How to manage drug-induced hepatitis?

From the Guidelines

The primary management of drug-induced hepatitis involves immediately discontinuing the offending medication and providing supportive care, as this approach has been shown to lead to excellent outcomes in most cases, with resolution typically occurring within 1 month, as noted in the 2020 guidelines from the American Association for the Study of Liver Diseases 1.

Key Considerations

• Discontinuation of the offending drug is crucial, as continued exposure can worsen liver damage.
• Supportive care includes monitoring liver function tests (ALT, AST, bilirubin, alkaline phosphatase) regularly until normalization.
• Patients should avoid alcohol and other potentially hepatotoxic medications, including acetaminophen, to prevent additional liver stress.
• Maintaining adequate hydration and ensuring proper nutrition are also important aspects of supportive care.

Severe Cases and Special Considerations

• In severe cases with significant liver dysfunction, hospitalization may be necessary for close monitoring and management of complications like coagulopathy or encephalopathy.
• For severe drug-induced liver injury with signs of liver failure, consultation with a hepatologist is essential to evaluate the need for liver transplantation.
• Corticosteroids may be considered in cases with autoimmune features or hypersensitivity reactions, though evidence for their routine use is limited, as discussed in the 2020 guidelines 1.
• The use of ursodeoxycholic acid (UDCA) may be beneficial in some cases of drug-induced cholestasis, as suggested by earlier studies 1, but its role in the management of drug-induced hepatitis is not well-defined.

Follow-Up and Prevention

• After recovery, patients should receive clear documentation of the hepatotoxic drug to avoid future re-exposure, as rechallenge often causes more severe and rapid liver injury.
• The LiverTox website, a joint effort of the Liver Disease Research Branch of the National Institute of Diabetes and Digestive and Kidney Diseases and the Division of Specialized Information Services of the National Library of Medicine, National Institutes of Health, is a valuable resource for evaluating suspected drug-induced liver injury, as mentioned in the 2020 guidelines 1.

From the FDA Drug Label

ACETAMINOPHEN ASSAYS - INTERPRETATION AND METHODOLOGY The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose.

The management of drug-induced hepatitis, specifically due to acetaminophen overdose, involves the administration of N-acetylcysteine (PO).

• Early treatment is crucial, with the most benefit seen when administered within 16 hours of the overdose.
• Assessment of the potential risk of hepatotoxicity should be done using plasma or serum acetaminophen concentrations, determined as early as possible, but no sooner than 4 hours following an acute overdose.
• Treatment with acetylcysteine should not be delayed while waiting for assay results, and it is better to err on the safe side when interpreting plasma levels 2.
• The effectiveness of acetylcysteine depends on maintaining or restoring glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite 2.

From the Research

Management of Drug-Induced Hepatitis

• The management of drug-induced liver injury (DILI) is generally symptomatic, with early referral to a liver transplant unit at the first hint of liver failure, especially in those with non-paracetamol-induced liver injury 3.
• Treatment strategies for DILI are still not well defined, but steroid and ursodesoxycholic acid (UDCA) combination therapy has been shown to be safe and effective in severe DILI cases 4.
• The primary goal is to identify DILI early when the patient's liver enzymes are elevated and to discontinue the offending agent as soon as possible to prevent further injury 5.
• The American College of Gastroenterology (ACG) published guidelines to aid the clinician in diagnosing DILI, which includes temporal association, clinical-biochemical features, type of injury, extrahepatic features, and the likelihood that a given agent is the culprit based on its known manifestations with prior cases 5.

Role of Ursodeoxycholic Acid (UDCA) in DILI

• UDCA has been shown to have some benefits in the treatment and prevention of DILI, with improvements in liver profile and a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention 6.
• However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI, and a well-designed randomized clinical trial (RCT) is needed to evaluate the role of UDCA in DILI 6.

Discontinuation of the Offending Agent

• Discontinuation of the offending agent is crucial in the management of DILI, and the mean time to biochemical resolution after discontinuation of the offending agent has been reported to be around 14.1 weeks 7.
• Early discontinuation of the offending agent can help prevent further liver injury and improve patient outcomes 3, 7.