Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury

Publication Date: May 1, 2021



1. In individuals with suspected hepatocellular or mixed DILI:
(a) Acute viral hepatitis (A, B, and C) and AIH should be excluded with standard serologies and HCV RNA testing. ( Very Low , Strong )
(b) Anti-HEV IgM testing may be considered in selected patients where there is heightened clinical suspicion (e.g., recent travel in an endemic area, DILI phenotype is atypical, or there is no readily identifiable culprit agent). It should however be noted that the performance of the currently available commercial tests is not clear. (Very Low, Conditional (weak))
(c) We recommend testing for acute cytomegalovirus, acute Epstein-Barr virus, or acute herpes simplex virus infection be undertaken if classical viral hepatitis has been excluded or clinical features such as atypical lymphocytosis and lymphadenopathy suggest such causes. (Very Low, Strong)
(d) We recommend evaluation for Wilson disease and Budd-Chiari syndrome when clinically appropriate. (Very Low, Strong)
2. In individuals with suspected cholestatic DILI:
(a) We recommend abdominal imaging (ultrasound, computed tomography scan, and MRI) be performed in all instances to exclude biliary tract pathology and infiltrative processes. (Low, Strong)
(b) We recommend limiting serological testing for PBC to those with no evidence of obvious biliary tract pathology on abdominal imaging. (Low, Strong)
(c) We suggest limiting endoscopic retrograde cholangiography to instances where routine imaging including MRI or endoscopic ultrasound is unable to exclude impacted common bile duct stones, PSC, or pancreaticobiliary malignancy. (Very Low, Conditional (weak))
3. When to consider a liver biopsy?
(a) We recommend performing a liver biopsy if AIH remains a competing etiology and if immunosuppressive therapy is contemplated. (, )
(b) We suggest performing a liver biopsy if there is unrelenting rise in liver biochemistries or signs of worsening liver function despite stopping the suspected offending agent. (, )
(c) We suggest performing a liver biopsy if peak ALT level has not fallen by >50% at 30–60 days after onset in cases of hepatocellular DILI or if peak Alk P has not fallen by >50% at 180 days in cases of cholestatic DILI despite stopping the suspected offending agent. (Very Low, Conditional (weak))
(d) We suggest performing a liver biopsy in cases of DILI where continued use or re-exposure to the implicated agent is contemplated. (Very Low, Conditional (weak))
(e) We suggest considering liver biopsy if liver biochemistry abnormalities persist beyond 180 days, especially if associated with symptoms (e.g., itching) or signs (e.g., jaundice and hepatomegaly), to evaluate for the presence of chronic liver diseases (CLDs) and chronic DILI. (Very Low, Conditional (weak))


4. We suggest using a prognostic model consisting of MELD, Charlson comorbidity index, and serum albumin in clinical practice for predicting 6-month mortality in individuals presenting with suspected DILI. A web-based DILI mortality calculator is available at http://gihep.com/calculators/hepatology/dili-cam/. ( Low , Conditional (weak) )


5. We strongly recommend against re-exposure to a drug thought likely to have caused hepatotoxicity, especially if the initial liver injury was associated with significant aminotransferase elevation (e.g., >5xULN, Hy's law, or jaundice). An exception to this recommendation is in cases of life-threatening situations where there is no suitable alternative. (LowStrong)


6. We recommend promptly stopping suspected agent(s) in individuals with suspected DILI, especially when liver biochemistries are rising rapidly or there is evidence of liver dysfunction. (LowStrong)
7. Although no definitive therapies are available either for idiosyncratic DILI with or without ALF, we suggest consideration of NAC treatment in adults with early stage ALF, given its good safety profile and some evidence for efficacy in early coma stage patients. (LowConditional (weak))
8. We suggest against using NAC for children with severe DILI leading to ALF. (LowConditional (weak))
9. There are no well-conducted studies to either recommend or refute corticosteroid therapy in patients with DILI. However, they may be considered in a subset of patients with DILI exhibiting AIH-like features. (LowConditional (weak))


10. We recommend encouraging patients to report use of HDS to their health care providers and be reminded that supplements are not subjected to the same rigorous testing for safety and efficacy as are prescription medications. (LowStrong)
11. We recommend applying the same diagnostic approach for DILI to suspected HDS-hepatotoxicity. That is, other forms of liver injury must be excluded through a careful history and appropriate laboratory testing and hepatobiliary imaging. Excluding other causes, the diagnosis of HDS-hepatotoxicity can be made with confidence in the setting of recent use of HDS. (LowStrong)
12. We recommend stopping all HDS in patients with suspected HDS-hepatotoxicity and continued monitoring for resolution of their liver injury. (LowStrong)
13. We recommend consideration of liver transplantation evaluation in patients who develop ALF and severe cholestatic injury from HDS-DILI. (LowStrong)


14. As the diagnosis of DILI in patients with CLD requires a high index of suspicion, we recommend exclusion of other more common causes of acute liver injury including a flare-up of the underlying liver disease. (LowStrong)
15. The decision to use potentially hepatotoxic drugs in CLD patients should be based on the risk vs benefit of the proposed therapy on a case-by-case basis. (LowConditional (weak))
16. There are no data to recommend a specific liver biochemistry monitoring plan when a potential hepatotoxic agent is prescribed in individuals with known CLD. Often, information contained in the package inserts is incomplete or unhelpful. Patients should be advised to promptly report any new onset symptoms such as scleral icterus, abdominal pain/discomfort, nausea/vomiting, itching, or dark urine. In addition, it is reasonable to monitor serum liver biochemistries at 4–6 weekly intervals, especially during the initial 6 months of treatment with a potentially hepatotoxic agent. (Very LowConditional (weak))

Recommendation Grading




Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury

Authoring Organization

Publication Month/Year

May 1, 2021

Supplemental Implementation Tools

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospital

Intended Users

Physician, nurse practitioner, nurse, physician assistant



Diseases/Conditions (MeSH)

D056486 - Chemical and Drug Induced Liver Injury


Clinical guidelines, Idiosyncratic drug-induced liver injury

Source Citation

Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. Am J Gastroenterol. 2021 May 1;116(5):878-898. doi: 10.14309/ajg.0000000000001259. PMID: 33929376.