http://www.ncbi.nlm.nih.gov/pubmed/27184533

Medina-Caliz I, Robles-Diaz M, Garcia-Muñoz B, Stephens C, Ortega-Alonso A, Garcia-Cortes M, Gonzalez-Jimenez A, Sanabria-Cabrera JA, Moreno I, Carmen Fernandez M, Romero-Gomez M, Navarro JM, Barriocanal AM, Montane E, Hallal H, Blanco S, Soriano G, Roman EM, Gomez-Dominguez E, Castiella A, Zapata EM, Jimenez-Perez M, Moreno JM, Aldea-Perona A, Hernandez-Guerra M, Prieto M, Zoubek ME, Kaplowitz N, Isabel Lucena M, Andrade RJ; Spanish DILI Registry.
J Hepatol. 2016 May 13. pii: S0168-8278(16)30188-X. doi: 10.1016/j.jhep.2016.05.003.

Abstract

BACKGROUND AND 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 preexisting disease affecting the liver and follow-up to resolution or ⩾1 year 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 ⩽1 year 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 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 antiinfectives (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.