HBV DNA levels are associated with clinically significant pa
HBV DNA levels are associated with clinically significant pathological events, such as cirrhosis; therefore, changes in the serum levels of HBV DNA could determine a risk for hepatocellular carcinoma. For on-treatment follow-up, HBeAg loss/seroconversion is important during the nucleoside therapy for CHB patients. In China and other East Asian countries, HBeAg seroconversion was achieved in approximately 44–47% of patients after 4–5 years of lamivudine-based treatment. Under lamivudine treatment, studies from several Taiwan reports indicated that the rate of HBeAg seroconversion was associated with the pretreatment ALT level.
ETV, a new guanosine nucleoside analog with specific activity against HBV DNA polymerase, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class. Compared with lamivudine and adefovir, ETV at 0.5 mg daily reportedly induces greater HBV DNA suppression, with HBV DNA becoming undetectable in 60–71% of HBeAg-positive patients and 88–90% of HBeAg-negative patients at 48–52 weeks. The HBeAg seroconversion rate was 31% by 2nd year, and the HBeAg seroconversion rate in 141 HBeAg-positive patients was 23% from 96th week to 240th week. Among patients treated with ETV at 0.5 mg daily, 83–90% patients had undetectable HBV DNA, and 24–44% patients had HBeAg seroconversion at 3rd year of the treatment.
ETV could suppress HBV DNA effectively, but the dynamic change of HBV DNA and corresponding HBeAg changes have not yet been clearly elucidated. Whether on-treatment follow-up HBV DNA is capable of predicting HBeAg seroconversion or seroclearance requires further investigation. To address these concerns, we conducted the present study to investigate whether on-treatment serum HBV DNA levels could predict HBeAg seroclearance during ETV-based therapy for HBeAg-positive CHB patients. In this Deferoxamine mesylate manufacturer retrospective, study patients were followed-up regularly every 12 weeks. Follow-ups included evaluations of serum HBV DNA levels at the 12th week, 24th week, and 48th week since the ETV treatment initiation. The results of our study provide important information with respect to the prediction of HBeAg seroclearance during ETV therapy among HBeAg-positive CHB patients.
Discussion ETV is one of the major treatments for patients with hepatitis B infection owing to its superior ability to effectively suppress HBV DNA. However, HBeAg seroconversion or seroclearance is one of the major goals of nucleoside treatment; therefore, a clinical indicator for predicting the absence of HBeAg would be useful during the on-treatment follow-up. In this study, one-third of the patients who achieved HBeAg seroclearance under ETV treatment did so within 96 weeks. Our results demonstrated that HBV DNA levels < 20 IU/mL at the 24th and 48th week could predict HBeAg loss within 96 weeks in ETV-treated CHB patients. A Chinese study involving lamivudine treatment for CHB demonstrated that CHB patients showed enhanced seroconversion rates, and up to two-thirds of patients with moderately elevated pretreatment ALT levels achieved HBeAg seroconversion after 3 years of therapy. Wang et al demonstrated that both baseline serum ALT levels > 5 times the upper normal limit and HBV DNA levels could predict HBeAg seroconversion. However, the baseline serum ALT level was not a predictor for HBeAg seroconversion during ETV treatment in our study as well as in another study. The reasons are possibly due to the variation of the baseline serum ALT level and the number of cases. A 4-year study reported that the baseline HBV DNA level was a significant factor associated with undetectable HBV DNA and HBeAg seroclearance at 1–3 years. Thus, undetectable HBV DNA could be considered as another predicting factor in HBeAg serological change. Our data indicated that HBV DNA levels < 20 IU/mL at both 24th week and 48th week were positively associated with favorable serological change in CHB patients with ETV treatment. This finding is consistent with previous studies. Additional predictors for HBeAg seroconversion during treatment have been studied, and serum HBV RNA levels may serve as a novel tool for the prediction of serological response during polymerase inhibitor treatment in HBeAg-positive patients. However, currently extracellular route is not commonly used in routine follow-up for CHB treatment. Among HBeAg-positive CHB patients, nucleoside could significantly improve the rates of histologic, virological, and biochemical profiles. Our results are similar to those of previous reports. Without significant and rapid HBV DNA suppression, ETV-treated CHB patients possibly need a longer treatment duration in order to obtain histological and serological benefits.