In patients with mild to moderate DILI, stopping the offending drug typically results in normalization of liver enzyme levels.20 Management of patients with moderate to severe DILI is mainly supportive; however, a patient with acute liver failure will require intensive care support.21,22 Consider hospital admission for patients who exhibit severe symptoms, such as intractable vomiting or severe dehydration, those who experience bleeding due to coagulation failure, and those who develop hepatic encephalopathy.21
When more aggressive steps are needed
N-acetylcysteine (NAC) should be considered for all patients with DILI who present with acute liver failure.12,23-25 NAC can be administered either orally or intravenously. The following 3 regimens have been well studied for patients with acetaminophen-induced liver injury:26
• Oral 72-hour regimen: Loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours up to 72 hours
• Intravenous 72-hour regimen: Loading infusion of 150 mg/kg over one hour, followed by 50 mg/kg over 4 hours, followed by 418.75 mg/kg over 67 hours
• Intravenous 21-hour regimen: Loading infusion of 150 mg/kg over one hour, followed by 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours.
Of these regimens, the 72-hour IV regimen has been found to be more effective than the 21-hour regimen for patients with acetaminophen-induced liver toxicity.26 A study of NAC administered as continuous infusion for 72 hours in patients with acute liver failure found that the transplant-free survival rate was 40% for NAC in comparison with 27% for placebo.26
L-carnitine can be used to treat valproate-induced hepatotoxicity. In a case-control study of 92 patients with severe, symptomatic, valproate-induced hepatotoxicity, nearly half of 42 patients treated with L-carnitine survived, but only 10% of 50 patients treated solely with aggressive supportive care survived.27 Greater benefit has been found for IV vs oral L-carnitine.27,28
Ursodeoxycholic acid (UDCA), 13 to 15 mg/kg, may be helpful for DILI patients with a cholestatic pattern of liver injury.
Other therapies. Steroids have no defined role in management of DILI except in autoimmune-type DILI. Other drugs, such as silymarin and antioxidants, have been used to treat other forms of hepatic toxicities and might be beneficial for patients with DILI.29,30
Liver transplantation may be necessary to prevent death due to acute liver failure in patients with severe DILI. Various criteria, including Kings College criteria,31 can be used to select which patients may best benefit from liver transplantation.
For most patients, hospitalization will not be necessary
Generally, patients with DILI have a good prognosis.20,30 About 70% of patients with DILI do not require hospitalization, and approximately 90% recover without reaching the threshold of acute liver failure. However, patients with acute liver failure have a poor prognosis; 40% will require liver transplantation.16,20
Traditionally, patients with a cholestatic pattern of liver injury have been considered to have a better prognosis than those with a hepatocellular pattern of liver injury. Patients whose DILI is the result of a hypersensitivity reaction to a drug also have a good prognosis. This may be because features such as skin rash prompt early diagnosis and discontinuation of the offending drugs.7
CASE › A liver specialist evaluates Mr. A and concludes that his liver injury was caused by his long-term heavy alcohol consumption and exacerbated by the amoxicillin/clavulanic acid he had recently been prescribed. After 2 days, Mr. A develops drowsiness and is admitted to the hospital for further management. He is managed in the intensive care unit under supervision of a gastroenterologist. A NAC infusion is started at a loading dose of 150 mg/kg to manage acute liver failure. Unfortunately, however, Mr. A succumbs to his illness.
CORRESPONDENCE
Piyush Ranjan, MD, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India 110029; drpiyushaiims@gmail.com.