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

Abstract

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. (HEPATOLOGY 2006;44: 1581-1588.)Abbreviations: DILI, drug-induced liver injury;

Hepatotoxicity in 2011: advancing resolutely

“…In the Spanish Registry study acute cholestatic/mixed patterns had a greater tendency toward chronicity when compared to the hepatocellular type (9 vs. 4%, respectively; p < 0.031) (27), although residual lesion severity was greater in the latter (30% of cirrhosis and 20% of chronic hepatitis). Cardiovascular and CNS drug classes are more prone to chronic hepatotoxicity induction (27).…”

“…In the Spanish Registry study acute cholestatic/mixed patterns had a greater tendency toward chronicity when compared to the hepatocellular type (9 vs. 4%, respectively; p < 0.031) (27), although residual lesion severity was greater in the latter (30% of cirrhosis and 20% of chronic hepatitis). Cardiovascular and CNS drug classes are more prone to chronic hepatotoxicity induction (27). Very recent analyses suggest that, regardless of the lesion's hepatocellular, cholestatic, or mixed pattern, most liver profile normalizations occur within one year, hence this cutoff could be most suitable to tell prolonged resolution from true chronic progression (28).…”

“…The primary therapeutic measure is immediate discontinuation of any non-essential drugs since the ongoing presence of a drug responsible for hepatotoxicity may result in higher probabilities of fulminant or chronic outcome (26,27). Drug discontinuation must lead to clinical improvement, albeit a worsening of liver function may be on occasion detected for several days or even weeks.…”

Drug-Induced Liver Injury

“…16 The poor prognostic implication of necrosis on biopsy have been appreciated in additional studies. 11,52 More formal analysis has additionally shown that the degree of necrosis, fibrosis stage, microvesicular steatosis, panacinar No specific associations Figure 7. Nodular regenerative hyperplasia due to a chemotherapeutic agent, showing compressed liver cell plates (arrows) alternating with a nodular area (asterisk) consisting of thickened plates (Gomori reticulin, original magnification 310).…”

Análisis de las causas, características y consecuencias de la reexposición al fármaco o compuesto responsable de un episodio de hepatotoxicidad

“…Merece destacarse asimismo que, aunque se realizó una biopsia hepática en un tercio de los pacientes de la serie, los hallazgos no fueron en general concluyentes para el diagnóstico de hepatotoxicidad, ya que el propio episodio de reexposición tenía un mayor peso. En circunstancias de reexposición la biopsia podría tener, pues, una utilidad principalmente de tipo pronósti-co. De hecho, en uno de estos episodios debido a bentazepam la biopsia fue consistente con una hepatitis cróni-ca activa, como ha sido previamente descrito con este fár-maco (21), y que incrementa el riesgo de persistencia de la lesión hepática (22,23). La indicación de la biopsia fue, en todo caso, más frecuente en la lesión hepatocelular, probablemente debido a que este tipo de lesión es más inespecífica, siendo más difícil su vinculación con la etiología tóxica (23).…”