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In their article on recent advances in alcoholic liver disease (ALD), Avila and coworkers1 also mention the little-studied approach of inhibiting overexpressed cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption,2 causes generation of reactive oxidative species (ROS) and oxidative stress and stimulates hepatic steatosis and fibrosis.3 4 ROS also results in lipid peroxidation products such as 4-hydroxynonenal, which binds to DNA and generates highly carcinogenic etheno DNA adducts.4 In rodents, ALD can be partly prevented by CYP2E1 knock out5 or by administration of the strong noncompetitive CYP2E1 inhibitor clomethiazole.6 Conversely, ALD is enhanced in mice overexpressing CYP2E1,7 underlying the potential role of CYP2E1 activity in ALD.
To study whether CYP2E1 inhibition also improves ALD in humans, we performed an open, randomised controlled clinical trial (EudraCT-Number 2012-005730-11, online supplemental materials 1–3), as approved by the responsible Ethics Committee of the Medical Faculty of Heidelberg University (AFmo-586/2014) (online supplemental material 4) and the German authorities (BfArM) in alcohol-dependent patients who were admitted to the hospital for alcohol detoxification therapy (ADT). After giving written informed consent (online supplemental material 5), ADT was performed either with clomethiazole …
WEH and HKS contributed equally.
Contributors The authors have contributed to this research as follows. NH: designed the protocol, organised and supervised the trial, analysed the data, wrote the manuscript. SM: supervision of the clinical part of the study. FS: collection and coordination of clinical data. BM: collection and coordination of clinical data. HT: collection and coordination of clinical data. JB: performed the chlorzoxazone measurements. TB: analysed the data. WEH: designed the protocol, analysed the data, wrote the manuscript. HKS: designed the protocol, analysed the data, wrote the manuscript, had access to all of the data and can vouch for the integrity of the data analyses.
Funding This research was funded in part by Heidelberger Volksbank eG.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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