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Drug-induced liver injury (DILI) – A diagnosis that is not easy but need to always keep in mind

Updated: Jul 11, 2019

On 6/11/19, Dr. Bader gave an excellent noon report on a case of drug-induced liver injury (DILI).


We discussed a previously healthy male with acute diffuse abdominal discomfort, rash on left side of the abdomen and dark urine. On workup, found to have abnormal LFTs but otherwise unremarkable imaging. He also had a negative hepatitis (viral, auto-immune) workup. Thorough history revealed recent use of herbal supplement called Fo-Ti (Fleece flower root).



Main points:

- DILI is a diagnosis of exclusion

  • According to AGA guidelines, in hepatocellular injury, first exclude acute viral hepatitis (HAV, HBV, HCV, HEV, CMV, EBV and HSV), autoimmune hepatitis (AIH), vascular liver disease (Budd-Chiari syndrome, ischemic liver injury) and Wilson’s disease.

  • In cholestatic pattern, first exclude biliary obstruction. Think about biliary autoimmune disease such as PBC (check AMA) and PSC (check p-ANCA). Others to think about are TPN and sepsis.

  • Liver imaging can reveal infiltrative hepatic disease and fatty liver diseases (NAFLD/NASH)

  • Also think about hemochromatosis and alpha-1-antitrypsin deficiency (check iron panel and alpha-1-antitrypsin level, respectively)

  • Once other possible causes excluded, think DILI!

- Clinical presentation can vary widely from non-specific symptoms (anorexia, N/V) to RUQ pain, skin rash, itching to acute liver failure (jaundice, encephalopathy, and INR >1.5)

- Clinical history (ask about herbal supplements, get names and ingredients!), time of drug exposure and course of liver damage are crucial points in the evaluation of patients with suspected DILI

- Pattern of liver damage can be hepatocellular (predominantly elevation of AST/ALT), cholestatic (predominantly elevation of Tbil/Alk phos) or mixed depending on the drug

- Idiosyncratic DILI can be considered a relatively rare event but it is one of the leading causes of acute liver failure

- Proper management is essential to avoid serious consequences

- Management involve stopping the offending drug

- N-acetylcysteine (NAC) may be beneficial for acute liver failure due to drug-induced liver injury

  • Rationale: For patients whose disease appears to be caused by etiologies other than acetaminophen, N-acetylcysteine may improve outcomes. In a randomized, controlled trial, NAC appeared to improve spontaneous survival when given during early coma stages (grades I and II) in the setting of non-acetaminophen acute liver failure including, for example, drug-induced liver injury ( Lee WM, et al. "Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure". Gastroenterology. 2009. 137(3):856-64.)

- Use NIH Livertox Database if you suspect specific drug causing liver injury: https://livertox.nih.gov

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