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In the past decade, different modalities of antiviral therapy have been adopted aimed at eradicating hepatitis C virus infection. Initially, interferon was used in monotherapy, then interferon combined with ribavirin and amantadine. Recently, interferon has been conjugated with polyethylene glycol to allow optimization of its pharmacokinetic properties and to improve its antiviral activity. This study focused on the characteristics of the skin reactions that we observed in 27 patients with naïve hepatitis C who received polyethylene glycol interferon-ribavirin-amantadine or polyethylene glycol interferon-ribavirin and in 10 previous non-responders to interferon monotherapy who were retreated with triple therapy. In 9 patients (7 on triple therapy) dermatitis-like lesions were observed, and in 5 the severity of the lesions necessitated withdrawal from therapy.

ABSTRACT— It was our aim to evaluate whether the baseline activity of 2–5 oligoadenylate synthetase (2–5 OAS) in serum and changes induced by the treatment with interferon are relevant factors in remission of chronic hepatitis C. Seventeen out of 30 adult patients with chronic hepatitis C were randomized to receive recombinant alpha‐2b interferon at the dosage of 3 MU three times weekly. By the end of the third month, nine patients had normalized transaminase levels and continued to receive 3 MU of interferon for an additional 3 months, whereas in eight non‐responders the dosage was increased to 6 MU for the same period of time. A single patient responded to the increased dosage. Baseline 2–5 OAS serum activity was significantly higher in patients with chronic hepatitis when compared with normal controls. Follow‐up on the 13 untreated cases showed that 2–5 OAS elevation was stable and unrelated to concomitant infections. Comparison of responders and non‐responders showed that the latter had higher baseline 2–5 OAS activity, tended to have an earlier and higher peak in the enzyme during the first 4 weeks of treatment, and maintained higher levels during the first 3 months of therapy. The increased dosage of interferon in this group led to an additional, although temporary, increase in 2–5 OAS. Our data suggest that HCV infection by itself induces elevated 2–5 OAS levels. The paradoxical increase in non‐responders indicates that monitoring of the enzyme in serum does not predict the response to interferon. The role of the 2–5 OAS pathway in inducing the antiviral state in HCV infection should be further evaluated at tissue level.

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INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.