Drug hepatotoxicity manifests with clinical signs and symptoms caused by an underlying pathologic injury. The clinical presentation may or may not suggest the underlying liver injury, and therefore, the types of injuries are sometimes described separately. Some drugs usually cause one clinical and pathologic injury, and other drugs can cause a variety of injuries, often making the diagnosis more challenging. People who drink alcoholic beverages regularly are at higher risk of developing severe liver damage from acetaminophen. Drinking alcohol regularly changes the way the liver breaks down certain medications.
- However, additional factors can dictate the severity of DILI.
- Doctors may sometimes use the following compounds to prevent liver injury from drugs.
- Dr. Milinkovic built her expertise in emergency medicine as a clinical fellow at a major trauma center before practicing at a central London teaching hospital throughout the pandemic.
- Having mild liver disease such as hepatitis C or fatty liver does not increase the risk that a given medication will be toxic to the liver.
Hepatotoxicity Diagnosis
Approximately 75% of the idiosyncratic drug reactions result in liver transplantation or death. Toxic liver disease, or drug-induced liver injury (DILI), is damage to your liver. It can cause serious symptoms or liver damage if you don’t get help. Some drugs can cause a type of liver damage known as drug-induced liver disease, or drug-induced liver injury. These drugs include both prescription and over-the-counter (OTC) medications.
Those at particular risk include children younger than 2 years, those with congenital metabolic disorders or organic brain disease, and those with seizure disorders treated with multiple anticonvulsants. Active liver disease or unexplained aminotransferase elevations are contraindications to use of these drugs. Exercise caution in patients with a recent history of liver disease or in persons who drink alcohol regularly and in large quantities. Cholestatic jaundice has been reported with repeated use of quinolones. Approximately 1.9% of patients taking ciprofloxacin show elevated ALT levels, 1.7% have elevated AST levels, 0.8% have increased alkaline phosphatase levels, and 0.3% have elevated bilirubin levels. Jaundice is transient, and enzyme levels return to the reference range.
Stay well-hydrated to support toxin elimination, and limit alcohol consumption, especially when taking medications. Competition for the same metabolic pathways represents a common interaction mechanism. When multiple Medications Affecting Liver drugs require the same CYP450 enzyme for metabolism, they compete for processing, potentially causing one or both to accumulate.
Medications, herbal supplements, chemicals, solvents, and alcohol are all possible causes of hepatotoxicity. Many of these are available without a prescription and can be purchased OTC at pharmacies, health stores, and online. Taking or using more than one OTC or prescription drug containing acetaminophen without the guidance of a healthcare provider is not recommended because of this risk. However, certain medications and supplements have the potential to cause damage to the liver cells, the flow of bile, or both.
For that reason your physician may obtain a baseline liver panel prior to starting a medication to be sure that it is normal. Medications that are known to be toxic to people with liver disease usually carry a warning regarding its use in people with liver problems. Steer clear of herbal supplements that could harm your liver. Talk to your doctor before you start any new medications or supplements. High levels could be a sign of liver damage, but could also mean another condition.
Diagnosis
- And while most medications are safe when taken as directed, older adults can be more sensitive to these risks, so it’s important to be aware and bring any concerns to your healthcare provider.
- Indications were that rechallenging a patient with this medication could be appropriate, and in more than 80% of cases, the alanine aminotransferase (ALT) abnormalities resolved or did not reoccur.
- In addition, even healthy persons should avoid taking 3,000 mg of acetaminophen daily for more than 3 to 5 days.
- It can cause serious symptoms or liver damage if you don’t get help.
- Amoxicillin causes a moderate rise in AST levels, ALT levels, or both, but the significance of this finding is unknown.
Cholestasis is defined as a reduction in bile flow resulting from reduced secretion or obstruction of the biliary tree. If any evidence indicates hepatocellular injury, it is called cholestatic hepatitis. Histology shows apoptotic bodies, small foci of necrosis, and, less often, ballooning with or without zone 3 necrosis. Bile accumulates in the cytoplasm of the liver cells, canaliculi, and Kupffer cells.
Statins/HMG-CoA reductase inhibitors (package insert)
The latency period of idiosyncratic drug reactions is highly variable; hence, obtaining a history of every drug ingested in the past 3 months is essential. People who are taking statins may have high liver enzyme levels on a blood test, which can be a sign of drug-induced liver damage. Your liver processes most medications through complex enzyme systems, making it vulnerable to drug-induced stress and damage.
Surprising Things That Can Increase Your Risk of Falling
You may also feel slowly worse over days or weeks of regular exposure. It usually takes two to three months to make a full recovery. During this time, you may get supportive care to address your symptoms.
In the case of acetaminophen, alcohol use leads to accumulation of a toxic byproduct of acetaminophen in the liver that can kill the liver cells. People who drink alcohol regularly should not take acetaminophen. Minor elevations (less than 3 to 5 times over normal level) may occur after starting a medication and do not indicate significant liver damage, the medication is continued and the liver tests are monitored. In most cases, the liver tests will return to normal despite continuing the medication. Toxic liver disease, or hepatotoxicity, is when you have damage to your liver.
In addition, poor diet, infections, and multiple hospitalizations are important reasons for drug-induced hepatotoxicity. If the liver tests are monitored, the medication should not be stopped if only minor elevations of liver tests are noted. Blood tests can usually detect evidence of liver damage before symptoms develop. Whether hepatotoxicity gets better on its own depends on the cause, duration, and the liver’s ability to heal itself. In mild cases, when exposure to the toxin or drug is temporary, the liver damage may reverse on its own.
An isolated report showing a moderate rise in bilirubin and/or aminotransferase levels is not in itself an indication for interrupting treatment. Rather, the decision should be based on repeated test results and trends in conjunction with the patient’s clinical condition. Persons with alcoholism are susceptible to drug toxicity because alcohol induces liver injury and cirrhotic changes that alter drug metabolism.
The cause of idiosyncratic DILI is a combination of risk factors that relate to the drug, the individual, and the environment. Also according to the AASLD guidelines, all patients who present within 4 hours of a single–time-point acetaminophen overdose should receive gastric lavage and activated charcoal. Hepatotoxicity from acetaminophen is due to the toxic metabolite NAPQI. Alcohol and other drugs induce cytochrome P-450-2E1 and may result in enhanced toxicity. They involve conjugation with a moiety (ie, acetate, amino acid, sulfate, glutathione, glucuronic acid) that further increases solubility. Subsequently, drugs with high molecular weight may be excreted in bile, while the kidneys excrete the smaller molecules.
This is particularly the case with idiosyncratic DILI, although risk factors can also contribute to intrinsic DILI. Some cases are acute, with the condition being only temporary, while others are chronic, meaning that it lasts for an extended period. However, people typically develop signs and symptoms within 3–6 months of taking the drug. The National Institute of Diabetes and Digestive and Kidney Diseases keeps a searchable database called LiverTox, which lists the medicines and herbal compounds that can damage the liver. Submassive necrosis, as the name suggests, may affect zone 1 (periportal) or zone 3 (central necrosis).
High levels of AST generally are a sign of liver damage or disease. ALT is an enzyme in the liver that helps change proteins into energy used by liver cells. Blood tests look for levels of liver enzymes that can show how well your liver is working.