Assessment of drug‐induced liver injury in clinical practice

Abstract

Currently, pharmaceutical preparations are serious contributors to liver disease, with hepatotoxicity ranking as the most frequent cause for acute liver failure and post-marketing regulatory decisions. The diagnostic approach of drug-induced liver injury (DILI) is still rudimentary and inaccurate because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favour a toxic aetiology. Clinical and laboratory data may also be assessed with algorithms or clinical scales, which may add consistency to the clinical judgment by translating the suspicion into a quantitative score. The CIOMS/RUCAM instrument is considered at present the best method for assessing causality in DILI, although it could be improved through the use of large database of bona fide DILI cases for validation criteria.

Drug-Induced Liver Injury: Twenty Five Cases of Acute Hepatitis Following Ingestion of Polygonum multiflorum Thunb

“…Considering those event of asymptomatic or mild hepatitis, the frequency of liver injury caused by P. multiflorum Thunb is expected to be high. The main constituents of Shou-Wu-Pain are polyphenols and anthraquinones - the latter is metabolized into anthrones and absorbed in the gastrointestinal tract, which can induce liver damage 13,15,17,27,28. To date, there are 6 case reports of P. multiflorum Thunb-induced hepatotoxicity14,15,17-20 although the mechanism of P. multiflorum Thunb-induced hepatotoxicity is still unclear.…”

Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport

“…Importantly, intracellular taurocholate accumulation increased with both of these drugs, possibly due to greater inhibition of efflux. This situation could potentially result in cholestasis with cellular damage which is, by definition, mixed hepatic injury (Lucena et al ., 2008). …”

“…Drug-induced liver injury (DILI), a clinical problem worldwide (reviewed in Lucena et al ., 2008; Norris et al ., 2008), is a leading reason for withdrawal of approved drugs from clinical use or mandated usage restrictions on drug labels, and frequently contributes to attrition of drug candidates during development (Bakke et al ., 1995; Kaplowitz, 2005; Kola and Landis, 2004). Numerous pathophysiological mechanisms underlie hepatotoxicity but remain poorly understood, and many cases of DILI are categorized as idiosyncratic ( i.e ., rare hepatotoxic reactions of unknown etiology).…”

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

“…Causality assessment was based on algorithms which are relatively simple to apply but where the weighting of each criterion can be somewhat arbitrary. Even though the RUCAM scale is considered at present as the best method for assessing causality in drug-induced liver disease, [45,46] the scale has some limitations, such as the poor definition of the items to be answered and the scarce diagnostic capability when two drugs are administered at the same time. This algorithm awards higher scores to the known hepatotoxic medications, and therefore it may tend to underestimate the causative role of any medication previously unknown to be hepatotoxic.…”