Drug-induced liver disease

　　There are hundreds of drugs that can cause varying degrees of liver damage, including those acting on the central nervous system such as chlorpromazine, tranquilizers, etc.; chemotherapeutic drugs such as sulfonamides, isoniazid, rifampicin, para-aminosalicylic acid, etc.; antibiotics such as tetracycline, erythromycin, etc.; antipyretic and analgesics such as indomethacin, phenylbutazone, acetaminophen, salicylates, etc.; anticancer drugs such as methotrexate, 6-mercaptopurine, 5-fluorouracil, etc. are relatively common; other drugs such as testosterone, estrogen, certain progesterone contraceptives, oral hypoglycemic agents such as tolbutamide, and certain traditional Chinese medicines such as kudzu root, Xanthium sibiricum, etc. can also cause drug-induced liver damage. The damage to the liver by drugs can be divided into two major categories:

　　1. Toxic liver damage caused by drugs This type is positively correlated with the dose, has a short incubation period, and can directly cause liver cell damage, leading to liver cell necrosis.

　　2. Liver damage caused by allergic reactions to drugs Some drugs can cause acute or delayed allergic reactions, and the allergic liver damage can be divided into 'cholestatic hepatitis' and 'hepatitis type' hepatitis. The degree of liver damage is unrelated to the amount of drug intake, the incubation period is usually long or indefinite, and it cannot be predicted in advance. This type has a genetic predisposition and may be due to the result of hereditary enzyme defects.

　　　In patients with cholestatic drug-induced liver disease accompanied by inflammation, symptoms can include fever, aversion to cold, weakness, nausea, abdominal distension, followed by jaundice and itching. Severe cases may have ascites, coagulation disorders, bleeding, liver cirrhosis, and hepatic encephalopathy.

　　Based on clinical features, drug-induced liver disease can be divided into acute and chronic types, with specific symptoms as follows:

　　1. Acute drug-induced liver disease

　　Acute liver cell injury, with acute drug-induced liver disease being the most common, presents with clinical manifestations similar to acute viral hepatitis, often with fever, weakness, anorexia, jaundice, and elevated serum transaminases. ALP and albumin are less affected, and hyperbilirubinemia and prolonged prothrombin time are related to the severity of liver injury. Mild cases can recover shortly after discontinuation of the drug (a few weeks to a few months), while severe cases may develop liver failure, with progressive jaundice, bleeding tendency, and hepatic encephalopathy, often resulting in death.

　　When allergic reactions are predominant, symptoms often include fever, rash, jaundice, lymphadenopathy, accompanied by moderate elevation of serum transaminases, bilirubin, and ALP. The history of drug exposure is usually short (within 4 weeks). When cholestasis is predominant, symptoms include fever, jaundice, upper abdominal pain, itching, tenderness in the upper right abdomen, and liver enlargement with significantly elevated serum transaminases, ALP, and conjugated bilirubin (34-500 μmol/L), elevated bile salts, lipoprotein X, GGT, and cholesterol, while anti-mitochondrial antibodies are negative. Generally, recovery occurs 3 months to 3 years after discontinuation of the drug, with a few cases showing disappearance of bile ducts and chronic progressive disease. Occasionally, bile duct damage may be irreversible, progressing to liver cirrhosis.

　　2. Chronic drug-induced liver disease

　　Chronic hepatitis caused by drugs has similar clinical manifestations to autoimmune chronic hepatitis, ranging from mild with no symptoms to severe with liver failure accompanied by hepatic encephalopathy. Biochemical manifestations are the same as those of chronic viral hepatitis, with elevated serum transaminases, G-GT, progressive disease leading to liver cirrhosis with hypoalbuminemia and coagulation dysfunction.

　　The prevention of drug-induced liver disease is crucial, and the main preventive measures in clinical practice are as follows:

　　1. Mastering the indications for medication, clinical physicians should be familiar with the properties and liver toxicity of the drugs used, try to use as few or no drugs with liver toxicity, and禁忌 in unclear indications, avoid drug abuse and long-term and large-scale medication.

　　2. Before taking medication, attention should also be paid to the individual condition of the patient, considering factors such as overall condition, age, gender, physiological and pathological conditions, nutritional status, drug tolerance, and mental state. For patients with liver and kidney diseases, newborns, pregnant women, and other patients, the selection and use of drugs and dosage should be carefully considered.

　　3. Special attention should be paid to medication for patients with a history of drug allergy or allergic constitution.

　　4. Once liver function abnormalities or jaundice occur, immediately stop drug treatment.

　　5. For patients with a history of drug-induced liver damage, it should be avoided to give the same or chemically similar drugs again.

　　The main clinical examination methods for drug-induced liver disease mainly include laboratory examination and imaging examination, as follows:

　　First, laboratory examination

　　1. All serum markers of various viral hepatitis are negative.

　　2. Serum bilirubin, transaminase, alkaline phosphatase, total bile acid, serum cholesterol, etc., can be increased to varying degrees, plasma albumin can decrease, severe cases may have prolonged prothrombin time, reduced activity, increased blood ammonia, decreased blood glucose, etc., blood leukocyte count increased (accounting for about 21%), normal or decreased.

　　3. Patients with allergic reactions have an increase in peripheral blood eosinophils (〉6% of which account for 35%), and the positive rate of drug-induced lymphocyte transformation test can reach more than 50%.

　　Second, imaging examination

　　1. B-ultrasound examination: Whether to perform it depends on the condition, and it is helpful for the diagnosis of fatty liver, liver cirrhosis, liver tumor, and liver vascular lesions.

　　2. CT examination: Indications and significance are similar to those of ultrasound.

　　3. Liver biopsy: It can determine the pathological type of liver damage, but cannot determine whether it is caused by drugs.

　　Patients with drug-induced liver disease should consume more foods rich in protein, such as fish, meat, eggs, milk, and soy products, which can enhance the body's immune function, promote the regeneration and repair of liver cells, and greatly help in the recovery of the disease. Eating more fungal foods, such as mushrooms, wood ear, and mushrooms, not only enhances the body's immune function but also prevents and fights cancer. Eating more foods rich in vitamins, such as animal liver, fresh vegetables and fruits, coarse grains, and mixed grains, can lead to vitamin absorption disorders when the liver is damaged, causing deficiencies in vitamin A, B-group vitamins, and vitamin C. Supplementing adequate amounts of vitamins can improve the body's immunity, benefit the repair of liver cells, and enhance detoxification functions.

　　Patients with drug-induced liver disease should avoid spicy and刺激性 foods, quit smoking and drinking, and eat less fried food. It is best not to eat turtle, because the protein content of turtle is very high, it is not easy to digest after eating, which will increase the metabolic burden on the liver.

　　In addition to discontinuing certain drugs that are definitely or may cause this disease, patients with drug-induced liver disease should have appropriate rest and strengthen nutrition, consume high-calorie, high-protein, vitamin-rich, and low-fat diet, and can also be treated through TCM syndrome differentiation and simple methods, as follows:

　　First, Treatment Based on Syndrome Differentiation

　　1. Damp-heat Steaming Syndrome

　　Treatment Method: Clearing and benefiting damp-heat.

　　Medicines: Modified Yin Chen Hao Decoction, Zhizi Bai Pi Decoction, and Yin Chen Wu Ling Powder combined. In the formula, Yin Chen, Zhizi, Huang Bai, and Rhubarb clear heat and remove dampness, benefit the gallbladder and relieve jaundice, Bai Zhu, Poria, Zhu Ling, and Ze Xie strengthen the spleen and remove dampness. For those with obvious jaundice, you can add Yujin, Dandelion, Jin Qian Cao, and Ling Xian, etc.; for nausea and vomiting, you can add Ban Xia, Zhu Ru, Xuan Fu Hua, Dai Zhe Shi, and Su Gen, etc.

　　2. Liver Qi Stagnation Syndrome

　　Treatment Method: Relieving liver depression and regulating the spleen and stomach.

　　Medicines: Modified Xiaoyao Powder. Bupleurum chinense relieves liver and regulates qi, White peony nourishes the liver and relieves pain, Angelica sinensis nourishes blood, Poria, White atractylodes, and Liquorice strengthen the spleen and stomach. For those with obvious胁痛, add Yuanhu and Xiangfu; for nausea, add Chenpi and Paeonia lactiflora; for belching, add Su Gen; for lack of appetite, add Jiao Suanxian.

　　Second, Simple Remedy Treatment

　　1. Mung Bean and Liquorice Soup: 60g of mung bean, 30g of Liquorice, decocted as a beverage.

　　2. Jaundice Remedy: 30g of茵陈, 30g of Dandelion, 15g of Poria, 5g of Rhubarb, 10g of Liquorice, decocted in water for oral administration.

　　3. Hypolipidemic Decoction: 30g of Hedyotis diffusa, 15g of Poria, 12g of Bupleurum chinense, 10g of Liquorice, decocted in water for oral administration.