Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use

JOURNAL OF HEPATOLOGY

卷:64

Article

Dyson, Jessica K.^1,2  Hutchinson, John³  Harrison, Laura³  Rotimi, Olorunda⁴  Tiniakos, Dina^2,5  Foster, Graham R.⁶  Aldersley, Mark A.³  McPherson, Stuart^1,2 

[1] Freeman Rd Hosp, Liver Unit, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England

[2] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[3] St James Univ Hosp, Liver Unit, Leeds, W Yorkshire, England

[4] St James Univ Hosp, Dept Histopathol, Leeds, W Yorkshire, England

[5] Royal Victoria Infirm, Dept Cellular Pathol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[6] Queen Marys Univ London, Blizard Inst, Liver Unit, London, England

关键词: Hepatotoxicity;    Direct-acting antivirals;    Drug induced liver injury;    Hepatitis C;    Sofosbuvir;    Ledipasvir;    Daclatasvir;    Oestrogens;   

DOI  :  10.1016/j.jhep.2015.07.041

来源: Elsevier

【 摘 要 】

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma. There have been rapid advances in HCV treatment with the development of oral direct-acting antivirals (DAAs). Studies have shown sustained virological response rates above 90% with combinations of DAAs, including patients with compensated cirrhosis. Thus far, significant drug toxicity has not been seen with these agents, but there is limited experience of using DAAs in decompensated HCV cirrhosis. This report describes the first experience of serious drug-induced hepatotoxicity with the new DAAs. The mechanism underlying these drug reactions is currently unknown. Few patients with decompensated cirrhosis have been treated with DAAs, so the exact pharmacokinetics in this population have not been characterised. In both cases presented here, patients were taking or had recently taken other drugs. It is possible that an unknown interaction or reaction to the drug combination caused the hepatotoxicity. Although the association with the DAAs is not proven these cases indicate that patients with advanced liver disease need close monitoring while on DAA therapy and if there is a significant unexplained deterioration in liver function the DAAs should be discontinued. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free