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The liver is a large, extremely important organ that has many functions, including filtering incoming blood from the digestive tract before sending it to the rest of the body, as well as processing nutrients. It also plays a critical role in detoxification of chemicals and metabolism (breakdown or chemical modification) of drugs, making it highly susceptible to injury by certain medications.
According to a national expert on the topic, “Drug-induced [liver] injury is the most frequent...
The liver is a large, extremely important organ that has many functions, including filtering incoming blood from the digestive tract before sending it to the rest of the body, as well as processing nutrients. It also plays a critical role in detoxification of chemicals and metabolism (breakdown or chemical modification) of drugs, making it highly susceptible to injury by certain medications.
According to a national expert on the topic, “Drug-induced [liver] injury is the most frequent reason cited for the withdrawal from the market of an approved drug, and it also accounts for more than 50 percent of the cases of acute liver failure in the United States today.”[1] Acute liver failure is a life-threatening condition characterized by rapid impairment of liver function.
There are more than 1,000 prescription and over-the-counter medications, as well as certain herbal and dietary supplements, that are implicated in liver injury, and the list continues to grow.[2],[3]
About drug-induced liver injury
Many classes of medications can cause drug-induced liver injury. Commonly used medications that can cause liver injury include certain antibiotics, antidepressants, antiepileptics (drugs for treating seizures), anticancer drugs and high blood pressure medications (see examples in the Table, below). Notably, the risk of developing drug-induced liver disease is higher in patients who are taking more than one of these drugs or who consume alcohol or other substances that are toxic to the liver.
Examples of Commonly Used Oral Drugs Associated With Drug-Induced Liver Injury[4]
| Drug Family | Generic Drug Name (Brand Name[s]†) |
|---|---|
| Abnormal heart rhythm drugs |
|
| Analgesics (pain drugs) |
|
| Antibiotics |
|
| Antidepressants |
|
| Antifungal drugs |
|
| Antihypertension drugs |
|
| Antiplatelet drugs |
|
| Antiviral drugs |
|
| Breast cancer drugs |
|
| Gout drugs |
|
| Nonsteroidal anti-inflammatory drugs |
|
| Prostate drugs |
|
| Seizure drugs |
|
| Smoking cessation drugs |
|
†Combination products were excluded from this table except for amoxicillin and clavulanate.
*Designated as Limited Use
**Designated as Do Not Use If Over 60
***Designated as Do Not Use
Drug-induced liver injury can develop within days or years of starting a drug[5] and can occur in different ways.[6] First, certain drugs at high doses, such as acetaminophen (TYLENOL) and aspirin (BAYER ASPIRIN, DURLAZA, VAZALORE), predictably cause liver injury. For all individuals, such drugs are intrinsically toxic to the liver cells, damaging them quickly if overdosed or used in combination with other liver toxicants such as alcohol.
Second, certain other drugs can cause an autoimmune allergic or inflammatory reaction to the liver.[7] For certain drugs, such as the abnormal heart rhythm drug amiodarone (PACERONE), these reactions occur more commonly with higher doses or increasing frequency of use.
Finally, some drugs cause idiosyncratic (rare and unpredictable) liver injury and failure. Of note, such drug-induced liver injury may occur regardless of dose and frequency of use.[8]
Risk factors
There are many risk factors that can predispose individuals to drug-induced liver injury.[9] Older patients have an increased risk of developing this adverse effect, both because of their use of multiple prescription drugs and their commonly impaired ability to metabolize or detoxify drugs. In contrast, younger individuals may have increased risk of injury with the use of certain drugs, such as valproic acid (generic only).[10]
Generally, the risk of developing liver injury is similar among men and women.[11] However, gender may be a risk factor with the use of specific drugs, such as the enhanced risk of liver injury in women taking the anti-inflammatory drug diclofenac (CAMBIA, ZIPSOR, ZORVOLEX).
Other risk factors include a family history of liver disease, genetics, alcohol use and concomitant exposure to other toxic chemicals, such as occupational exposures.
The presence of certain preexisting liver conditions also may elevate the risk of toxicity from drugs that are metabolized by the liver.[12]
Diagnosis and treatment
Symptoms of liver injury, whether due to an adverse drug reaction or another cause like viral hepatitis, include jaundice (yellow skin or eyes), nausea, vomiting, pain in the right upper abdomen, itching, fatigue and dark urine. Routine blood tests can be used to confirm the presence of liver injury.
Diagnosis of drug-induced liver disease is challenging because it is largely based on the exclusion of other causes of liver disease.[13] Several factors, such as the onset of liver disease in relation to when the suspected medication was started as well as the documented toxicity of such medication to the liver, can generally support the presence of drug-induced liver injury.
If appropriate, after a discussion with your doctor, discontinuing the causative drug(s) should be the first approach to treating drug-induced liver injury. Depending on early identification and withdrawal of offending drugs, drug-induced liver injury can resolve completely, but sometimes progression to liver failure, the need for a liver transplant and even death can occur.[14] In cases of severe drug poisoning or overdose, hospitalization is critical.
What You Can Do
To protect yourself from drug-induced liver injury, make a list of your current medications and consult your doctor about their potential risk to cause this adverse effect. If any of your medications has this risk, be alert for symptoms of liver injury and discuss with your doctor whether you need blood tests to monitor your liver function. Avoid consuming alcohol if any of your medications can cause liver adverse effects.
References
[1] Lee WM. Drug-induced hepatotoxicity. N Engl J Med. 2003;349(5):474-85.
[2] Larson AM. Drug-induced liver injury. UpToDate. May 10, 2019.
[3] Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov. 2005;4(6): 489-499.
[4] Larson AM. Drug-induced liver injury. UpToDate. May 10, 2019.
[5] Hoofnagle JH, Björnsson ES. Drug-induced liver injury— Types and phenotypes. N Engl J Med. 2019;381(14):264-273.
[6] Ibid.
[7] Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov. 2005;4(6):489-499.
[8] Ibid.
[9] Katarey D, Verma S. Drug-induced liver injury. Clin Med (Lond). 2016;16(6):s104-s109.
[10] Björnsson ES. Epidemiology, predisposing factors, and outcomes of drug-induced liver disease. Clin Liver Dis. 2020;24(1):1-10.
[11] Ibid.
[12] Ibid.
[13] Hoofnagle JH, Björnsson ES. Drug-induced liver injury — Types and phenotypes. N Engl J Med. 2019;381(14):264-273.
[14] David S, Hamilton JP. Drug-induced liver injury. US Gastroenterol Hepatol Rev. 2010;6(January 1):73-80.
