Drug induced liver injury (DILI) refers to the liver damage caused by the drug itself and/or its metabolites. In recent years, the incidence of DILI has been increasing with the introduction of new drugs in various specialties and the increasingly widespread clinical applications. Foreign reports of drug-related liver injury account for 10%-15% of the overall adverse drug reactions, 10% of adult liver disease, and 10%-25% of fulminant liver failure. In the United States, DILI is the leading cause of acute liver failure. The Department of Infectious Diseases, Wuhan Union Medical College Hospital, Wei Ping, has a wide range of drugs that cause liver injury, including anti-tuberculosis drugs (isoniazid, rifampin, pyrazinamide, sodium para-aminosalicylate), Chinese herbal medicines (heshouwu, cassia, licorice, peppermint, rhubarb, lei gong teng), antipyretic and analgesic drugs (acetaminophen, aspirin, pau taisong), antibiotics (macrolides, penicillins, quinolones), anticonvulsants, antineoplastic drugs, etc. The liver is an important organ for drug aggregation, transformation and metabolism, and the metabolic process of most drugs in the liver includes two phases: transformation and binding, namely phase I metabolism and phase II metabolism. Phase I metabolic reactions mainly include oxidation, reduction and hydrolysis reactions, after this phase, the polarity of the drug increases, i.e., the water solubility increases, and it is easy to be excreted. After this phase, the drug can combine with glucuronide, methyl, sulfur, glycine and other groups to form more polar substances, which are excreted through bile or urine. Some drugs require only phase I metabolism, while others require both phase I and phase II metabolism to complete. The genes for phase I and II metabolizing enzymes in the liver are polymorphic in the population, and therefore, tolerance and sensitivity to drugs vary greatly among individuals. Several factors influence the susceptibility to DILI, such as genetic factors, age, gender, underlying disease, nutritional status, and the interaction between multiple drugs. Drugs cause liver injury mainly through two mechanisms: one mechanism is the direct toxic effect of drugs and their intermediate metabolites on the liver: drugs are metabolized by CYP to produce reactive metabolites such as electrophile groups and free radicals, which are usually detoxified by junction with glutathione (GSH). It does not produce liver damage. However, when overdose or hereditary drug metabolism is abnormal, excessive toxic metabolites such as electrophile groups and free radicals are produced, which deplete GSH in the liver and cause protein structural damage, inactivation, DNA damage and oxidative stress by interacting with cellular macromolecules (such as proteins and nucleic acids). These metabolites also disrupt ion gradients, impair calcium ion transport, damage mitochondrial proteins, inhibit ATP synthesis, etc., ultimately leading to apoptosis and necrosis of hepatocytes and even causing liver failure. This type of drug-related liver injury is dose-dependent, predictable, and can be replicated in animals. Another mechanism is the body’s idiosyncratic response to the drug: both allergic (immune idiosyncratic) and metabolic (metabolic idiosyncratic). The former is mainly due to the drug or its active metabolites acting as semi-antigens that bind to endogenous proteins to form immunogenic autoantigens that can induce hepatocyte death or destruction; such immunogens can also be recognized by CD4+ cells and induce the production of some cytokines that further activate CD8+ T cells, causing Fas or perforin-mediated hepatocyte apoptosis and cell injury. The latter is mainly associated with genetic polymorphisms of individual drug-metabolizing enzymes, which appear to have a reduced ability to metabolize drugs, allowing the accumulation of drug prototypes or/and intermediate metabolites and producing toxicity to hepatocytes. The clinical manifestations of DILI vary from asymptomatic liver function abnormalities to acute and chronic hepatitis and even cirrhosis. Severe cases can lead to liver failure. According to the criteria established by the International Council for Organization of Medical Sciences (CIOMS) in 1989, DILI is classified into hepatocellular, cholestatic and mixed types, which were revised by the Drug Hepatotoxicity Steering Committee of FDA in 2005. The three types of diagnostic criteria are as follows: ① hepatocellular injury: serum ALT elevated at least 2 times above the upper limit of normal value, serum ALP normal; or ALT/ALP elevation ratio ≥ 5; ② cholestatic liver injury: ALP elevated more than 2 times the upper limit of normal value, ALT normal or ALT/ALP elevation ratio ≤ 2. ③ mixed liver injury: that is, serum ALT and ALP levels are elevated at the same time, with ALT levels elevated The clinical manifestations, biochemical changes and histopathology of DILI are almost the same as those of other hepatitis. The following points can be used as diagnostic references: ① there is a clear correlation between the time of appearance of liver damage symptoms and liver biochemical abnormalities after drug treatment; ② the liver biochemical indexes return to normal rapidly after drug discontinuation; ③ liver damage due to other etiologies can be excluded; ④ the ALT level increases to at least 2 times the normal value after drug administration again. If ① to ③ of the above criteria are met, or if 2 of ① to ③ are met, plus ④, the diagnosis of drug-related liver injury can be made. The first and foremost treatment for DILI is to discontinue the drug that causes liver damage, and to avoid drugs with the same or similar chemical structure or pharmacological effects as the drug. Some diseases cannot be discontinued or the choice of drugs is limited, such as anti-rejection drugs for post-transplant patients and chemotherapeutic drugs for tumor patients, when the patient’s liver damage is not serious, the drug can be replaced with similar drugs (less side effects such as liver damage) and liver function is closely monitored. Early removal and excretion of liver damage-causing drugs from the body The residual drugs in the gastrointestinal tract can be removed within 6 hours by gastric lavage, diarrhea and the addition of activated carbon adsorbent for those who have mistakenly consumed or taken a large amount of liver damage-causing drugs. Diuresis, hemodialysis, and blood ultrafiltration can also be used to promote the excretion and removal of drugs. Supportive therapy The patient is advised to rest in bed and given symptomatic supportive therapy to maintain the stability of the internal environment, preserve the function of vital organs, promote the regeneration of liver cells, and apply albumin or fresh blood plasma if necessary. Application of special antidotes There are few special antidotes available for drug-related liver damage, except for the immediate application of N-acetylcysteine after acetaminophen overdose. According to the literature, the efficacy of applying ursodeoxycholic acid for cholestasis caused by amoxicillin and potassium clavulanate is relatively certain; adenosylmethionine can increase the level of reduced glutathione in the blood, which is effective in the treatment of drug-related liver damage; thiopronine, diammonium glycyrrhizate, reduced glutathione and traditional Chinese medicine have been reported for the prevention and treatment of drug-related liver damage. Artificial liver support therapy and liver transplantation In patients with liver failure, artificial liver support therapy and liver transplantation can be considered.