Pharmacologic liver damage is a liver disease, also known as pharmacologic hepatitis, caused by toxic damage from drugs or allergic reactions to drugs during treatment. Theoretically, pharmaceutical liver damage can occur with any drug that is metabolized through the liver. During the use of anti-tuberculosis drugs, drug-induced liver damage is the most common and most harmful complication. Many patients need to stop anti-tuberculosis treatment, and cases of liver failure or even death caused by anti-TB drugs occur from time to time, which need to be paid great attention by clinicians. 1, the incidence of DILI caused by anti-tuberculosis drugs The incidence of anti-tuberculosis drug-induced liver damage reported by different countries and regions is different, and even varies greatly, from as low as 2.5% to as high as 34.9%. This variation is related to multiple factors such as ethnicity, socioeconomic status, geographic location and investigators’ diagnostic criteria for DILl, prevalence of viral hepatitis, and prophylactic treatment. Most of the reports of DILl are from Europe, Asia and the United States of America, with a higher incidence in India among Asian countries. Different anti-tuberculosis drugs have different chances of causing DILI. For Europeans and Americans isoniazid has a higher chance of causing DILI, in our country pyrazinamide and rifampicin are the most common drugs causing DILI. Next include isoniazid, other rifamycins, propylthioisonicotinamide, p-aminosalicylic acid etc. Group II, III and V drugs are less likely to cause DILI. 2. Risk factors associated with DILI due to antituberculosis drugs Risk factors associated with DILI include: (1) Gender and age: Drug induced liver injury is relatively more common in females. In the age distribution, the elderly and newborns are prone to drug-induced liver damage. The occurrence of DILI in the elderly may be associated with decreased activity of the microsomal enzyme system, natural decline in liver and kidney function, and increased comorbidities, increased access to medications as well as increased accumulation of drugs in the body. Newborns have an underdeveloped hepatic drug-metabolizing enzyme system and are therefore more likely to develop DILI than adults. (2) Lifestyle: Unhealthy lifestyles, such as alcohol abuse, staying up late, irregular diets, unclean diets, and exhaustion are all likely to lead to the development of DILI. (3) Genetic factors: Genetic idiosyncratic body mass or variations in genetic factors can increase the sensitivity of some individuals to certain medications. For example, slow acetylation individuals are prone to DILl, the incidence rate is significantly higher than that of the fast acetylation type, and are prone to severe DILl; genetic polymorphisms in some enzymes related to drug metabolism (e.g., P450 isozymes) may lead to the metabolism of the drug in some individuals with special metabolism. In addition, drugs or other metabolites act as semi-antigens that junction with liver-specific proteins to become antigens causing allergic inflammatory injury. Therefore, patients who are allergic or have a history of drug allergy are more likely to develop drug hepatitis. (4) Influence of comorbidities on the occurrence of drug-induced liver damage: the incidence of DILI is higher in patients with chronic liver disease, renal insufficiency, and malnutrition. Anti-tuberculosis drugs need to be used for a long period of time and are multi-drug combinations, so special attention should be paid to patients’ comorbidities as well as comorbid drug use in the course of anti-TB treatment. The superposition of a large number of drugs together will make it more difficult to determine whether DILI has occurred, and will bring difficulties to the follow-up treatment. 3, the occurrence mechanism and clinical manifestations of DILl caused by antituberculosis drugs Most drugs need to be metabolized through the liver after entering the human body, including oxidation, reduction, hydrolysis, hydroxylation, desulfuration or decarboxylation and other chemical reactions, and then excreted by the biliary system. Therefore, the mechanism of drug damage to the liver includes: the direct toxic effect of drug metabolites on the hepatobiliary system, metabolic process and product-induced allergic liver damage. There is no special difference in the mechanism of liver damage between anti-tuberculosis drugs and other drugs, which are specifically divided into: (1) toxic liver damage: anti-tuberculosis drugs undergo cytochrome P450 action in the liver, and metabolites such as electrophilic radicals, free radicals, and oxygens bind to molecules such as proteins, nucleic acids, and lipids and have toxic effects on hepatobiliary cells, leading to cell damage or even death. This type of DILI tends to be dose-dependent in relation to the dose administered, and a cumulative effect can occur. (2) Metabolic liver damage: the anti-tuberculosis drug itself or its metabolites act as semi-antigens that bind to specific proteins in the liver to become antigens, which are processed by macrophages and recognized by immunoreactive cells, leading to a metabolic reaction. This type of DILI is also common, independent of the dose of the drug, and is mainly influenced by the sensitization state of the organism and individual genetic differences. And it is often accompanied by systemic or localized hypersensitivity manifestations. The majority of DILI caused by anti-tuberculosis drugs occurs within 2 months of starting anti-tuberculosis treatment, and some patients appear in the middle and late stages of treatment, or even after the end of anti-tuberculosis treatment. The form of clinical manifestations is not significantly different from that of regular drug-induced DILI. Some patients have no clinical symptoms and only abnormal liver function is found in routine examination, which is less severe liver damage, often with transient transaminase elevation. With the aggravation of hepatocellular damage or the increase of bilirubin, clinical symptoms such as gastrointestinal symptoms like epigastric discomfort, nausea, anorexia, as well as yellow staining of the skin and sclera, and deepening of the color of the urine begin to appear. If the lesion continues to progress, manifestations of liver failure will occur, including worsening jaundice, ascites, hypoproteinemia, coagulation dysfunction, hepatic encephalopathy, and multiple organ insufficiency. In some patients, DILI is due to the body’s hypersensitivity reaction, and the manifestations of hepatitis will be accompanied by local and systemic hypersensitivity phenomena, such as rash, high fever, malaise, muscle pain, superficial lymph node enlargement, hepatosplenomegaly, arthritis, and myocarditis, etc., and in severe cases, there is a combination of hemolytic anemia, exfoliative dermatitis, and acute renal failure, etc. Laboratory examination usually reveals eosinophilia and Antidrug antibodies can be detected. Diagnosis and treatment of DILl caused by anti-tuberculosis drugs The diagnosis of DILI caused by anti-tuberculosis drugs mainly relies on exclusionary diagnosis, and according to its clinical characteristics, the main points of diagnosis include: (1) DILI appears after the start of anti-tuberculosis treatment, usually about 2 months, and some patients may appear in the middle and late stages of treatment. (2) Liver function gradually improves after stopping anti-tuberculosis drugs. (3) Rule out other combinations of drugs. (4) Positive reaction after re-administration of drugs. According to this diagnostic criteria, most cases can be clarified. The use of anti-tuberculosis drugs is a combination of multiple drugs, and often there is a combination of drugs, so the liver function damage that occurs during the course of anti-tuberculosis treatment is not always caused by anti-tuberculosis drugs, due to the limited types of anti-tuberculosis drugs, the discontinuation of the drug has a greater impact on the current and subsequent anti-tuberculosis treatment, so in the process of diagnosing anti-tuberculosis drug-induced DILI, special attention should be paid to exclude other causes. (1) Comorbidities: viral hepatitis, alcoholic liver disease, schistosomiasis, autoimmune liver disease, etc. These causes are relatively easy to recognize. These causes are relatively easy to recognize, and often the liver function abnormalities have already appeared before the treatment, and the direct basis of viral activity and elevated immunological antibodies can be found. Some patients develop liver damage caused by liver and gallstones, tumors, and infections during the course of treatment, which is also easy to determine based on medical history. (2) Medication for comorbidities: Some TB patients have been taking traditional Chinese medicines, immunosuppressants, hormones, and even tumor chemotherapeutic drugs for a long time due to comorbidities, and these are the drugs that may cause DILI. In addition, patients may also take cold and flu medicines, antibiotics and so on during the six-month or even longer treatment, which can also lead to the occurrence of DILI. (3) Lifestyle: For some patients, especially those who develop liver function abnormalities in the middle and late stages of anti-tuberculosis treatment, there is a need to focus on whether there are lifestyle causes of liver damage. Staying up late, alcohol abuse, exertion, mental stress, diet and other causes may lead to liver function damage. (4) Hepatic tuberculosis: A less common condition is liver function abnormality due to tuberculosis in the liver itself, such as hematogenous disseminated tuberculosis combined with hepatic tuberculosis, hepatic tuberculous abscess, etc. In this case, anti-tuberculosis treatment may cause liver function abnormality. In this case, anti-tuberculosis treatment will instead promote the recovery of liver function. If liver function abnormality occurs during the course of anti-tuberculosis treatment, the treatment should be comprehensively adjusted according to the degree of liver function injury and comprehensive assessment of the patient’s tuberculosis condition, related risk factors and systemic condition. If only ALT <3 times elevated, and no obvious symptoms, no jaundice, can not stop anti-TB drugs, under close observation to protect the liver treatment, and monitor the changes in liver function. The drugs with higher chance of liver damage can also be discontinued as appropriate, and the remaining drugs can be continued. If ALT is >3-fold elevated or total bilirubin is >2-fold elevated, all anti-TB drugs in the original regimen should be promptly discontinued, and active hepatoprotective therapy should be given with close observation. If the tuberculosis disease is more serious, it is better to use the drugs with less chance of liver function damage, such as the drugs in the second group, the third group and the fifth group. In this case, the anti-TB principle of “combination therapy” should still be met, and the use of single drugs is not recommended. If liver damage continues to worsen, more aggressive hepatoprotective therapy should be used, and artificial livers may be used if available. As for the liver-protecting treatment itself, there is a wide variety of drugs, each with its own advantages, and in principle, it is sufficient to choose a combination of two or three drugs with different effects. It should be noted that liver-protecting drugs themselves may also have damage to the liver, and the effects of liver-protecting drugs should not be exaggerated. It is very important to give the damaged liver sufficient rest and functional adjustment. One type of DILI caused by anti-tuberculosis drugs is allergic liver damage. For such patients with high fever, generalized rash, rapid increase in liver function in a short period of time and no other special conditions, the use of hormone therapy often has unexpected therapeutic effects. With the improvement of liver function, whether to use the anti-TB drugs in the original program again should be distinguished from the specific situation. (1) If the patient’s liver damage is very serious and even liver failure is life-threatening, the reuse of the drugs in the original regimen has a great risk and should be stopped and other alternative drugs should be chosen. (2) Patients with less severe liver damage and faster recovery of liver function after active treatment should weigh the pros and cons and consider using the drugs in the original regimen, but should avoid the drugs with a higher chance of liver damage in the original regimen, the most common ones being pyrazinamide and rifamycin (especially rifampicin). (3) Patients with transient elevation of liver function, which rapidly returns to normal after treatment, some of the patients have a transient reaction due to the increased burden of liver function, and all the drugs in the original regimen can be used in the subsequent treatment, but the changes in liver function should be closely monitored, and other factors leading to hepatic function damage should be avoided. (5) For patients whose liver function shows obvious improvement but never fully returns to normal. Most of these patients have underlying liver disease, such as viral hepatitis B. In addition to active treatment of comorbidities, the use of subsequent anti-tuberculosis drugs should be based on the principle that it should not lead to a significant increase in liver function on the basis of the existing, and drugs that have a higher chance of liver damage in the original program should be avoided for re-use. 6, Summary The prognosis of DILI due to anti-TB drugs is related to the type of its clinical manifestations and is influenced by individual, drug and environmental factors. Most patients with DILI can be cured after timely detection of DILI, liver preservation and symptomatic supportive treatment. However, when bile enzyme separation, liver failure, and hepatic encephalopathy occur, the prognosis is extremely poor. Anti-TB drug-induced DILI is clinically more common and harmful, whether prophylactic liver-protecting treatment can bring benefits to patients has no definite basis, the author’s current group is leading the study of prophylactic liver-protecting treatment of diamine glycyrrhizinate, with the participation of many units across the country, and the results of the study are worthy of anticipation. In conclusion, during the course of anti-tuberculosis treatment, liver function changes should be routinely monitored, especially for patients with combined chronic liver disease, old age, pregnancy and idiopathic patients. Once liver damage is detected, close attention should be paid to changes in the condition and active treatment should be provided, and if necessary, anti-tuberculosis medication should be discontinued and active liver-protecting treatment should be given.