Search

Unlabelled: 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 one-time 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)., (© 2016 by the American Association for the Study of Liver Diseases.)

Unlabelled: Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants and 1,708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time-dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥ 10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1,000-9,999, 100-999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5- and 10-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability., Conclusion: Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B., (© 2014 by the American Association for the Study of Liver Diseases.)

Unlabelled: 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., (Copyright © 2013 by the American Association for the Study of Liver Diseases.)