Introduction

Drug-induced hepatotoxicity is one of the main forms of iatrogenic pathology, which is often under-diagnosed. Numerous drugs are implicated and can cause hepatic damage reproducing the whole spectrum of non-iatrogenic liver pathology, ranging from a simple transient disturbance of the liver balance to fulminant, life-threatening hepatitis.

Aims & Methods

The aim of our work is to study the etiological profile and therapeutic management of drug-induced hepatitis.
This is a retrospective descriptive monocentric study from January 2010 to August 2023 of patients with drug-induced hepatitis in the Hepato-Gastro-Enterology and Proctology Department “Medicine B”.
Diagnosis was based on the elimination of infectious, immunological and toxic causes of hepatitis. For all patients, viral serologies for hepatotropic viruses and a pharmacovigilance investigation were carried out before concluding that the cause was drug-induced.

Results

194 patients were included in our study, with a mean age of 44.2 years, ranging from 23 to 84 years. Female predominance was observed, with 110 women (56.7%) versus 84 men (43.2%), so, a F/H sex ratio of 1.3.
In 59 cases (30.4%), liver damage was discovered by chance during a biological check-up. In the other cases, clinical manifestations were dominated by jaundice in 112 patients (57.7%), followed by asthenia in 42 patients (21.6%), pruritus in 35 cases (18%) and fever in 17 cases (8.7%). Liver function tests showed cytolysis in 97 cases (50%), mixed disease in 74 patients (38.1%), and cholestasis in 23 patients (11.8%). The time to onset of clinical or biological signs of hepatotoxicity ranged from 03 days to 09 months. Severe acute hepatitis occurred in 70 cases (36%), including 48 cases (24.7%) of fulminant hepatitis. Viral serologies were negative in all cases. Liver biopsy was consistent with drug-induced hepatitis in 35 cases (18%). The main drugs implicated were anti-tuberculosis drugs in 110 cases (56.7%), followed by immunosuppressants, particularly azathioprine in 44 cases (22.6%), then paracetamol in 23 cases (11.8%), antidepressants in 6 cases (3%), and non-steroidal anti-inflammatory drugs (NSAIDs) in 3 cases (1.5%). Other drugs were less frequently associated with liver dysfunction, such as: allopurinol, fluconazole (1 case: 0.5%), synthetic antithyroid drugs (1 case: 0. 5%), antiepileptics (Carbamazepine) (1 case: 0.5%), hypolipidemics (1 case: 0.5%), ciprofloxacin (1 case: 0.5%), anti TNF (Adalimumab) (1 case: 0.5%), and anti-angoretics (1 case: 0.5%).
Discontinuation of the treatment in question was considered in all patients. Patients with fulminant acute hepatitis were managed in intensive care, and N-acetylcysteine was introduced in patients admitted for paracetamol-induced hepatitis. The outcome was favorable in 160 patients (82.4%), while 34 patients (17.5%) died.

Conclusion

Drug-induced hepatitis is a delicate condition, given its polymorphic presentation and the diversity of potentially hepatotoxic drugs prescribed. Diagnosis is based on the elimination of other possible causes of liver dysfunction, a suggestive or compatible chronology between the administration of the drug and the onset of hepatitis, and a favorable evolution after discontinuation of the drug. Prevention requires compliance with prescribing rules, early detection of signs of therapeutic intolerance and rigorous monitoring of progress under treatment.