Drug-induced liver disease in the elderly

Introduction to drug-induced liver disease in the elderly Drug-induced hepatic disease (abbreviated as drug-induced liver disease) refers to liver damage caused by the drug itself or its metabolites. It can occur in healthy people who have no previous history of liver disease or who have had serious illnesses. Different degrees of liver damage occur after the use of a certain drug, which is called liver. At present, there are at least 600 kinds of drugs that can cause liver disease. The main clinical manifestations are hepatocyte necrosis, cholestasis, intracellular microlipid deposition or chronic hepatitis, cirrhosis and so on. basic knowledge The proportion of the disease: the incidence rate of the elderly over 60 years old is about 0.8% -2% Susceptible people: the elderly Mode of infection: non-infectious Complications: liver cirrhosis, hepatic encephalopathy

The cause of drug-induced liver disease in the elderly

Cause

There are hundreds of drugs that can cause liver damage of varying degrees, among which drugs that act on the central nervous system, such as chlorpromazine, are stable; chemotherapy drugs such as sulfonamides, isoniazid, rifampicin, p-aminosalicylic acid, etc. Antibiotics: erythromycin, benzomethoxazole penicillin; antiviral drugs: zidovudine, antipyretic analgesics such as indomethacin, phenylbutazone, acetaminophen, salicylic acid, etc., anticancer drugs Such as methotrexate, 6-thiopurine, 5-fluorouracil; other such as testosterone, estrogens, certain progesterone contraceptives, anti-thyroid drugs, and certain Chinese medicines such as xanthium, Xanthium, etc. can also cause drugs Sexual liver damage.

Pathogenesis

Pathogenesis

(1) The direct toxic effect of drugs and their intermediate metabolites on the liver. This type is positively correlated with the dose, and the incubation period is short, causing hepatocyte necrosis, which can be predicted.

(2) Allergic reactions of the body to allergic reactions to drugs or drug-specific reactions to produce intermediate metabolites, and allergic liver damage can be divided into "spleen-type" hepatitis and "hepatitis-type" hepatitis, the degree of damage to the liver and The intake of drugs is irrelevant, the incubation period is mostly long, and it cannot be predicted beforehand. This type has a genetic tendency and may be the result of genetic enzyme defects.

2. The degree of pathological drug-induced liver damage varies greatly, and the clinicopathological classification is as follows:

(1) Acute type:

1 liver cell type:

A. Hepatitis type: mild or punctate or focal necrosis, severe acute subacute severe hepatitis, seen in drugs such as carbon tetrachloride, acetaminophen, isoniazid and halothane.

B. Fatty liver type: Hepatic cell fatty changes, but also necrosis, inflammation and stagnation, found in a large number of intravenous tetracycline asparaginase.

2 intrahepatic stagnation type:

A. Simple stagnation type: liver stagnation in the central area of hepatic lobules, generally no liver parenchymal cell damage, no inflammatory reaction, see testosterone derivatives, jaundice caused by methyltestosterone is more common, oral contraceptives are also May cause jaundice.

B. stagnation with inflammation: capillaries, hepatocytes and stellate cells have cholestasis, more prominent in the central area of the lobules, accompanied by inflammatory cell infiltration and focal necrosis in the portal area, representative drug chlorpromazine.

3 mixed type: a lot of drugs caused by liver damage is not easy to classify, pathological changes mainly liver parenchymal damage, focal central area, even banded or large pieces of necrosis, sometimes accompanied by mild stagnation.

(2) Chronic type:

1 Chronic hepatitis type: Some drugs can cause chronic active hepatitis, and its pathological changes are similar to autoimmune active hepatitis, including fragmentary necrosis around the hepatic lobules, infiltration of inflammatory cells in the portal area and hepatic lobule, destruction of leaflet boundary plates, fibers Tissue hyperplasia, etc., can be accompanied by changes in subacute severe hepatitis, seen in isoniazid, sulfonamide, halothane, propylthioximidine.

2 cirrhosis type: methotrexate, inorganic arsenic, asparaginase, etc., can occur liver cell steatosis, liver fibrosis or portal cirrhosis pathological changes.

3 chronic stagnation type: liver pathology showed capillary bile duct thrombosis, hepatic cells and stellate cell pigmentation, small bile duct hyperplasia and pseudo bile duct formation.

4 other: long-term oral contraceptives cause hyperplastic changes in liver nodules, leading to benign liver adenomas, testosterone derivatives can cause benign and malignant liver tumors, phenylbutazone, phenytoin caused by liver granuloma, some drugs cause intrahepatic veins Occlusion and hepatic vein thrombosis.

Elderly drug-induced liver disease prevention

Primary prevention: For patients with a history of drug allergies or allergies, special attention should be paid to the use of drugs. Patients with a history of drug-induced liver damage should avoid giving the same or similar chemically similar drugs to patients with liver and kidney disease. For the disabled, the use and dosage of the drug should be carefully considered.

Secondary prevention: During the medication, the patient pays special attention to monitoring blood, liver and kidney functions and monitoring the side effects of the drug.

Tertiary prevention: discontinue drugs that may cause liver disease, give liver protection and non-specific detoxification treatment to prevent liver failure and hepatic encephalopathy.

Risk factors and interventions: Once the patient has fever, jaundice, anorexia, fatigue and elevated serum transaminases, immediately stop using the drug, let the patient rest in bed, reasonable nutrition, ensure calories, vitamin supply, care and non-specific detoxification treatment , severe liver damage and obvious cholestasis, can be given to hepatocyte growth hormone and Simeita treatment, combined with hepatic encephalopathy, arginine and hexavalent amino acid treatment.

Complications of drug-induced liver disease in the elderly Complications, liver cirrhosis, hepatic encephalopathy

It can be complicated by chronic drug-induced liver disease, progressive type leads to cirrhosis, and severe cases can occur with hepatic encephalopathy and liver failure.

Symptoms of drug-induced liver disease in the elderly Common symptoms Loss of appetite, skin itching, bleeding, right upper quadrant pain, nausea, coagulopathy, fever, liver failure, hypoproteinemia

There is a history of receiving drugs, acute drug-induced liver disease is the most common, when hepatocyte necrosis is dominant, the clinical manifestations resemble acute viral hepatitis: fever, loss of appetite, fatigue, nausea, jaundice and serum transaminases (normal 2 to 30 times ), ALP and albumin are less affected, hyperbilirubinemia and prolongation of prothrombin time are related to the severity of liver damage. Patients with mild disease can recover in short-term after stopping the drug (weeks to several months). Fulminant liver failure, progressive jaundice, bleeding tendency and hepatic encephalopathy, often occur.

Acute drug-based acute liver, often with fever, rash, jaundice, swollen lymph nodes, with serum aminotransferase, bilirubin and ALP moderately elevated, drug exposure history is shorter (within 4 weeks).

The drug-based liver with cholestasis is fever, jaundice, upper abdominal pain, itching, right upper quadrant tenderness, liver hypertrophy with mild elevation of serum transaminase, ALP elevation (2 to 10 times), and bilirubin increased significantly ( 34-500mol/L) bile salts, lipoproteins, GGT and cholesterol are elevated, while mitochondrial antibodies are negative, usually recovered from 3 months to 3 years after discontinuation of the drug, a few cases of bile duct disappearance with chronic progressive process, and bile duct injury is irreversible , progress to cirrhosis.

Drug-induced chronic hepatitis is similar to the clinical manifestations of autoimmune chronic hepatitis, mild to asymptomatic, and heavier to liver failure with hepatic encephalopathy, biochemical performance is the same as chronic viral hepatitis, serum transaminase, GGT is elevated, Progressive causes cirrhosis with hypoproteinemia and coagulopathy.

Examination of drug-induced liver disease in the elderly

In acute allergic liver damage, the number of white blood cells and eosinophils increased, and the liver function was characterized by elevated serum aminotransferase (ALT) and alkaline phosphatase (ALP), followed by serum bilirubin. Leucine aminopeptidase (LAP), -glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), elevated serum bile acid concentration, plasma albumin can also be reduced, urinary tricholemia can be positive .

Liver biopsy is useful for the diagnosis of certain difficult cases.

Diagnosis and identification of drug-induced liver disease in the elderly

Diagnostic criteria

The diagnosis of the drug liver can be comprehensively diagnosed according to the history of medication, clinical symptoms, blood liver function test, liver biopsy and the effect after drug withdrawal.

1 medication history: any patient with liver disease must ask about the drugs taken within 3 months before the onset, including the dose, route of administration, duration and other drugs used at the same time.

2 There is no liver disease, evidence of viral hepatitis and other causes of liver disease.

3 Whether the primary disease may affect the liver.

4 In the past, there was no history of drug allergy or history of allergic diseases. In addition to medication, any related allergic reactions such as rash and eosinophilia were found to be important for the diagnosis of liver.

Diagnostic criteria for liver disease caused by drug allergic reactions:

1 1 to 4 weeks after taking the drug, liver dysfunction occurred.

2 The first symptoms are mainly fever, rash, itchy skin and jaundice.

3 The peripheral blood eosinophils increased (up to 6% or more) at the onset of the disease.

4 drug sensitivity test (lymphocyte culture test, skin test) is positive.

5 occasionally re-medication can cause liver disease, with 14 or 15 can be diagnosed, with 12 or 13 can be diagnosed, liver biopsy in the early stage of the disease can help identify the type of lesion and understand the degree of liver damage.

Differential diagnosis

Need to differentiate diagnosis: viral hepatitis, systemic bacterial infection, postoperative intrahepatic cholestasis, choledochitis with acute pancreatitis, bile duct injury, congestive heart failure, liver function deterioration of chronic liver disease.

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