From the Editor’s desk....: August 2018

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Alpha-1 antitrypsin deficiency (AATD) is a common genetic disorder causing chronic liver disease. The PiZ mutation results in misfolded alpha-1 antitrypsin protein (Z-AAT) leading to hepatocyte damage and progressive liver disease. It has been proposed that RNAi-based approaches that silence production of hepatic Z-AAT could be useful in these patients. In this issue, Turner et al. performed two important studies. First, they conducted a double-blind, randomised trial in healthy volunteers receiving escalating doses of the investigational agent ARC-AAT. The second study consisted of a randomised trial in 11 PiZZ genotype AATD patients who received ARC-AAT or placebo. A dose-response in serum AAT reduction was observed at doses ≥4 mg/kg with similar relative reductions in PiZZ patients and healthy volunteers at 4 mg/kg. The study was terminated early because of toxicity findings related to the delivery vehicle (ARC-EX1) seen in a non-human primate study. The authors conclude that PiZZ and healthy volunteers responded similarly to ARC-AAT with a remarkable knockdown of hepatic AAT production. This promising approach should be tested in future studies that modify the drug vehicle. Corrigendum to “From the Editor’s Desk August 2018” [J Hepatol 69 (2018) 265–268]Journal of HepatologyVol. 69Issue 4PreviewIt has come to our attention that when citing the paper by Ferriero et al. the author’s name was misspelt ‘Ferreiro’ in the text and the figure caption. Please note that the correct name for this author is ‘Ferriero’. In the figure cited for this paper the arrow between Pyruvate and Acetyl-coA should be pointing from Pyruvate to Acetyl-coA, as in the original paper. We apologise for these errors which have now been corrected in the online version of this manuscript. Full-Text PDF