Homo sapiens Transcriptome or Gene expression

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. We conducted an open-label pilot trial 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. Eighteen subjects with advanced liver fibrosis received simtuzumab 700mg IV every 2 weeks for 22 weeks. Treatment was well tolerated with no discontinuations due to adverse events. No significant change was seen in hepatic venous pressure gradient or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsies and longitudinal serum suggested up-regulation of TGFß3 and IL-10 pathways with treatment. In summary, simtuzumab was well tolerated in HCV and HIV infected subjects with advanced liver disease. Putative modulation of TGFß3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials.