Published in:
01-12-2016 | Hepatitis B (JK Lim, Section Editor)
Future Therapy for Hepatitis B Virus: Role of Nucleos(t)ide Analogues and Pegylated Interferon Therapy
Published in: Current Hepatology Reports | Issue 4/2016
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Purpose of Review
The goal of chronic hepatitis B (CHB) therapy is an improvement in clinical outcomes, but surrogate markers include viral suppression, hepatitis B e-antigen (HBeAg) seroconversion, and, more recently, hepatitis B surface antigen (HBsAg) clearance, labeled as “functional cure.” The current therapy of CHB is based on two strategies: either a finite course of pegylated interferon (pegIFN) or an indefinite duration of oral nucleos(t)ide analogues (NAs). NAs with high antiviral potency and barrier to resistance have become the mainstay of therapy due to ease of use, tolerability, and cost. However, optimization of these two therapeutic modalities has not been fully explored to maximize outcomes, which include combination therapy.
Recent Findings
Initial randomized control trials with approved NAs and pegIFN as de novo combinations did not appear to show benefit compared to pegIFN alone, but meta-analyses now show that there are significant improvements in undetectable HBV DNA, HBeAg loss and seroconversion, and HBsAg loss. However, many patients remain on long-term NA therapy, and a strategy to increase HBeAg seroconversion and preferably HBsAg clearance are needed. Such strategies include switch (sequential) or add-on pegIFN to patients already on NAs. An add-on pegIFN strategy in HBeAg-negative CHB (PEGAN study) has shown 8% HBsAg clearance after 48 weeks of therapy, and a switch strategy (OSST study) showed a similar result—8.5% HBsAg clearance. However, the ultimate goal of HBsAg seroclearance remains still <10% despite these strategies.
Summary
It may be possible to improve these outcomes further by selecting patients with lower quantitative HBsAg (qHBsAg) levels and to predict outcomes based on on-treatment qHBsAg responses.