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

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

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

Journal

Journal of hepatology

ISSN: 1600-0641

Titre abrégé: J Hepatol

Pays: Netherlands

ID NLM: 8503886

Informations de publication

Date de publication:
07 2021

Historique:

received: 16 09 2020

revised: 13 01 2021

accepted: 15 01 2021

pubmed: 5 2 2021

medline: 5 2 2022

entrez: 4 2 2021

Statut: ppublish

Résumé

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

Sections du résumé

BACKGROUND & AIMS

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.

Identifiants

DOI: 10.1016/j.jhep.2021.01.029 PMID: 33539847

pubmed: 33539847

pii: S0168-8278(21)00043-X

doi: 10.1016/j.jhep.2021.01.029

pii:

doi:

Substances chimiques

Anti-Infective Agents 0

Aspartate Aminotransferases EC 2.6.1.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

86-97

Investigateurs

R J Andrade (RJ)

M I Lucena (MI)

C Stephens (C)

M García Cortés (MG)

M Robles-Díaz (M)

A Ortega-Alonso (A)

J Pinazo (J)

B García Muñoz (BG)

R Alcántara (R)

A Hernández (A)

M D García Escaño (MDG)

E Del Campo (E)

I Medina-Cáliz (I)

J Sanabria-Cabrera (J)

A González-Jiménez (A)

R Sanjuán-Jiménez (R)

A Cueto (A)

I Álvarez-Álvarez (I)

E Bonilla (E)

D Di Zeo (D)

H Niu (H)

M Villanueva (M)

A Papineau (A)

M Jiménez Pérez (MJ)

R González Grande (RG)

S López Ortega (SL)

I Santaella (I)

A Ocaña (A)

P Palomino (P)

M C Fernández (MC)

G Peláez (G)

A Porcel (A)

M Casado (M)

M González Sánchez (MG)

M Romero-Gómez (M)

R Millán-Domínguez (R)

B Fombuena (B)

R Gallego (R)

J Ampuero (J)

J A Del Campo (JAD)

R Calle-Sanz (R)

L Rojas (L)

A Rojas (A)

A Gil Gómez (AG)

E Vilar (E)

G Soriano (G)

C Guarner (C)

E M Román (EM)

M A Quijada Manuitt (MAQ)

R M Antonijoan Arbos (RMA)

J Sánchez Delgado (JS)

M Vergara Gómez (MV)

H Hallal (H)

E García Oltra (EG)

J C Titos Arcos (JCT)

A Pérez Martínez (AP)

C Sánchez Cobarro (CS)

J M Egea Caparrós (JME)

A Castiella (A)

E Zapata (E)

J Arenas (J)

A Gómez García (AG)

F J Esandi (FJ)

S Blanco (S)

P Martínez Odriozola (PM)

J Crespo (J)

P Iruzubieta (P)

J Cabezas (J)

A Giráldez Gallego (AG)

E Del P Rodríguez Seguel (EDP)

M Cuaresma (M)

J González Gallego (JG)

F Jorquera (F)

S Sánchez Campos (SS)

P Otazua (P)

A de Juan Gómez (A)

J Salmerón (J)

A Gila (A)

R Quiles (R)

J M González (JM)

S Lorenzo (S)

M Prieto (M)

I Conde Amiel (IC)

M Berenguer (M)

M García-Eliz (M)

J Primo (J)

J R Molés (JR)

A Garayoa (A)

M Carrascosa (M)

E Gómez Domínguez (EG)

L Cuevas (L)

M Farré (M)

E Montané (E)

A M Barriocanal (AM)

A L Arellano (AL)

Y Sanz (Y)

R M Morillas (RM)

M Sala (M)

H Masnou Ridaura (HM)

M Bruguera (M)

P Gines (P)

S Lens (S)

J C García (JC)

Z Mariño (Z)

M Hernández Guerra (MH)

J M Moreno Sanfiel (JMM)

C Boada Fernández Del Campo (CB)

M Tejedor (M)

R González Ferrer (RG)

C Fernández (C)

M Fernández Gil (MF)

J L Montero (JL)

M de la Mata (M)

J Fuentes Olmo (JF)

E M Fernández Bonilla (EMF)

J M Moreno (JM)

P Martínez-Rodenas (P)

M Garrido (M)

C Oliva (C)

P Rendón (P)

J García Samaniego (JG)

A Madejón (A)

J L Calleja (JL)

J L Martínez Porras (JLM)

J L Cabriada (JL)

J M Pérez-Moreno (JM)

C Lara (C)

Informations de copyright

Déclaration de conflit d'intérêts

Conflict of interest The authors have no conflict of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.