Toward functional cure of hepatitis B: Is combination therapy the key?

Section snippets

Background and context

Chronic hepatitis B virus (HBV) infection is a major health burden and it is estimated that 3% of the world’s population are chronically infected.¹ Infected individuals are at risk of developing chronic liver disease leading to cirrhosis, liver-related complications and development of hepatocellular carcinoma (HCC).² Antiviral treatment with nucleos(t)ide analogues (NA) effectively suppresses HBV DNA replication thereby reducing the risk of disease progression and HCC development in patients

Objectives, methods and findings

In the phase II study published in the New England Journal of Medicine, 160 patients with chronic HBV infection and established effective NA treatment without clinically significant fibrosis or cirrhosis were randomly assigned to receive (A) xalnesiran 100 mg or (B) 200 mg, (C) xalnesiran 200 mg plus ruzotolimod 150 mg, (D) xalnesiran 200 mg plus pegylated interferon alfa (PEG-IFN), all in addition to continued NA treatment, or (E) NA alone.⁹ The total treatment duration was 48 weeks in all

Significance of findings

This study demonstrated that combination treatment with a small-interfering RNA (xalnesiran) and an immune-modulatory agent (ruzotolimod or PEG-IFN) in addition to continued NA treatment led to HBsAg loss in a substantial proportion of patients. Interestingly, response rates were higher in patients receiving PEG-IFN compared to the TLR7 agonist ruzotolimod. The reasons for these differences are unclear but could be due to the broader immunomodulatory activity of IFN, which affects both the

Financial support

The authors did not receive any financial support to produce this manuscript.

Conflict of interest

The author of this study declares that they do not have any conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.