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

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• 作者：Jessica K. Dyson¹ ; ² ; ^{jessicadyson@doctors.org.uk" class="auth_mail" title="E-mail the corresponding author} ; John Hutchinson³ ; Laura Harrison³ ; Olorunda Rotimi⁴ ; Dina Tiniakos² ; ⁵ ; Graham R. Foster⁶ ; Mark A. Aldersley³ ; Stuart McPherson¹ ; ²
• 关键词：HCV ; Hepatitis C virus ; HCC ; hepatocellular carcinoma ; DAAs ; direct-acting antivirals ; HIV ; human immunodeficiency virus ; MELD ; Model for End-stage Liver Disease ; RNA ; ribonucleic acid ; SIRS ; systemic inflammatory response syndrome ; HBV ; Hepatitis B virus ; HBsAg ; Hepatitis B surface antigen ; HBc antibody ; Hepatitis B core antibody ; HAV ; Hepatitis A virus ; IgM ; immunoglobulin M ; HEV ; Hepatitis E virus ; DILI ; drug induced liver injury ; PCOS ; polycystic ovarian syndrome ; UKELD ; United Kingdom Model
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：64
• 期：1
• 页码：234-238
• 全文大小：723 K

文摘

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.