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Interferon-treated HDV may impact natural killer cells

Chronic hepatitis delta virus-infected patients being treated with pegylated interferon-alfa therapy may experience a change in natural killer cell subsets, according to data from a recent study.

Researchers conducted an analysis of natural killer (NK) cells in 31 chronically hepatitis delta virus (HDV)-infected patients before and during treatment with interferon-alfa-2a (IFN-a), then compared the results with 15 patients with hepatitis B virus (HBV) mono-infection and 49 healthy controls. To measure IFN-a responsiveness associated with NK cell differentiation, 20 healthy donors — 10 with immature and 10 with terminal NK cell phenotypes — were used. Researchers used multicolor flow cytometry to identify major NK cell subsets in peripheral blood mononuclear cells (PBMCs) from all patients.

According to the results, untreated HDV-infected patients experienced a higher than normal frequency of NK cells in peripheral blood with unaltered phenotypic NK cell differentiation status. Long-term IFN-a treatment of HDV-infected patients, however, affected NK cell differentiation status, with selective loss of terminally differentiated NK cells and relative enriched immature NK cell subsets. High frequency of CD56 NK cells at baseline had a positive association with IFN treatment outcomes. The percentage of total NK cells was greater in HDV-infected patients (13.8%) compared with healthy controls (9.8%). The frequency of CD56dim NK cells was higher in patients, whereas an increase was seen for the CD56 NK cell subset compared with healthy controls. No differences in frequency of CD56dim CD16dim NK cells were observed between healthy controls and patients with either HBV mono-infection.

“We report that chronic untreated hepatitis delta, as well as prolonged antiviral treatment with peg-IFN-a has a significant effect on NK cell frequencies, differentiation status, and function, and switches intracellular signaling from STAT4 to STAT1,” researchers said. “Furthermore, high levels of CD56dim NK cells at baseline were positively associated with treatment outcome. Given the severity of chronic hepatitis delta compared with other chronic viral hepatitis infections, more studies on the immunopathogenesis of this disease are clearly warranted.”

Disclosure: The researchers report no relevant financial disclosures.