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

Abstract

While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for lefluonomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including HLA genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.

Ayurveda metallic-mineral ‘Bhasma’-associated severe liver injury

“…Several studies have shown some benefit in using corticosteroids, ursodeoxycholic acid, N -acetyl cysteine, plasma exchange or liver assist devices to ameliorate liver injury in patients with severe DILI and in the presence of progressive liver failure, liver transplantation for curative intend, which is what we followed in our patient 18. Taking into consideration current available data in the scientific literature, we believe that the severe DILI seen in our patient was strongly associated with the use of Ayurveda Bhasma.…”

Worsening cholestasis and possible cefuroxime-induced liver injury following “successful” therapeutic endoscopic retrograde cholangiopancreatography for a distal common bile duct stone: a case report

“…The place of steroids in drug-induced cholestasis is equivocal [6]. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features.…”

Corticosteroid therapy in drug‐induced liver injury: Pros and cons

“…However, with an aging population, medication use is becoming diverse and complex. Thus, DILI is becoming a serious medical issue and will become even more serious in the future …”

“…Thus, DILI is becoming a serious medical issue and will become even more serious in the future. 5,7,8 Most patients with DILI will recover spontaneously after withdrawal of the suspected drug and have no long-term sequelae, but there are a proportion of patients who did not survive the hepatotoxicity. Large-scale studies have showed that the mortality of DILI patients is approximately 10%.…”