Interferon Therapy of Chronic Hepatitis B

Abstract

Chronic hepatitis B (CHB) results from the inability of the host's immune system to control viral replication. Interferon-α (IFN-α) therapy can convert CHB into inactive hepatitis B virus (HBV) infection in 20-30% of the treated patients. In spite of the low response rate, IFN-α therapy has the advantage of having a limited duration and being effective even after therapy, as demonstrated by a much higher incidence of HBsAg clearance in responders to IFN-α than in naturally occurring inactive HBsAg carriers. IFN-α has multiple antiviral, antiproliferative, and immunomodulatory activities and targets: cellular genes (IFN-stimulated genes) activating different pathways of antiviral defense in infected and noninfected cells, HBV replication blocking the RNA-containing core particle formation and accelerating their decay, degrading pregenomic RNA, and modulating the nuclear viral minichromosome (covalently closed circular DNA) activity by targeting its epigenetic regulation and both innate and adaptive immune response. The interference of viral heterogeneity and genetic polymorphisms of the host on IFN-α susceptibility is under investigation. Only a better understanding of the complex interplay between the different activities of IFN-α would warrant the amelioration of current therapeutic strategies and the design of new therapeutic approaches. The study of on-treatment dynamics of HBV infection by means of combined quantitative monitoring of serum HBV DNA and HBsAg warrant tailoring treatment at the single-patient level and can help to make treatment more cost-effective by using the different combinations of currently available antivirals, including IFN, more appropriately. Integrated molecular and clinical knowledge in a systems medicine fashion is mandatory to further improve antiviral therapy in CHB.

Prediction model for sustained hepatitis B e antigen seroconversion to peginterferon alfa‐2a in chronic hepatitis B

“…The CHB patients in this study were mostly infected with HBV genotype B or C, but response rates did not differ significantly between genotype groups. Using multivariable logistic regression analysis, previous studies found no significant differences among CHB patient genotypes despite trends suggesting that genotype B may have a slightly better response to PEG‐IFN therapy than genotype C . Therefore, single parameters were of limited value for predicting HBeAg seroconversion or HBsAg loss and guiding decisions about initiating PEG‐IFN therapy.…”

Hepatitis regulation by the inflammasome signaling pathway

“…This study demonstrates that AIM2 is associated with an HBV‐clearing immune response and that during chronic HBV this component of the immune response is likely dampened. Of interest is that type‐1 interferon treatment of HBV‐infected patients can lead to reduced or permanent elimination of HBV replication . However, in most patients treated with IFN‐α, the effect is transient, and patients show exacerbated hepatitis in the end.…”

Interactome Map Reveals Phospholipid Scramblase 1 as a Novel Regulator of Hepatitis B Virus X Protein

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 IFN-α has been used for the treatment of HBV infection for two decades. 45 IFN-α belongs to the IFN-α/β system, which mediates antiviral, antiproliferative, immune, and other cellular effects.…”