Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis

Leina S Alrabadi, Anne Dutton, Anahita Rabiee, Scott J Roberts, Yanhong Deng, Laura Cusack, Marina G Silveira, Maria Ciarleglio, Richard Bucala, Rajita Sinha, James L Boyer, David N Assis, Leina S Alrabadi, Anne Dutton, Anahita Rabiee, Scott J Roberts, Yanhong Deng, Laura Cusack, Marina G Silveira, Maria Ciarleglio, Richard Bucala, Rajita Sinha, James L Boyer, David N Assis

Abstract

Background & aims: Psychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators.

Methods: The perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded.

Results: Seventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks.

Conclusions: MBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH.

Clinical trials registration: This study is registered at ClinicalTrials.gov (NCT02950077).

Lay summary: Autoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis.

Keywords: AIH, autoimmune hepatitis; ALT, alanine aminotransferase; Autoimmune hepatitis; BSCS, brief self-control scale; Cytokines; MBSR; MBSR, mindfulness-based stress reduction; MIF, macrophage migratory inhibitor factor; PSS, perceived stress scale; Psychological stress; REDCap, research electronic data capture; SRRS, social readjustment rating scale; Stress reduction; ULN, upper limits of normal.

Conflict of interest statement

The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

© 2022 The Author(s).

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Individual participant data throughout the study. Perceived stress survey and brief self-control scale scores, alanine aminotransferase (ALT), and prednisone doses by study participants at baseline, completion of mindfulness-based stress reduction (8 weeks), and follow-up at 8 months and 1 year.
Fig. 2
Fig. 2
Impact of mindfulness-based stress reduction on quality of life measures. (A) Median perceived stress survey (PSS) and brief self-control scale (BSCS) scores at given time intervals. (B) PSS and BSCS scores for study participants in biochemical remission at baseline. (C) PSS and BSCS scores for study participants with active autoimmune hepatitis at baseline. Non-parametric Wilcoxon signed rank test.
Fig. 3
Fig. 3
Impact of mindfulness-based stress reduction on disease activity. (A) Median alanine aminotransferase (ALT) change at given time points for study participants with elevated ALT at baseline, and median prednisone use change at given time points. (B) ALT and prednisone changes in study participants in biochemical remission at baseline. (C) ALT and prednisone changes for study participants with active autoimmune hepatitis at baseline. Non-parametric Wilcoxon signed rank test.
Fig. 4
Fig. 4
Impact of mindfulness-based stress reduction (MBSR) on peripheral cytokine levels. (A) Peripheral blood levels of cytokines IL-23, IL-17, IL-10, IL-8, IL-6, CD74 and MIF (represented as the CD74/MIF ratio) measured at baseline and post-MBSR (8 weeks). (B) Cytokine levels for study participants in biochemical remission at baseline. (C) Cytokine levels for study participants with active autoimmune hepatitis at baseline. Non-parametric Wilcoxon signed rank test.

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