Profile of drug-induced liver injury due to antibiotics in patients with chronic liver disease

Abstract

Background: Patients with chronic liver disease (CLD) may be more susceptible to drug-induced liver injury (DILI) through reduced drug clearance, aberrant metabolism, altered excretion, or impaired adaptive responses. The diagnosis of DILI may identify a reversible cause for acute decompensation. Aim: The aim was to study the profile and outcomes of DILI in CLD patients. Patients and Methods: A total of 400 consecutive in patients with CLD who had been received antibiotic therapy between September 2015 and April 2016 were prospectively studied for features suggestive of DILI. The Naranjo Adverse Drug Reaction (ADR) Probability Scale was used for identifying ADRs in CLD patients. Results: Sixty-three (15.8%) patients were identified by Naranjo Scale. The most common etiology of CLD in these patients was alcohol (49.2%); hepatitis C virus (7.9%), NASH (4.3%), cryptogenic (14.3%), and hepatitis B virus (5.6%) were other common causes. DILI was more common in Child class C (52.4%) as compared to Child B (30.2%) and Child A (17.4%). Thirteen (20.6%) patients had hepatitic, 17 (27%) had cholestatic, and 33 (52.45) had a mixed pattern. There were six cases with DILI due to anti-tubercular treatment. Clarithromycin (9 cases), clindamycin (9 cases), amoxicillin-clavulanate (7 cases), and co-trimoxazole (5 cases) were the most common antibiotics causing DILI in CLD patients. Forty-three (68.2%) recovered, 11 (17.4%) expired, 3 (4.7%) developed acute on chronic liver failure, and 2 (3.1%) underwent liver transplant. Conclusions: Definitive diagnosis of DILI in CLD patients is difficult, and it is often a diagnosis of exclusion. Exposure to a potentially hepatotoxic agent, the temporal profile of liver function test changes after initiation and withdrawal of antibiotics is useful pointers. Early diagnosis of DILI, even if not definitive, may help in timely intervention and affect outcomes in CLD patients.