During a health checkup, many people get very nervous when they see an elevated ALT, thinking they have viral hepatitis, and rush to the liver clinic. When the possibility of hepatitis is ruled out, many people think they are safe and sound. In fact, ALT is not only elevated when you have hepatitis. There are dozens of causes of ALT elevation. If a physical examination reveals that ALT is elevated and viral hepatitis is ruled out, it should not be taken lightly and further investigation of the cause is necessary. ALT is found in many tissues and organs in the human body, and its content in the body organs is in the following order: liver, kidney, heart muscle, brain, skeletal muscle, lung, testis and uterus. When lesions or damage occur in these tissues and organs, they can cause different degrees of elevated serum ALT levels. Since the highest level of ALT is found in hepatocyte plasma, it is most significantly elevated when hepatocytes are damaged. In clinical practice, when a patient has elevated ALT in the serum, the presence of liver disease should be considered first. In addition to hepatitis A, B, C, D, and E, which cause elevated ALT, many other pathogenic factors can also cause hepatocellular damage. Non-alcoholic fatty liver disease With the high prevalence of obesity and diabetes, non-alcoholic fatty liver disease has now become one of the common chronic liver diseases in China, posing a serious health risk. Patients with this disease may have non-specific symptoms and signs such as weakness, dyspepsia, vague pain in the liver area, hepatosplenomegaly, etc. They may have overweight and/or visceral obesity, increased fasting glucose, dyslipidemia, hypertension, etc. Serum ALT may be mildly to moderately increased (less than 5 times the upper limit of normal value), and serious cases may progress to cirrhosis. For the diagnosis of fatty liver, the first step should be based on imaging findings such as ultrasound or CT, and detailed medical history to clarify the cause. Based on laboratory tests and pathological histological examination of liver puncture biopsy, it should be determined whether it is simple fatty liver or steatohepatitis, and other diseases should be excluded. Alcoholic liver disease Alcoholic liver disease can be caused by long-term heavy alcohol consumption. Initially, it is usually characterized by fatty liver, which can develop into alcoholic hepatitis, alcoholic liver fibrosis and alcoholic cirrhosis, and in severe alcohol abuse, it can lead to extensive hepatocellular necrosis or even liver failure. The diagnosis of alcoholic liver disease should be considered when the patient has a history of long-term alcohol consumption (generally more than 5 years, with an alcohol equivalent of ≥40g/day for men and ≥20g/day for women, or a history of heavy drinking within 2 weeks, with an alcohol equivalent of >80g/day), elevated serum ALT, and an abdominal ultrasound or CT examination suggesting fatty liver. Clinically, the disease may be asymptomatic or with right upper abdominal distension and pain, loss of appetite, fatigue, weight loss, jaundice, etc. As the disease worsens, signs and symptoms such as neuropsychiatric, spider nevus, and liver palms may be present. Autoimmune liver disease This is inflammation and hepatocyte necrosis caused by the patient’s autoimmune system attacking the liver. The common ones are autoimmune hepatitis, primary biliary cirrhosis, and sclerosing cholangitis. These diseases are mostly seen in women, are chronic and progressive, and can progress to cirrhosis or even hepatocellular carcinoma. Clinically, in addition to elevated serum ALT and immunoglobulins, autoantibodies, such as antinuclear, antimitochondrial, and anti-smooth muscle antibodies, are also present in the serum of these patients. Drugs that may cause hepatocellular damage include anti-TB drugs (e.g., isoniazid, rifampin, etc.), sulfonamides, tetracyclines, macrolides, antipyretics (e.g., aspirin, etc.), anticancer drugs, sulfonylureas, certain lipid-lowering drugs (e.g., statins), antithyroid drugs (e.g., tapazole), and certain traditional Chinese medicines. Most of these patients’ liver function can be restored to normal after stopping liver-damaging drugs or applying liver-protective or enzyme-lowering drugs. Biliary tract disorders Gallbladder inflammation, cholelithiasis, bile duct obstruction and pancreatic disorders can also increase ALT. Endocrine system diseases Among the endocrine diseases causing ALT elevation, the most common one is hyperthyroidism. Connective tissue diseases Systemic lupus erythematosus can cause damage to multiple systems and organs throughout the body, including the liver, and in adults, such as Still’s disease, can also cause damage to liver function. Infectious diseases Non-hepatophilic viruses, such as EBV and cytomegalovirus infections can cause hepatocellular lesions resulting in elevated serum ALT. Severe bacterial infections, such as sepsis and typhoid fever, can cause liver damage. Heart diseases Such as acute myocardial infarction, myocarditis, infective endocarditis, etc. When acute infarction occurs, the coronary blood supply is drastically reduced or interrupted, causing severe and persistent acute ischemia of the corresponding myocardium leading to myocardial necrosis, prompting the release of large amounts of enzymes from necrotic cells into the blood, causing ALT to rise. Muscle diseases such as dermatomyositis and polymyositis can result in skin damage, muscle damage, decreased muscle strength, muscle atrophy and fibrosis to the point of loss of function. In addition, pregnancy, strenuous exercise, excessive fatigue, insomnia, etc. can also cause ALT elevation.