Overview
The liver is the main organ of drug concentration, transformation and metabolism, especially oral drugs are absorbed from the gastrointestinal tract and enter the liver, and the concentration in the liver is higher than that in the blood and other organs. Due to the toxic effects of drugs and metabolites or allergic reactions of the body to drugs, the liver is damaged, causing inflammation of liver tissue, which is drug-induced liver damage. Some drugs are directly toxic to hepatocytes and damage all structures of hepatocytes without selectivity; some drugs initially only interfere with a metabolic process in hepatocytes, and only later indirectly contribute to hepatocyte steatosis or necrosis; there are also drug-induced liver damage that occurs only in some individuals and belongs to a metabolic reaction (immune response) of the body, through antigen (drugs are mostly semi-antigens ) antibody binding, interfering with the structure and function of hepatocytes. According to the pathological manifestations of the liver, drug-related liver damage is generally classified into three types, namely hepatocellular, bile duct obstruction and hepatocellular bile duct type. After the occurrence of liver damage, the clinical manifestation is often liver enlargement, abnormal liver function or jaundice. If the drug can be discontinued in time, most of them can be restored to normal; very few patients can further deteriorate and develop secondary hepatic steatosis. Drug-related liver damage is most common in hepatocellular lesions.
Causes of disease
1, in order to treat the disease, taking hepatotoxic drugs. This is very common, such as the use of hypoglycemic drugs for diabetic patients, anti-TB drugs for TB patients, immunosuppressive drugs for organ transplant patients, etc.. And these drugs happen to have damage to the liver.
2, the patient’s own indiscriminate use of drugs. Some people do not find a doctor, they go to the pharmacy to buy drugs, but do not understand the adverse effects of the drugs purchased, buy and use, resulting in liver damage.
3, gullible advertising, buy fake drugs.
4, mixed use of Chinese and Western drugs, Chinese drug preparations added to Western drugs, which then combined with Western drugs, taking the amount of drugs over the limit.
Types
1, only cause intrahepatic biliary sludge, small bile duct and capillary bile duct bile embolism and no hepatocyte necrosis and inflammatory reaction Drugs belonging to this category are: oral contraceptives, methyltestosterone, etc.
2, can cause biliary stagnation and hepatocyte necrosis two aspects of the lesions belong to this category of drugs: chlorpromazine, thiouracil, erythromycin, phenothiazine, sulfonamide, etc..
When the above two types of drugs are discontinued or reduced, the lesion reaction disappears, so the medication will not cause the above lesions when it is used according to medical advice.
3, cause more obvious hepatocyte necrosis hepatocytes have fatty degeneration, eosinophilia and obvious necrosis and accompanied by inflammatory reaction. Drugs belonging to this category include: halothane (inhalational anesthetics), paracetamol (antipyretic and analgesic), isoniazid, aminomethylfolate (anticancer drug), tetracycline, etc. Some of these injuries can be recovered after discontinuation of the drugs, but if they are taken in large quantities continuously, the lesions progress and eventually lead to hepatic sclerosis and hepatic insufficiency.
Manifestations
Drug-induced hepatitis usually occurs 1 to 4 weeks after drug administration, and the specific manifestations are more or less the same as other hepatitis, with hepatocellular damage as the main manifestation, including fatigue, loss of appetite, nausea and vomiting, yellow urine, discomfort in the liver area, liver enlargement with pressure pain, elevated transaminases, and elevated eosinophils in the blood picture; with bile stasis as the main manifestation, with bile stasis in the small intrahepatic bile ducts and hepatocellular damage, manifesting In those cases where bile stasis is predominant, it is manifested as bile stasis in the small intrahepatic bile ducts with hepatocellular damage, manifested as yellow staining of the skin, sclera, and urine, itching of the skin, and light-colored stools.
Severe drug-related liver damage can also cause extensive hepatic necrosis, resulting in heavy hepatitis, severe jaundice, coagulation dysfunction and hepatic encephalopathy, and in some cases, upper gastrointestinal bleeding. If the diagnosis and treatment are not timely, it may be life-threatening. Hepatocellular necrosis is life-saving with life-saving treatment, but the necrotic tissue may be replaced by extensive fibrous connective tissue, forming post-necrotic cirrhosis.
Diagnosis
(1) In patients with liver disease, the possibility of drug-induced disease should be considered, therefore, a detailed history of drug administration, such as the dose of medication, the time of starting and stopping medication, and the interval from the onset of the disease, should be inquired. Literature data show that about 50% to 70% of patients with drug-induced hepatitis develop within 2 weeks of drug administration, and about 80% to 90% develop within 8 weeks. In addition, it should be known what kind of drugs or chemicals have been exposed occupationally.
(2) Pay attention to the presence of allergic signs such as fever, skin and mucous membrane damage, rash, arthralgia and eosinophilia. The size of the liver should also be noted, as some drugs can cause asymptomatic hepatomegaly.
(3) Attention should be paid to differentiate from acute and chronic viral hepatitis, obstructive jaundice and hepatic sclerosis.
(4) Liver biopsy, when inflammation in the portal area with a large number of eosinophilic infiltrates and biliousness is seen, is beneficial for the diagnosis of drug-related hepatitis.
(5) It is believed that a drug skin allergy test is helpful for diagnosis after recovery from liver disease. It is recommended to use a small dose of the relevant drugs for the stimulation test, and to measure the activity of a variety of serum enzymes before and after the drug, and after the drug is measured several times in succession are significantly higher than before the drug, can be considered drug hepatitis. However, the drug provocation test is only 40% to 60% positive, and some repeat dosing time is long, the provocation test also has a certain risk, so it should not be used easily.
Countermeasures
Once the diagnosis of drug hepatitis is confirmed, the known or suspected drugs should be stopped immediately, the activity should be reduced, and liver-protective and detoxifying drugs should be given, such as vitamins, liver-protective and enzyme-lowering classic drug – Shuilinjia, etc. Apply symptomatic detoxifying drugs according to the specific type of drug causing liver toxicity, e.g. for drug hepatitis caused by isoniazid, use high-dose intravenous drip of vitamin B6. For those with allergies and deep jaundice, adrenocorticosteroids can be used, and the dosage will be gradually reduced when the condition improves.
Treatment principles
(1) Immediately stop the use of drugs that are damaging to the liver.
(2) General treatment is the same as for other causes of acute and chronic hepatitis, such as timely rest, giving a high-calorie, high-protein diet, and if there is bleeding or hepatic coma, it should be treated as bleeding or hepatic coma.
(3) Supplement with B vitamins and vitamin C. Add vitamin K if there is a tendency of bleeding.
(4) Try to use agents with special therapeutic effects, such as isoniazid-induced hepatitis with larger doses of vitamin B6.
(5) If there is allergy, deep jaundice and serious condition, adrenal glucocorticoids can be used, and the dose will be gradually reduced after the condition is reduced.
(6) Patients with cholestasis type should be treated with phenobarbital and cholestrol, and those with heavy jaundice can be treated with Chinese herbal medicine Yinjianhuang.
Prevention
(1) Doctors and patients should be familiar with the performance and adverse reactions of the drugs used, and try to use less or no hepatotoxic drugs.
②Never use the drug reluctantly when it does not meet the indications of the therapeutic drug, and use the drug strictly according to the indications and dosage specified in the drug manual.
③Patients with a history of drug allergy and liver and kidney diseases should be more cautious with drugs and use them as little as possible.
④For those who must use drugs, try to use drugs with less hepatotoxicity among similar drugs, or replace them with other drugs. For those who must use it, it can be used for a short time or alternatively.
⑤ When using new drugs, be sure to regularly check liver function and monitor the occurrence of adverse reactions. When combining drugs, drug interactions need to be taken into account to avoid superimposed liver damage.
Why do drugs cause hepatitis?
First, the direct hepatotoxic effects of drugs and their metabolites cause the destruction of hepatocyte membranes and cytoskeleton, or cause nucleic acid transformation and mutation leading to hepatocyte death.
Second, some drugs interfere with certain aspects of cellular metabolism, such as inhibiting the activity of enzymes or impeding a certain secretion process, resulting in reduced liver function.
Third, drugs with enzyme inducer effects can accelerate the metabolism of the drug itself and other drugs, producing more toxic products and damaging liver cells; drugs with enzyme inhibitor effects can increase the concentration of other drugs, increasing their toxicity or causing the accumulation of drugs in the liver, resulting in liver damage.
Fourth, the allergic reaction caused by drugs and their metabolites, through cellular immunity or humoral immunity, causing liver cells to be recognized and killed by the immune system, damaging liver function and even causing severe hepatitis.
What are the drugs that cause drug-related hepatitis?
There is a wide range of drugs that cause drug-related hepatitis, and there are many Chinese and Western drugs that are hepatotoxic, and the most common Western drugs are.
1, antibiotics, such as anti-tuberculosis drugs rifampin, isoniazid, etc.; macrolides, such as erythromycin, spiramycin, etc.; tetracyclines, etc.
2.Antipyretic and analgesic drugs: aspirin, pautaceone, etc.
3.Anti-psychotic drugs: chlorpromazine, fenadine.
4, antidepressants: amitriptyline.
5, anti-epileptic drugs: sodium valproate.
6, sedative drugs: phenobarbital, etc.
7.Anti-hyperthyroidism drugs: tabazol, methylphenidate, propylthioxypyrimethamine, etc.
8.Anti-tumor drugs: mitomycin, rejuvenomycin, cyclophosphamide, etc.
9.Glucose-lowering drugs: euglycemia, bethanechol, etc.
10.Cardiovascular drugs: Isoptin, Amprolium, etc. Chinese herbal medicines include Qing Dai, Neem, Shan Dou Root, Shan Ciguan, etc.