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Meta-Analysis
. 2022 Oct;163(4):1079-1089.e5.
doi: 10.1053/j.gastro.2022.06.073. Epub 2022 Jul 2.

Liver Stiffness on Magnetic Resonance Elastography and the MEFIB Index and Liver-Related Outcomes in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Individual Participants

Veeral Ajmera  1 , Beom Kyung Kim  2 , Kun Yang  3 , Abdul M Majzoub  4 , Tarek Nayfeh  5 , Nobuharu Tamaki  6 , Namiki Izumi  7 , Atsushi Nakajima  8 , Ramazan Idilman  9 , Mesut Gumussoy  9 , Digdem Kuru Oz  10 , Ayse Erden  10 , Natalie E Quach  3 , Xin Tu  3 , Xinlian Zhang  3 , Mazen Noureddin  11 , Alina M Allen  12 , Rohit Loomba  13
Affiliations
Meta-Analysis

Liver Stiffness on Magnetic Resonance Elastography and the MEFIB Index and Liver-Related Outcomes in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Individual Participants

Veeral Ajmera et al. Gastroenterology. 2022 Oct.

Abstract

Background & aims: Magnetic resonance elastography (MRE) is an accurate biomarker of liver fibrosis; however, limited data characterize its association with clinical outcomes. We conducted an individual participant data pooled meta-analysis on patients with nonalcoholic fatty liver disease to evaluate the association between liver stiffness on MRE and liver-related outcomes.

Methods: A systematic search identified 6 cohorts of adults with nonalcoholic fatty liver disease who underwent a baseline MRE and were followed for hepatic decompensation, hepatocellular carcinoma, and death. Cox and logistic regression were used to assess the association between liver stiffness on MRE and liver-related outcomes, including a composite primary outcome defined as varices needing treatment, ascites, and hepatic encephalopathy.

Results: This individual participant data pooled meta-analysis included 2018 patients (53% women) with a mean (± standard deviation) age of 57.8 (±14) years and MRE at baseline of 4.15 (±2.19) kPa, respectively. Among 1707 patients with available longitudinal data with a median (interquartile range) of 3 (4.2) years of follow-up, the hazard ratio for the primary outcome for MRE of 5 to 8 kPa was 11.0 (95% confidence interval [CI]: 7.03-17.1, P < .001) and for ≥ 8 kPa was 15.9 (95% CI: 9.32-27.2, P < .001), compared with those with MRE <5 kPa. The MEFIB index (defined as positive when MRE ≥3.3 kPa and Fibrosis-4 ≥1.6) had a robust association with the primary outcome with a hazard ratio of 20.6 (95% CI: 10.4-40.8, P < .001) and a negative MEFIB had a high negative predictive value for the primary outcome, 99.1% at 5 years. The 3-year risk of incident hepatocellular carcinoma was 0.35% for MRE <5 kPa, 5.25% for 5 to 8 kPa, and 5.66% for MRE ≥8 kPa, respectively.

Conclusion: Liver stiffness assessed by MRE is associated with liver-related events, and the combination of MRE and Fibrosis-4 has excellent negative predictive value for hepatic decompensation. These data have important implications for clinical practice.

Keywords: Ascites; Cirrhosis; Nonalcoholic Fatty Liver Disease; Portal Hypertension; Varices.

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Conflict of interest statement

Potential conflict of interests:

RL serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals and Viking Therapeutics. In addition his institutions received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Co-founder of LipoNexus Inc.

Figures

Figure 1:
Figure 1:
Cumulative incidence of (A) primary composite outcome, (B) ascites, (C) varices needing treatment and (D) hepatic encephalopathy by liver stiffness cut points on MRE < 5 kPa, 5–8 kPa and ≥ 8 kPa.
Figure 2:
Figure 2:
Cumulative incidence of (A) primary composite outcome, (B) ascites, (C) varices needing treatment and (D) hepatic encephalopathy by MEFIB index, with positive defined as a combination of MRE ≥ 3.3 kPa and FIB-4 ≥ 1.6.
Figure 3:
Figure 3:
Cumulative incidence of hepatocellular carcinoma by (a) liver stiffness cut points on MRE < 5 kPa, 5–8 kPa and ≥ 8 kPa and (b) MEFIB index, with positive defined as a combination of MRE ≥ 3.3 kPa and FIB-4 ≥ 1.6.
See this image and copyright information in PMC

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