To explore the predictive role of serum quantitative HBsAg in predicting treatment response towards IFNα-1b in hepatitis B e antigen-positive chronic hepatitis B patients.
Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type-I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative forhepatitis B surface antigen.
Conclusion: These findings highlight a host gene, UBE2L3, contributing to the susceptibility to persistent HBV infection; UBE2L3 may be involved in IFN-mediated viral suppression and serve as a potential target in the prevention and treatment of HBV infection.
The use of IFNs for the treatment of viral infectious diseases on their antiviral activity may become an important therapeutic option, for example, IFN-α is well known for the successful treatment of hepatitis B and C virus infections, and interest is increasing in the antiviral efficacy of other novel IFN classes and their potential applications.
In lamivudine-naive patients, abatement of HBV DNA<10(3) copies/ml by pretreatment with PEG-IFN-alpha2a completely prevents the emergence of YMDD mutants after 24 months of lamivudine monotherapy.
However, these sustained response rates can be significantly increased by carefully selecting candidates for PEG-IFN therapy based upon baseline ALT and HBV DNA levels, viral genotype and IL28B polymorphisms, by extending PEG-IFN therapy beyond 48 weeks and, most importantly, by applying early on-treatment stopping rules based upon HBsAg kinetics.
In summary, our study suggests that HBV precore protein, specifically the p22 form, impedes JAK-STAT signaling to help the virus evade the host innate immune response and, thus, causes resistance to IFN therapy.<b>IMPORTANCE</b> Chronic hepatitis B virus (HBV) infection continues to be a major global health concern, and patients who fail to mount an efficient immune response to clear the virus will develop a life-long chronic infection that can progress to chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma.
The choice of patients with higher chance of sustained response (SR) to PEG-IFN can be made with pre-treatment and on-treatment factors; recent studies evidenced the role of early drop of serum hepatitis B surface antigen (HBsAg) as predictor of SR.
In the cell-culture-based HBV infection models, the sensitivity of HBV to IFN-α in hepatocytes is determined more by the cell-intrinsic IFN response than by viral genotype, and improvement of the IFN response in HepG2-NTCP cells promotes the efficacy of IFN-α against HBV.(Hepatology 2018;67:1237-1252).
Identifying the key negative factors and elucidating the regulating mechanism are essential for improving anti-HBV (hepatitis B virus) efficacy of IFNα.
Hepatitis B surface antigen (HBsAg) decline was significantly associated with elevated CD86<sup>+</sup> pDC% (r = 0.348, P = 0.015) during PEG-IFN-α-2a treatment.
A total of 257 patients with chronic HBV, treated with PEG-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL).
Endogenous HBV-CpG ODNs from the HBV genome induce IFN-α production so that nanoparticle-encapsulated HBV-CpG may act as an HBsAg vaccine adjuvant and may also represent a potent therapeutic agent for the treatment of chronic HBV infection.
The content of HBV DNA in the supernatant of co-cultivation of HepG2.2.15 cells and PBMCs without stimulated materials was higher than that stimulated by HBcAg and IL-18 at various concentrations of HBcAg and IL-18 together with IL-12/IFN-alpha 1b.
Among children with hepatitis B envelope antigen-positive genotype C chronic HBV infection, we compared the efficacy of combination therapy with nucleotide analogues and IFN-α in 11 children with 12 historical cases treated with IFN monotherapy.