Drug-Induced Liver Injury: 5 Things to Know

Nancy S. Reau, MD


March 07, 2019

3. Alcohol ingestion has a surprising relationship with acetaminophen.

Contrary to what one might think about alcohol being a risk factor for hepatotoxicity, ingesting alcohol and acetaminophen together does not increase the risk for hepatotoxicity due to the acetaminophen. In fact, the rate of liver injury was found to be substantially lower (5.1% vs 15.2%) in those who had an acute acetaminophen overdose with alcohol ingestion compared with acetaminophen alone.[8] Alcohol, as a substrate of CYP2E1, may lower the risk for liver injury by competing with acetaminophen for the enzymes, thus decreasing the amount of the toxic metabolite produced. The role of chronic alcohol ingestion is controversial, especially when those with an alcohol use disorder stay within the therapeutic recommendations for acetaminophen. Still, most clinicians recommend a lower daily dose of acetaminophen for these patients, as repeated supratherapeutic doses of acetaminophen are well recognized to increase the risk for hepatotoxicity.[9]

Patients with advanced liver disease should also limit their acetaminophen intake.[8] Cirrhosis, regardless of the etiology, reduces the metabolism of acetaminophen.

Therefore, given the potential risk, patients with either an alcohol use disorder or underlying liver disease should be advised to limit their daily amount of acetaminophen to less than 2 g/day.

4. Risk for DILI from statins may be overestimated.

Clinicians may be hesitant to prescribe statins to patients with liver disease and thus miss an important opportunity to reduce cardiovascular risk. This is especially true in conditions like nonalcoholic fatty liver disease (NAFLD), where cardiovascular disease is the leading cause of mortality.

Mild to moderate transient asymptomatic elevations in serum aminotransferase levels are common with statins. This phenomenon occurs early after the initiation of therapy but eventually normalizes, despite ongoing therapy.[10] So, this is a lab abnormality and not a true liver injury; liver biopsy shows no histopathologic change.

According to the Drug-Induced Liver Injury Network (DILIN), only 3.4% of reported drug-induced liver injuries were linked to statins, confirming its rare occurrence.[11] Growing evidence also shows that statins may actually reduce the risk for liver cancer and improve outcomes in those diagnosed with hepatocellular carcinoma.[12] Although we do not recommend starting a statin to reduce the risk for liver cancer, clinicians should not be afraid to use this class of agents to reduce the risk for cardiovascular disease.


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