Pegylated IFN-α, despite a finite duration of therapy, has a substantial adverse event profile, and patients struggle to stay on treatment for the full 48 weeks. In contrast, NAs require long-term therapy, perhaps lifelong, in order to achieve the benefits outlined above. This

is because Selleck Fulvestrant the NAs have little effect on the virological goal of eradicating HBV covalently closed circular DNA (cccDNA) from infected hepatocytes and markers of active viral replication, including HBV DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), leading to a key endpoint for achieving cure through HBsAg antibody (anti-HBs) seroconversion. Recent mathematical modeling has estimated the time to HBsAg loss/anti-HBs seroconversion with the existing NAs at over 30 years.2 Thus, problems of compliance and resistance, even with the most potent NAs, will almost certainly emerge. In the human immunodeficiency virus (HIV)-1/acquired immune deficiency

syndrome (AIDS) treatment armamentarium, there are over 20 drugs from six major classes3 directed against multiple targets in the HIV life cycle,4 including entry, enzyme action, assembly, and release. These drugs are used very effectively in synergistic combinations that form the basis of successful highly active antiretroviral therapy regimens.5 From this level of control of active HIV replication, patients can be expected to have a normal lifespan, and HIV-AIDS researchers are preparing new strategies to eradicate Bumetanide HIV from the infected host. This goal has been given the PXD101 mouse highest priority by national funding agencies. In contrast, in the hepatitis B treatment arena, more drugs targeted to other parts of the viral life cycle are desperately needed if HBV control and eradication are to be achieved. Fortunately, the news from the front line in the battle against HBV and its satellite virusoid, hepatitis

delta virus (HDV), is encouraging. aa, amino acid; AIDS, acquired immune deficiency syndrome; anti-HBs, HBsAg antibody; cccDNA, covalently closed circular DNA; CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HDV, hepatitis delta virus; HIV, human immunodeficiency virus; IFN-α, interferon-α; NA, nucleos(t)ide analogue; NTCP, sodium taurocholate cotransporting polypeptide. In this issue of HEPATOLOGY, two papers from the University Hospital Heidelberg group led by Stephan Urban report some critical next steps.6, 7 The investigators focused on early events, both in vitro and in vivo, in the HBV life cycle, namely attachment followed by specific binding to a receptor usually expressed on the cell surface. These steps account for the striking host species specificity (humans, higher primates, and Tupaia belangeri) and tissue tropism (liver) of HBV.