Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

Abstract

I nfection with hepatitis B virus (HBV) causes acute and chronic hepatitis and is strongly associated with the development of cirrhosis and hepatocellular carcinoma. Immediately after infection of hepatocytes, the viral DNA is transferred to the nucleus, where the viral polymerase is removed, and the double-stranded, open circular DNA is converted to a covalently closed circular DNA molecule (cccDNA). During chronic HBV infection (CH-B), cccDNA accumulates in hepatocyte nuclei, apparently at a level of about 5-50 copies per cell, where it persists as a minichromosome and functions as the template for the transcription of viral genes. 1 The RNA pregenome, in addition to producing capsid and polymerase proteins, becomes encapsidated and is reverse-transcribed. A particularity of the hepadnavirus life cycle is that DNA-containing nucleocapsids can either recycle back to the nucleus to amplify and maintain the pool of cccDNA or become enveloped and secreted into the blood, where new viral particles can spread to other hepatocytes. 2,3 Because cccDNA is the transcriptional template of the virus, it is required for maintenance of HBV infection.Evidence from the woodchuck hepatitis virus system indicated that the pool of cccDNA persisted even when viral production was strongly reduced by the presence of nucleoside analogues. 4,5 Woodchuck studies 6,7 and recent

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

“…4,6,9 Furthermore, for the most part, the available data were not derived from independent studies but were incorporated into studies in which either a combination was used or a comparison with PEG-IFN was made. 7,[10][11][12]14,29 Therefore, the data in this study are valuable because the clinical significance of serial qHBsAg was systematically analyzed in patients treated with ETV as a first-line therapy for CHB.…”

“…8,9 To date, the potential role of qHBsAg in antiviral therapy monitoring has been studied largely in patients receiving pegylated interferon (PEG-IFN). [10][11][12] Moucari et al 13 reported that an early drop in qHBsAg was highly predictive of a sustained virological response (SVR) in HBeAg(À) patients. This was similar to the results obtained by Brunetto et al, 14 who found that an on-treatment decline of qHBsAg was significantly associated with sustained HBsAg clearance.…”

Should chronic HBV infected patients with normal ALT treated: debate

“…However, it has been postulated that with prolonged suppressive therapy, cccDNA may become depleted through natural cell division and cell death [36]. Studies with each of the available nucleos(t)ide therapies-lamivudine [37], adefovir [38], and entecavir [39] and combination treatment with pegylated interferon alpha-2b and adefovir dipivoxil [40] have supported this concept.…”

Controversies Regarding the Hepatitis B Immune Globulin Prophylaxis (HBIG) for Liver Transplantation Recipients

“…Neff et al [13] found that none of the 51 patients with undetectable HBV DNA pre-LT experienced evidence of HBV viral recurrence post-LT regardless of the different prophylactic strategy [30,50] . However, following studies showed that suppression of HBV-DNA in serum does not indicate clearance of the virus from hepatocytes [46,66] and the long half-life of cccDNA in reinfected hepatocytes is responsible for viral recurrence following OLT [67][68][69][70][71] . Therefore, the authors suggested the complete withdrawal of prophylaxis with caution.…”