However, the the effects of SK channels in colonic relaxation cau

However, the the effects of SK channels in colonic relaxation caused by estrogen is not well understood. Methods: The contractile activity of muscle strips from male Sprague-Dawley rats was estimated,

and colonic smooth muscle cells (SMCs) were grown in primary culture. buy Apoptosis Compound Library Results: We found that 17β-estradiol (E2) inhibited colonic contractility, while the tissues responded to apamin, an SK channel inhibitor, with a transient increase in tension after carbachol-induced peak contractions. Preincubation with apamin partially prevented E2-induced relaxation. Double immunofluorescence staining showed that two SK channel subtypes, SK2 and SK3, are coexpressed with α-actin in colonic SMCs. The quantitative ratio of SK transcriptional expression in colonic SMCs was SK3 > SK2. E2 treatment significantly increased SK3 expression in colonic SMCs. The peak expression of SK3 was evident after 12 h and 24 h stimulation with 50 nM E2, which was considered the most effective concentration in vitro. SK3 expression was downregulated by ICI 182780, an estrogen receptor (ER) antagonist,

but was not influenced by bovine serum albumin–conjugated E2. Furthermore, the effect of find more the ERα-selective agonist PPT on the expression of SK3 was almost the same as E2, while the ERβ-selective agonist DPN did not influence SK3 protein expression. Conclusion: Apamin-sensitive 上海皓元 SK3 channels may be involved in the E2-induced relaxing effect on rat colonic smooth muscle, and that this effect is mediated via the ERα. Key Word(s): 1. Estradiol; 2. SK channels; 3. Muscle contraction; 4. Colon; Presenting Author: CHAN-JUAN ZHONG Additional Authors: LI-PING DUAN

Corresponding Author: LI-PING DUAN Affiliations: Peking Uninversity Third Hospital Objective: Chronic stress can increase esophageal mucosa permeability and epithelial intercellular spaces (ICS), which is accompanied by increasing mucosal mast cells (MCs). It’s unknown of how MCs could involve in the process of stress-induced barrier function in gut. We try to explore the roles of MCs play in stress-induced esophageal barrier function. Methods: MCs intact wildtype Brown Norway rats (+/+) and MCs deficient gene-mutant rats (Ws/Ws) were subjected to chronic restraint stress (CRS) for 7 days. All rats were sacrificed at the 8th day and tissue/blood was harvested. Stress state was confirmed by weight loss and analysis of serum stress-related hormones. ICSs were measured by transmission electron microscope (TEM) and tight junction proteins (TJPs) were accessed to evaluate the epithelial barrier dysfuntion after stress. MCs were counted by alcian blue staining and their activation status was evaluated.

However, the the effects of SK channels in colonic relaxation cau

However, the the effects of SK channels in colonic relaxation caused by estrogen is not well understood. Methods: The contractile activity of muscle strips from male Sprague-Dawley rats was estimated,

and colonic smooth muscle cells (SMCs) were grown in primary culture. Selleckchem Ferroptosis inhibitor Results: We found that 17β-estradiol (E2) inhibited colonic contractility, while the tissues responded to apamin, an SK channel inhibitor, with a transient increase in tension after carbachol-induced peak contractions. Preincubation with apamin partially prevented E2-induced relaxation. Double immunofluorescence staining showed that two SK channel subtypes, SK2 and SK3, are coexpressed with α-actin in colonic SMCs. The quantitative ratio of SK transcriptional expression in colonic SMCs was SK3 > SK2. E2 treatment significantly increased SK3 expression in colonic SMCs. The peak expression of SK3 was evident after 12 h and 24 h stimulation with 50 nM E2, which was considered the most effective concentration in vitro. SK3 expression was downregulated by ICI 182780, an estrogen receptor (ER) antagonist,

but was not influenced by bovine serum albumin–conjugated E2. Furthermore, the effect of selleck the ERα-selective agonist PPT on the expression of SK3 was almost the same as E2, while the ERβ-selective agonist DPN did not influence SK3 protein expression. Conclusion: Apamin-sensitive 上海皓元医药股份有限公司 SK3 channels may be involved in the E2-induced relaxing effect on rat colonic smooth muscle, and that this effect is mediated via the ERα. Key Word(s): 1. Estradiol; 2. SK channels; 3. Muscle contraction; 4. Colon; Presenting Author: CHAN-JUAN ZHONG Additional Authors: LI-PING DUAN

Corresponding Author: LI-PING DUAN Affiliations: Peking Uninversity Third Hospital Objective: Chronic stress can increase esophageal mucosa permeability and epithelial intercellular spaces (ICS), which is accompanied by increasing mucosal mast cells (MCs). It’s unknown of how MCs could involve in the process of stress-induced barrier function in gut. We try to explore the roles of MCs play in stress-induced esophageal barrier function. Methods: MCs intact wildtype Brown Norway rats (+/+) and MCs deficient gene-mutant rats (Ws/Ws) were subjected to chronic restraint stress (CRS) for 7 days. All rats were sacrificed at the 8th day and tissue/blood was harvested. Stress state was confirmed by weight loss and analysis of serum stress-related hormones. ICSs were measured by transmission electron microscope (TEM) and tight junction proteins (TJPs) were accessed to evaluate the epithelial barrier dysfuntion after stress. MCs were counted by alcian blue staining and their activation status was evaluated.

pylori eradication, mean intraocular pressure and mean visual fie

pylori eradication, mean intraocular pressure and mean visual field parameters improved. Regarding blepharitis, H. pylori eradication improved ocular cytology results.96 By analyzing 186 blepharitis patients, cytology revealed that blepharitis was more severe in urea-breath-test-positive patients than in negative ones. BMN 673 in vivo In addition, clinical improvement of blepharitis was noted in approximately half of the patients after eradication. A study on idiopathic central serous chorioretinopathy showed that eradication is effective, as it leads to a faster reabsorption of subretinal fluid.97 Diminished halitosis after eradication suggested a causal link between H. pylori infection and

halitosis.98,99 These studies indicate that H. pylori eradication may reduce the production of substances responsible for bad breath. Besides, H. pylori is a common finding in cases of vocal fold minimal lesions, and thus eradication should be considered for vocal fold see more polyps, vocal fold nodules, posterior granulomas, and right vocal fold nodules.100 Similarly, the palatine tonsil represents an extragastric reservoir of H. pylori that facilitates its

oral transmission. A study of 23 patients with recurrent aphthous stomatitis showed a significant reduction in recurrence and amelioration time after eradication.101 H. pylori may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. There were changes in thyroid function tests after H. pylori eradication in subjects who did not respond to high doses of thyroxine treatment.102 After eradication, thyroid-stimulating hormone was decreased in all subjects, and factitious thyrotoxicosis developed in 21% of these cases. Through these findings, the authors found 上海皓元 that H. pylori gastritis may be responsible for an inadequate response to the treatment in hypothyroid cases and that H. pylori eradication in the cases receiving high doses of thyroxine has a risk for factitious tyrotoxicosis.102 Cap polyposis, a rarely encountered disease

characterized by multiple distinctive inflammatory colonic polyps located on the rectum and distal colon, can be cured by H. pylori eradication.103H. pylori might be a good option for cap polyposis since no specific treatment has been established. H. pylori eradication can improve localized vulvodynia.104 There is increasing evidence on the possible role of H. pylori in pre-eclampsia, hyperemesis gravidarum, intrauterine growth retardation, polycystic ovary syndrome, and cervicovaginal secretions. However, there are no data on complete regression after H. pylori eradication in such conditions. Regarding rheumatoid arthritis, amelioration of symptoms and laboratory indices have been reported after H. pylori eradication over a 2-year follow-up period.105 Besides, H.

pylori eradication, mean intraocular pressure and mean visual fie

pylori eradication, mean intraocular pressure and mean visual field parameters improved. Regarding blepharitis, H. pylori eradication improved ocular cytology results.96 By analyzing 186 blepharitis patients, cytology revealed that blepharitis was more severe in urea-breath-test-positive patients than in negative ones. selleck chemical In addition, clinical improvement of blepharitis was noted in approximately half of the patients after eradication. A study on idiopathic central serous chorioretinopathy showed that eradication is effective, as it leads to a faster reabsorption of subretinal fluid.97 Diminished halitosis after eradication suggested a causal link between H. pylori infection and

halitosis.98,99 These studies indicate that H. pylori eradication may reduce the production of substances responsible for bad breath. Besides, H. pylori is a common finding in cases of vocal fold minimal lesions, and thus eradication should be considered for vocal fold NSC 683864 polyps, vocal fold nodules, posterior granulomas, and right vocal fold nodules.100 Similarly, the palatine tonsil represents an extragastric reservoir of H. pylori that facilitates its

oral transmission. A study of 23 patients with recurrent aphthous stomatitis showed a significant reduction in recurrence and amelioration time after eradication.101 H. pylori may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. There were changes in thyroid function tests after H. pylori eradication in subjects who did not respond to high doses of thyroxine treatment.102 After eradication, thyroid-stimulating hormone was decreased in all subjects, and factitious thyrotoxicosis developed in 21% of these cases. Through these findings, the authors found 上海皓元 that H. pylori gastritis may be responsible for an inadequate response to the treatment in hypothyroid cases and that H. pylori eradication in the cases receiving high doses of thyroxine has a risk for factitious tyrotoxicosis.102 Cap polyposis, a rarely encountered disease

characterized by multiple distinctive inflammatory colonic polyps located on the rectum and distal colon, can be cured by H. pylori eradication.103H. pylori might be a good option for cap polyposis since no specific treatment has been established. H. pylori eradication can improve localized vulvodynia.104 There is increasing evidence on the possible role of H. pylori in pre-eclampsia, hyperemesis gravidarum, intrauterine growth retardation, polycystic ovary syndrome, and cervicovaginal secretions. However, there are no data on complete regression after H. pylori eradication in such conditions. Regarding rheumatoid arthritis, amelioration of symptoms and laboratory indices have been reported after H. pylori eradication over a 2-year follow-up period.105 Besides, H.

Despite this disadvantage, ASL estimates of CBF appeared to be of

Despite this disadvantage, ASL estimates of CBF appeared to be of sufficient quality to localize regions of highest vascularity when compared with DSC. A statistically significant, positive linear correlation was observed between ASL and DSC estimates of mean normalized CBF within both FLAIR hyperintense (Pearson’s correlation coefficient, R2 = .706, P < .0001) and contrast-enhancing regions (Pearson's correlation coefficient, R2 = .809, P < .0001) on a per patient basis (Figs 2A, B). The GSK-3 beta pathway linear slope that best explained the correlation between normalized

ASL and DSC estimates of CBF in all tumors was .72 ± .04 standard error of the mean (SEM) for FLAIR hyperintense and .68 ± .03 SEM for contrast-enhancing PR-171 supplier regions, suggesting DSC had about a 3:1 higher dynamic range of CBF measurements

compared to ASL. Similarly for glioblastoma patients, a statistically significant linear was observed in FLAIR (Pearson’s correlation coefficient, R2 = .829, P < .0001) and contrast-enhancing regions (Pearson's correlation coefficient, R2 = .872, P < .0001). The linear relationship between ASL and DSC estimates of CBF in glioblastomas was similar to that of all tumors, measuring .74 ± .05 SEM for FLAIR and .66 ± .04 SEM for contrast-enhancing regions. These results suggest overall estimates of tumor blood flow may be similar between the two techniques, albeit to a different level of sensitivity and dynamic range. Surprisingly, only a minority of patients examined in the current study demonstrated a statistically significant linear correlation between DSC and ASL measurements of relative CBF on a voxel-wise basis for areas of FLAIR and contrast-enhanced regions. As illustrated in Figure

3A, some patients did illustrate a strong voxel-wise association 上海皓元医药股份有限公司 between the two measurements of CBF, specifically showing a 2:1 correspondence (slope ∼.5) between DSC and ASL DSC. The vast majority of patients, however, had voxel-wise relationships similar to those illustrated in Figure 3B, where no apparent linear relationship was evident. Approximately 31% of glioblastoma patients (4 of 13) demonstrated a significant voxel-wise linear correlation between DSC and ASL measurements of CBF with FLAIR hyperintense regions and only 38% of glioblastoma patients (5 of 13) showed a significant correlation in contrast-enhancing regions (Chi-Squared Goodness of Fit, χ2red > 1.0, P < .05). Interestingly, both patients with anaplastic astrocytoma (WHO III) had a significant voxel-wise correlation between DSC and ASL measurements of CBF in both FLAIR and postcontrast regions of interest (Chi-Squared Goodness of Fit, χ2red > 1.0, P < .05).

Hepatocyte-specificity was conferred by using the transthyretin (

Hepatocyte-specificity was conferred by using the transthyretin (TTR)25 promoter. These mice were Selleck Ibrutinib then bred with

the AlbCre Klf6fl(+/+) mice. Altogether, this breeding strategy yielded four lines of mice: (1) Klf6fl(+/+) mice (used as controls) with endogenous Klf6; (2) AlbCre Klf6fl(+/+) mice with hepatocyte-specific Klf6 depletion and no SV1; (3) SV1 Klf6fl(+/+) mice with hepatocyte-specific SV1 overexpression and endogenous Klf6, and; (4) SV1 AlbCre Klf6fl(+/+) mice with hepatocyte-specific SV1 overexpression on a background of Klf6 depletion. All mice appeared phenotypically normal (Supporting Fig. 1A,B), with normal liver architecture and no spontaneous tumorigenesis. Hepatocyte-specific overexpression of SV1 and endogenous KLF6 levels were validated in the SV1 Klf6fl(+/+) transgenics by immunoblot and immunostaining (Supporting Fig. 1C,D). Of note, due to an inverted distal LoxP site AlbCre Klf6fl(+/+) mice have a partial Klf6 depletion and are effectively hypomorphic rather than complete knockouts (F. DeSauvage, pers. commun.; see Supporting Fig. 1C,D). To assess the propensity of each of these four mouse lines toward hepatocarcinogenesis, animals were injected with a single intraperitoneal dose (5 mg/kg) of DEN at 2 weeks of age,2 and tumor development was assessed at 3, 6, and

9 months JNK inhibitor and compared to nontransgenic littermates. At 3 months there were no macro- or microscopically visible tumors. At 6 months 57% (4/7) of the Klf6fl(+/+) controls had microscopic tumors compared to 83% (5/6) in the SV1 Klf6fl(+/+) transgenics and 100% of both the AlbCre Klf6fl(+/+)) (13/13) and the SV1 AlbCre Klf6fl(+/+) (7/7) animals (not significant) (Supplemental Table 1). Tumors were significantly larger in the AlbCre Klf6fl(+/+) mice (P < 0.05) (Fig. 2A,B) and contained a significantly higher tumor grade in the SV1 Klf6fl(+/+) transgenics (P < 0.05) and even more so in SV1 AlbCre Klf6fl(+/+) mice (P < 0.005) (Fig. 2C,D) at 6 months after DEN injection. These findings indicate that both

Klf6 depletion and SV1 overexpression independently promote tumorigenesis after DEN treatment by increasing the size and advancing the histologic grade of the tumors. The tumorigenic activities of Klf6 depletion and/or SV1 overexpression 上海皓元 at 6 months were more clearly evident at 9 months, with both more (Fig. 3A, P < 0.001; 3B, P < 0.05) and larger tumors (Fig. 3C, P < 0.05) in SV1 AlbCre Klf6fl(+/+) mice, resulting in a significantly greater tumor burden (Fig. 3D) and heavier livers (P < 0.01) (Supporting Fig. 2) than Klf6fl(+/+) controls. Interestingly, this trend was also observed in both Klf6-depleted mice (AlbCre Klf6fl(+/+)) and in SV1-transgenic mice (SV1 Klf6fl(+/+)), but only the combination of both defects led to an additive and significant effect, reinforcing the contribution of the SV1/Klf6 ratio in hepatocarcinogenesis.

Hepatocyte-specificity was conferred by using the transthyretin (

Hepatocyte-specificity was conferred by using the transthyretin (TTR)25 promoter. These mice were find more then bred with

the AlbCre Klf6fl(+/+) mice. Altogether, this breeding strategy yielded four lines of mice: (1) Klf6fl(+/+) mice (used as controls) with endogenous Klf6; (2) AlbCre Klf6fl(+/+) mice with hepatocyte-specific Klf6 depletion and no SV1; (3) SV1 Klf6fl(+/+) mice with hepatocyte-specific SV1 overexpression and endogenous Klf6, and; (4) SV1 AlbCre Klf6fl(+/+) mice with hepatocyte-specific SV1 overexpression on a background of Klf6 depletion. All mice appeared phenotypically normal (Supporting Fig. 1A,B), with normal liver architecture and no spontaneous tumorigenesis. Hepatocyte-specific overexpression of SV1 and endogenous KLF6 levels were validated in the SV1 Klf6fl(+/+) transgenics by immunoblot and immunostaining (Supporting Fig. 1C,D). Of note, due to an inverted distal LoxP site AlbCre Klf6fl(+/+) mice have a partial Klf6 depletion and are effectively hypomorphic rather than complete knockouts (F. DeSauvage, pers. commun.; see Supporting Fig. 1C,D). To assess the propensity of each of these four mouse lines toward hepatocarcinogenesis, animals were injected with a single intraperitoneal dose (5 mg/kg) of DEN at 2 weeks of age,2 and tumor development was assessed at 3, 6, and

9 months BEZ235 manufacturer and compared to nontransgenic littermates. At 3 months there were no macro- or microscopically visible tumors. At 6 months 57% (4/7) of the Klf6fl(+/+) controls had microscopic tumors compared to 83% (5/6) in the SV1 Klf6fl(+/+) transgenics and 100% of both the AlbCre Klf6fl(+/+)) (13/13) and the SV1 AlbCre Klf6fl(+/+) (7/7) animals (not significant) (Supplemental Table 1). Tumors were significantly larger in the AlbCre Klf6fl(+/+) mice (P < 0.05) (Fig. 2A,B) and contained a significantly higher tumor grade in the SV1 Klf6fl(+/+) transgenics (P < 0.05) and even more so in SV1 AlbCre Klf6fl(+/+) mice (P < 0.005) (Fig. 2C,D) at 6 months after DEN injection. These findings indicate that both

Klf6 depletion and SV1 overexpression independently promote tumorigenesis after DEN treatment by increasing the size and advancing the histologic grade of the tumors. The tumorigenic activities of Klf6 depletion and/or SV1 overexpression MCE公司 at 6 months were more clearly evident at 9 months, with both more (Fig. 3A, P < 0.001; 3B, P < 0.05) and larger tumors (Fig. 3C, P < 0.05) in SV1 AlbCre Klf6fl(+/+) mice, resulting in a significantly greater tumor burden (Fig. 3D) and heavier livers (P < 0.01) (Supporting Fig. 2) than Klf6fl(+/+) controls. Interestingly, this trend was also observed in both Klf6-depleted mice (AlbCre Klf6fl(+/+)) and in SV1-transgenic mice (SV1 Klf6fl(+/+)), but only the combination of both defects led to an additive and significant effect, reinforcing the contribution of the SV1/Klf6 ratio in hepatocarcinogenesis.

A total of 483

patients with 79 events were used to evalu

A total of 483

patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor Ivacaftor cost of liver-related outcomes. Conclusion: Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C. (HEPATOLOGY 2011;) Predicting clinical outcomes in patients with chronic hepatitis C has been a challenge. Most models to predict clinical ABT199 and histological outcomes have used baseline clinical or laboratory data.1-7 However, as the severity of liver disease changes over time, so do the surrogate laboratory tests that reflect the state of liver function. Therefore, a prognostic model should take the time factor into account and a laboratory parameter measured serially over time may be more accurate in predicting outcome compared to a single measurement obtained at baseline. In clinical practice, physicians

use serial clinical data and patterns of laboratory values during follow-up to counsel patients on their risks of adverse outcomes. 上海皓元 Thus, a patient with more rapidly deteriorating laboratory values is expected to have a higher risk of an adverse outcome than a patient with stable laboratory values even though the baseline laboratory values of the two patients may be similar. This approach of using serial laboratory data

to compute time-dependent Model for Endstage Liver Disease (MELD) scores has been shown to be more accurate in predicting wait list mortality than listing MELD in patients waiting for liver transplantation.8-10 The HALT-C (hepatitis C long-term treatment against cirrhosis) trial enrolled 1,050 patients with advanced hepatitis C followed prospectively to 8.7 years for clinical outcomes.11 All the patients had laboratory tests at each study visit. The aim of this analysis was to develop models comprising baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict outcomes in patients with advanced hepatitis C. AFP, alpha fetoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CT, computed tomography; HALT-C, hepatitis C long-term treatment against cirrhosis; HCC, hepatocellular carcinoma; HR, hazards ratio; INR, international normalized ratio; MELD, Model for Endstage Liver Disease; MRI, magnetic resonance imaging. The design of the HALT-C trial has been described.

(HEPATOLOGY 2011;) The detection of hepatitis B surface antigen (

(HEPATOLOGY 2011;) The detection of hepatitis B surface antigen (HBsAg) in serum was pivotal to the find more discovery of hepatitis B virus (HBV) more than 4 decades

ago and remains the cornerstone of diagnosis today.1-3 HBsAg seroclearance is considered to be the closest thing to a cure for chronic hepatitis B (CHB): it reflects immunological control of the infection and confers an excellent prognosis in the absence of preexisting cirrhosis or concurrent infections with other viruses.2-6 Not surprisingly, HBsAg seroclearance has attracted considerable attention in both natural history studies and therapeutic trials. The incidence of spontaneous HBsAg seroclearance is low, especially in younger patients. Interferon (IFN) therapy appears to be able to enhance the rate of HBsAg seroclearance from 0.72% (controls) to 2.25% per year in European

patients and from 0.07% to 0.43% per year in Asian patients.6 A greater understanding of the factors influencing HBsAg levels might enable us to improve this still further. Recently, a MAPK Inhibitor Library clinical trial wealth of new data on HBsAg quantitation has emerged, and it is becoming apparent that information on HBsAg levels can add to our understanding of both the natural history of the disease and its response to therapy. This is a good time to review and discuss issues concerning the clinical utility of HBsAg quantitation and the ways in which this may help us with patient management in the future. ALT, alanine aminotransferase; anti-HBe, antibody to hepatitis B e antigen; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B; ETV, entecavir; HBeAg, hepatitis B e antigen; HBsAg,

hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IFN, interferon; LAM, lamivudine; LdT, telbivudine; NA, nucleos(t)ide analogue; NPV, negative predictive value; PEG-IFN, pegylated interferon; PPV, positive predictive value; TDF, tenofovir. Our understanding of the pathogenesis and natural history of CHB has been facilitated by technological advances that have improved the sensitivity of both serological assays for quantifying antigens (including HBsAg) and polymerase chain reaction assays MCE公司 for measuring HBV DNA. Several independent groups have compared HBsAg and HBV DNA levels during different phases of the disease, and their findings have been rather consistent. To put these findings into context, we must consider the HBsAg production pathway and the ways in which this is related to serum HBV DNA levels and intrahepatic covalently closed circular DNA (cccDNA). HBsAg is produced by more than one pathway (Fig. 1): the translation of transcriptionally active cccDNA molecules, which serve as a template for replication, and the translation of viral genes transcribed from integrated HBV DNA sequences in the host genome.

(HEPATOLOGY 2011;) The detection of hepatitis B surface antigen (

(HEPATOLOGY 2011;) The detection of hepatitis B surface antigen (HBsAg) in serum was pivotal to the CT99021 discovery of hepatitis B virus (HBV) more than 4 decades

ago and remains the cornerstone of diagnosis today.1-3 HBsAg seroclearance is considered to be the closest thing to a cure for chronic hepatitis B (CHB): it reflects immunological control of the infection and confers an excellent prognosis in the absence of preexisting cirrhosis or concurrent infections with other viruses.2-6 Not surprisingly, HBsAg seroclearance has attracted considerable attention in both natural history studies and therapeutic trials. The incidence of spontaneous HBsAg seroclearance is low, especially in younger patients. Interferon (IFN) therapy appears to be able to enhance the rate of HBsAg seroclearance from 0.72% (controls) to 2.25% per year in European

patients and from 0.07% to 0.43% per year in Asian patients.6 A greater understanding of the factors influencing HBsAg levels might enable us to improve this still further. Recently, a Wnt activation wealth of new data on HBsAg quantitation has emerged, and it is becoming apparent that information on HBsAg levels can add to our understanding of both the natural history of the disease and its response to therapy. This is a good time to review and discuss issues concerning the clinical utility of HBsAg quantitation and the ways in which this may help us with patient management in the future. ALT, alanine aminotransferase; anti-HBe, antibody to hepatitis B e antigen; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B; ETV, entecavir; HBeAg, hepatitis B e antigen; HBsAg,

hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; IFN, interferon; LAM, lamivudine; LdT, telbivudine; NA, nucleos(t)ide analogue; NPV, negative predictive value; PEG-IFN, pegylated interferon; PPV, positive predictive value; TDF, tenofovir. Our understanding of the pathogenesis and natural history of CHB has been facilitated by technological advances that have improved the sensitivity of both serological assays for quantifying antigens (including HBsAg) and polymerase chain reaction assays MCE for measuring HBV DNA. Several independent groups have compared HBsAg and HBV DNA levels during different phases of the disease, and their findings have been rather consistent. To put these findings into context, we must consider the HBsAg production pathway and the ways in which this is related to serum HBV DNA levels and intrahepatic covalently closed circular DNA (cccDNA). HBsAg is produced by more than one pathway (Fig. 1): the translation of transcriptionally active cccDNA molecules, which serve as a template for replication, and the translation of viral genes transcribed from integrated HBV DNA sequences in the host genome.