Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry.

A chronic adverse reaction may occur in some instances of drug-induced liver injury (DILI), even despite drug cessation. In our study, we obtained records from a Spanish registry and evaluated cases of DILI with biochemical evidence of long-term damage. Chronic outcome was defined as a persistent biochemical abnormality of hepatocellular pattern of damage more than 3 months after drug withdrawal or more than 6 months after cholestatic/mixed damage. Data on 28 patients with a chronic clinical evolution (mean follow-up 20 months) between November 1995 and October 2005 were retrieved (18 female; overall mean age 55 yr) and accounted for 5.7% of total idiosyncratic DILI cases (n = 493) submitted to the registry. The main drug classes were cardiovascular and central nervous system (28.5% and 25%, respectively), which, in contrast, represented only 9.8% and 13%, respectively, of all DILI cases. The most frequent causative drugs were amoxicillin-clavulanate (4 of 69 cases), bentazepam (3 of 7 cases), atorvastatin (2 of 7 cases), and captopril (2 of 5 cases). Patients with cholestatic/mixed injury (18 of 194 cases [9%]) were more prone to chronicity than patients with hepatocellular injury (10 of 240 cases; P < .031). In the case of chronic hepatocellular injury, 3 patients progressed to cirrhosis and 2 to chronic hepatitis. In the cholestatic/mixed group, liver biopsy indicated cirrhosis in 1 patient and ductal lesions in 3 patients. In conclusion, cholestatic/mixed type of damage is more prone to become chronic while, in the hepatocellular pattern, the severity is greater. Cardiovascular and central nervous system drugs are the main groups leading to chronic liver damage.

Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity: a prospective series from Spain.

Amoxicillin-clavulanate (AC) hepatotoxicity has been reported to exhibit a higher predominance of cholestatic types of damage, especially in males. However, the determinants of its clinical expression are unknown. This study prospectively evaluated the profile of AC hepatotoxicity. Data on all cases of hepatotoxicity reported to the Spanish Registry attributed to AC and assessed as definite or probable on the Council for International Organizations of Medical Sciences (CIOMS) scale were collated and compared to published case series. Hepatotoxicity related to amoxicillin-clavulanate was identified in 69 patients (36 males; mean age 56 years) representing 14% of all cases of hepatotoxicity submitted to the Registry. There was an overall sex distribution and the predominant pattern of lesion was hepatocellular (36%) which occurred at a shorter duration of treatment (P < .03). Mean time lapse between therapy initiation and jaundice onset was 16 days. Late onset of symptoms following end of treatment occurred in half the cases. Multiple logistic regression analysis identified advancing age as the factor associated with the development of cholestatic/mixed type of injury (odds ratio for an age interval for 1 year: 1.045 [95% CI = 1.013-1.078; P = .005). An unfavorable outcome was seen in 7% of patients. In conclusion, age is the most important determinant in the biochemical expression of AC hepatotoxicity; younger age is associated with cytolytic damage and shorter treatment duration, whereas cholestatic/mixed type of damage is related to older age and prolonged AC therapy.