Dammermann W, et al. – In chronic hepatitis C (CHC) patients, autoantibodies against inosine–5'–monophosphate–dehydrogenase–2 (IMPDH2; “rods and rings” pattern) develop under treatment with peg–interferon (IFN) and ribavirin (RBV), an inhibitor of IMPDH2. This work was planned to assess the influence of the alternative therapy with direct–acting antivirals (DAA)/ribavirin on anti–IMPDH2 autoantibody generation and the use of anti–IMPDH2 development as a marker for therapy outcome (sustained virologic response, SVR). CHC genotype 1 (GT1) patients treated with IFN/first–generation DAA/RBV developed anti–IMPDH2 autoantibodies comparable to previous studies including patients under IFN/RBV therapy. Anti–IMPDH2 titers proved not useful as a marker for therapy outcome in CHC GT1 patients.

Methods

• Authors undertook analysis of a “real life” cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/first–generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV–treated CHC GT1 patients.
• First–generation DAA included boceprevir (BOC) or telaprevir (TPR).
• They tested serum autoantibodies by indirect immunofluorescence (IFA) using recombinant IMPDH2 expressing HEK293 cells and native HEp2–cells as substrates.

Results

• During therapy, 64/163 (39%) CHC patients turned anti–IMPDH2 positive, but only 43/163 (26%) indicated “rods and rings” structures in addition.
• Anti–IMPDH2 negative results were obtained in 99/163 (61%) patients.
• In this study, 53/104 (51%) CHC patients receiving IFN/DAA/RBV therapy were anti–IMPDH2 positive and 38/104 (37%) were in parallel anti–“rods and rings” positive.
• There appeared no significant association of HCV clearance/SVR rate after IFN/DAA/RBV therapy and anti–IMPDH2 status.