Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure

Acute Liver Failure Study Group

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background & Aims: Fewer than 50% of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. Methods: We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. Results: Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. Conclusions: A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440.

Original languageEnglish (US)
Pages (from-to)606-612.e3
JournalClinical Gastroenterology and Hepatology
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

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Galectins
Acute Liver Failure
Survival
Pharmaceutical Preparations
Liver Transplantation
Chemical and Drug Induced Liver Injury
End Stage Liver Disease
Kupffer Cells
Acetaminophen
Systemic Inflammatory Response Syndrome
Mortality
Liver
Liver Diseases
Immunity

Keywords

  • Innate Immune Responses
  • Prediction
  • SIRS
  • Stratification

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure. / Acute Liver Failure Study Group.

In: Clinical Gastroenterology and Hepatology, Vol. 14, No. 4, 01.04.2016, p. 606-612.e3.

Research output: Contribution to journalArticle

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title = "Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure",
abstract = "Background & Aims: Fewer than 50{\%} of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. Methods: We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. Results: Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. Conclusions: A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440.",
keywords = "Innate Immune Responses, Prediction, SIRS, Stratification",
author = "{Acute Liver Failure Study Group} and Rosen, {Hugo R.} and Biggins, {Scott W.} and Toshiro Niki and Jane Gralla and Holly Hillman and Mitsuomi Hirashima and Michael Schilsky and Lee, {William M.} and Larson, {Anne M.} and Iris Liou and Timothy Davern and Oren Fix and Timothy McCashland and Hay, {J. Eileen} and Natalie Murray and Shaikh, {A. Obaid S} and Andres Blei and Daniel Ganger and Atif Zaman and Han, {Steven H B} and Robert Fontana and Brendan McGuire and Chung, {Raymond T.} and Alastair Smith and Robert Brown and Jeffrey Crippin and Edwin Harrison and Adrian Reuben and Santiago Munoz and Rajender Reddy and Stravitz, {R. Todd} and Lorenzo Rossaro and Raj Satyanarayana and Tarek Hassanein",
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T1 - Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure

AU - Acute Liver Failure Study Group

AU - Rosen, Hugo R.

AU - Biggins, Scott W.

AU - Niki, Toshiro

AU - Gralla, Jane

AU - Hillman, Holly

AU - Hirashima, Mitsuomi

AU - Schilsky, Michael

AU - Lee, William M.

AU - Larson, Anne M.

AU - Liou, Iris

AU - Davern, Timothy

AU - Fix, Oren

AU - McCashland, Timothy

AU - Hay, J. Eileen

AU - Murray, Natalie

AU - Shaikh, A. Obaid S

AU - Blei, Andres

AU - Ganger, Daniel

AU - Zaman, Atif

AU - Han, Steven H B

AU - Fontana, Robert

AU - McGuire, Brendan

AU - Chung, Raymond T.

AU - Smith, Alastair

AU - Brown, Robert

AU - Crippin, Jeffrey

AU - Harrison, Edwin

AU - Reuben, Adrian

AU - Munoz, Santiago

AU - Reddy, Rajender

AU - Stravitz, R. Todd

AU - Rossaro, Lorenzo

AU - Satyanarayana, Raj

AU - Hassanein, Tarek

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background & Aims: Fewer than 50% of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. Methods: We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. Results: Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. Conclusions: A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440.

AB - Background & Aims: Fewer than 50% of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. Methods: We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. Results: Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. Conclusions: A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440.

KW - Innate Immune Responses

KW - Prediction

KW - SIRS

KW - Stratification

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DO - 10.1016/j.cgh.2015.09.040

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SN - 1542-3565

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