Abstract
Over 257 million individuals worldwide are chronically infected with the Hepatitis B Virus (HBV). Nucleos(t)ide analogues (NAs) are the first-line treatment option for most patients. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both potent, safe antiviral agents, have a high barrier to resistance, and are now off patent. They effectively suppress HBV replication to reduce the risk of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Treatment is continued long-term in most patients, as NA therapy rarely induces HBsAg loss or functional cure. Two diverging paradigms in the treatment of chronic hepatitis B have recently emerged. First, the public health focussed “treat-all” strategy, advocating for early and lifelong antiviral therapy to minimise the risk of HCC as well as the risk of HBV transmission. In LMICs, this strategy may be cost saving compared to monitoring off treatment. Second, the concept of “stopping” NA therapy in patients with HBeAg-negative disease after long-term viral suppression, a personalised treatment strategy aiming for long-term immune control and even HBsAg loss off treatment. In this manuscript, we will briefly review the current standard of care approach to the management of hepatitis B, before discussing emerging evidence to support both the “treat-all” strategy, as well as the “stop” strategy, and how they may both have a role in the management of patients with chronic hepatitis B.
Highlights
More than 257 million people, or 3.2% of the world’s population, are estimated to be living with chronic hepatitis B infection (CHB) [1,2]
Treatment for CHB is currently recommended for people with high Hepatitis B Virus (HBV) DNA levels in blood, in combination with evidence of hepatic necro-inflammation and/or moderate-advanced hepatic fibrosis (Table 1) [4,5,7]
The recent observation that the rate of incident hepatocellular carcinoma (HCC) starts to fall after 5 years of nucleot(s)ide analogues (NAs) therapy and that the benefit increases over time, suggests that longer duration of therapy is required to achieve maximum risk reduction
Summary
More than 257 million people, or 3.2% of the world’s population, are estimated to be living with chronic hepatitis B infection (CHB) [1,2]. TDF and ETV are highly effective, well tolerated, and have a high genetic barrier to resistance In this context, there is an emerging argument for starting NA therapy early in the immunotolerant phase of disease, to suppress HBV replication and minimise the long-term risk of HCC. The recent observation that the rate of incident HCC starts to fall after 5 years of NA therapy and that the benefit increases over time, suggests that longer duration of therapy is required to achieve maximum risk reduction It raises the important question of whether starting treatment earlier than currently recommended by guidelines might improve clinical outcomes.
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