Features and Outcomes of 899 Patients with Drug-induced Liver Injury: The DILIN Prospective Study
By N. Chalasani, Herbert L. Bonkovsky, Robert J. Fontana, William M. Lee, A. Stolz, J. Talwalkar, K. Reddy, Paul B. Watkins, Victor J. Navarro, H. Barnhart and 64 more. Gastroenterology, 2015
833 citations recorded by the source corpus.
Background & Aims The drug-induced liver injury network (DILIN) is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. Methods In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. Results Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P=.09) and mortality was significantly higher (16% vs 5.2%; P<.001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared to those without liver disease (6.7% vs. 1.5%, p=0.006). Forty-one cases with latency ≤ 7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared to individuals younger than 65 y, individuals 65 y or older (n=149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. Conclusion Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared to patients without. Further studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality.
Subfields: Emergency Medicine, Hepatology, Pharmacology
View Paper: https://www.semanticscholar.org/paper/fe1f851b9cd8cc52843b60e4526d5feec3c95c29
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In Hepatology
Citations in the corpus
- EASL Clinical Practice Guidelines: Drug-induced liver injury. (2019, background): “6% of their patients with DILI to be 65 years or older.(16,64) However, data from a populationbased study in Iceland demonstrates a clear increase in DILI incidence with increased age, whereby 15–29-year olds had”
- ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. (2021, background): “, nitrofurantoin, minocycline, and statins; Table 6) (15).”
- Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases (2019, background): “Gender Mainly women(187) Female predominance, but men also affected(2,384,467) Acute onset Majority (>60%)(231) 20%(2,136) Hypersensitivity (fever, rash, eosinophilia) Up to 30%(231,232,613) Unusual(2,384,467) Temporal relationship with drug Positive(231-234) Negative(2,56,188) HLA DRB1*03:01 or DR”
- Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update (2019, background): “Results from the drug-induced liver injury network have demonstrated that mortality in 89 patients with pre-existing liver disease was 16% which was significantly higher than the 5% mortality in 810 patients with underlying liver disease [32].”