Hepatitis delta virus (HDV) persists during liver regeneration by transmitting HDV RNA to dividing cells even in the absence of hepatitis B virus (HBV) coinfection. Therefore the strong persistence capacities of HDV may explain why HDV clearance is difficult to achieve in HBV/HDV chronically infected patients, according to study results published in Gut.1

HDV infection is associated with severe liver disease and progression to cirrhosis, liver decompensation, hepatocellular carcinoma, and death.2 HBV plays an essential role as a helper virus for HDV transmission, and HDV infection usually occurs either upon simultaneous coinfection with HBV or as a superinfection in individuals already infected with HBV.1 It has been shown that HDV can persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. Therefore, researchers evaluated the impact of cell proliferation on HDV persistence in vitro and in vivo. In vitro, they infected genetically labeled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma (HepG2) cells with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B. In vivo, cell proliferation was triggered by transplanting primary human hepatocytes isolated from HBV/HDV-infected humanized mice into naïve mice. They found that HDV endures cell division in vitro and in vivo, and that cell division leads to the clonal expansion of HDV-positive cell clusters. This mechanism enables HDV to propagate among daughter cells even in the absence of HBV coinfection and despite the presence of the entry inhibitor Myrcludex-B.  

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The researchers concluded that, “Taken together, the persistence capacity of HDV determined here and in previous studies highlights the importance to develop antivirals, which directly target HDV replication in combination with reinfection of human hepatocytes.”1

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1. Giersch K, Bhadra OD, Volz T, et al. Hepatitis delta virus persists during liver regeneration and is amplified through cell division both in vitro and in vivo. Gut. 2019;68:150-157.

2. Fattovich G, Giustina G, Christensen E, et al. Influence of hepatitis delta virus infection
on morbidity and mortality in compensated cirrhosis type B. The European Concerted
Action on Viral Hepatitis (Eurohep)
. Gut. 2000;46:420-426.