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Chronic hepatitis B (CHB) puts 250 million people or more at a greatly increased risk to develop terminal liver disease.1 The causative agent, hepatitis B virus (HBV), is a small hepatotropic DNA virus that replicates via reverse transcription.2 Persistence of infection is the combined result of an inadequate host immune response3 and the stability of a special episomal form of the virus genome termed covalently closed circular (ccc) DNA.4 5 Associating with host and viral proteins into a minichromosome, cccDNA serves as template for all viral RNAs and thus progeny virions (figure 1). A true cure of CHB would thus require elimination of cccDNA from a patient’s liver; this is rarely achieved by current CHB therapies with type I interferon or nucleos(t)ide analogues (NAs) which inhibit HBV reverse transcription. Also, none of the new anti-HBV drugs in clinical development,6 including entry inhibitors such as Myrcludex-B (Myr-B)7 which block the interaction between HBV and its receptor Na+-taurocholate cotransporting polypeptide (NTCP; figure 1), directly target cccDNA. Not even recovery from acute self-limited hepatitis B appears to eradicate all cccDNA molecules although their number (corresponding to at least the ~1010 infected hepatocytes at the peak of infection) is massively reduced by the immune system within a few weeks,3 mostly with fully maintained liver function.
Contributors MN devised and wrote the article.
Funding The author acknowledges funding by the Infect-ERA project hepBccc and by the Deutsche Forschungsgemeinschaft through the Transregional Collaborative Research Center TRR179.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
Correction notice This article has been corrected since it published Online First. Figure 1 has been corrected.
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