a subset of target genes. It was first demonstrated in plants that miRNAs can suppress transcription of a target messenger RNA (mRNA) by base pairing with the 3′-untranslated region (UTR) of their target mRNAs.1, 2 In case of perfect or nearly perfect

pairing, the target mRNA becomes degraded. In many cases, pairing with the respective mRNAs is imperfect, leading to translational repression of the latter.3 Since their discovery, more than 1000 miRNAs have been identified in the human genome, and growing evidence points toward an important role

of many miRNAs in tumorigenesis. In the liver, different approaches were previously taken to identify miRNAs that regulate hepatocarcinogenesis. As such, miRNA expression patterns in human hepatocellular carcinoma (HCC) collectives were analyzed by the application of microarray technology.4-6 However, given the large interstudy variance of deregulated miRNAs in these studies and the frequently growing number of miRNAs that have been discovered, new intelligent screening methods are needed to find miRNAs with a functional relevance for the specific disease model of interest. The group of Xianghuo find more He at the Shanghai Cancer Institute now present a novel interesting approach to identify miRNAs that play an important role in hepatocarcinogenesis.7 Their study was based on a literature

screen of chromosomal areas with frequent amplifications or deletions occurring in HCC. Within these areas of potential chromosomal breakpoints, they identified MCE 129 miRNA-coding sequences and tested their expression in human HCC samples collected from the surgical specimen archive of the Qidong Liver Cancer Institute, Jiangsu Province, China. Semiquantitative polymerase chain reaction and genomic real-time polymerase chain reaction experiments on these specific tumor samples revealed 22 miRNAs with genome copy gains or losses. Of these, microRNA-151 (miR-151) was the most frequently amplified (56.1% gain) and showed a markedly up-regulated expression. This miRNA was shown to be localized to chromosome 8q24.3, a common recurrent amplification region in HCC.8 Moreover, it resides within intron-22 of the host gene FAK (focal adhesion kinase). The encoded protein of which is also known as PTK2 (protein thyrosine kinase 2), a key signaling molecule involved in the regulation of cell motility9 (Fig. 1), suggesting a functional synergism between the respective miRNA and its hosting gene. Indeed, expression of miR-151 showed tight correlation with FAK expression in HCC tissues and cell cultures.7 In further experiments, the authors demonstrated a functional role of miR-151 in tumor invasion and metastasis in vitro and in vivo.

The nucleotide sequence of PyAOX consists of 1,650 bp, including a 5′ untranslated region (UTR) of 170 bp, a 3′ UTR of CP 673451 148 bp, and an open reading frame (ORF) of 1,332 bp that can be translated into a 443-amino-acid residue with a molecular mass of 47.33 kDa and a putative isoelectric point (pI) of 9.71. The putative amino acids had 50%–61% identity with AOX genes in Eukaryota and higher plants and had AOX-like characteristics.

The expression of PyAOX mRNA in different stages of the life cycle, conchospores, filamentous thalli (conchocelis stage), and leafy thalli, was detected by real-time quantitative PCR (qPCR). The highest level of expression, which was observed in filamentous thalli, was three times higher than that observed in leafy thalli. The next highest level, which was observed in the conchospores, was twice as high as that observed in leafy thalli. We showed that an alternative respiration pathway existed in P. yezoensis with a noninvasive microsensing system. The contribution of the alternative pathway to total respiration in filamentous thalli was greater than that in leafy thalli. This result was consistent

with the level of AOX gene expression observed in different stages of the life cycle. “
“Spermatogenesis and auxospore development were studied in the freshwater centric diatom Hydrosera triquetra. Spermatogenesis was unusual, lacking depauperating cell divisions within the spermatogonangium. Instead, a series of mitoses occurred within an undivided cell to produce a multinucleate plasmodium with peripheral nuclei, which then underwent meiosis. 32 or 64 sperm budded off from the plasmodium leaving check details a large residual cell containing all the chloroplasts.

Similar development 上海皓元医药股份有限公司 apparently occurs in Pleurosira, Aulacodiscus, and Guinardia, these being so distantly related that independent evolution of plasmodial spermatogenesis seems likely. After presumed fertilization, the Hydrosera egg cell expanded distally to form a triangular end part. However, unlike in other triangular diatoms (Lithodesmium, Triceratium), the development of triradiate symmetry was not controlled by the ‘canonical’ method of a perizonium that constrains expansion to small terminal areas of the auxospore wall. Instead, the auxospore wall lacked a perizonium and possessed only scales and a dense mat of thin, apparently entangled strips of imperforate silica. No such structures have been reported from any other centric diatoms, the closest analogues being instead the incunabular strips of some raphid diatoms (Nitzschia and Pinnularia). Whether these silica structures are formed by the normal method (intracellular deposition within a silica deposition vesicle) is unknown. As well as being more rounded than vegetative cells, the initial cell is aberrant in its structure, since it has a less polarized distribution of the ‘triptych’ pores characteristic of the species. This article is protected by copyright. All rights reserved.

The choice of lab assay for treatment monitoring is another open issue [22]. The most widely used method is the FVII:C assay; probably the most appropriate tool for monitoring the treatment with plasma-derived FVII concentrates

as pdFVII infusions in FVII Fulvestrant deficient patients are a simple substitution of the deficient factor [6]. The mechanisms underlying the haemostatic efficacy of rFVIIa in FVII deficient patients are yet to be elucidated, but probably they cannot be explained by simple replacement of the deficient FVII [23]. Those mechanisms may be related to rFVIIa biding to platelets and to the subsequent local, platelet-mediated delivery of high concentrations of FVIIa to sites of vascular injury, or to platelet activitation. The FVII:C assay might not therefore be accurate for lab monitoring of rFVIIa administration in FVII deficient patients [22-24]. The results of our study indicate that the frequency of rFVIIa administrations in FVII deficient patients undergoing surgical interventions can be safely limited to three injections per day of procedure followed by 1–2 selleck chemicals llc injections on subsequent days. Our mean dose on day of surgery – 50 to 111.1 μg kg−1, and the mean dose on the following days – 18–49.3 did

not differ significantly from those used in other studies [9, 10, 15, 16]. In a recently published article, the total dose of rFVIIa for two patients who underwent total hip and knee replacement was 263 and 241 μg kg−1 respectively [10]. These numbers are lower as compared to our

patients subjected to THR who consumed 412.9 and 444.4 μg kg−1 of rFVIIa respectively. However, both the above-mentioned patients from the Mariani’s study experienced bleeding complications in the perioperative period [10]. In the same study, one patient underwent major orthopaedic surgery for the forearm tumour without any bleeding complications, yet he consumed rFVIIa in the amount comparable to our patients, i.e. 417 μg kg−1 [10]. None of our patients developed excessive bleeding even though FVII:C on the 上海皓元医药股份有限公司 first post-op day returned nearly to the baseline level. It is noteworthy that in contrast to other studies our patients did not receive antifibrinolytics, so the rFVIIa efficacy results obtained in our study were not biased by the use of other haemostatic agents. We are aware of the limitations of our study; the small number of patients and lack of control group. We were also unable to avoid protocol deviation in one case (increased dose of rFVIIa in patient no 04 – see Table 2). Nevertheless, we decided to share our observations with the haemophilia treaters community because there is undoubtedly a need to standardize the treatment protocols for surgical interventions in FVII deficient patients. Our treatment regimen requires further refinement and our aim is to continue data collection in our Centre.

The choice of lab assay for treatment monitoring is another open issue [22]. The most widely used method is the FVII:C assay; probably the most appropriate tool for monitoring the treatment with plasma-derived FVII concentrates

as pdFVII infusions in FVII selleck inhibitor deficient patients are a simple substitution of the deficient factor [6]. The mechanisms underlying the haemostatic efficacy of rFVIIa in FVII deficient patients are yet to be elucidated, but probably they cannot be explained by simple replacement of the deficient FVII [23]. Those mechanisms may be related to rFVIIa biding to platelets and to the subsequent local, platelet-mediated delivery of high concentrations of FVIIa to sites of vascular injury, or to platelet activitation. The FVII:C assay might not therefore be accurate for lab monitoring of rFVIIa administration in FVII deficient patients [22-24]. The results of our study indicate that the frequency of rFVIIa administrations in FVII deficient patients undergoing surgical interventions can be safely limited to three injections per day of procedure followed by 1–2 PI3K inhibitor injections on subsequent days. Our mean dose on day of surgery – 50 to 111.1 μg kg−1, and the mean dose on the following days – 18–49.3 did

not differ significantly from those used in other studies [9, 10, 15, 16]. In a recently published article, the total dose of rFVIIa for two patients who underwent total hip and knee replacement was 263 and 241 μg kg−1 respectively [10]. These numbers are lower as compared to our

patients subjected to THR who consumed 412.9 and 444.4 μg kg−1 of rFVIIa respectively. However, both the above-mentioned patients from the Mariani’s study experienced bleeding complications in the perioperative period [10]. In the same study, one patient underwent major orthopaedic surgery for the forearm tumour without any bleeding complications, yet he consumed rFVIIa in the amount comparable to our patients, i.e. 417 μg kg−1 [10]. None of our patients developed excessive bleeding even though FVII:C on the medchemexpress first post-op day returned nearly to the baseline level. It is noteworthy that in contrast to other studies our patients did not receive antifibrinolytics, so the rFVIIa efficacy results obtained in our study were not biased by the use of other haemostatic agents. We are aware of the limitations of our study; the small number of patients and lack of control group. We were also unable to avoid protocol deviation in one case (increased dose of rFVIIa in patient no 04 – see Table 2). Nevertheless, we decided to share our observations with the haemophilia treaters community because there is undoubtedly a need to standardize the treatment protocols for surgical interventions in FVII deficient patients. Our treatment regimen requires further refinement and our aim is to continue data collection in our Centre.

Ibtx, a MaxiK blocker, inhibited LPS-induced cytokine production in both alcohol-naive and in chronic alcohol-exposed model KC lines. Modulation of Hepatocytes via MaxiK did not affect the degree of steatosis, indicating that modulation of MaxiK is unlikely to affect intracellular fat deposition.

In conclusion, we report novel finding that MaxiK channel is key to development of alcohol-induced liver tissue injury. We further detail that MaxiK/p subunit is important in regulation of inflammation but not steatosis in ASH in mice. These results suggest potential therapeutic targets in transition from hepatic steatosis (HS) to steatohepatitis (SH) phase of ALD. Disclosures: The following people AZD8055 have nothing to disclose: Tracie C. Lo, Keisaku Sato, Angela Dolganiuc Background and aim: Alcoholic Hepatitis (AH) often progresses to multiple organ dysfunction (MOD) and early death. Many patients present systemic inflammatory response syndrome (SIRS) at admission, even in the absence of an infection. We evaluated the impact of infection-associated and sterile SIRS on patients’ Maraviroc chemical structure outcome as well as the role of serum biomarkers. Methods: 162 patients with biopsy-proven AH were included. MOD was defined as dysfunction of two or more organs. SIRS and infections were assessed in all patients. Logistic regression analyses identified variables independently associated with MOD and 90-day mortality. Procalcitonin, high sensitivity

C-re-active medchemexpress protein (hsCRP) and lipopolysaccharide (LPS) serum levels were measured at admission. Results: 58 patients (35.8%) developed MOD. 90-day mortality was higher among patients who developed MOD than among those that did not (62.1% vs. 3.8%, p<.001). 75 patients (46.3%) fulfilled SIRS criteria at admission. The presence of SIRS independently predicted MOD and mortality. 30.7% of the patients with SIRS presented an infection at admission, while 69.3% did not. The latter were classified as sterile SIRS. The course of patients with sterile and infection-associated SIRS was similar in terms of MOD development and mortality (Figure 1). All three biomarkers showed a significant correlation with AH severity

and outcome. Pro-calcitonin levels were higher in patients that developed MOD than in those that did not (0.75 vs 0.31, p=.001). Importantly, among patients with SIRS at admission, procalcitonin levels were higher in infection-associated SIRS than in sterile SIRS (0.89 ng/ml vs. 0.35 ng/ml, p = .015). LPS levels predicted MOD development and in-hospital infections. Interestingly, LPS at admission predicted the response to steroids (100% vs. 39.9% response rate in patients with LPS <1.3 EU/ml vs. >1.3 EU/ml, respectively). Conclusions: Infection-associated and sterile SIRS are both a major determinant of MOD and mortality in AH. Procalcitonin levels can help identifying patients with infection. LPS levels may predict the response to steroids.

Ibtx, a MaxiK blocker, inhibited LPS-induced cytokine production in both alcohol-naive and in chronic alcohol-exposed model KC lines. Modulation of Hepatocytes via MaxiK did not affect the degree of steatosis, indicating that modulation of MaxiK is unlikely to affect intracellular fat deposition.

In conclusion, we report novel finding that MaxiK channel is key to development of alcohol-induced liver tissue injury. We further detail that MaxiK/p subunit is important in regulation of inflammation but not steatosis in ASH in mice. These results suggest potential therapeutic targets in transition from hepatic steatosis (HS) to steatohepatitis (SH) phase of ALD. Disclosures: The following people ZD1839 clinical trial have nothing to disclose: Tracie C. Lo, Keisaku Sato, Angela Dolganiuc Background and aim: Alcoholic Hepatitis (AH) often progresses to multiple organ dysfunction (MOD) and early death. Many patients present systemic inflammatory response syndrome (SIRS) at admission, even in the absence of an infection. We evaluated the impact of infection-associated and sterile SIRS on patients’ Selleckchem BGJ398 outcome as well as the role of serum biomarkers. Methods: 162 patients with biopsy-proven AH were included. MOD was defined as dysfunction of two or more organs. SIRS and infections were assessed in all patients. Logistic regression analyses identified variables independently associated with MOD and 90-day mortality. Procalcitonin, high sensitivity

C-re-active MCE公司 protein (hsCRP) and lipopolysaccharide (LPS) serum levels were measured at admission. Results: 58 patients (35.8%) developed MOD. 90-day mortality was higher among patients who developed MOD than among those that did not (62.1% vs. 3.8%, p<.001). 75 patients (46.3%) fulfilled SIRS criteria at admission. The presence of SIRS independently predicted MOD and mortality. 30.7% of the patients with SIRS presented an infection at admission, while 69.3% did not. The latter were classified as sterile SIRS. The course of patients with sterile and infection-associated SIRS was similar in terms of MOD development and mortality (Figure 1). All three biomarkers showed a significant correlation with AH severity

and outcome. Pro-calcitonin levels were higher in patients that developed MOD than in those that did not (0.75 vs 0.31, p=.001). Importantly, among patients with SIRS at admission, procalcitonin levels were higher in infection-associated SIRS than in sterile SIRS (0.89 ng/ml vs. 0.35 ng/ml, p = .015). LPS levels predicted MOD development and in-hospital infections. Interestingly, LPS at admission predicted the response to steroids (100% vs. 39.9% response rate in patients with LPS <1.3 EU/ml vs. >1.3 EU/ml, respectively). Conclusions: Infection-associated and sterile SIRS are both a major determinant of MOD and mortality in AH. Procalcitonin levels can help identifying patients with infection. LPS levels may predict the response to steroids.

Our aim is to describe the performance, accuracy and safety profile of 19G and 22G Procore needles (Cook Medical Inc, Limerick Ireland). Methods: We retrospectively reviewed patients referred to for EUS-FNB with 19G and 22G ProCore needles. Seventeen patients were identified with 24 lesions. EUS-FNB was performed with a convex array linear echoendoscope (Olympus, GF-UCT140-AL5, Japan) attached to Prosound α5/SSD-500 (Aloka Co. Ltd. Tokyo, Japan) ultrasound machine. Results were compared to surgical histopathology, or global clinical and radiological assessment and follow-up on non-operated cases. Results: EUS-FNBs were technically feasible in

21 (87.5%) cases. Clinical data of 21 lesions

from 17 patients (14 male, 3 females) were included for analysis. Mean age of patients Barasertib cost were 63.6 ± 10.6 years, (range 39.2–75.6). Both 19G and 22G ProCore needle were used in 9 (42.9%) and 12 (57.1%) lesions. Mean size of lesion was 29.2 ± 12.8 mm, (range 10.0–62.0 mm). Mean passes performed were 2.3 ± 1.2 (range 1–5) with median of 3 passes. Three cases from 22G needle did not yield adequate tissue. No statistical significance in the type of needle used for sampling adequacy (p = 0.229). The sensitivity, CAL-101 purchase specificity, positive predictive value and negative predictive value and accuracy for malignancy were 100.0%. No complication was noted. Conclusion: The performance of EUS-FNB with 19G and 22G ProCore needle is an accurate and safe procedure in our center.

Both needles were suitable for tissue procurement. Key Word(s): 1. Endoscopic; 2. Fine needle biopsy; 3. Ultrasound; 4. ProCore; Presenting Author: LIPING YAO Additional Authors: HONGBO ZHANG, ZHIGUO LIU, NA LIU, KAICHUN WU, DAIMING 上海皓元 FAN Corresponding Author: LIPING YAO Affiliations: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University Objective: Achalasia is a chronic progressive benign disease with severe morbidity and difficult management. Peroral endoscopic myotomy (POEM) is a novel endoscopic operation for the treatment of achalasia. This study presents 6-month symptomatic and physiological outcomes after POEM for achalasia. Methods: Nineteen esophageal achalasia patients who underwent POEM in our institution between December 2011 and October 2012 were enrolled. Under general anesthesia, initial incision was made on the posterior wall of the esophagus after submucosal injection. Submucosal tunnel was created and extended below the lower esophageal sphincter (LES) onto the gastric cardia. Hemostatic clips were used to close the mucosal entry. Pre- and postoperative symptoms were quantified with Eckardt scores.

Similar

to the HSC activation process following liver injury, quiescent and nondividing Epigenetics Compound Library cell line HSCs acquire dramatic phenotypic changes upon activation by cancer cells, and transdifferentiate into myofibroblasts. The phenotypic changes include expression of α-smooth muscle actin (α-SMA) and tenascin C, development of actin stress fibers, increased motility and proliferation, and increased production of growth factors and ECM constituents. Liver metastases of pancreatic cancer in mice are surrounded by myofibroblasts (Fig. 2). Although myofibroblasts can derive from HSCs, bone marrow–derived fibrocytes, portal tract fibroblasts, hepatocytes, or cholangiocytes after epithelial–mesenchymal transition, HSCs are a predominant cell type that is activated and transdifferentiated into myofibroblasts when micrometastases develop in the sinusoidal LY2835219 cell line area of liver lobules.1 Accumulating in vitro and in vivo data suggest that activated HSCs promote tumor cell migration, growth, and survival. For example, coculture of HSCs with tumor cells in vitro significantly increased invasion and proliferation of tumor cells.12

Similarly, in a three-dimensional spheroid coculture system, HSCs promoted growth of tumor cells and diminished the extent of central necrosis of tumor cell spheroids.13 Consistent with these data, conditioned medium of activated HSCs was shown to promote the proliferation, migration, or invasion of tumor cells in vitro.13-17In vivo, coimplantation of HSCs or myofibroblasts with tumor cells into

medchemexpress mice resulted in a larger tumor mass that correlated with enhanced angiogenesis.13-15, 18, 19 Furthermore, portal vein implantation of Lewis lung carcinoma cells into mouse livers demonstrated that metastatic growth in the liver was associated with higher densities of myofibroblasts.20 Ju et al. have evaluated the prognostic potential of activated HSCs in 130 human hepatocellular carcinoma (HCC) cases and found that activated HSCs independently contributed to high recurrence or death rates.21 Activated HSCs were also associated with higher rates of early recurrence, suggesting that they may potentiate the further dissemination of tumor cells into new areas of the liver.21 Similarly, patients with high α-SMA expression exhibited the worst outcome from intrahepatic cholangiocarcinoma.12 Taken together, these data suggest that activated HSCs may create a reactive stroma that facilitates tumor growth in the liver. A discussion of the mechanisms by which they do so follows (Fig. 1). Activated HSCs produce an increased number of growth factors and cytokines to stimulate the proliferation, adhesion, and migration of cancer cells. Shimizu et al. have identified that conditioned medium of activated HSCs contained PDGF-AB, hepatocyte growth factor (HGF), and TGF-β, which were able to enhance the proliferation and migration of colon carcinoma LM-H3 cells in vitro.17 These data were confirmed by Amann et al.

Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis,

Roche, Santaris The following people have nothing to disclose: Heng Chi, Bettina E. Hansen, Erik H. Buster The HBsAg inactive carrier (IC) stage is considered to have a good prognosis. However, this knowledge is based mostly on retrospective data and insensitive HBV DNA assays. The aim of the current study is to better characterize the IC stage through a well characterized prospectively followed single center cohort. Of the initial cohort of 129 patients diagnosed as ICs, at year 5, 22 had been excluded (19 learn more lost to follow-up (FU) and 3 anti HDV positive). The rest of 107 (64 f,43 m, median age 48 [19-74]) were prospectively followed with monthly serum ALT, HBVDNA determinations for the first

year and 3 monthly thereafter. Quantitative serum HBsAg Akt inhibitor were determined q6 months. HBVDNA was determined with TaqMan PCR and HBsAg with Architect assay (Abbott). HBV DNA, ALT and HBsAg levels were lower in ICs compared to control HBe Ag negative CHB patients (p<0.0001 and p<0.001 and <0.001 respectively). AUROC for HBsAg was 0,86 (95%CI: 0.80-0.92). A cut-off of 3705 IU/ml revealed sensitivity of 73% and specificity of 84% for diagnosing the IC. In 92 patients with liver biopsy, fibrosis score was 0 in 77 and necroinflammatory score was <6 in 82. Patients were divided into two groups: stable group (HBVDNA continiously <2000 IU/ml, n=64) and unstable groups (n:43) with HBV DNA MCE fluctuations between < and > 2000 IU/mL based on monthly HBVDNA determinations

in the first year of FU. Gender, HAI, fibrosis score, BMI and ALT levels were similar in the stable and unstable groups. Stable group patients had lower baseline HBsAg levels compared to those with unstable HBVDNA (967±1862 IU/mLvs3803±4481 p<0.001). 4 patients developed reactivation. All of them were in unstable group. Majority of unstable patients (65%) continued to have fluctuating HBV DNA levels whereas 35% became stable carriers. HBsAg clearance occurred in 15 patients (14 stable and 1 in the unstable group) during 60 months of FU. Cumulative probability of HBsAg seroconversion was 1.8%, 6.1%, 10.8% and 14.5% at the end of 2, 3,4 and 5 year FU respectively. Baseline HBsAg levels in patients who developed seroconversion were lower compared to the rest of patients (20[0.1-280] vs 884 [1.6-17360], p<0.0001). 13 of 15 patients who developed HBsAg clearance had baseline HBsAg < 60IU/mL. Conclusion:1 .Quantitative HBsAg should be considered as an adjunct for the diagnosis of the IC state. 2. Distinction is needed between a “stable inactive carrier” and an unstable carrier. The former group may be the true IC whereas the latter group may evolve to the true IC state. 3.

Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis,

Roche, Santaris The following people have nothing to disclose: Heng Chi, Bettina E. Hansen, Erik H. Buster The HBsAg inactive carrier (IC) stage is considered to have a good prognosis. However, this knowledge is based mostly on retrospective data and insensitive HBV DNA assays. The aim of the current study is to better characterize the IC stage through a well characterized prospectively followed single center cohort. Of the initial cohort of 129 patients diagnosed as ICs, at year 5, 22 had been excluded (19 Metformin lost to follow-up (FU) and 3 anti HDV positive). The rest of 107 (64 f,43 m, median age 48 [19-74]) were prospectively followed with monthly serum ALT, HBVDNA determinations for the first

year and 3 monthly thereafter. Quantitative serum HBsAg CH5424802 nmr were determined q6 months. HBVDNA was determined with TaqMan PCR and HBsAg with Architect assay (Abbott). HBV DNA, ALT and HBsAg levels were lower in ICs compared to control HBe Ag negative CHB patients (p<0.0001 and p<0.001 and <0.001 respectively). AUROC for HBsAg was 0,86 (95%CI: 0.80-0.92). A cut-off of 3705 IU/ml revealed sensitivity of 73% and specificity of 84% for diagnosing the IC. In 92 patients with liver biopsy, fibrosis score was 0 in 77 and necroinflammatory score was <6 in 82. Patients were divided into two groups: stable group (HBVDNA continiously <2000 IU/ml, n=64) and unstable groups (n:43) with HBV DNA 上海皓元 fluctuations between < and > 2000 IU/mL based on monthly HBVDNA determinations

in the first year of FU. Gender, HAI, fibrosis score, BMI and ALT levels were similar in the stable and unstable groups. Stable group patients had lower baseline HBsAg levels compared to those with unstable HBVDNA (967±1862 IU/mLvs3803±4481 p<0.001). 4 patients developed reactivation. All of them were in unstable group. Majority of unstable patients (65%) continued to have fluctuating HBV DNA levels whereas 35% became stable carriers. HBsAg clearance occurred in 15 patients (14 stable and 1 in the unstable group) during 60 months of FU. Cumulative probability of HBsAg seroconversion was 1.8%, 6.1%, 10.8% and 14.5% at the end of 2, 3,4 and 5 year FU respectively. Baseline HBsAg levels in patients who developed seroconversion were lower compared to the rest of patients (20[0.1-280] vs 884 [1.6-17360], p<0.0001). 13 of 15 patients who developed HBsAg clearance had baseline HBsAg < 60IU/mL. Conclusion:1 .Quantitative HBsAg should be considered as an adjunct for the diagnosis of the IC state. 2. Distinction is needed between a “stable inactive carrier” and an unstable carrier. The former group may be the true IC whereas the latter group may evolve to the true IC state. 3.