Add-on of pegylated interferon alpha–2a (PEG-IFN) triggers antigen-independent TNF-alpha production by CD4+ T cells in patients with pretreated chronic hepatitis B

αααHepatitis B virus surface antigen (HBsAg) to anti-HBs seroconversion is considered to be the ultimate goal of chronic hepatitis B treatments. Unfortunately, this goal is rarely achieved with the currently available therapeutic approaches. In a pilot study we evaluated the effect of add-on PEG-IFN (given in a standard dose) after HBV replication had been controlled by nucleos(t)ide analogue therapy in a cohort of 12 patients. We analysed HBsAg seroconversion and the induction of HBV-specific T cell responses.Peripheral blood mononuclear cells were isolated at week 0, 4, 8, 12, and 24 of PEG-IFN therapy. Quantity and quality of circulating HBsAg- and HBcAg-specific CD4+ and CD8+ T cells was analyzed by 10-parameter flow cytometry. During PEG-IFN add-on, a continuous decline of HBsAg was observed in 2 patients followed by anti-HBs seroconversion. Quantity of circulating HBsAg- and HBcAg-specific CD4+ and CD8+ T cells increased within the first 12 weeks of PEG-IFN treatment in several patients but HBV-specific T cell responses did not correlate with HBsAg seroconversion. Other anti-viral T cell responses (CMV-, EBV-, Influenza-specific) remained unchanged in quality and quantity.Unexpectedly we found an exceptionally high antigen-independent increase of TNF-α production by CD4+ T cells (median 1.8% of total CD4+ T cells during vs. 0.25% prior to PEG-IFN) with a peak between week 4 and 8. Particularly this observation held true for patients with treatment failure. Interestingly the 2 HBsAg seroconverters had significantly lower numbers of TNF-α producing CD4+ T cells in the early phase of treatment. In conclusion, neither quantity nor quality of peripheral HBsAg- and HBcAg-specific T cells can be used as an indicator for treatment-induced HBsAg seroconversion. Further investigations are mandatory to clarify whether antigen-independent TNF-α production may represent a predictor for treatment failure in this setting.

HBV - PEG-IFN - TNF