Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

Phenobarbital Use as Adjunct to Benzodiazepines in the Treatment of Severe Alcohol Withdrawal Syndrome

Severe AWS （alcohol withdrawal syndrome） and AWD （alcohol withdrawal associated delirium） are common indications for intensive care unit admissions. Approximately 25% of patients with severe alcohol withdrawal require prolonged critical care hospital courses, often complicated by respiratory failure, need for mechanical ventilation due to administration of sedative continuous infusions and development of nosocomial infections. Although benzodiazepines are the mainstay of therapy for alcohol withdrawal, some patients exhibit benzodiazepine-refractory alcohol withdrawal. The use of phenobarbital as adjunct to benzodiazepines has been shown in studies to be effective in enhancing therapeutic responsiveness to benzodiazepines and reducing the need for mechanical ventilation. The objective of this study is to evaluate whether severe alcohol withdrawal treatment based on combining symptom-triggered benzodiazepine therapy with adjunctive phenobarbital will result in decreased mechanical ventilation rates, decreased use of continuous sedative infusions, decreased time to withdrawal symptom resolution and decreased length of stay in the intensive care unit. Chart reviews were utilized to determine total amount of benzodiazepine and phenobarbital use, need for mechanical ventilation, requirement of continuous lorazepam, dexmedetomidine or propofol infusions, average intensive care unit length of stay and incidence of adverse effects.