Corticosteroid Therapy in a Case of Severe Cholestasic Hepatitis Associated with Amoxicillin–Clavulanate

Abstract

Amoxicillin-clavulanate is the most common drug involved in drug-induced liver injury and the single most frequently prescribed product leading to hospitalization for drug-induced liver disease in Spain. The liver damage most frequently associated with amoxicillinclavulanate is cholestasic type. The latency period between first intake and onset of symptoms is 3-4 weeks on average. A 76-year-old man developed fever, pruritus, and jaundice 3 weeks after having completed treatment with amoxicillin-clavulanate. Liver function tests showed cholestasic hepatitis (up to 50.75 mg/dL of total serum bilirubin level). The ultrasound-guided liver biopsy revealed severe canalicular cholestasis and portal and lobular eosinophilic infiltrates. Prednisone and ursodeoxycholic acid therapy were then prescribed. The patient became symptom-free with normal liver function tests. Amoxicillin-clavulanate can cause hepatocellular, cholestasic, or mixed liver injury. The presence of eosinophilic infiltrates in the liver biopsy and the clinical signs of hypersensitivity in some of the cholestasic cases suggest a pathophysiological immunoallergic mechanism. For this reason, corticosteroid treatment should be considered for patients with severe cholestasic liver injury.

An Uncommon Side Effect of a Commonly Used Antibiotic: Amoxicillin-Clavulanic Acid Induced Hepatitis

“…There have been postulates that idiosyncratic immune-allergic reactions are the cause. 7 8 9) This postulate is based on the fact that hepatotoxicity coexists with hypersensitivity reactions such as skin rashes and hypereosinophilia, with the presence of specific antibodies like anti-mitochondrial type 6, anti-liver/kidney microsome 2, and anti-liver microsomal antibodies, 9) and liver biopsy showing eosinophilic infiltrates. 9) Genetic associations with human leukocyte antigen class II antigens such as DRB1*1501-DRB5*0101-DQB1*0602 haplotype have also been found.…”

“…Liver biopsies have been used to diagnose it, as mentioned in many of the case reports, and the typical findings associated with it include peri-portal lymphocytic infiltration and hepatocyte damage. 8 9) A liver biopsy was not done in this case, since other causes were ruled out and amoxicillin-clavulanic acid induced hepatotoxicity was highly suspected. This is an important message.…”

“… 9) Symptomatic treatment is all that is usually required. Since the mech of hepatic injury has been postulated to be inflammatory, some have suggested treatment with corticosteroids, 8) but no clear reduction in morbidity has been established.…”

Corticosteroid therapy in drug‐induced liver injury: Pros and cons

“…On the contrary, several investigations did show the beneficial effect of corticosteroids in DILI patients . Hou et al retrospectively collected data from 70 DILI patients with hepatocellular injury type and TB ≥10 × the upper limit of normal (ULN), of whom 20 received corticosteroid step‐down therapy.…”

“…On the contrary, several investigations did show the beneficial effect of corticosteroids in DILI patients. [30][31][32][33] Hou et al 30 retrospectively collected data from 70 DILI patients with hepatocellular injury type and TB ≥10 × the upper limit of normal (ULN), of whom 20 received corticosteroid step-down therapy. The results revealed that all patients treated with corticosteroids showed resolution of their symptoms with no side effects, whereas six (12%) patients died and seven (14%) patients developed chronic liver disease in the nonsteroid therapy group.…”