Profile of Drug-Induced Liver Injury in Patients With Chronic Liver Disease

Introduction: Patients with chronic liver disease (CLD) may be more susceptible to drug induced liver injury (DILI) via reduced drug clearance, aberrant metabolism, altered excretion, or impaired adaptive responses. Diagnosis of DILI may identify a reversible cause for acute decompensation. Methods: 200 consecutive inpatients with CLD who had been received antibiotic therapy between Sept and Dec 2015 were prospectively studied for features suggestive of DILI. The Naranjo adverse drug reaction (ADR) probability scale was used for identifying ADRs in CLD patients. The Maria and Victorino (M&V) assessment scale was used for causality assessment. Results: Thirty six (18%) patients were identified by Naranjo scale. The most common etiology of CLD in these patients was alcohol (50%); HCV (13.9%), NASH (8.3%), cryptogenic (8.3%), HBV (5.6%) were other common causes. DILI was more common in Child class C (58.3%) as compared to Child B (27.8%) and Child A (13.9%). 8 patients had hepatitic-, 5 had cholestatic-, and 23 had mixed pattern. By M&V scale, there were 2 definite, 8 probable, 11 possible cases of DILI while 12 were found to be unlikely and 3 were excluded. Antitubercular therapy (ATT) was implicated as definite DILI in 2 cases and probable in 1 case. Clarithromycin (6 cases), amoxicillin-clavulanate (4 cases) and clindamycin (4 cases) were most common antibiotics causing DILI in CLD patients. 25 (69.4%) recovered, 8 (21.9%) expired, 2 (5.6%) developed acute on chronic liver failure and 1 (2.8%) underwent liver transplant. Conclusion: Definitive diagnosis of DILI in CLD patients is difficult; and it is often a diagnosis of exclusion. Exposure to a known hepatotoxic agent, temporal profile of LFT changes after initiation and withdrawal of antibiotics are useful pointers. Early diagnosis of DILI, even if not definitive, may help in timely intervention and affect outcomes in CLD patients.