An optimized short‐term steroid therapy for chronic drug‐induced liver injury: A prospective randomized clinical trial

Huang, Ang; Zhu, Yun; Liu, Shuhong; Sun, Ying; Liu, Zherui; Liang, Qing‐sheng; Zhao, Jun; Chang, Bin‐xia; Bi, Jing‐feng; Liu, Jiang‐tao; Zhai, Xing‐ran; Xie, Huan; Li, Ning; Tian, Hui; Han, Lin; Zhuang, Yingjie; Ma, Hongbin; Teng, Guang‐ju; Zhang, Wei; Aithal, Guruprasad P.; Ji, Dong; Zhao, Jingmin; Zou, Zhengsheng

Abstract

Background and Aims
The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR.

Methods
A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety.

Results
Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed.

Conclusions
Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).

Citation

Huang, A., Zhu, Y., Liu, S., Sun, Y., Liu, Z., Liang, Q., Zhao, J., Chang, B., Bi, J., Liu, J., Zhai, X., Xie, H., Li, N., Tian, H., Han, L., Zhuang, Y., Ma, H., Teng, G., Zhang, W., Aithal, G. P., …Zou, Z. (2024). An optimized short‐term steroid therapy for chronic drug‐induced liver injury: A prospective randomized clinical trial. Liver International, 44(6), 1435-1447. https://doi.org/10.1111/liv.15899

• Journal Article Type: Article
• Acceptance Date: Mar 4, 2024
• Online Publication Date: Mar 14, 2024
• Publication Date: 2024-06
• Deposit Date: Jul 24, 2024
• Publicly Available Date: Jul 25, 2024
• Journal: Liver International
• Print ISSN: 1478-3223
• Electronic ISSN: 1478-3231
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 44
• Issue: 6
• Pages: 1435-1447
• DOI: https://doi.org/10.1111/liv.15899
• Keywords: Hepatology
• Public URL: https://nottingham-repository.worktribe.com/output/32470881
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/liv.15899