Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

J Hepatol. 2021 Jul;75(1):86-97. doi: 10.1016/j.jhep.2021.01.029. Epub 2021 Feb 1.


Background & aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period.

Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected.

Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%).

Conclusions: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management.

Lay summary: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.

Keywords: DILI; Hepatotoxicity; causative agents; drug-induced autoimmune hepatitis; epidemiology; liver-related death; outcome; risk factors; therapy in DILI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Anti-Infective Agents* / pharmacology
  • Anti-Infective Agents* / toxicity
  • Aspartate Aminotransferases / analysis*
  • Chemical and Drug Induced Liver Injury* / diagnosis
  • Chemical and Drug Induced Liver Injury* / epidemiology
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / therapy
  • Chronic Disease / epidemiology
  • Female
  • Humans
  • Liver Diseases / epidemiology
  • Liver Function Tests / methods
  • Liver Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Mortality
  • Platelet Count / methods
  • Platelet Count / statistics & numerical data
  • Prognosis
  • Registries / statistics & numerical data
  • Risk Assessment / methods*
  • Risk Factors
  • Spain / epidemiology


  • Anti-Infective Agents
  • Aspartate Aminotransferases