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March 17, 2020; 94 (11) Article

Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy

Georgia Zeng, Ross Penninkilampi, View ORCID ProfileJoga Chaganti, View ORCID ProfileSara Montagnese, View ORCID ProfileBruce J. Brew, View ORCID ProfileMark Danta
First published January 9, 2020, DOI: https://doi.org/10.1212/WNL.0000000000008899
Georgia Zeng
From the Faculty of Medicine (G.Z., B.B., M.D.), St Vincent's Clinical School, UNSW; Departments of Gastroenterology (G.Z., M.D.), Medical Imaging (J.C.), and Neurology and Immunology (B.B.), St Vincent's Hospital; Faculty of Medicine (R.P.), South Western Sydney Clinical School, UNSW, Sydney, Australia; and Department of Medicine (S.M.), University of Padua, Italy.
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Ross Penninkilampi
From the Faculty of Medicine (G.Z., B.B., M.D.), St Vincent's Clinical School, UNSW; Departments of Gastroenterology (G.Z., M.D.), Medical Imaging (J.C.), and Neurology and Immunology (B.B.), St Vincent's Hospital; Faculty of Medicine (R.P.), South Western Sydney Clinical School, UNSW, Sydney, Australia; and Department of Medicine (S.M.), University of Padua, Italy.
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Joga Chaganti
From the Faculty of Medicine (G.Z., B.B., M.D.), St Vincent's Clinical School, UNSW; Departments of Gastroenterology (G.Z., M.D.), Medical Imaging (J.C.), and Neurology and Immunology (B.B.), St Vincent's Hospital; Faculty of Medicine (R.P.), South Western Sydney Clinical School, UNSW, Sydney, Australia; and Department of Medicine (S.M.), University of Padua, Italy.
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Sara Montagnese
From the Faculty of Medicine (G.Z., B.B., M.D.), St Vincent's Clinical School, UNSW; Departments of Gastroenterology (G.Z., M.D.), Medical Imaging (J.C.), and Neurology and Immunology (B.B.), St Vincent's Hospital; Faculty of Medicine (R.P.), South Western Sydney Clinical School, UNSW, Sydney, Australia; and Department of Medicine (S.M.), University of Padua, Italy.
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Bruce J. Brew
From the Faculty of Medicine (G.Z., B.B., M.D.), St Vincent's Clinical School, UNSW; Departments of Gastroenterology (G.Z., M.D.), Medical Imaging (J.C.), and Neurology and Immunology (B.B.), St Vincent's Hospital; Faculty of Medicine (R.P.), South Western Sydney Clinical School, UNSW, Sydney, Australia; and Department of Medicine (S.M.), University of Padua, Italy.
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Mark Danta
From the Faculty of Medicine (G.Z., B.B., M.D.), St Vincent's Clinical School, UNSW; Departments of Gastroenterology (G.Z., M.D.), Medical Imaging (J.C.), and Neurology and Immunology (B.B.), St Vincent's Hospital; Faculty of Medicine (R.P.), South Western Sydney Clinical School, UNSW, Sydney, Australia; and Department of Medicine (S.M.), University of Padua, Italy.
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Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy
Georgia Zeng, Ross Penninkilampi, Joga Chaganti, Sara Montagnese, Bruce J. Brew, Mark Danta
Neurology Mar 2020, 94 (11) e1147-e1156; DOI: 10.1212/WNL.0000000000008899

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Abstract

Objective Various imaging modalities have been used to explore pathogenic mechanisms and stratify the severity of hepatic encephalopathy (HE). The hypothesis of this meta-analysis was that there is a progressive identifiable derangement of imaging measures using magnetic resonance spectroscopy (MRS) related to the severity of the HE.

Methods Studies with more than 10 cases and HE diagnosis were identified from the electronic databases PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino Americana em Ciências da Saúde (LILACS), and Cochrane Central Register of Controlled Trials (CENTRAL) through July 25, 2018. Participants were stratified into healthy controls and patients with non-HE (NHE) (cirrhosis without HE), minimal HE (MHE), and overt HE (OHE). Analyses were organized by metabolite studied and brain region examined. Statistical meta-analysis was performed using the metafor package in R (v3.4.1). Pooled standardized mean differences between patient groups were calculated using a random effects model.

Results We identified 31 studies (1,481 patients) that included data for cirrhosis-related HE. We found the parietal region to be the most reliable in differentiating between patients with and without MHE, with standard mean differences of +0.82 (95% confidence interval [CI] +0.49 to +1.15, p < 0.0001, I2 = 37.45%) for glutamine/glutamate, −0.36 (95% CI −0.61 to −0.10, p = 0.007, I2 = 20.00%) for choline, and−0.77 (95% CI −1.19 to −0.34, p = 0.0004, I2 = 67.48%) for myo-inositol. We also found that glutamine/glutamate was the metabolite that reliably correlated with HE grade in all brain regions.

Conclusions The meta-analysis reveals that MRS changes in glutamine/glutamate, choline, and myo-inositol, particularly in the parietal lobe, correlate with the severity of HE. MRS may be of value in the assessment of HE.

Glossary

CHE=
covert hepatic encephalopathy;
Cho=
choline-containing compounds;
CI=
confidence interval;
CLD=
chronic liver disease;
Glx=
glutamate + glutamine;
HE=
hepatic encephalopathy;
MHE=
minimal hepatic encephalopathy;
MI=
myo-inositol;
MRS=
magnetic resonance spectroscopy;
NAA=
N-acetylaspartate;
NHE=
cirrhosis with no hepatic encephalopathy;
OHE=
overt hepatic encephalopathy;
PHES=
Psychometric Hepatic Encephalopathy Score;
SMD=
standard mean difference

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received June 10, 2019.
  • Accepted in final form September 20, 2019.
  • © 2020 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Author response: A meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy
    • Mark Danta, Hepatologist, St Vincent's Clinical School, Faculty of Medicine, UNSW (Sydney, Australia)
    • Sara Montagnese, Hepatologist, University of Padua (Padua, Italy)
    Submitted January 18, 2020
  • Reader response: A meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy
    • Vinod K. Gupta, Physician-Medical Director, Migraine-Headache Institution, Gupta Medical Center (New Delhi, India)
    Submitted January 09, 2020
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