Drug-induced liver injury (DILI) is emerging as a burning topic for academics, clinicians, pharmaceutical companies and regulatory bodies, as number of publications are increasing over the past fifteen years. Updated information has also raised an important question, whether we know everything about DILI. Iproniazid, cinchophen, and sulfonamides were amongst the first drugs with hepatotoxic effects to be identified, and by the mid-1960s, hepatotoxic agents including halothane, isoniazid (INH), carbamazepine, phenytoin and alpha methyldopa and by the mid-1980s close to 1000 drugs were associated with hepatotoxicity. Nevertheless, information of diagnostic and pathophysiologic principles are still same. Clinically, DILI ranges from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure. It remains a leading cause of emergent liver transplant. Several registries have been created, including the United States Drug-Induced Liver Injury Network, to enhance data of all aspects of DILI. In addition, the launch of LiverTox and other online hepatotoxicity resources has augmented awareness of DILI. The first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology in 2013 are given below.

• Known duration of exposure
• Concomitant medications and diseases
• Response to dechallenge (and rechallenge if performed)
• Presence or absence of symptoms, rash, eosinophilia
• Performing sufficient exclusionary tests (viral serology, imaging, etc.) to reflect the injury pattern and acuteness of liver function tests (e.g., acute viral serology for A, B and C and autoimmune hepatitis when presenting with acute hepatocellular injury; routine testing for hepatitis E virus not recommended because of the problems with current commercial assays; Epstein-Barr virus, cytomegalovirus, and other viral serology if lymphadenopathy, atypical lymphocytosis present)
• Sufficient time to determine clinical outcome - did the event resolve or become chronic?
• Use of liver biopsy
• Often not required if the acute injury resolves
• Helpful in confirming clinical suspicion of DILI but rarely pathognomonic
• Useful to differentiate between Drug-Induced autoimmune hepatitis and idiopathic autoimmune hepatitis
• Useful to rule out underlying chronic viral hepatitis, non-alcoholic fatty liver disease, alcoholic liver disease, or other chronic liver disease
• Used to exclude DILI where re-exposure or ongoing use of an agent is expected
• Rechallenge: Generally best avoided, unless there is no alternative treatment
• Use of Causality Assessment Methods
• Roussel Uclaf Causality Assessment Method is best considered an adjunct to expert opinion (it should not be the sole diagnostic method)
• Consensus opinion
• Expert consultation
• For patients with chronic viral hepatitis, DILI requires a high index of suspicion, knowledge of a stable clinical course before the new medication, and monitoring of viral loads to rule out flares of the underlying disease
• Assigning causality to herbal compounds and dietary supplements can be especially difficult; require knowledge of all ingredients and their purity.

Various global registries have also been established along with the guideline for diagnosis and management. Although, identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have increased knowledge of the effect of DILI, there are still some lacunae left in its complete comprehension.Source: Alempijevic T, Zec S, Milosavljevic T. Drug-induced liver injury: Do we know everything?. World J Hepatol. 2017;9(10):491-502.