Mechanism of viral persistence and resistance to nucleoside and nucleotide analogs in chronic Hepatitis B virus infection

Abstract

To cite this version:

Selection of a Multiple Drug-Resistant Hepatitis B Virus Strain in a Liver-Transplanted Patient

“…Due to the spontaneous error rate of the viral polymerase and the accumulation of viral genome mutations during the natural history of infection, the viral quasi-species may undergo significant changes under the selective pressure of antiviral therapy with the selection of drug resistant mutants 8 .…”

The half-life of hepatitis B virions

“…10 Adefovir interferes with the priming of reverse transcription as well as elongation of the viral minus strand DNA. 11 The rate of inhibition of these drugs is concentration dependent, 10 and as with HIV, the ability to block full maturation of capsids is dependent on the length of the remaining second-strand DNA piece required for production of mature capsids competent for envelopment and secretion. 12 This explains why de novo production of HBV virions under lamivudine and adefovir is almost completely suppressed whereas prevention of initial cccDNA formation through repair of the 200-base gap is limited.…”

Management of Chronic Hepatitis B: An Overview of Practice Guidelines for Primary Care Providers

“…This is because of the presence of covalently closed circular HBV DNA (cccDNA) inside the nuclei of infected hepatocytes, which is the stable genetic component of HBV that may persist even after HBsAg loss has occurred, thereby allowing HBV reactivation. 21,55 Thus, even with consolidation therapy, HBV recurrence is frequent, with ϳ40% to 80% of patients experiencing virologic relapse after stopping therapy. 56 -61 Therefore, in clinical practice, a considerable proportion of patients will require long-term, if not indefinite, treatment with NUCs to maintain these end points and prevent HBV reactivation.…”

“…55,72,73 Current antiviral therapies target the synthesis of serum HBV DNA but not cccDNA 21 ; however, there is evidence suggesting that cccDNA levels can also be reduced to some degree with NUCs, 74 -76 but more studies are needed to confirm these findings. Combination therapy plus IFNs and NUCs may result in a greater reduction in cccDNA levels, 77 possibly as a result of an immune-modulatory attack of infected hepatocytes.…”