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Due to a lack of specific biomarkers,the diagnosis of drug-induced liver injury(DILI) mainly depends on the method of exclusion. The Roussel Uclaf Causality Assessment Method(RUCAM) scale is the most widely used causality assessment scale and is relatively objective,but it is still waiting for further improvement. Another method is global introspection or expert opinion,which is relatively subjective,and the simplified global introspection method is commonly used in clinical practice. The Structured Expert Opinion Procedure(SEOP)created by the US DILI network(DILIN) is very complicated and time-consuming and thus cannot be used in clinical practice. The drug rechallenge test(DRT) with a positive result is considered the gold standard for the diagnosis of DILI,but DILI cannot be excluded based on the negative result of DRT. The value of lymphocyte transformation test(LTT),modified LTT,monocyte-derived hepatocyte-like cell lactate-dehydrogenase release test,and various predictive models for drug hepatotoxicity in the diagnosis of DILI awaits further assessment.The differential diagnosis of autoimmune-mediated DILI and traditional autoimmune liver diseases usually depends on liver biopsy,the type and titer of autoantibody,and response to glucocorticoids. Reasonable timing of drug withdrawal and application of anti-inflammatory liver-protecting drugs may help most DILI patients recover. Generally,the prophylactic use of anti-inflammatory liver-protecting drugs is not recommended,except in special situations. In-depth studies are needed for the precise diagnosis and prevention/treatment of DILI. [ABSTRACT FROM AUTHOR]

Up to now, the diagnosis of drug-induced liver injury (DILI) still relies on the exclusive method, and the Roussel Uclaf Causality Assessment Method (RUCAM) is the most commonly used scale. Since the release of the first version of RUCAM scale in 1993, the second version was released in 2015, in which the definition and scoring criteria of each key element were revised appropriately and explained in detail. The Structured Expert Opinion Process (SEOP) was designed by the workgroup of DILI network prospective study, but since it is too complicated and time- and energy-consuming, its application in clinical practice is limited. This article introduces the research and development history and application method of RUCAM, as well as the modifications made in the 2015 version of RUCAM, and briefly compares the difference in bias between RUCAM and SEOP in the diagnosis of DILI. It is pointed out that both RUCAM and SEOP have marked interobserver and intraobserver variabilities, and therefore, it is necessary to explore a more objective, reproducible, accurate, and convenient strategy for the diagnosis of DILI. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury( DILI) with extrahepatic adverse drug reaction( EHADR) is the injury of extrahepatic organs which is caused by the same drug inducing liver injury and may occur simultaneously or successively with DILI,such as the skin,gastrointestinal tract,blood system,cardiovascular system,and bone and joint system,and it should be taken seriously in clinical practice. DILI with EHADR is not rare,and its pathogenesis may be associated with various factors including the physicochemical properties,distribution,metabolism,excretion,biological activity,and immunological properties of drugs,host genetic background,and underlying diseases. The diagnosis and treatment of DILI with EHADR is more challenging than that of DILI alone. [ABSTRACT FROM AUTHOR]

Drug-induced cholestasis (DRIC) mainly includes cholestasis-type and mixed-type drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method scale should be used to determine the causality between drug and cholestasis and other etiologies should be excluded. Liver biopsy may help with differential diagnosis. Drugs should be stopped after the development of DRIC to avoid stimulation, and ursodeoxycholic acid should be administered for treatment. DRIC has a complex pathogenesis, which involves the direct toxicity of drugs and their metabolites on hepatocytes and the biliary tree, immune and inflammatory response, gene polymorphism and inhibition of key enzymes and transporters in the pathways of drug metabolism and efflux, and HLA gene polymorphisms. Clarification of these pathogeneses helps with the early warning, prevention, and optimized treatment of DRIC. [ABSTRACT FROM AUTHOR]