Search

Hepatitis B virus ( HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus ( HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti- HCV therapy and compared those between interferon ( IFN)-free direct-acting antiviral ( DAA) therapies and IFN-based therapies. Three hundred and twenty-two patients with HCV infection receiving anti- HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV- DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti- HBs positivity, changes in anti- HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN-free DAA therapies and 72 were treated with IFN-based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN-free DAA therapies, while no patient developed HBV reactivation after IFN-based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti- HBs titre to <12 mIU mL−1 by the end of treatment. The decline changes of anti- HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN-free DAA therapies. Low levels of anti- HBs and their decrease to <12 mIU mL−1 after treatment are significant risk factors for HBV reactivation or reappearance. [ABSTRACT FROM AUTHOR]

Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also be responsible for differences in the clinical outcome and response to antiviral treatment in different population groups. [ABSTRACT FROM AUTHOR]

The biological implications of substitutions L60V and I97L in the core (c) gene of hepatitis B virus (HBV) were investigated in order to determine whether they could change the immunogenicity of HBcAg or influence the immune response in mice. Three strains of recombinant adenoviruses– AdHBV-WT, AdHBV-L60V and AdHBV-I97L– containing wild-type or mutant HBV genomes were constructed using the AdEasy system and used to infect BALB/c mice intranasally. Infected mice produced anti-HBc efficiently to comparable levels. IgG1 and IgG2a specific for HBcAg were present in mice sera, and the response was dominated by IgG2a. The lymphocyte proliferative response specific for HBcAg was assessed by [3H]-thymidine uptake. We found that AdHBV-WT induced a stronger T-cell proliferation response than AdHBV-L60V and AdHBV-I97L. In conclusion, the L60V and I97L substitutions had no influence on humoral immune responses, but could downregulate T-cell responses to HBcAg, suggesting that L60V and I97L were immune escape mutants. [ABSTRACT FROM AUTHOR]

Hepatitis B is a serious disease that is endemic in many parts of the world. A significant proportion of patients with chronic hepatitis B (CHB) are infected with a variant form of the hepatitis B virus (HBV) which decreases or abolishes the production of hepatitis B e-antigen (HBeAg). The purpose of this literature review is to describe the epidemiology of HBeAg-negative CHB (e-CHB) worldwide. A literature search was conducted to identify studies pertaining to e-CHB and underlying variants (precore and core promoter). Fifty studies were included in our analysis. The median prevalence of e-CHB among patients with chronic HBV infection was 33% in the Mediterranean, 15% in Asia Pacific, and 14% in the USA and Northern Europe. The pre core stop codon variant was detected in a median of 60% (range 0–100%) of HBeAg-negative patients overall, 92% in the Mediterranean, 50% in Asia Pacific and 24% in the USA and Northern Europe. There were very few data on the prevalence of core promoter variants outside Asia where the median prevalence among HBeAg-negative patients was 77%. This literature review revealed that e-CHB is more common than previously suspected and that it is present worldwide with marked variations in the prevalence of associated HBV variants across different geographical regions. Additional research using population based samples of adequate size based on a consensus definition of e-CHB and using standardized HBV DNA assays is needed to better estimate the true prevalence of e-CHB and its associated HBV variants. [ABSTRACT FROM AUTHOR]

Chronic hepatitis due to pre-core hepatitis B virus (HBV) mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). HBeAg-negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with pre-core stop codon mutation at nucleotide 1896 (mainly selected in non-A HBV genotypes), but also with other pre-core changes or with mutations in the basic core promoter region (mainly in HBV genotype A). In chronic HBV infections, pre-core mutants can be detected both in patients with HBeAg-negative CHB and in inactive hepatitis B surface antigen (HBsAg) carriers. The diagnosis of HBeAg-negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased alanine aminotransferase (ALT) and serum HBV-DNA levels and exclusion of other causes of liver disease. The differential diagnosis between patients with CHB and inactive HBsAg carriers can be made only by close follow-up of aminotransferase activity and viraemia levels, although the cut-off level of serum HBV DNA has not been definitely determined. IgM anti-HBc levels have also been suggested as an index that increases the diagnostic accuracy for transient hepatitis flares, while liver biopsy confirms the diagnosis and evaluates the severity of the liver disease. Interferon-α (IFN-α) and lamivudine are the two drugs that have been tried, mainly in the management of HBeAg-negative CHB. A 12-month course of IFN-α achieves sustained biochemical remission in about 20% of patients, which has been associated with improvement in the long-term outcome of this subset. A 12-month course of lamivudine is rather ineffective, maintaining remission in less than 15% of patients after cessation of therapy. Long-term lamivudine is associated with progressively increasing rate of virological and subsequent biochemical breakthroughs due to YMDD mutants, with approximately 30%... [ABSTRACT FROM AUTHOR]