Drug Induced Liver Injury

Drug-induced liver injury (DILI) can present as cholestasis, hepatitis or as a mixed picture.  DILI can be either dose-related (eg with paracetamol) or idiosyncratic.   A cholestatic picture of DILI is more common in older patients while a pattern of hepatocellular damage is more common in younger patients.

A persons susceptibility to idiosyncratic DILI is a mixture of genetic predisposition, age, gender (females more susceptible), existing medical conditions (eg diabetes increases severity) and immune factors.

DILI is clinically significant both because it is the leading cause of acute liver injury and also because it is the leading cause of aborted development or withdrawal of otherwise promising drugs.

Drugs associated with DILI include:
- anti HIV agents
- antibiotics  (penicillins - esp co-amoxiclav, macrolides, isoniazid)
- CNS agents (phenytoin, carbamazepine,  sodium valproate, gabapentin, risperidone, tricyclic antidepressants)
- analgesics (NSAIDs, paracetamol)
- antihypertensives (ACE-inhibitors)
- antiglycaemics (metformin, pioglitazone)
- others (atorvastatin, herbal health supplements)

Management:
- stop precipitating drug
- supportive management
- ? n-acetylecysteine

Most patients recover fully from DILI once the offending drug is withdrawn but a small number develop chronic liver disease.

References
Ghabril, M., Chalasani, N. and Bjornsson, E. Drug-induced liver injury: a clinical update. Curr Opin Gastroenterol. 2010; 26(3): 222-226.
Padda, M. et al. Drug induced cholestasis. Hepatology. 2014; 53(4): 1377-1387.
Tajiri, K. and Shimizu, Y. Practical guidelines for diagnosis and management of drug-induced liver injury. Word J Gastroenterol. 2008; 14(44):677
Yuan, L. and Kaplowitz, N. Mechanisms of Drug Induced Liver Injury. Clin Liver Dis. 2013; 17(4): 507-518.