Management of drug-induced liver disease

Abstract

The treatment and prevention of drug-induced liver injury starts with the recognition of hepatotoxicity at the earliest possible time so that the suspected drug can be discontinued expeditiously. Both liver enzyme monitoring and vigilance for signs of hypersensitivity involving the liver are useful strategies for many agents known to cause hepatocellular necrosis leading to liver failure. Specific antidotes to prevent or limit hepatic damage exist for only a few drugs, the most important being N-acetylcysteine for the treatment of acetaminophen hepatotoxicity. Corticosteroids are of unproven benefit in the setting of fulminant failure. Ursodiol may be helpful in instances of cholestatic injury. For other agents, supportive measures and the increasing use of liver-assist devices as well as emergency liver transplantation are available when drug injury evolves into irreversible liver failure. It is hoped that a better understanding of hepatotoxicity mechanisms will lead to the development of more specific and effective forms of therapy in the near future.

The Art and Science of Diagnosing and Managing Drug-induced Liver Injury in 2015 and Beyond

“…It has long been axiomatic that if a drug causing acute DILI is discontinued, the injury is expected to resolve (206). Hepatocellular injury generally does so within several weeks, while cholestatic injury can take up to several months (78,207).…”

“…Liver associated enzyme monitoring was born out of the observation that if a drug is stopped prior to crossing the threshold of ALF, recovery can be expected (7,206). While dozens of drugs have had ALT monitoring recommended (139), it remains largely unproven that the time, expense and inconvenience of performing such monitoring is actually effective.…”

“…Lagging behind all of the advances in the detection, diagnosis, and prevention of DILI is our ability to treat acute DILI (6,73,206). The cardinal rule to limit injury is to stop the suspected offending agent as soon as possible (7,73).…”

“…In some cases this means discontinuing a drug that is efficacious, and in situations where there are no alternative agents, the patient may be deprived of a beneficial medication, especially if causality is in doubt (111). Some patients have received ursodiol or steroids in cases of cholestatic DILI, although such treatment has been met with only anecdotal success (70,73,206,244).…”

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review

“…[1] The management of acute (or chronic) drug-induced liver injury (DILI), including herbal and dietary supplement induced liver injury (HDSLI) has not changed appreciably since we reviewed this topic 15 years ago. [2] It still involves a process that begins with the recognition of hepatic injury and assigning causality to a specific agent. [3] After making a diagnosis of DILI, a decision must be made regarding whether or not the suspected drug can be continued with frequent monitoring to determine if tolerance or drug adaptation is present, or if the injury meets criteria where the drug needs to be stopped temporarily or permanently.…”