Towards an HBV cure: state-of-the-art and unresolved questions—report of the ANRS workshop on HBV cure

Abstract

HBV infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Although HBV infection can be efficiently prevented by vaccination, and treatments are available, to date there is no reliable cure for the >240 million individuals that are chronically infected worldwide. Current treatments can only achieve viral suppression, and lifelong therapy is needed in the majority of infected persons. In the framework of the French National Agency for Research on AIDS and Viral Hepatitis 'HBV Cure' programme, a scientific workshop was held in Paris in June 2014 to define the state-of-the-art and unanswered questions regarding HBV pathobiology, and to develop a concerted strategy towards an HBV cure. This review summarises our current understanding of HBV host-interactions leading to viral persistence, as well as the roadblocks to be overcome to ultimately address unmet medical needs in the treatment of chronic HBV infection.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…Several definitions of cure have been proposed following several international workshops. 241,242 A true cure may not be feasible because HBV DNA is integrated into the host genome. Furthermore, among persons who recovered from acute hepatitis B, viral cccDNA can still be detected in the liver explaining the reactivation of HBV replication when these 'recovered' persons are profoundly immunosuppressed.…”

“…First phase clinical trials are ongoing for several of these agents. 241,243 Several potential target mechanisms for immune modulation to engender or restore HBV specific immune responses in conjunction with profound inhibition of HBV replication and HBsAg production to attain immunological control have been suggested. 241 Combinations of antiviral therapy targeting multiple steps in the HBV lifecycle that suppress viral replication and viral antigen production and immune modulatory therapy to restore immune response to HBV will likely be needed to achieve the goal of a HBV 'cure'.…”

Vaccination contre l’hépatite B

“…Parmi les nouvelles molécules immunomodulatrices, les agonistes de TLR (Toll-like receptors) sont en cours d'essai (pour revue [42]). Leur combinaison avec les vaccins thérapeutiques et les molécules antivirales actuelles devraient permettre d'obtenir un contrôle soutenu et persistant du virus jusqu'au but final qui est l'élimination du virus du foie, de l'AgHBs du sérum, et la guérison [43]. ‡…”

Immune therapy for hepatitis B

“…Over time, more efficacious and safer NAs have been developed. These drugs are capable of (I) reducing or eliminating HBV DNA in sera; (II) inducing hepatitis B e antigen (HBeAg) negativity; (III) causing seroconversion to antibody to HBeAg (antiHBe); (IV) reducing or negativity of circulating HBsAg; (V) inducing production of antibodies to HBsAg (anti-HBs); (VI) ameliorating liver damage, and delaying progression to complications (such as LC and HCC) in some, but not all, patients with CHB (11)(12)(13)(14). However, long-term follow up revealed that treatment-induced HBeAg seroconversion with suppressed viral replication is not sustainable in considerable numbers of CHB patients.…”