It is often said that drugs can cure diseases, but they can also cause diseases. Although this is common knowledge, in clinical practice, it is customary to pay more attention to whether the drug can treat the disease well, but often neglect the possible adverse reactions caused by drugs.
”Drug liver”, as the name implies, is drug-induced liver damage, and is one of the important adverse drug reactions. Clinically, there are few patients who visit the clinic with unexplained elevated transaminases and are finally confirmed to have “drug liver” through detailed medical history. Yimin Mao, Department of Gastroenterology, Shanghai Renji Hospital
In an increasingly aging society, the use of drugs (including traditional Chinese medicine) and nutritional supplements, and the exposure to various chemicals in the environment are increasing, while the lack of knowledge about the rational application of drugs can lead to an increased risk of “drug liver”. In recent years, with the announcement and disclosure of the “poison capsule incident” and “hemorrhoid capsule”, the safety of drugs, especially “drug liver”, has attracted widespread attention from the whole society. Therefore, in clinical treatment, it is especially important to avoid the corresponding adverse reactions brought about by drugs as far as possible, and to stay away from “drug liver” and understand the knowledge about “drug liver”.
What does “drug liver” mean?
In the treatment of any disease, the application of conventional therapeutic doses of drugs that cause varying degrees of liver damage is called “drug liver”.
Why does “drug liver” occur?
Since all drugs enter the body and need to be metabolized, and the liver contains enzymes related to drug metabolism, almost all known drugs are metabolized in the liver, and of course, the liver can bear the brunt of drug-mediated diseases.
Usually, the occurrence of “drug liver” includes two situations: first, some drugs themselves or their metabolites in the body have different degrees of direct toxic effects on the liver, therefore, some patients can develop liver injury when applying such drugs, and the higher the dose, the greater the risk of “drug liver”. The risk of “drug liver” increases with higher doses. Since the drug or metabolite is known to have direct hepatotoxicity, the occurrence of “drug liver” is often predictable and easy to prevent when applying this type of drug. Second, the drug itself or its metabolites in the body are “non-toxic” to the liver, and the occurrence of “drug liver” is often not related to the “drug” but to the “person”. “The majority of patients who use drugs do not develop liver injury, and only a very small number of patients can develop liver injury. Usually, liver injury in this case is related to the patient’s own metabolic or allergic idiosyncrasies, such as significant abnormalities in the metabolism of a drug or allergies to drug components. Therefore, for these very few people, drug-induced liver injury is often more serious once it occurs, even causing liver failure and life-threatening, when the occurrence of “drug liver” is often difficult to predict and difficult to prevent.
What is the incidence of “drug-induced liver”?
The exact incidence of drug-related liver injury in the general population is difficult to estimate because of the difficulty of monitoring, and because patients and physicians do not report drug-related liver injury in a timely manner for various reasons. Data from France show that the incidence of “drug-related liver” is 14 per 100,000 person-years, which is higher than the 1-2 per 100,000 person-years estimated in other European and American countries. Data from abroad show that 2-5% of patients hospitalized for “jaundice” are caused by drugs, about 10% of patients hospitalized for “acute hepatitis” are caused by drugs, and about 10% of patients hospitalized for “acute liver failure About 30-40% of the patients hospitalized for “acute liver failure” were caused by drugs. Although there are no standardized studies reporting the incidence of drug-induced liver disease in China, it is assumed that the absolute number of drug-induced liver disease is also a large population, considering the large population base and the wide range of drug users in our country.
What drugs are likely to cause “drug-related liver disease”?
Since some drugs that can cause “drug liver” are directly toxic to the liver, while others are not directly toxic and are related to the patient’s own metabolism or allergic idiosyncrasies, theoretically, any drug (including health care products) has the potential to cause liver damage.
Foreign studies show that non-steroidal anti-inflammatory and analgesic drugs, antibiotics, etc. are the most common drugs causing liver damage in Europe and the United States. Anti-tuberculosis drugs, anti-tumor drugs, drugs for the treatment of neurological diseases, drugs for the treatment of psychiatric diseases, drugs for the treatment of cardiovascular and cerebrovascular diseases, drugs for the treatment of metabolic diseases, antifungal drugs, immunosuppressive drugs, hormonal drugs (including oral contraceptives) are all drugs known to cause liver damage more frequently. Therefore, it is important to monitor the application of these drugs to detect early signs of liver injury and take appropriate measures to avoid liver injury or more serious liver injury.
Are Chinese medicines “free of adverse effects”?
Chinese medicine is “safe and non-toxic” and does not cause adverse reactions, while western medicine is “toxic”, which is the long-standing understanding of many people about Chinese medicine. But, unfortunately, this is a serious misconception. Reports from Korea and Singapore suggest that Chinese herbal medicines are the most common drugs causing liver injury in their countries. In recent years, the incidence of liver injury caused by natural drugs, including herbal medicines, has also been increasing in China, and “Hemorrhoid capsule” is a typical example. The author once met a case of serious liver injury, which was finally confirmed to be caused by taking creams for winter tonic. Clinically, among many patients who visit the clinic for unexplained elevated transaminases or serious liver injury, a significant percentage of patients have a history of taking Chinese medicine when their medical history is carefully questioned. There are 72 kinds of herbal medicines that are clearly hepatotoxic, and the common ones are pyrrole bilane alkaloids, staphylocarpus spp, rhubarb, lei gong vine, cassia, he shou wu, fish gall bladder, aconite, etc. Given that the composition of herbal medicines is very complex and the interactions between the components are not well understood, the damage to the liver should be closely monitored when taking them.
How to interpret the liver function test report when “drug liver” is suspected?
Liver function tests that show a significant increase in ALT and/or AST are usually indicative of hepatocellular damage, and an increase in ALT of more than 3 times the upper limit of normal is called “drug liver”. If the main manifestation is a significant increase in alkaline phosphatase (AKP) and/or glutamyl transpeptidase (GGT), with an increase in AKP of more than 2 times the upper limit of normal, we call this a cholestatic “drug liver”. In other cases, there are patients who have both elevated ALT and elevated AKP or GGT, which is called a mixed type of “drug liver”.
In the liver function test report, in addition to the above-mentioned enzymatic indicators, we should also pay attention to total bilirubin, albumin, prothrombin time and other indicators. Abnormalities in these indicators, such as significantly higher total bilirubin, significantly lower albumin and significantly longer prothrombin time, usually mean that the liver is more seriously damaged, and the real function of the liver is damaged. Clinically, the presence of “bile enzyme separation” (a decrease in aminotransferase levels but a significant increase in total bilirubin) is often characteristic of severe liver injury, and the prognosis for these patients is poor, with acute liver failure and an increased risk of death, which is not a good thing when aminotransferase decreases.
In patients with drug-induced liver injury, if ALT levels exceed 3 times the upper limit of normal and total bilirubin levels exceed 2 times the upper limit of normal, the prognosis for these patients is equally poor, with a mortality rate of up to 10%.
What are the serious consequences of “drugged liver”?
The liver damage caused by “drug liver” can be acute, subacute or chronic. The types of injury can include all known liver pathologies, such as acute/subacute hepatocellular injury, acute/cholestasis, chronic hepatitis, autoimmune liver disease, fatty liver, cirrhosis, hepatic vascular disease, liver tumors, etc.
Drug-induced liver injury varies in severity, and people react differently to drugs. With the same drug, some people will experience corresponding liver damage, while others will not. In some people, the damage is relatively minor, with only transient abnormalities in liver enzymes (transaminases), and the liver enzymes can normalize on their own or not rise further significantly when the suspected drug is continued. However, in some people, liver injury may progress to liver dysfunction and acute liver failure, leading to death or the need for liver transplantation, whether or not the suspected drug is discontinued. Currently, the severity of drug-related liver injury is classified globally into 6 levels: Level 0, no adverse effects, tolerated; Level 1: only increased liver enzymes, most patients adapt; Level 2: mild loss of hepatocyte function detected; Level 3: severe disease requiring hospitalization; Level 4: acute liver failure; Level 5: death or need for liver transplantation.
”What are the clinical signs and symptoms of drug-induced liver disease?
”The clinical symptoms of drug-induced liver disease are not specific. Some patients may have symptoms similar to those of hepatitis, such as weakness, fatigue, poor appetite, upper abdominal discomfort, nausea, vomiting, jaundice, darkening of the urine, and itching of the skin. In addition, it may sometimes be accompanied by some manifestations of extrahepatic tissue damage, such as fever, arthropathy, rash, and increased eosinophilia. Therefore, when these suspicious symptoms appear, the possibility of “drug liver” should be considered.
Who is at high risk for “drug-induced liver disease”?
Elderly people are at high risk for drug-related liver disease because of the combination of multiple drugs and children because they are not fully developed. In addition, people with allergies, alcoholics, obesity, diabetes, liver disease, and reduced kidney function are all at high risk for drug-induced liver disease. For example, women have a higher rate of liver injury when taking halothane, diclofenac, furantoin and dex-propoxyphene, while men have a higher chance of liver injury when taking amoxicillin/clavulanic acid, acetaminophen, azathioprine, etc.
How can I avoid “drug liver” as much as possible?
The following methods can help you avoid the occurrence of “drug liver” as much as possible and prevent more serious liver injury.
1. When treating the primary disease, medication should be administered under the guidance of an experienced physician or clinical pharmacist.
2. Read the instructions carefully before treatment to confirm that the therapeutic drug used is consistent with the indications for the primary disease in the instructions, and understand the therapeutic dose, duration of treatment, whether there are reports of liver injury, drug interactions, precautions and other information.
3. need to confirm that the drug is within the expiration date before use.
4. storing the drug according to the requirements in the instructions.
5. confirmation that there is no previous history of allergy to the drug to be taken.
6.The dose and method of administration are consistent with the instructions, and avoid arbitrarily increasing the dose or extending the course of treatment.
7. avoid, as far as possible, the simultaneous use of multiple drugs unless it is necessary.
8.Communicate with physicians to avoid, as far as possible, the use of therapeutic drugs that have been reported to have hepatotoxicity.
9.During the course of medication, pay attention to the emergence of some non-specific symptoms, and communicate with the doctor as soon as they appear.
10.For those who have to take therapeutic drugs that have been reported to have hepatotoxicity, they need to monitor liver function regularly and communicate with the physician who treats the original disease in time to decide whether the original treatment plan needs to be changed once signals or abnormalities appear.
11. Once liver injury occurs, you should visit a professional hepatologist at the same time to seek the best treatment plan.
Taking medication is to cure the disease, not to add to it, and the best strategy is to obtain the maximum expected therapeutic effect with the least therapeutic risk. Therefore, reducing the occurrence of drug-derived diseases and damage to the liver in the course of drug therapy should be given sufficient attention.