SYSTEMATIC REVIEW: Drug induced liver injury: Alternative causes in case series as confounding variables. Br J Clin Pharmacol. 2018 Apr 01;: Authors: Teschke R, Danan G Abstract AIMS: Drug-induced liver injury (DILI) is rare as compared to the worldwide frequent acute or chronic liver diseases. Therefore, patients included in series of suspected DILI are at high risk of not having DILI, whereby alternative causes may confound the DILI diagnosis. The aim of this review is to evaluate published case series of DILI for alternative causes. METHODS: Pertinent studies were identified using a computerized search of the Medline database for publications from 1993 through 30 October 2017. We used the following terms: drug hepatotoxicity, drug induced liver injury, hepatotoxic drugs combined with diagnosis, causality assessment, and alternative causes. RESULTS: Alternative causes as variables confounding the DILI diagnosis emerged in 22 published DILI case series, ranging from 4% to 47%. Among 13,335 cases of suspected DILI, alternative causes were found more likely in 4,555 patients (34.2%), suggesting that DILI was probably not DILI. Biliary diseases such as biliary obstruction, cholangitis, choledocholithiasis, primary biliary cholangitis, and primary sclerosing cholangitis were among the most missed diagnoses. Alternative causes included hepatitis B, C, and E, CMV, EBV, ischemic hepatitis, cardiac hepatopathy, autoimmune hepatitis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and alcoholic liver disease. CONCLUSIONS: In more than one third of published global DILI case series, alternative causes as published in these reports confounded the DILI diagnosis. In the future, published DILI case series should include only patients with secured DILI diagnosis, preferentially established by prospective use of scored items provided by robust diagnostic algorithms such as the updated RUCAM (Roussel Uclaf Causality Assessment Method). PMID: 29607530 [PubMed – as supplied by publisher]

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SYSTEMATIC REVIEW: Drug induced liver injury: Alternative causes in case series as confounding variables.