2014 American Association for the Study of Liver Diseases Annual Meeting: Hepatitis B Highlights Hot Topics Summary 1. Effectiveness of long-term NA consolidation therapy According to international guidelines, consolidation therapy for 6 to 12 months prior to discontinuation of NA therapy increases sustained virologic response (SVR). Chi et al. performed a statistical analysis of 94 patients who discontinued treatment after at least 1 year of NA therapy and found that although patients may have been HBeAg positive or HBeAg negative at the beginning of treatment, all patients were HBeAg negative at the time of treatment discontinuation and no HBV DNA was detected (<200 IU/ mL). Regardless of HBeAg status at the beginning of treatment, 64% of patients experienced a relapse within 5 years after stopping NA therapy. Consolidation therapy for at least 3 years reduced the relapse rate and increased the rate of HBsAg regression. The results of this study suggest the need for an appropriate extension of the 6-12 months of consolidation therapy recommended by current guidelines. Maintaining low levels of viremia with long-term NA therapy Potent NA therapy (e.g. tenofovir) maintains a high level of viral suppression and improves liver fibrosis, and no viral resistance has been found in patients with long-term follow-up in the available data. Even 5 years after treatment, low levels of viral replication (below the lower limit of quantification) can be found in those on NA therapy. In contrast, the absence of low levels of viremia is associated with HBeAg regression and serological conversion. Therefore, further evaluation of the mechanisms of viral replication in the absence of significant drug resistance is warranted. These data also provide a basis for intensive viral suppression. 3. Reduction of HBV covalent closed-loop DNA levels Lai et al. reported that long-term NA therapy significantly reduced covalent closed-loop DNA (cccDNA) levels of HBV. Although small amounts of intrahepatic HBV DNA are still detectable in all patients, cccDNA is no longer detectable in 45% of patients. intact HBV DNA can be a source of detectable intrahepatic HBV DNA and HBsAg. Continuous long-term NA treatment reduces cccDNA to undetectable levels, suggesting that this indicator could be a possible criterion for treatment endpoints. 4. Longitudinal study of HBV infection serologically characterized HBV replication at a sustained low level after serological conversion of HBsAg. Seto et al. used a high-sensitivity HBsAg kit to evaluate 109 patients who had shown serological conversion to HBsAg. The results showed that HBsAg could be detected in the serum of a high proportion of patients during the "HBsAg-negative phase" of HBV infection. 5. Vertical transmission of HBV from mother to child Particular attention should be paid to the vertical transmission of HBV from mother to child when the mother has a high viral load level and is HBeAg positive. Due to the limited safety data available, the use of antiviral therapy during pregnancy to reduce maternal viral load remains a difficult issue. Several safety and efficacy data on antiviral therapy in this area were shared at the AASLD annual meeting, attracting much attention. (1) Tenofovir Huang et al. studied the use of tenofovir antiviral therapy throughout pregnancy. The results showed that all infants were negative for HBV DNA in cord blood and all 20-48 week old infants were negative for HBsAg and HBV DNA. The subjects tolerated the drug well, and no congenital diseases were reported in the infants. Yi et al. also evaluated the safety of managing elevated alanine aminotransferase (ALT) levels with tenofovir dosing throughout pregnancy. At 28 weeks of age, no infants in the tenofovir group had positive HBsAg results, compared with 6.5% of infants in the group whose mothers did not receive treatment. The researchers found that treatment with tenofovir throughout pregnancy was safe for both mother and child. Tenofovir treatment suppressed maternal viremia while controlling ALT levels to within the normal range, thus potentially reducing the rate of infant immunoprophylactic failure. (2) Tenbivudine Sheng et al. evaluated the safety and efficacy of tenbivudine in pregnancy for the prevention of vertical transmission of HBV from mother to child. The study used more than 4500 pregnant women with chronic HBV infection (immune tolerance) as the study population. Of these, 6% were HBsAg carriers, 67% were positive for HBeAg, and 83% tested positive for HBV DNA. The study showed that the use of tibivudine in pregnant women with severe viremia chronic infection in late pregnancy is safe and effective in preventing vertical transmission of HBV from mother to child. At 7 months postpartum, no infants in the dosing group were evaluated for HBV infection. Anti-HBs treatment correlated with greater detectability of HBsAg in the serum. Quantitative detection of serum HBsAg may potentially help to distinguish occult HBV infection from prior HBV infection.