Elderly drug-induced liver disease

　　There are hundreds of drugs that can cause varying degrees of liver damage, including central nervous system drugs such as chlorpromazine and diazepam; chemotherapy drugs such as sulfonamides, isoniazid, rifampin, para-aminosalicylic acid, etc., antibiotics: erythromycin, benzathine penicillin; antiviral drugs: zidovudine, antipyretic and analgesics such as indomethacin, phenylbutazone, acetaminophen, salicylic acid, etc., anticancer drugs such as methotrexate, 6-mercaptopurine, 5-fluorouracil; other drugs such as androgens, estrogens, certain progesterone contraceptives, antithyroid drugs, and certain traditional Chinese medicines such as Coptis chinensis, Xanthium sibiricum, etc., can also cause drug-induced liver damage.

　　Drugs are metabolized in the liver, through a series of drug metabolism enzymes (abbreviated as drug enzymes, including cytochrome P-450, monooxygenase, cytochrome C reductase, etc.) on the smooth endoplasmic reticulum of liver cells, and coenzyme II (reduced form NADPH) in the cytoplasm, through oxidation, reduction, or hydrolysis to form corresponding intermediate metabolites (phase I reaction), and then combine with glucuronic acid or other amino acids (phase II reaction, i.e., drug biotransformation) to form water-soluble final products, which are excreted from the body. Final metabolites with a molecular weight greater than 200 are excreted through the biliary system into the intestines, while the rest are excreted through the kidneys.

　　The mechanism of drug-induced liver injury may be: ① Direct toxic effects of drugs and their intermediate metabolites on the liver, which can be predictable for this type of drug-induced liver disease; ② Allergic reactions or idiosyncratic reactions (idiosyncracy) to intermediate metabolites generated by the body's allergic reactions or specific quality reactions to drugs. This is an immune reaction of the body to drugs and their metabolites or to complexes formed by drugs and their metabolites covalently bound to macromolecules in the liver. This type of drug-induced liver disease is unpredictable.

　　The pathogenesis of drug-induced liver disease can directly lead to liver damage through various pathways, such as altering the physical properties (viscosity) and chemical properties (cholesterol/phospholipidation) of the liver cell membrane, inhibiting K+ and Na+-ATPase on the cell membrane, interfering with the uptake process of liver cells, disrupting the function of the cytoskeleton, forming insoluble complexes in bile, and selectively destroying cell components, covalently binding with key molecules, interfering with specific metabolic pathways or structural processes, and indirectly causing liver damage.

　　Elderly patients with acute drug-induced liver disease may develop chronic drug-induced liver disease, leading to cirrhosis in progressive cases. Severe cases may result in hepatic encephalopathy and liver failure. Liver failure is a clinical syndrome that occurs due to widespread and severe damage to liver cells and severe紊乱 in metabolic function of the body, abbreviated as liver failure. Liver failure occurs in many severe liver diseases, with a dangerous prognosis and often poor outcomes.

　　In clinical practice, drug-induced liver disease in the elderly is mainly divided into four types, with the following symptoms.

　　1. Patients with a history of drug use commonly suffer from acute drug-induced liver disease, which is primarily characterized by liver cell necrosis. When the clinical manifestations are similar to acute viral hepatitis, they include fever, loss of appetite, fatigue, nausea, jaundice, and elevated serum transaminases (2 to 30 times the normal level), with minimal impact on ALP and albumin. Hyperbilirubinemia and prolonged prothrombin time are related to the severity of liver damage. Mild cases can recover shortly after discontinuation of medication (within a few weeks to months); severe cases may lead to fulminant liver failure, progressive jaundice, bleeding tendency, and hepatic encephalopathy, often resulting in death.

　　2. Acute drug-induced liver disease mainly with allergic reactions often presents with fever, rash, jaundice, lymphadenopathy, accompanied by moderate elevation of serum transaminases, bilirubin, and ALP. The history of drug exposure is short (within 4 weeks).

　　3. Drug-induced liver disease mainly with cholestasis presents with fever, jaundice, upper abdominal pain, itching, right upper quadrant tenderness, and liver enlargement with mild elevation of serum transaminase, marked elevation of ALP (2-10 times), and significant increase in conjugated bilirubin (34-500 μmol/L). Elevated bile salts, lipoproteins, GGT, and cholesterol, while mitochondrial antibodies are negative. Generally, recovery occurs within 3 months to 3 years after discontinuation of medication, with a few cases showing bile duct disappearance and chronic progressive disease. Bile duct injury is irreversible and progresses to liver cirrhosis.

　　Chronic hepatitis caused by drugs has similar clinical manifestations to autoimmune chronic hepatitis, ranging from asymptomatic to severe with hepatic encephalopathy due to liver failure. Biochemical findings are similar to chronic viral hepatitis, with elevated serum transaminases and GGT. Progressive disease leads to liver cirrhosis with hypoalbuminemia and coagulation dysfunction.

　　The graded prevention measures for elderly drug-induced liver disease are as follows:

　　1. Tier 1 prevention

　　Pay special attention to medication in patients with a history of drug allergy or allergic constitution. Avoid giving the same or chemically similar drugs to patients with a history of drug-induced liver damage. For patients with liver and kidney diseases, and those with nutritional disorders, the use and dosage of drugs should be carefully considered.

　　2. Tier 2 prevention

　　During medication, pay special attention to monitoring blood counts, liver, and kidney function. Monitor for drug side effects.

　　3. Tier 3 prevention

　　Discontinue medications that may cause drug-induced liver injury. Provide liver protection and non-specific detoxification treatment to prevent liver failure and hepatic encephalopathy.

　　4. Risk factors and intervention measures

　　If a patient develops fever, jaundice, anorexia, fatigue, and elevated serum transaminase levels, discontinue the relevant medication immediately. Have the patient rest in bed, receive reasonable nutrition, ensure calorie and vitamin intake. Provide nursing care and non-specific detoxification treatment. For severe liver damage and obvious cholestasis, treatment with hepatocyte growth factors and S-met is recommended. For those with hepatic encephalopathy, arginine and hexapeptide treatment is given.

　　Acute allergic liver damage is characterized by an increase in the number of white blood cells and eosinophils, with elevated liver function, primarily indicated by increased serum transaminase (ALT), alkaline phosphatase (ALP); other possible elevations include serum bilirubin, leucine aminopeptidase (LAP), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), and increased serum bile acid concentration; plasma albumin may also decrease; urinary bile acids may be positive.

　　After elderly patients have drug-induced liver disease, they should pay more attention to diet and try to reduce the burden on the liver. The following points should be paid attention to in diet:

　　1. Patients should eat more foods with high protein content, such as meats, fish, eggs, dairy products, and various bean products, which are beneficial for the repair of liver cells;

　　2. Patients should limit the intake of high-sugar and high-fat foods, otherwise they may accumulate in the liver, form fatty liver, and thereby worsen the condition.

　　3. Patients should eat more fresh vegetables and fruits such as pumpkin, carrots, spinach, cucumbers, tomatoes, apples, grapes, etc. On one hand, they can meet the human body's needs for vitamins and minerals; on the other hand, they can prevent the deterioration of the condition and promote the recovery of the condition.

　　4. Patients should eat more fungal foods such as mushrooms, shiitake, and mushrooms, which not only can improve human immunity but also have the effects of inhibiting tumors and anti-cancer. In addition, patients should pay attention not to eat too much fried, greasy, spicy, and刺激性 foods in daily life.

　　The treatment of elderly patients with drug-induced liver disease mainly includes stopping the use of pathogenic drugs, and then assisting with other treatment methods. The specific plan is as follows:

　　1. Treatment

　　1. Routine treatment

　　(1) General treatment: Stopping the use of drugs that cause drug-induced liver disease or may cause drug-induced liver disease is an important treatment. Most patients can gradually improve or recover after stopping the relevant drugs. Rest in bed in a timely manner and gradually increase activities after the condition improves.

　　(2) Drug treatment:

　　Glycyrrhizin (Gantai Le, Glucuronic Acid Lactone): It plays an important role in the detoxification process in the body. Many toxic substances and drugs are excreted after combining with this product, and it can reduce the activity of liver amylase, prevent glycogenolysis, increase liver glycogen, and reduce fat storage, so it can be used for the treatment of drug-induced liver disease. Dosage: Oral: 0.1-0.2g, 3 times a day; intramuscular or intravenous injection: 0.1-0.2g, 1-2 times a day.

　　Thiopurine (Kaisilei): It is a new type of metabolic improvement and detoxification agent, with strong preventive and therapeutic effects on liver injury caused by carbon tetrachloride, ethanol, and D-galactose, preventing the accumulation of triglycerides, protecting the structure of liver mitochondria, and improving its function. Dosage: 0.1-0.2g per dose, intravenous infusion, course of treatment 2-4 weeks.

　　Glutathione (Tiet, Atormolan) in its reduced form participates in various important biochemical and metabolic reactions in the body, inhibits the production of peroxides in liver tissue and the accumulation of triglycerides, preventing liver cell变性, necrosis caused by ethanol, and the occurrence of liver fibrosis and other damages. Pharmacological studies have confirmed that it also has a preventive and therapeutic effect on liver injury caused by carbon tetrachloride. Dosage: 0.6g per dose, 1-2 times a day, intramuscular or intravenous injection.

　　④ Adenosine Methionine (Semeprime): It is a compound produced by the action of adenosine methionine enzyme on methionine and adenosine triphosphate (ATP). It can effectively enhance the metabolism of liver cells, promote the excretion of bile, reduce liver bile stasis, and help restore liver function. Dosage: 1000mg added to 250ml of 5% to 10% glucose solution for intravenous infusion.

　　⑤ Vitamin C: It is a water-soluble vitamin that can be used to treat liver damage in acute hepatitis and chronic poisoning by arsenic, mercury, lead, benzene, etc., and can enhance the body's resistance. It can be administered intravenously by adding 3-5g to glucose or normal saline.

　　⑥ Corresponding detoxifiers should be given for relevant drugs: for example, for liver damage caused by isoniazid, a large dose of vitamin B6 can be administered intravenously; for liver damage caused by excessive dose of acetaminophen (paracetamol), acetylcysteine should be administered intravenously promptly. Methionine (methylthionine) can also be used for treatment.

　　⑦ For patients with allergic reactions, severe jaundice, and severe illness, appropriate doses of adrenal cortical hormones can be used concurrently, and the dosage can be gradually reduced after the condition improves, which can be continued for 2-3 weeks.

　　Patients with severe jaundice or liver function failure should consider plasma exchange therapy. Severe patients, if conditions permit, should undergo liver transplantation.

　　2. Optimal Treatment

　　(1) Thiopurone (Kaisailai): 0.1-0.2g, once a day, intravenous infusion, for a course of 2-4 weeks.

　　(2) Glutathione (Tiet): 1.2g added to 250ml of 5% or 10% glucose solution for intravenous infusion, for a course of 2-4 weeks.

　　(3) Drug-induced liver disease mainly caused by bile stasis can be treated with adenosine methionine, 1000mg added to 250ml of 5% or 10% glucose for intravenous infusion, once a day, for a course of 2-4 weeks.

　　3. Rehabilitation Treatment

　　During the acute stage, bed rest is required, and light, palatable, and nutritious food should be consumed. Gradually increase activities after the condition improves. During the recovery period, appropriate physical exercise such as Tai Chi and Qigong can be performed.

　　II. Prognosis

　　Delaying timely treatment for drug-induced liver injury can result in a mortality rate of about 10%. If treated promptly, the prognosis is generally good.