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Drug-induced hepatitis

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

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What is drug-induced hepatitis?

Drug-induced hepatitis involves inflammation of the liver, caused by medication. Drug-induced hepatitis is similar to acute viral hepatitis but parenchymal destruction tends to be more extensive. Certain drugs can cause damage to the liver in a variety of ways:

  • Acute hepatocellular damage:

    • Dose-unrelated - eg, antituberculous drugs, halothane, anticonvulsants.

    • Dose-related - eg, alcohol, paracetamol poisoning, amiodarone, methotrexate.

    • Both dose-unrelated and dose-related liver cell damage - eg, azathioprine.

  • Autoimmune hepatitis: drugs implicated in drug-induced autoimmune hepatitis include antimicrobials, such as nitrofurantoin and minocycline, non-steroidal anti-inflammatory drugs, statins as well as anti-tumor necrosis agents.1

  • Cirrhosis - eg, alcohol, methotrexate.

  • Hepatic tumours - eg, anabolic steroids, combined oral contraceptives.

  • Intrahepatic cholestasis: either dose-unrelated (eg, carbimazole, erythromycin, phenothiazines) or dose-related (eg, anabolic steroids, azathioprine, oestrogens).

  • Gallstones - eg, clofibrate, oestrogens.

Drug-induced liver injury can occur in overdose or at therapeutic dosing, either because of direct, intrinsic drug hepatotoxicity or as a result of idiosyncratic (unpredictable) hepatotoxicity.2 About 10% of cases are idiosyncratic.3

How common is drug-induced hepatitis? (Epidemiology)4

  • Drug-induced liver injury is the most common cause of acute liver failure in the western world. However idiosyncratic drug-induced liver injury is an uncommon adverse event when taking prescription or non-prescription medications.

  • It is difficult to assess the true incidence because of different diagnostic criteria and under-reporting. However, recent population-based studies estimate the incidence to vary between 13.9-19.1 cases per 100,000 people per year.

  • Approximately 15% of patients with autoimmune hepatitis have drug-induced liver disease.5

  • The development of drug-induced liver disease is dependent on the drug as well as individual patient factors, including genetic predisposition, age, gender, pre-existing liver disease and comorbidities.

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Drug-induced hepatitis symptoms

There is no specific or diagnostic clinical presentation, laboratory test or histological pattern to aid in the diagnosis of drug-induced liver disease. Clinical features vary with the pattern and severity of injury, which vary with the particular drug and the individual patient.6

  • Often detected by routine drug monitoring - eg, disease-modifying antirheumatic drugs.

  • Symptoms and signs are similar to other causes of liver damage. Thus, identifying drug-induced hepatitis relies on the history of exposure more than any particular finding on examination or investigation.

  • Clinical evidence of sensitivity to a medication may occur on the first day of its use or not until several months later, depending on the medication.

  • Usually, the onset is abrupt, with chills, fever, rash, pruritus, arthralgia, headache, abdominal pain, anorexia, nausea and vomiting.

  • Later, overt evidence of liver damage, such as jaundice, dark urine and an enlarged and tender liver, may develop.

  • Two general pathogenic mechanisms are recognised:

    • Predictable or direct: usually promptly follows an exposure to a new medication. The mechanism appears to be due to direct toxicity or a toxic metabolite - eg, paracetamol.

    • Unpredictable or idiosyncratic: may be related to immune hypersensitivity; rash, fever and eosinophilia are typically present. These reactions follow exposure by a few weeks - eg, Augmentin®.

  • Late-onset idiosyncratic reactions are difficult to recognise. They follow exposure by many months and usually do not display features of hypersensitivity - eg, isoniazid.

Differential diagnosis7

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Medication-induced liver injury typically presents in one of three clinical patterns:

  • Hepatitis: elevated AST/ALT - eg, paracetamol poisoning, thiazolidinediones, statins.

  • Cholestasis: elevated alkaline phosphatase - eg, chlorpromazine, erythromycin, oestrogens.

  • Mixed picture with damage to both biliary canaliculi and hepatocytes: variable elevations in aminotransferases and alkaline phosphatase - eg, Augmentin®.

  • Investigations may also need to include an assessment for other causes of hepatitis and may include hepatitis viral serology, antinuclear antibodies, copper and iron levels, abdominal ultrasound, CT/MRI scan and liver biopsy.

See also the article on Abnormal Liver Function Tests.

Drug-induced hepatitis treatment and management8 9

  • There is no specific treatment for drug-induced hepatitis other than discontinuing the medication that is causing the problem.

  • People with acute hepatitis should avoid physical exertion, alcohol, paracetamol and any other hepatotoxic substances.

  • Unfortunately, other than the use of N-acetylcysteine for paracetamol hepatotoxicity, there are no specific antidotes for drug-induced liver disease.

  • Supportive care for acute liver failure and even liver transplantation may be required.


Liver failure is a possible but uncommon complication of drug-induced hepatitis. The risk of acute liver failure is dependent on the degree of abnormality of liver enzyme levels and the presence of pre-existing liver disease. The risk is higher in women.10 11


  • Usually symptoms subside when the causative drug has been discontinued and drug-related hepatitis subsides within days or weeks after the offending drug is stopped.

  • Reactions may be severe and even fatal.

  • Patients with jaundice have approximately 10% risk of liver-related mortality and/or need for liver transplantation.9

Prevention of drug-induced hepatitis

  • Careful prescribing and, when recommended, monitoring of all medication in line with established guidelines.

  • Always consider drugs as a cause of any patient presenting with hepatitis in order to provide early effective management.

Further reading and references

  • British National Formulary (BNF); NICE Evidence Services (UK access only)
  • Kleiner DE; Drug-induced Liver Injury: The Hepatic Pathologist's Approach. Gastroenterol Clin North Am. 2017 Jun;46(2):273-296. doi: 10.1016/j.gtc.2017.01.004.
  1. Tan CK, Ho D, Wang LM, et al; Drug-induced autoimmune hepatitis: A minireview. World J Gastroenterol. 2022 Jun 28;28(24):2654-2666. doi: 10.3748/wjg.v28.i24.2654.
  2. Kumachev A, Wu PE; Drug-induced liver injury. CMAJ. 2021 Mar 1;193(9):E310. doi: 10.1503/cmaj.202026.
  3. Leise MD, Poterucha JJ, Talwalkar JA; Drug-induced liver injury. Mayo Clin Proc. 2014 Jan;89(1):95-106. doi: 10.1016/j.mayocp.2013.09.016.
  4. Katarey D, Verma S; Drug-induced liver injury. Clin Med (Lond). 2016 Dec;16(Suppl 6):s104-s109. doi: 10.7861/clinmedicine.16-6-s104.
  5. Yeong TT, Lim KH, Goubet S, et al; Natural history and outcomes in drug-induced autoimmune hepatitis. Hepatol Res. 2015 May 5. doi: 10.1111/hepr.12532.
  6. Fisher K, Vuppalanchi R, Saxena R; Drug-Induced Liver Injury. Arch Pathol Lab Med. 2015 Jul;139(7):876-87. doi: 10.5858/arpa.2014-0214-RA.
  7. Teschke R, Danan G; Drug induced liver injury with analysis of alternative causes as confounding variables. Br J Clin Pharmacol. 2018 Jul;84(7):1467-1477. doi: 10.1111/bcp.13593. Epub 2018 May 14.
  8. Weiler S, Merz M, Kullak-Ublick GA; Drug-induced liver injury: the dawn of biomarkers? F1000Prime Rep. 2015 Mar 3;7:34. doi: 10.12703/P7-34. eCollection 2015.
  9. Bjornsson ES; Clinical management of patients with drug-induced liver injury (DILI). United European Gastroenterol J. 2021 Sep;9(7):781-786. doi: 10.1002/ueg2.12113. Epub 2021 Jun 28.
  10. Lo Re V 3rd, Haynes K, Forde KA, et al; Risk of Acute Liver Failure in Patients with Drug-Induced Liver Injury: Evaluation of Hy's Law and a New Prognostic Model. Clin Gastroenterol Hepatol. 2015 Jun 26. pii: S1542-3565(15)00844-7. doi: 10.1016/j.cgh.2015.06.020.
  11. Robles-Diaz M, Lucena MI, Kaplowitz N, et al; Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology. 2014 Jul;147(1):109-118.e5. doi: 10.1053/j.gastro.2014.03.050. Epub 2014 Apr 1.

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The information on this page is written and peer reviewed by qualified clinicians.

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