INSERM, U1052, Cancer Research Center of Lyon, Lyon University, Lyon, France; Hepatology Department, Hospices Civils de Lyon, Lyon, France.
The management of treatment failure in patients with chronic hepatitis B, remains a clinical concern. Incomplete viral suppression and the emergence of drug resistance are key determinants of treatment failure. The correct choice of a potent first-line therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance have significantly lower rates of resistance compared with those with a low barrier to resistance. Management of treatment failure requires precise clinical and virological monitoring as well as early treatment intervention with appropriate noncross-resistant antivirals. Long-term surveillance of treatment efficacy and possible emergence of drug resistance is necessary in patients who have been sequentially treated with multiple antivirals. The identification of novel treatment targets remains a major research goal to improve the efficacy of current antiviral therapy through combination therapy regimens.