Integrating host and HBV characteristics, this study aimed to develop models for predicting long-term cirrhosis and hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV) patients. This analysis included hepatitis B surface antigen (HBsAg)-seropositive and anti-HCV-seronegative participants from the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (R.E.V.E.A.L.-HBV) cohort. Newly developed cirrhosis and HCC were ascertained through regular follow-up ultrasonography, computerized linkage with national health databases, and medical chart reviews. Two-thirds of the participants were allocated for risk model derivation and another one-third for model validation. The risk prediction model included age, gender, HBV e antigen (HBeAg) serostatus, serum levels of HBV DNA, and alanine aminotransferase (ALT), quantitative serum HBsAg levels, and HBV genotypes. Additionally, the family history was included in the prediction model for HCC. Cox's proportional hazards regression coefficients for cirrhosis and HCC predictors were converted into risk scores. The areas under receiver operating curve (AUROCs) were used to evaluate the performance of risk models. Elder age, male, HBeAg, genotype C, and increasing levels of ALT, HBV DNA, and HBsAg were all significantly associated with an increased risk of cirrhosis and HCC. The risk scores estimated from the derivation set could accurately categorize participants with low, medium, and high cirrhosis and HCC risk in the validation set (P < 0.001). The AUROCs for predicting 3-year, 5-year, and 10-year cirrhosis risk ranged 0.83-0.86 and 0.79-0.82 for the derivation and validation sets, respectively. The AUROC for predicting 5-year, 10-year, 15-year risk of HCC ranged 0.86-0.89 and 0.84-0.87 in the derivation and validation sets, respectively. Conclusion: The risk prediction models of cirrhosis and HCC by integrating host and HBV profiles have excellent prediction accuracy and discriminatory ability. They may be used for clinical management of chronic hepatitis B patients. (HEPATOLOGY 2013;58:546-554) C hronic hepatitis B is a significant global health threat with more than 350 million affected people. 1 The Asian-Pacific region is a hyperendemic area of chronic hepatitis, and a major cause of endstage liver diseases including cirrhosis and hepatocellular carcinoma (HCC). 2 Globally, at least one-third of liver cirrhosis was attributable to chronic hepatitis B, 3 and a significant proportion of chronic hepatitis B virus (HBV) infections eventually progress to HCC. 4,5 Abbreviations: ALT, alanine aminotransferase; AUROC, area under receiver operating curve; HBV, hepatitis B virus; HBeAg, HBV e antigen; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; R.E.V.E

CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers.

The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer’s disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility as well as an unclear path for moving basic discovery towards clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state-of-the-art. Additionally, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and towards clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional hand-off model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.

Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.

Serum levels of hepatitis B virus (HBV) DNA ( £ 2000 IU/mL) and hepatitis B surface antigen (HBsAg) (<1000 IU/mL) have been shown to distinguish inactive carriers with high accuracy. The goal of this study was to validate the predictability of onetime measurement of quantitative HBsAg and HBV DNA levels for inactive carrier status and chronic hepatitis B (CHB) progression in a community-based cohort. This study included 1529 participants chronically infected with HBV genotype B or C from the REVEAL-HBV cohort. They were ascertained as inactive or active CHB after 18 months of follow-up. Validity of the one-time measurement was assessed by sensitivity, specificity, and receiver operating characteristic curves, while associations with clinical outcomes were calculated with Cox proportional hazards regressions. The one-time baseline measurement of HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL distinguished inactive carriers from active CHB with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 71%, 85%, 83%, 74%, and 78%, respectively. Those identified as inactive carriers using the one-time baseline measurement had multivariate adjusted hazard ratios of 0.36 (95% confidence interval [CI], 0.20-0.63) and 0.36 (0.23-0.56) for hepatocellular carcinoma and liver cirrhosis, respectively, and an adjusted rate ratio of 6.97 (95% CI, 5.21-9.33) for HBsAg seroclearance. Areas under the receiver operating characteristic curve of predicting these outcomes using the one-time definition were similar to those obtained when using long-term follow-up defined carrier status for prediction. Conclusion: This study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for future inactive carriers. This single-point strategy provides new and complementary information useful for management of patients with chronic hepatitis B infection. (HEPATOLOGY 2016;64:381-389) C hronic hepatitis B (CHB) infection is a large global health problem due to its widespread geographical prevalence and its varying clinical consequences, which range from inflammation and infection to liver cirrhosis and hepatocellular carcinoma (HCC).(1) The characterization of patients with CHB is often divided into hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. It is well-known that HBeAg-seropositive patients are at increased risk for HCC, and HBeAg seroconversion is an important milestone for clinical management of these patients.(2,3) On the other hand, HBeAg-negative patients can be defined clinically as inactive carriers or as patients with active CHB. Inactive carriers typically have HBV DNA levels <2,000 IU/mL and normal alanine aminotransferase (ALT) levels, whereas those with active CHB have HBV DNA levels >2,000 IU/mL with fluctuations that reach >20,000 IU/mL in some patients, accompanied by intermittent or persistent ALT elevation. (2,4) Previous studies have shown that compared with individuals with active CHB, inactive carriers have a significantly bett...