Which type of drugs cause major liver damage?

The liver is a vital organ that performs many important functions in the body. It processes nutrients, filters waste products from the blood, regulates cholesterol, helps fight infections, and metabolizes drugs and alcohol. However, certain medications can cause damage to the liver, potentially leading to liver injury and dysfunction. In this article, we will examine which types of drugs pose the greatest risk of liver toxicity.

What are the functions of the liver?

The liver has over 500 vital functions. Some key roles include:

– Producing bile to help digest fats
– Filtering and detoxifying chemicals from the blood
– Metabolizing drugs and alcohol
– Synthesizing proteins and cholesterol
– Storing essential vitamins and minerals
– Removing bacteria and toxins from the blood

When the liver becomes damaged, it cannot perform these critical functions properly. This can lead to a dangerous buildup of toxins in the body.

What causes drug-induced liver injury?

Many different prescription and over-the-counter (OTC) medications can cause drug-induced liver injury. The mechanisms include:

– Direct toxicity – the drug or its metabolites directly damage liver cells. For example, acetaminophen overdose.

– Immune-allergic reactions – the drug triggers an allergic reaction or autoimmune response that attacks the liver.

– Mitochondrial toxicity – the drug impairs mitochondrial function, leading to hepatocyte death. This is often seen with nucleoside reverse transcriptase inhibitors used to treat HIV.

– Bile duct damage – the drug causes cholestasis or bile duct injury that impairs bile flow.

The manifestation of liver injury depends on the mechanism. It may present as hepatitis (inflammation), cholestasis (impaired bile flow), steatosis (fatty liver), fibrosis, or cirrhosis in severe cases. The timing also varies – some drugs cause immediate injury, while others take weeks or months of use to inflict damage.

What types of drugs commonly cause liver damage?

The major drug classes linked to liver toxicity include:


Acetaminophen (Tylenol, paracetamol) is one of the most common medications that can cause liver damage. At therapeutic doses, it is safe. But at higher doses, its toxic metabolite NAPQI accumulates and can severely injure hepatocytes. Acetaminophen overdose is the top cause of acute liver failure in many Western countries.

Anti-tuberculosis medications

Isoniazid, rifampin and pyrazinamide used to treat tuberculosis can all cause drug-induced liver injury. These medications are part of the standard first-line TB treatment regimen, so close monitoring of liver enzymes is required.

Anti-seizure medications

Certain anti-epileptic drugs like valproic acid (Depakote), carbamazepine (Tegretol) and phenytoin (Dilantin) have been associated with liver toxicity. Patients on these medications should have periodic liver function testing.

Lipid-lowering agents

Statins like atorvastatin (Lipitor) and other cholesterol medications can rarely cause abnormal liver tests. The risk of severe liver injury is very low. However, periodic monitoring of liver enzymes is still recommended.

Immunosuppressant medications

Tacrolimus (Prograf) and cyclosporine used after organ transplantation may cause varying degrees of liver toxicity. Azathioprine (Imuran) has also been linked to liver injury. Steroids like prednisone have fewer hepatotoxic effects.

Anticancer drugs

Many chemotherapy agents can cause liver damage. The most common include methotrexate, doxorubicin (Adriamycin), and 6-mercaptopurine (Purinethol). Newer targeted therapies like sorafenib (Nexavar) and pazopanib (Votrient) used to treat cancers also carry risks of liver toxicity.

Anti-HIV medications

Several HIV medications can cause liver injury, especially in those with underlying liver disease. These include efavirenz (Sustiva), nevirapine (Viramune), lopinavir/ritonavir (Kaletra), and the nucleotide reverse transcriptase inhibitors tenofovir (Viread) and adefovir (Hepsera).

Anabolic steroids and oral contraceptives

Anabolic steroids often abused by athletes and illegal steroid use can cause a rare liver tumor called hepatic adenoma. Birth control pills may also very rarely be associated with hepatic adenomas. These tumors are usually benign but can rupture and cause internal bleeding.


Some broad-spectrum antibiotics like amoxicillin-clavulanate (Augmentin), trimethoprim-sulfamethoxazole (Bactrim), and nitrofurantoin (Macrobid) can cause idiosyncratic liver injury. Fluoroquinolones like ciprofloxacin (Cipro) have also been implicated.

Anti-fungal medications

Ketoconazole and other anti-fungal drugs may cause liver toxicity in some patients. Itraconazole (Sporanox) can also lead to liver enzyme elevations. Voriconazole (Vfend) is considered to have lower risk of hepatotoxicity compared to earlier generation anti-fungals.

Non-steroidal anti-inflammatory drugs

While rare, traditional NSAIDs like ibuprofen (Advil, Motrin) and naproxen (Aleve) have been associated with drug-induced liver injury. Cases have also been reported with the COX-2 inhibitors celecoxib (Celebrex) and valdecoxib (Bextra). Acetaminophen is actually classified as an NSAID but has risks of liver toxicity distinct from the other NSAIDs.

What factors increase the risk of DILI?

Certain factors can heighten an individual’s risk of drug-induced liver toxicity:

– Pre-existing liver disease – the damaged liver is more vulnerable to injury

– Genetic polymorphisms – affect drug metabolizing enzymes like CYP450

– Multiple medications – risk rises with polypharmacy

– High doses – exceeds the liver’s metabolic capacity

– Long duration of treatment – increased cumulative exposure

– Excess alcohol intake – compounds hepatic toxicity

– Age – elderly and very young more susceptible

– Obesity and malnutrition – alter drug disposition

– HIV/hepatitis co-infection – impaired immunity and liver function

What are the symptoms of drug-induced liver damage?

Drug-induced liver injury may present with general symptoms like:

– Fatigue and weakness
– Loss of appetite and weight loss
– Nausea and vomiting
– Abdominal pain
– Jaundice – yellow skin and eyes
– Itching of the skin
– Dark urine
– Pale stools

Blood tests typically show elevated liver enzymes like AST, ALT, ALP, along with high bilirubin levels and low serum albumin. There may also be signs of liver failure like prolonged INR and low platelets.

How is drug-induced liver injury diagnosed?

Diagnosing medication-related liver toxicity involves:

– Detailed history of prescription and OTC drug use, including doses and duration

– Physical exam to look for signs of liver disease

– Lab tests to assess liver enzymes, function, and rule out viral hepatitis

– Liver imaging like ultrasound, CT, or MRI scan if needed

– Liver biopsy in some cases to evaluate level of damage

– Ruling out other potential causes like alcohol, viruses, toxins, autoimmune disease

– Checking for hypersensitivity if immunologic reaction likely

– Genetic testing if metabolic issue suspected

– Recurrence of liver injury on re-exposure to the drug

How is drug-induced liver damage treated?

The key steps in treating drug-induced hepatotoxicity are:

– Immediately stopping the offending medication

– Supportive care – managing symptoms and hydration

– Liver protecting agents like N-acetylcysteine

– Corticosteroids if immunologic mechanism

– Plasma exchange if hypersensitivity reaction

– Liver transplant if severe liver failure develops

– Avoiding re-exposure to the culprit drug

– Addressing any underlying liver disease

Most cases resolve within weeks to months of stopping the medication. However, some cases progress to chronic liver injury or liver failure, which require specialized hospital care.

How can drug-induced liver damage be prevented?

Strategies to help prevent drug-induced liver injury include:

– Avoiding unnecessary medications

– Using lowest effective drug dose and duration

– Monitoring liver enzymes during treatment

– Avoiding combining hepatotoxic drugs

– Watching for drug interactions

– Educating patients on early signs of liver injury

– Choosing alternative agents with lower toxicity

– Prescribing N-acetylcysteine with high-risk medications

– Individualizing therapy based on risk factors

– Conducting genetic testing to detect metabolic issues

– Advocating removal of harmful drugs from market

Careful selection and monitoring of medications along with patient education can help prevent many cases of drug-induced liver damage.


A number of prescription and over-the-counter medications across diverse drug classes have the potential to cause drug-induced liver injury. Acetaminophen overdose is the leading single cause, while anti-tuberculosis drugs, anti-seizure medications, cholesterol drugs, immunosuppressants, cancer drugs, HIV medications and antibiotics are also frequently implicated. Underlying liver disease, genetics, polypharmacy, high doses and other factors can heighten risk. Early recognition of symptoms like jaundice and prompt discontinuation of the offending drug is crucial. Preventative strategies like periodic liver enzyme monitoring, lower drug doses and avoiding drug combinations are key to reducing drug-related liver damage. Increased awareness among healthcare professionals and patients of the drugs that pose a substantial risk of hepatotoxicity is essential. With careful prescribing and monitoring, many cases of harmful liver injury can be avoided.

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