Effects of antiviral therapy on the cellular immune response in patients with chronic hepatitis B

Abstract

Abstract.A weak T-cell immune response to the hepatitis B virus (HBV) is hypothesized to be the primary cause of chronic HBV infection. Emerging evidence suggests that long-term effective antiviral therapy restores the HBV-specific T-cell response from exhaustion. However, the extent to which the cellular immune response can be restored following the persistent suppression of HBV replication by antiviral therapy remains unclear. In order to investigate this question, 46 patients with chronic hepatitis B (CHB) treated with nucleos(t) ide analogues who demonstrated persistent suppression of HBV replication [defined as undetectable HBV DNA, hepatitis B e antigen (HBeAg) negative and adherence to antiviral therapy], 22 untreated CHB patients, 15 patients with acute hepatitis B (AHB) and 10 healthy adults were recruited. HBV-specific interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay and HBV-specific T-cell proliferation analysis were performed with a panel of overlapping peptides covering the envelope and core antigens. Data from this study showed that the HBV-specific immune responses to the peptide pools of the envelope and core protein in the treated patients were stronger than those in the untreated CHB patients, but significantly weaker than those in the AHB patients and healthy adults. A higher frequency of response to S than C peptide pools was confirmed by the IFN-γ ELISPOT assay in the treated CHB patients. The restoration of antiviral immunity was clearly associated with a reduction in HBV DNA and the duration of HBV DNA suppression. In conclusion, the HBV-specific immune responses in the CHB patients can be significantly restored from exhaustion following the persistent suppression of HBV replication as a result of antiviral treatment with nucleos(t)ide analogues.

Slow reduction of IP-10 Levels predicts HBeAg seroconversion in chronic hepatitis B patients with 5 years of entecavir treatment

“…Furthermore, during last 4 years of the 5 year post-ETV treatment, only IL-4, IL-6 and MIP-1α continued to decrease, while other factors increased to varying degrees. This implies the host immune response varies with the stages of chronic HBV infection and exhibits diverse processes during the antiviral treatment30.…”

Survival Disparity Between Antiviral-Treated and Antiviral-Naïve Patients Who Develop Their First HBV-Associated Hepatocellular Carcinoma

“…al. demonstrated that in CHB patients, antiviral therapy restored these HBV-specific immune responses, and subsequently suppressed HBV replication [30]. However, it is unclear if this immune reconstitution may inadvertently contribute to the progression to HCC in certain individuals due to dysfunctional inflammatory responses causing DNA damage, genomic instability, etc.…”

Expression of PBMC apoptosis-related factors in patients with chronic hepatitis B and their relationships with clinical prognosis

“…Gene type, virus load and immune response function are important factors in HBV infection and chronicity. Therefore, the reduction of immune response function is the main reason of continuous replication of HBV in the body and the increasing viral load ( 4 ). Peripheral blood mononuclear cells (PBMC) play an important role in the process of antiviral immune response, and excessive apoptosis of PBMC after viral infection leads to the reduction of the bodys antiviral immune response function and an increase of virus load ( 5 , 6 ).…”