Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury

(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)

(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))

(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))