The scientific basis of combination therapy for chronic hepatitis B functional cure.
Fiche publication
Date publication
janvier 2023
Journal
Nature reviews. Gastroenterology & hepatology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Lim SG, Baumert TF, Boni C, Gane E, Levrero M, Lok AS, Maini MK, Terrault NA, Zoulim F
Lien Pubmed
Résumé
Functional cure of chronic hepatitis B (CHB) - or hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy - is now the goal of treatment, but is rarely achieved with current therapy. Understanding the hepatitis B virus (HBV) life cycle and immunological defects that lead to persistence can identify targets for novel therapy. Broadly, treatments fall into three categories: those that reduce viral replication, those that reduce antigen load and immunotherapies. Profound viral suppression alone does not achieve quantitative (q)HBsAg reduction or HBsAg loss. Combining nucleos(t)ide analogues and immunotherapy reduces qHBsAg levels and induces HBsAg loss in some patients, particularly those with low baseline qHBsAg levels. Even agents that are specifically designed to reduce viral antigen load might not be able to achieve sustained HBsAg loss when used alone. Thus, rationale exists for the use of combinations of all three therapy types. Monitoring during therapy is important not just to predict HBsAg loss but also to understand mechanisms of HBsAg loss using viral and immunological biomarkers, and in selected cases intrahepatic sampling. We consider various paths to functional cure of CHB and the need to individualize treatment of this heterogeneous infection until a therapeutic avenue for all patients with CHB is available.
Référence
Nat Rev Gastroenterol Hepatol. 2023 01 11;: