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. 2016 Sep;65(3):532-42.
doi: 10.1016/j.jhep.2016.05.003. Epub 2016 May 13.

Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury

Inmaculada Medina-Caliz  1 , Mercedes Robles-Diaz  1 , Beatriz Garcia-Muñoz  2 , Camilla Stephens  1 , Aida Ortega-Alonso  2 , Miren Garcia-Cortes  1 , Andres González-Jimenez  2 , Judith A Sanabria-Cabrera  2 , Inmaculada Moreno  1 , M Carmen Fernandez  3 , Manuel Romero-Gomez  4 , Jose M Navarro  5 , Ana M Barriocanal  6 , Eva Montane  6 , Hacibe Hallal  7 , Sonia Blanco  8 , German Soriano  9 , Eva M Roman  9 , Elena Gómez-Dominguez  10 , Agustin Castiella  11 , Eva M Zapata  11 , Miguel Jimenez-Perez  12 , Jose M Moreno  13 , Ana Aldea-Perona  14 , Manuel Hernández-Guerra  15 , Martin Prieto  16 , Miguel E Zoubek  2 , Neil Kaplowitz  17 , M Isabel Lucena  18 , Raul J Andrade  1 ; Spanish DILI registry
Affiliations

Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury

Inmaculada Medina-Caliz et al. J Hepatol. 2016 Sep.

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.

Keywords: Chronic; Hepatotoxicity; Risk factors; Statins.

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Conflict of interest statement

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Figures

Fig. 1.
Fig. 1.. Flow chart of the study cohort.
Fig. 2.
Fig. 2.. Time to liver injury resolution in 285 patients with acute idiosyncratic drug-induced liver injury who recovered classified by type of damage.
An additional 13 patients (not included) had not recovered after 3 years. Chol, cholestatic; HC, hepatocellular; Mix, mixed.
Fig. 3.
Fig. 3.. Median of ALP, ALT and TB values during the first year from DILI onset in acute and chronic groups.
Each time interval includes 15 days.
See this image and copyright information in PMC

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