Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury
Official guideline from the American College of Gastroenterology.
summary by Maureen Whitsett, MD Shannon Chang, MD
Diagnosis
Hepatocellular, Cholestatic, or Mixed
Conduct a thorough history for temporal relationship and competing medications and substances. By convention, R≥5 is labeled as hepatocellular DILI, R<2 is labeled cholestatic DILI, and 2< R <5 is labeled “mixed” DILI. (R Factor for Liver Injury)
N/A
Should exclude hep A, B, C, and autoimmune hepatitis with standard serologies and HCV RNA.
Strong recommendation
Very low quality evidence
Routine anti-HEV IgM testing is not recommended, but should consider if clinical suspicion (e.g. recent travel to endemic area).
Conditional recommendation
Very low quality evidence
If atypical lymphocytosis and lymphadenopathy present and viral hepatitis panel negative, should test for acute HSV, CMV, EBV.
Strong recommendation
Very low quality evidence
Should consider Wilson’s and Budd-Chiari when clinically appropriate. Should screen for Wilson’s with ceruloplasmin, particularly in patients <40 years old. Consider additional workup (urine copper, slit-lamp exam) if strong clinical suspicion. Should consider Budd-Chiari especially if tender hepatomegaly and/or ascites.
Strong recommendation
Low quality evidence
Cholestatic DILI
Should perform abdominal imaging (CT or US) in all cases to rule out biliary tract pathology and infiltrative processes.
Strong recommendation
Low quality evidence
Should limit testing for primary biliary cirrhosis to those with no obvious pathology on imaging.
Strong recommendation
Low quality evidence
Should limit ERCP to cases where routine imaging cannot exclude impacted CBD stones, PSC, or pancreaticobiliary malignancy.
Strong recommendation
Very low quality evidence
Liver Biopsy
Should consider liver biopsy if AIH is a competing etiology and immunosuppressive therapy considered.
Strong recommendation
Low quality evidence
May consider liver biopsy if liver biochemistries keep rising or signs of worsening liver function despite stopping suspected offending drug.
Strong recommendation
Very low quality evidence
May consider liver biopsy if peak ALT fails to fall by >50% at 30-60 days after onset (hepatocellular DILI) or peak alk Phos fails to fall by >50% if cholestatic DILI by 180 days.
Conditional recommendation
Very low quality evidence
May consider liver biopsy if continued use or re-exposure to the drug is expected.
Strong recommendation
Very low quality evidence
May consider liver biopsy if liver biochemistry abnormalities persist beyond 180 days and chronic DILI or chronic liver disease is suspected.
Conditional recommendation
Very low quality evidence
Management
Suspected Offending Agents
Re-exposure to suspected offending agent is strongly discouraged, especially if significant aminotransferase elevation occurred (i.e., >5x ULN), Hy’s law, or jaundice. Exception is if the suspected agent is life-saving and no suitable alternative.
Strong recommendation
Low quality evidence
Should promptly stop suspected offending agents liver biochemistries rising rapidly or if evidence of liver dysfunction.
Strong recommendation
Low quality evidence
Little evidence exists supporting corticosteroid use in acute liver failure and there are no controlled trials examining the role of steroids in DILI.
N/A
NAC
No definitive therapies are available (idiosyncratic DILI with or without ALF), but may consider NAC in adults with early-stage ALF - good safety profile, some evidence for efficacy in early coma stage patients.
Conditional recommendation
Low quality evidence
NAC not recommended in children with ALF from severe DILI.
Strong recommendation
Low quality evidence
Herbal and Dietary Supplements (HDS)
Patients should be encouraged to report use of HDS and be reminded that supplements do not undergo the same safety and efficacy testing as prescription medications.
Strong recommendation
Low quality evidence
Same diagnostic approach for DILI applies to HDS-hepatotoxicity. HDS is a diagnosis of exclusion and is more likely in the setting of recent HDS use.
Strong recommendation
Low quality evidence
If HDS-hepatotoxicity is suspected, should stop all HDS and monitor for resolution of liver injury.
Strong recommendation
Low quality evidence
DILI in Chronic Liver Disease (CLD)
DILI in CLD requires high index of suspicion and exclusion of other more common causes of acute liver injury (e.g. flare-up of underlying disease).
Strong recommendation
Low quality evidence
If using potentially hepatotoxic drugs in CLD patients, should base decision on risk vs benefit and on case-by-base basis.
Strong recommendation
Low quality evidence
If prescribing potentially hepatotoxic medications to patients with CLD, counsel patients on promptly reporting any new symptoms. Additionally, consider monitoring liver biochemistries at 4-6 weekly intervals.
Conditional recommendation
Very low quality evidence
What do the icons mean?
How strong is the ACG's recommendation?
Strong recommendation
Intervention's desirable effects clearly outweigh undesirable effects.Moderate recommendation
Further research likely to impact confidence in estimate of effect.
Conditional recommendation
Uncertainty in tradeoffs between desirable & undesirable effects of intervention.Weak recommendation
Uncertainty in tradeoffs between desirable & undesirable effects of intervention.
N/A
No recommendation was assigned.High quality evidence
Further research unlikely to change guideline authors' confidence in estimate of effect.
Moderate-high quality evidence
Between high and moderate levels of evidence.
Moderate quality evidence
Further research likely to impact confidence in estimate of effect.
Low quality evidence
Further research expected to have important impact in confidence in estimate of effect.Very low quality evidence
Effect is very uncertain.N/A
No evidence was assigned.
