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Simtuzumab treatment of advanced liver fibrosis in HIV and HCV ‐infected adults: results of a 6‐month open‐label safety trial
Author(s) -
Meissner Eric G.,
McLaughlin Mary,
Matthews Lindsay,
Gharib Ahmed M.,
Wood Bradford J.,
Levy Elliot,
Sinkus Ralph,
Virtaneva Kimmo,
Sturdevant Dan,
Martens Craig,
Porcella Stephen F.,
Goodman Zachary D.,
Kanwar Bittoo,
Myers Robert P.,
Subramanian Mani,
Hadigan Colleen,
Masur Henry,
Kleiner David E.,
Heller Theo,
Kottilil Shyam,
Kovacs Joseph A.,
Morse Caryn G.
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13177
Subject(s) - medicine , tolerability , liver biopsy , liver disease , gastroenterology , hepatitis c virus , adverse effect , hepatitis c , fibrosis , chronic liver disease , immunology , biopsy , pathology , virus , cirrhosis
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 ( LOXL 2) 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 ‐β3 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 ‐β3 and IL ‐10 pathways during simtuzumab treatment merits investigation in future trials.