A novel microRNA-based prognostic model outperforms standard prognostic models in patients with acetaminophen-induced acute liver failure
Autor: | Oliver D. Tavabie, Constantine J. Karvellas, Siamak Salehi, Jaime L. Speiser, Christopher F. Rose, Krishna Menon, Andreas Prachalias, Michael A. Heneghan, Kosh Agarwal, William M. Lee, Mark J.W. McPhail, Varuna R. Aluvihare, W.M. Lee, Anne M. Larson, Iris Liou, Oren Fix, Michael Schilsky, Timothy McCashland, J. Eileen Hay, Natalie Murray, A. Obaid S. Shaikh, Andres Blei, Daniel Ganger, Atif Zaman, Steven H.B. Han, Robert Fontana, Brendan McGuire, Raymond T. Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwin Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R. Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, Jodi Olson, Ram Subramanian, James Hanje, Bilal Hameed, Ezmina Lalani, Carla Pezzia, Corron Sanders, Nahid Attar, Linda S. Hynan, Valerie Durkalski, Wenle Zhao, Jaime Speiser, Catherine Dillon, Holly Battenhouse, Michelle Gottfried |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty Logistic regression 03 medical and health sciences Liver disease 0302 clinical medicine Internal medicine medicine Blood test Humans Acetaminophen Liver injury Hepatology medicine.diagnostic_test business.industry digestive oral and skin physiology Analgesics Non-Narcotic Middle Aged medicine.disease Prognosis Liver regeneration Transplantation MicroRNAs 030104 developmental biology Logistic Models ROC Curve Case-Control Studies Biomarker (medicine) 030211 gastroenterology & hepatology Female Chemical and Drug Induced Liver Injury business Biomarkers Liver Failure medicine.drug |
Zdroj: | Journal of hepatology. 75(2) |
ISSN: | 1600-0641 |
Popis: | Background & Aims Acetaminophen (APAP)-induced acute liver failure (ALF) remains the most common cause of ALF in the Western world. Conventional prognostic models, utilising markers of liver injury and organ failure, lack sensitivity for mortality prediction. We previously identified a microRNA signature that is associated with successful regeneration post-auxiliary liver transplant and with recovery from APAP-ALF. Herein, we aimed to use this microRNA signature to develop outcome prediction models for APAP-ALF. Methods We undertook a nested, case-control study using serum samples from 194 patients with APAP-ALF enrolled in the US ALF Study Group registry (1998-2014) at early (day 1-2) and late (day 3-5) time-points. A microRNA qPCR panel of 22 microRNAs was utilised to assess microRNA expression at both time-points. Multiple logistic regression was used to develop models which were compared to conventional prognostic models using the DeLong method. Results Individual microRNAs confer limited prognostic value when utilised in isolation. However, incorporating them within microRNA-based outcome prediction models increases their clinical utility. Our early time-point model (AUC = 0.78, 95% CI 0.71–0.84) contained a microRNA signature associated with liver regeneration and our late time-point model (AUC = 0.83, 95% CI 0.76–0.89) contained a microRNA signature associated with cell-death. Both models were enhanced when combined with model for end-stage liver disease (MELD) score and vasopressor use and both outperformed the King’s College criteria. The early time-point model combined with clinical parameters outperformed the ALF Study Group prognostic index and the MELD score. Conclusions Our findings demonstrate that a regeneration-linked microRNA signature combined with readily available clinical parameters can outperform existing prognostic models for ALF in identifying patients with poor prognosis who may benefit from transplantation. Lay summary While acute liver failure can be reversible, some patients will die without a liver transplant. We show that blood test markers that measure the potential for liver recovery may help improve identification of patients unlikely to survive acute liver failure who may benefit from a liver transplant. |
Databáze: | OpenAIRE |
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