Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial.

Autor:	Etzion O; Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel.; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Hamid S; Aga Khan University and Hospital, Karachi, Pakistan., Lurie Y; Shaare Zedek Medical Center, Jerusalem, Israel., Gane EJ; Auckland City Hospital, Auckland, New Zealand., Yardeni D; Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel.; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Duehren S; Division of Hepatology, Department of Medicine, The Program for Experimental and Theoretical Modeling, Loyola University Medical Center, Maywood, Illinois, USA., Bader N; Aga Khan University and Hospital, Karachi, Pakistan., Nevo-Shor A; Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel.; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Channa SM; Department of Gastroenterology, Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan., Cotler SJ; Division of Hepatology, Department of Medicine, The Program for Experimental and Theoretical Modeling, Loyola University Medical Center, Maywood, Illinois, USA., Mawani M; Aga Khan University and Hospital, Karachi, Pakistan., Parkash O; Aga Khan University and Hospital, Karachi, Pakistan., Dahari H; Division of Hepatology, Department of Medicine, The Program for Experimental and Theoretical Modeling, Loyola University Medical Center, Maywood, Illinois, USA., Choong I; Eiger BioPharmaceuticals, Inc., Palo Alto, California, USA., Glenn JS; Departments of Medicine (Division of Gastroenterology and Hepatology) and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2023 Jun 01; Vol. 77 (6), pp. 2093-2103. Date of Electronic Publication: 2023 Feb 20.
DOI:	10.1097/HEP.0000000000000309
Abstrakt:	Background and Aims: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV. Approach and Results: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-364); and bilirubin 0.5 mg/dL (0.2-1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation. Conclusions: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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