Development and Adaptive Function in Individuals With SCN2A-Related Disorders.
Authors: Goad BS, Rodda J, Allen M, Bamborschke D, Overmars I, Kerr RJ, Bushlin I, Chopra S, Coorg R, Dabscheck G, Freeman JL, Mackay MT, Devinsky O, Guerrini R, Parrini E, Bölsterli B, Hughes I, Huh LL, Kamate M, Kunz AB, Melikishvili G, Miteff C, Myers KA, Olson HE, Poduri A, Pillai S, Riney CK, Sinclair A, Calvert S, Reynolds TQ, Martinez AR, Russo A, Sadleir LG, Sanchez-Albisua I, Sartori S, Shea S, Smith-Hicks CL, Spooner CG, Thomas RH, Ardern-Holmes SL, Webster RI, Valeriani M, Veggiotti P, Masnada S, Ware TL, Yoong M, Berecki G, De Dominicis A, Specchio N, Trivisano M, Møller RS, Wolff M, Fazeli W, Scheffer I, Howell KB
Journal: Neurology
mental health
psychology
open access
Abstract
Idiosyncratic drug-induced liver injury (DILI) attributed to various drugs and herbal and dietary supplements (HDSs) accounts for up to 6% of hospitalized patients with severe acute liver injury (ALI). The majority (80%) of patients with ALI related DILI fully recover following suspect drug discontinuation, but some may progress to acute liver failure (ALF) with mental status changes and require emergency liver transplantation (LT). Idiosyncratic DILI is also a leading cause of ALF in Western countries. Overall, adult patients with non–acetaminophen (APAP)-related ALF including idiosyncratic DILI have a <50% likelihood of spontaneous survival (SS) and frequently need to be assessed for emergency LT. A prognostic model consisting of readily available clinical and laboratory bedside parameters is needed to identify hospitalized DILI patients at greatest risk for adverse outcomes so that they can be rapidly triaged to a LT center. The aim of the current study was to identify admission clinical and laboratory variables associated with 21-day adverse outcomes in a large cohort of idiosyncratic DILI patients prospectively enrolled in the US ALFSG (Acute Liver Failure Study Group) registry study. A multivariable model was constructed and internally validated using bootstrap methodology and compared with other published prognostic scores including the Model for End-Stage Liver Disease (MELD) and King’s College Criteria (KCC) scores. Between January 1998 to August 2019, 3364 adult patients were enrolled in the ALFSG Registry study funded by the National Institute of Diabetes, Digestive and Kidney Diseases. Written informed consent was obtained from subject or legal next of kin. All centers adhered to local Institutional Review Board requirements. ALF was defined by presence of hepatic encephalopathy (HE) and coagulopathy with an international normalized ratio (INR) ≥1.5, an illness duration of ≤26 weeks, and no known previous liver disease. ALI was defined as hospitalized patients with an INR >2.0, a serum alanine aminotransferase (ALT) >10 times upper limit of normal, and total bilirubin >3.0 mg/dL but without encephalopathy at presentation.