On-treatment monitoring of HBV DNA levels: predicting response and resistance to oral antiviral therapy at week 24 versus week 48

The suppression of hepatitis B viral (HBV) load correlates with favorable histologic, biochemical, and serologic responses in clinical trials of patients with chronic hepatitis B (CHB). The ability to identify patients who will not experience durable viral suppression in response to a specific antiviral regimen affords the opportunity for early treatment modification to optimize outcomes and avoid the development of antiviral resistance. Substantial evidence demonstrates that on-treatment serum HBV DNA levels are predictive of virologic response and risk of resistance. Regional clinical practice guidelines for the management of CHB universally recommend monitoring serum HBV DNA levels at treatment week 24. However, the value of this time point as a predictor of long-term success may not be applicable to all types of antiviral therapy. Indeed, each oral nucleos(t)ide analog (NA) antiviral therapy has a unique profile of potency, genetic barriers to resistance, and viral kinetics that may affect the optimal time point for on-treatment monitoring. This review discusses available data for appropriate predictors for long-term response and antiviral resistance for patients receiving specific oral NA antiviral therapy. Guidelines for on-treatment monitoring are also discussed.