Chronic liver injury induced by drugs and toxins

Drug-induced liver injury (DILI) occurs in a small fraction of individuals exposed to drugs, herbs or dietary supplements and is a relatively rare diagnosis compared with other liver disorders. DILI can be serious, resulting in hospitalization and even life-threatening liver failure, death or need for liver transplantation. Toxic liver damage usually presents as an acute hepatitis viral-like syndrome or as an acute cholestasis that resolves upon drug discontinuation. However, un-resolving chronic outcome after acute DILI can ensue in some subjects, the mechanisms and risk factors for this particular evolution being yet scarcely known. Furthermore, the definition of chronicity after acute DILI is controversial, regarding both the time frame of liver injury persistence and the magnitude of the abnormalities required. Besides this, in some instances the phenotypes and pathological manifestations are those of chronic liver disease at the time of DILI diagnosis. These include non-alcoholic fatty liver disease, vascular lesions, drug-induced autoimmune hepatitis, chronic cholestasis leading to vanishing bile duct syndrome and even cirrhosis, and some drugs such as amiodarone or methotrexate have been frequently implicated in some of these forms of chronic DILI. In addition, all of these DILI phenotypes can be indistinguishable from those related to other etiologies, making the diagnosis particularly challenging. In this manuscript we have critically reviewed the more recent data on chronicity in DILI with a particular focus on the epidemiology, mechanisms and risk factors of atypical chronic DILI phenotypes.