Idiosyncratic Drug-Induced Liver Injury Is Associated With Substantial Morbidity and Mortality Within 6 Months From Onset

Abstract

BACKGROUND & AIMS Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. METHODS Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. RESULTS Patients’ median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%–6.1%) and 32 died (5%; 95% CI, 3.2%–6.5%); 53% of the deaths were liver related. Asian race, itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and earlier heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). CONCLUSIONS Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient’s race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.

Mortality associated with drug-induced liver injury (DILI)

“…Chronic liver failure was associated with death or liver transplantation in univariate analysis but not in multivariate analysis, which is agreement with two previous studies by the DILIN group (6,8). It is conceivable, like the authors point out, that this is due to lack of power.…”

“…The DILIN group had previously published their findings on the prognosis of 660 DILI patients 6 months after onset of DILI, where 9.4% of patients died or underwent liver transplantation (6).…”

Drug-induced liver injury: an overview over the most critical compounds

“…A temporal relationship usually exists between the discontinuation of the drug and improvement in liver tests. Compared with hepatocellular type of DILI, improvement in liver tests is generally slower after discontinuation of drugs leading to cholestatic reactions (Björnsson and Davidsdottir 2009;Fontana et al 2014). …”

Idiosyncratic drug‐induced liver injury: A short review

“…In those experiencing iDILI, recent data suggest that chronicity occurs in approximately 13.6% of cases 16. Patients who presented with cholestatic iDILI were more likely to develop chronic iDILI compared to those who presented with hepatocellular iDILI 35. Chronic iDILI may resemble AIH and might respond to corticosteroids, provided that blood markers and biopsy findings are suggestive of this diagnosis.…”