Symptoms of drug-induced hepatotoxicity

summary

At present, the classification of drug-induced liver damage is not completely satisfactory, but most acute cases can be divided into hepatocyte type, cholestasis type (with or without inflammation) and mixed type. Some drugs can cause chronic liver damage including tumor. Drug induced hemolysis can cause unconjugated hyperbilirubinemia and mild jaundice, but no real liver damage, Therefore, the liver function test was normal

Symptoms of drug-induced hepatotoxicity

Direct cytotoxicity most of the drugs with direct hepatotoxicity can lead to dose-related liver necrosis and damage other organs (such as kidney). There are several kinds of liver damage caused by these drugs, such as necrosis and fat infiltration in area 3 of hepatic acini (central lobular area) caused by carbon tetrachloride and related hydrocarbons; Phosphorus mainly caused necrosis of the hepatic acinar zone 1 (around the portal vein); Ingestion of all kinds of mushrooms of genus Muscovy resulted in fatal hemorrhagic necrosis of liver; Large dose of tetracycline, especially in pregnant women, can cause diffuse infiltration of fat droplets in the liver, and the clinical manifestations are similar to hepatitis

Acute overdose of acetaminophen is an important cause of fulminant liver failure (see section 263, acetaminophen poisoning). In adults, acetaminophen dose > 10-15g or > 4G / D can cause glutathione depletion in the liver for several days, If this effect is saturated, free intermediate metabolites can bind with large molecules in the liver, resulting in liver necrosis mainly located in the area 3 of hepatic acini. Microvascular injury is obviously an important mechanism of early liver damage

The liver damage is usually obvious 2-5 days after ingestion of paracetamol, and the clinical and biochemical evidence of acute hepatocyte necrosis also appears; Acetylcysteine can supplement glutathione, which can prevent liver necrosis. For example, it can save patients' lives if it is used within 10-12 hours after poisoning; Acetylcysteine is non-toxic and can be administered orally and intravenously at a dose of 140 mg / kg for the first time, then 70 mg / kg every 4 hours for 3 consecutive days. The intravenous dose is 300 mg / kg for 20 hours, half of which needs to be injected within 15 minutes. There is evidence that paracetamol can also cause chronic liver damage

matters needing attention

Chronic drug-induced liver injury is similar to chronic hepatitis. In addition to liver damage, there may also be extrahepatic manifestations. Individual patients may develop cirrhosis, which is often caused by the sustained development of inflammation due to the failure of timely termination of liver damage drugs or the induction of immune dysfunction. Therefore, doctors and patients should pay great attention to drug-induced liver injury.