期刊
LIVER INTERNATIONAL
卷 36, 期 12, 页码 1783-1792出版社
WILEY-BLACKWELL
DOI: 10.1111/liv.13177
关键词
hepatic venous pressure gradient; lysyl oxidases; magnetic resonance elastography; transforming growth factor beta-3
资金
- United States National Institutes of Health (NIH) Intramural Research Program
- NIH Bench to Bedside Award - Office of AIDS Research
- National Cancer Institute [HHSN261200800001E]
- NIH
- Gilead Sciences
- NIH Clinical Center, NIAID
- NIDDK
Background: Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed. Aim: The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease. Methods: Eighteen subjects with advanced liver fibrosis received simtuzumab 700 mg intravenously every 2 weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (HVPG) and to stage fibrosis. Results: Treatment was well-tolerated with no discontinuations due to adverse events. No significant changes were seen in HVPG or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsy and serum samples suggested up-regulation of TGF-beta 3 and IL-10 pathways with treatment. Conclusion: In this open-label, pilot clinical trial, simtuzumab treatment was well-tolerated in HCV- and HIV-infected subjects with advanced liver disease. Putative modulation of TGF-beta 3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials.
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