Serum Levels of Hepatitis B Surface Antigen and DNA Can Predict Inactive Carriers With Low Risk of Disease Progression

Abstract

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...

Natural history of serum HBV‐RNA in chronic HBV infection

“…Undetectable levels of viral RNA (< 200 copies mL −1 ) in the serum therefore do not indicate effective inactivation of viral transcriptional activity in the liver. Second, our findings also lead us to question whether a proportion of IC patients who have detectable levels of serum HBV‐RNA is prone to viral reactivation and whether these patients should be recommended for treatment with antivirals . Third, the levels and composition of intrahepatic viral nucleic acids in patients with HBeAg‐negative IA hepatitis are comparable to those of HBeAg‐positive IA patients, indicating that the primary difference between these two groups stems from host immunological factors rather than viral replication.…”

Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers

“…In a recent landmark study, Brunetto et al demonstrated that in individuals with HBV genotype D, a combined cut-off of ≤2000 IU/mL for HBV DNA levels and <1000 IU/mL for HBsAg levels could identify the IC state, with 91.1% sensitivity and 95.4% specificity 16. Liu et al used the same cut-offs in a large cohort of Asian patients with HBV genotypes B and C and identified ICs, with a sensitivity and specificity of 71% and 85%, respectively 36. In the present study, the absence of reactivations in our IC cohort could be confirmed during a mean period of 33.2±21.9 (range, 24–72) months.…”

HBV DNA Integration: Molecular Mechanisms and Clinical Implications

“…Seroconversion to an anti-HBeAg-positive state and the elimination of many (but not all) HBV-infected hepatocytes heralds the entry into the inactive HBV carrier phase. In this phase, low HBV titres are observed and liver injury progression is slower compared to the preceding immune reactive phase [15,16]. Reactivation of virus replication can occur in this phase, driving chronic inflammation with flares of virological breakthrough which defines the HBeAg-negative chronic hepatitis phase [5,6].…”