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

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• 作者：Inmaculada Medina-Caliz¹ ; ^a ; ^&dagger ; ; Mercedes Robles-Diaz¹ ; ^a ; ^&dagger ; ; Beatriz Garcia-Muñ ; oz¹ ; Camilla Stephens¹ ; ^a ; Aida Ortega-Alonso¹ ; Miren Garcia-Cortes¹ ; ^a ; Andres Gonzá ; lez-Jimenez¹ ; Judith A. Sanabria-Cabrera¹ ; Inmaculada Moreno¹ ; ^a ; M. Carmen Fernandez² ; Manuel Romero-Gomez³ ; ^a ; Jose M. Navarro⁴ ; Ana Mª ; Barriocanal⁵ ; Eva Montane⁵ ; Hacibe Hallal⁶ ; Sonia Blanco⁷ ; German Soriano⁸ ; ^a ; Eva M. Roman⁸ ; ^a ; Elena Gó ; mez-Dominguez⁹ ; Agustin Castiella¹⁰ ; Eva M. Zapata¹⁰ ; Miguel Jimenez-Perez¹¹ ; Jose M. Moreno¹² ; Ana Aldea-Perona¹³ ; Manuel Herná ; ndez-Guerra¹⁴ ; Martin Prieto¹⁵ ; ^a ; Miguel E. Zoubek¹ ; Neil Kaplowitz¹⁶ ; M. Isabel Lucena¹ ; ^a ; ^{lucena@uma.es" class="auth_mail" title="E-mail the corresponding author} ; Raul J. Andrade¹ ; ^a ; on behalf of the Spanish DILI registry
• 关键词：DILI ; drug-induced liver injury ; ALP ; alkaline phosphatase ; TB ; total bilirubin ; ULN ; upper limit of normal ; AST ; aspartate aminotransferase ; ALT ; alanine aminotransferase ; INR ; international normalized ratio ; R ; ratio ; HC ; hepatocellular ; Chol ; cholestatic ; Mix ; mixed ; CIOMS ; Council for International Organizations of Medical Sciences ; RUCAM ; Roussel Uclaf causality assessment method ; NASH ; non-alcoholic steatohepatitis
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：65
• 期：3
• 页码：532-542
• 全文大小：1177 K

文摘

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 ⩾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 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.