Inmaculada Medina-Caliz1, Mercedes Robles-Diaz1, Beatriz Garcia-Muñoz2, Camilla Stephens1, Aida Ortega-Alonso2, Miren Garcia-Cortes1, Andres González-Jimenez2, Judith A Sanabria-Cabrera2, Inmaculada Moreno1, M Carmen Fernandez3, Manuel Romero-Gomez4, Jose M Navarro5, Ana M Barriocanal6, Eva Montane6, Hacibe Hallal7, Sonia Blanco8, German Soriano9, Eva M Roman9, Elena Gómez-Dominguez10, Agustin Castiella11, Eva M Zapata11, Miguel Jimenez-Perez12, Jose M Moreno13, Ana Aldea-Perona14, Manuel Hernández-Guerra15, Martin Prieto16, Miguel E Zoubek2, Neil Kaplowitz17, M Isabel Lucena18, Raul J Andrade1. 1. Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 2. Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. 3. Servicio de Farmacia, Hospital de Torrecárdenas, Almería, Spain. 4. UCM Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 5. Area Integrada de Gestión de Medicina Interna, Hospital Costa del Sol, Marbella, Málaga, Spain. 6. Servicio de Farmacología Clínica, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. 7. Servicio de Digestivo, Hospital Morales Meseguer, Murcia, Spain. 8. Servicio de Aparato Digestivo, Hospital de Basurto, Bilbao, Vizcaya, Spain. 9. Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 10. Servicio de Aparato Digestivo, Hospital Universitario 12 de Octubre, Madrid, Spain. 11. Servicio de Digestivo, Hospital de Mendaro, Guipúzcoa, Spain. 12. Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Regional de Málaga, Málaga, Spain. 13. Servicio de Digestivo, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. 14. Servicio de Farmacología Clínica, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain. 15. Servicio de Digestivo, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain. 16. Unidad de Hepatología, Hospital La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 17. USC Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, CA, United States. 18. Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: lucena@uma.es.
Abstract
BACKGROUND & AIMS: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. METHODS: 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. RESULTS: Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. CONCLUSIONS: One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. LAY SUMMARY: Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.
BACKGROUND & AIMS: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. METHODS: 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. RESULTS: Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. CONCLUSIONS: One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. LAY SUMMARY:Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.
Authors: Paul H Hayashi; Don C Rockey; Robert J Fontana; Hans L Tillmann; Neil Kaplowitz; Huiman X Barnhart; Jiezhan Gu; Naga P Chalasani; K Rajender Reddy; Averell H Sherker; Jay H Hoofnagle Journal: Hepatology Date: 2017-08-26 Impact factor: 17.425
Authors: Naga Chalasani; K Rajender K Reddy; Robert J Fontana; Huiman Barnhart; Jiezhun Gu; Paul H Hayashi; Jawad Ahmad; Andrew Stolz; Victor Navarro; Jay H Hoofnagle Journal: Am J Gastroenterol Date: 2017-08-01 Impact factor: 10.864