2026 ECNP Congress

PS02-2120

Depressive symptoms following interferon-free direct-acting antiviral treatment in patients with hepatitis C: a systematic review and meta-analysis

Ana Pejcic — N. Djordjevic · University of Kragujevac, Faculty of Medical Sciences- Department of Pharmacology and Toxicology, Kragujevac, Serbia

2026 ECNP Congress

Introduction

Depression is a common extrahepatic manifestation of chronic hepatitis C virus (HCV) infection (≈24.5% prevalence), likely driven by neuroinflammatory processes, central nervous system involvement, and psychosocial factors [1]. Prior interferon-based treatment was strongly associated with psychiatric adverse effects, including the onset and worsening of depressive symptoms. Conversely, interferon-free direct-acting antiviral (DAA) regimens achieve high rates of sustained virologic response with improved tolerability, but their impact on depressive symptoms remains unclear, with studies showing reductions [2], increases [3], or no significant change [4] following treatment.

Objectives

To evaluate changes in depressive symptoms in patients with HCV infection following interferon-free DAA treatment and synthesize data from studies reporting continuous measures of depressive symptoms, comparing baseline (pre-treatment) scores with assessments during treatment, at the end of treatment (EOT), or during post-treatment follow-up.

Methods

Protocol of this systematic review and meta-analysis was registered in PROSPERO (CRD420261365752). PubMed/MEDLINE, Web of Science, Scopus, and SCIndeks were searched up to April 12, 2026, with additional backward and forward citation searching up to April 18, 2026. Eligible studies were original clinical studies of any design that assessed depressive symptoms using validated instruments at baseline (pre-treatment) and at least one follow-up time point in HCV patients receiving interferon-free DAA treatment. Data analysis was conducted using Meta-Essentials: Workbooks for meta-analysis (Version 1.5) [5]. Effect sizes were pooled using random-effects meta-analysis and expressed as Hedges’ g with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s Q test and I² statistics. Subgroup and moderator (meta-regression) analyses were conducted, where possible, to explore sources of significant heterogeneity. Sensitivity and publication bias analyses were also conducted.

Results

Twenty-five studies (24 non-randomized and one randomized) met eligibility criteria. Depressive symptoms significantly decreased from baseline to the longest available follow-up (25 studies, 4,393 participants; Hedges’ g = –0.48, 95% CI from –0.85 to –0.11), although significant heterogeneity (p<0.001, I²=96.78%) was observed and no publication bias was detected. No significant changes in depressive symptoms were observed during treatment, considering that 95% CI included zero (9 studies, 2,130 participants; Hedges’ g = –0.34, 95% CI from –0.69 to 0.00), nor at EOT (8 studies, 612 participants; Hedges’ g = –0.61, 95% CI from –1.44 to 0.22) with significant heterogeneity (p<0.001 for both; I²=95.43% and I²=97.83%, respectively). In contrast, a significant reduction in depressive symptoms was observed during post-treatment follow-up (18 studies, 3,191 participants; Hedges’ g = –0.61, 95% CI from –1.12 to –0.09), again with significant heterogeneity (p<0.001, I²=97.61%) but no indication of publication bias. Findings remained robust across sensitivity analyses, except for the outcome assessed during treatment. Meta-regression and subgroup analyses identified several potential sources of heterogeneity, including mean age, geographic region, and the proportions of treatment-naïve patients, patients with a psychiatric history, and those receiving ribavirin.

Conclusions

Depressive symptoms seem to decrease following interferon-free DAA treatment at longer follow-up, particularly post-treatment. However, these findings should be interpreted with caution due to substantial heterogeneity across studies and the predominantly observational nature of the included evidence, underscoring the need for well-designed prospective studies.

References

  1. Rose, S., Chakravarty, R., Sahoo, S., Premkumar, M., 2024. Chronic Hepatitis C Infection: Antivirals, Depression, and Anxiety, in: Martin, C.R., Preedy, V.R., Patel, V.B., Rajendram, R. (Eds.), Handbook of the Behavior and Psychology of Disease. Springer, Cham, 1–23.
  2. Danilescu, C.M., Sandulescu, D.L., Pirlog, M.C., Streba, C.T., Rogoveanu, I., 2021. Depressive and Anxious Symptoms in Hepatitis C Virus Infected Patients Receiving DAA-Based Therapy. Diagnostics (Basel) 11 (12), 2237.
  3. Khalil, M.A., Shousha, H.I., El-Nahaas, S.M., Negm, M.I., Kamal, K., Madbouly, N.M., 2021. Depression in patients with chronic hepatitis-C treated with direct-acting antivirals: A real-world prospective observational study. J. Affect. Disord. 282, 126–132.
  4. Gallach, M., Vergara, M., da Costa, J.P., Miquel, M., Casas, M., Sanchez-Delgado, J., Dalmau, B., Rudi, N., Parra, I., Monllor, T., Sanchez-Lloansí, M., Dosal, A., Valero, O., Calvet, X., 2018. Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C. PLoS One 13 (12), e0208112.
  5. Suurmond, R., van Rhee, H., Hak, T., 2017. Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis. Res. Synth. Methods 8 (4), 537–553.