Brief Clinical Observation
Acute liver and renal failure during treatment with buprenorphine at therapeutic dose

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Abstract

Buprenorphine is a semi-synthetic opioid derivative commonly used in the treatment of heroin addiction. Life-threatening complications have been described following overdoses while few cases of hepatotoxicity due to drug use at therapeutic doses have been recently described in hepatitis C virus carriers. In these cases, however, histological assessment was not exhaustive and no extra-hepatic organ failure was observed. We describe herein a case of acute liver and kidney failure in a patient with previously latent hepatitis C virus chronic infection following recommended doses of buprenorphine. Histology did not demonstrate any feature compatible with hepatitis C virus reactivation or liver cirrhosis and suspension of the treatment led to the resolution of both liver and kidney failure. Causality criteria fulfillment indicates a high probability of buprenorphine-induced liver toxicity. No signs of pre-existant kidney impairment or of pre- or post-renal causes were observed. Since buprenorphine is metabolized through cytochrome P450 3A4, we genotyped six genetic polymorphisms previously described in poor metabolizers but could not confirm these pharmacogenetic bases in this case. In conclusion, we surmise that buprenorphine at suggested doses can induce liver and kidney failure in susceptible individuals, possibly through direct mitochondrial toxicity.

Introduction

Buprenorphine (BPN), a semi-synthetic opioid derivative acting on morphine receptors, is currently prescribed for analgesic purposes and, more recently, for the maintenance treatment of heroin addiction [1]. Doses as high as 32 mg/day given sublingually are considered effective and safe for prolonged treatments [2]. However, acute hepatitis occurrence has been reported following misuse [3], massive overdose [4], and also therapeutic doses [5]. However, in the latter cases, no signs of renal involvement were observed and no liver histology provided. We herein describe the first known case of acute liver and renal failure secondary to BPN at recommended sublingual regimen and we investigate the possible pharmacogenomic bases.

Section snippets

Case report

A 33-year-old man with a history of heroin addiction, alcohol abuse, and hepatitis C virus (HCV) infection was admitted to our Unit for severe acute hepatitis and renal failure. The patient had been abstinent from alcohol for over 6 months and undergoing a detoxification program for 3 months with methadone until switching to BPN 20 mg/day sublingually 3 weeks prior to our observation. Importantly, renal function was repeatedly normal at any of the previous medical evaluations. At admission, the

Conflict of interest statement

None declared.

References (18)

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