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.
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.
Identifying the key negative factors and elucidating the regulating mechanism are essential for improving anti-HBV (hepatitis B virus) efficacy of IFNα.
Inhibition of miR-3613-3p decreased relative expressions of IFN-α and IFN-β, HBV DNA copies, and increased the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels, whereas miR-3613-3p overexpression reversed these changes in vitro and in vivo.
In this study, 74 patients with chronic HBV infection who had virological responses to 180 μg/week Peg-IFNα-2a treatment were included; 38 (20 and 18 HBeAg positive and negative, respectively) of these patients were treated with 245 mg/day TDF, and 36 (20 and 16 HBeAg positive and negative, respectively) were treated with 0.5 mg/day ETV upon relapse after initial treatment discontinuation.
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 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).
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.
The largest reduction was observed in mice given NVR3-778 + peg-IFN; in all mice in this group, the serum level of HBV DNA was below the limit of quantification.
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).
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.
The inclusion criteria for patients were as follows: (1) treatment-naive and treated with PEG IFN-α/RBV, (2) HCV RNA was present in serum for over 6 months before treatment, (3) negative forhepatitis B (HBV) or HIV infection and (4) lacked any other hepatic diseases.All participants in this study were Chinese Han population and infected with HCV genotype 1b and treated with subcutaneous PEG IFN-α at a dose of 180 µg once a week with the addition of 800-1000 mg/d RBV according to weight orally for 48 weeks.
No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively).
A one-year course of Peg-IFN has the advantage of providing immune-mediated control of the hepatitis B virus (HBV) infection, the possibility of achieving a sustained off-treatment response in nearly 30% of the patients and ultimately, HBsAg loss in approximately 30%-50% of the latter patients during long-term off treatment follow-up.
Standard treatment in HBV infection includes IFN-α, nucleoside, or nucleotide analogs, which has direct antiviral activity and immune modulatory capacities.