Unconventional T cells in chronic hepatitis B patients on long‐term suppressive therapy with tenofovir followed by a Peg‐ IFN add‐on strategy: A randomized study

Summary HBV eradication in chronic hepatitis B ( CHB ) subjects is rarely achieved with either nucleos(t)ide analogues ( NA ) or pegylated interferon (Peg‐ IFN ), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long‐term treatment with tenofovir ( TDF ) and HBV suppression were enrolled and randomized 1:2 to either receive Peg‐ IFN ‐α‐2a add‐on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsA g occurred in the add‐on group compared with the NA group at W12 ( P  = .016) and at W24 ( P  = .012). A decline of qHBsA g ≥0.5 log 10 at week 24 occurred in 4 of 10 patients in the add‐on arm and 1 of 20 in the NA arm, respectively ( P  = .03). HB sAg loss was seen in 20% of subjects in the add‐on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT ( P  = .03) and γδ T cells ( P  = .03) as well as fewer γδ T cells expressing Vδ2 T‐cell receptors ( P  = .005). No changes in unconventional T‐cell frequency and function were shown in both add‐on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB . Despite a greater qHBsA g decline of add‐on patients, our data failed to detect any effect of Peg‐ IFN treatment on unconventional T cells.