ABSTRACT

Drug-induced liver disease is a common clinical problem. Although adverse reactions appear

rare, occurring in 1:10,000 to 1:100,000 individuals exposed to a given drug (1), incidence

figures in a study from France for all types of hepatic drug reactions were 13.9G2.4 per 100,000,

with 12% being hospitalized and 6% dying from the adverse reaction. The author believes that

this is an underestimate of the true incidence of drug-induced liver disease (2). Similarly, in a

report from the United States, the medical records of an HMO were examined for elevated

liver tests. They found an incidence of 40.6 cases per 100,000 for drug-associated liver test

abnormalities when compared with an incidence of 15.4 per 100,000 for alcohol as a cause of the

elevated liver tests (3). Adverse hepatic drug reactions are common in the outpatient setting

as well. In one report, 84% of adverse hepatic drug reactions occurred in outpatients (2).

Identification of hepatotoxic drug reactions in the outpatient setting is difficult as multiple

healthcare providers may prescribe medications for a given patient and if the reaction is

delayed, as with clavulanic acid-containing drugs, cause and effect may be difficult to establish.

In addition, the spontaneous reporting of adverse drug reactions is more likely to occur

with hospital-based physicians than with nonhospital-based physicians, leading to an under-

estimate of the frequency of drug-induced hepatotoxicity in outpatients (4). Thus, the clinician

is likely to see a number of patients with drug-induced liver injury during the course of their

practice and the management of these patients will be a common issue. This chapter will focus

on how to manage the patient with drug-induced liver injury. A brief discussion of how the

diagnosis is established is followed by a discussion of whether or not discontinuation of

the offending medication is required and whether a rechallenge or use of a medication of the

same class is safe. Treatment of complications of the adverse reactions will also be discussed

and, lastly, the criteria for referral to a liver transplant center will be reviewed. Although the

author will attempt to use data from studies to support most of the recommendations provided

in this chapter, on occasion the recommendations will be based on the author’s experience in

managing these types of patients.