Noninvasive Liver Stiffness Measure Shows Diagnostic, Prognostic Potential

Stefano Ciardullo, MD

Credit: University of Milano-Bicocca

Vibration-controlled transient elastography may be a viable noninvasive alternative to liver biopsy for the diagnosis and prognosis of liver stiffness in patients with nonalcoholic liver disease (NAFLD), according to a systematic review and meta-analysis.

Findings from the meta-analysis of studies measuring liver stiffness with vibration-controlled transient elastography showed a strong association between increased noninvasive liver stiffness measurement and all-cause mortality in patients with NAFLD.¹

“Evidence of a prognostic ability of [vibration-controlled transient elastography] in patients with NAFLD, which is the most common indication for the [vibration-controlled transient elastography] examination in most countries, is critical to strengthen the recommendation to perform it in everyday clinical practice,” wrote investigators.¹ “The present study corroborates available evidence suggesting a role for [vibration-controlled transient elastography] not only as a tool for diagnosis, but also for outcome prediction.”

A main complication of NAFLD, cirrhosis occurs as the liver produces fibrosis while trying to stop inflammation.² Fibrosis can be reversed if detected early enough and the underlying liver disease can be cured or treated. The stage and degree of liver damage is frequently determined through a liver biopsy. However, imaging tests like vibration-controlled transient elastography may offer a noninvasive alternative for diagnosis and prognosis.³

To assess the nature and magnitude of the association between increased liver stiffness measurement obtained through vibration-controlled transient elastography and all-cause mortality in patients with NAFLD, Stefano Ciardullo, MD, assistant professor in the department of medicine and surgery at the University of Milano Bicocca Monza in Italy, and a team of investigators designed their research endeavor as a systematic review and meta-analysis of observational cohort studies. Investigators searched PubMed, MEDLINE, and Scopus databases up to April 2023 for studies with a longitudinal design, ≥1 year duration of follow-up, assessment of the relationship between liver stiffness measurement and all-cause death, availability of a measure of association with 95% confidence intervals (CI), and a diagnosis of liver steatosis through imaging techniques or liver biopsy.¹

Investigators identified 517 articles in their initial literature search. Cross-sectional studies, editorials, congress abstracts, case reports, studies not excluding alternative causes of liver steatosis, and studies performed in the pediatric population were excluded. Based on title and abstract screening, 501 articles were excluded. After examining the full text of the remaining 16 studies, investigators selected 7 cohort studies including 18,771 individuals (47.1% men) with a mean follow-up of 3.6 (2.1-5.5) years for analysis.¹

Investigators extracted information on study design, country, follow up duration, proportion of participants with obesity and diabetes, the liver stiffness measurement cutoff, the outcome of interest, and covariates included in the multivariable regression models. Studies were evaluated for their quality following the Newcastle–Ottawa Scale.¹

Upon analysis, elevated liver stiffness measurement was associated with a hazard ratio (HR) of 2.10 (95% CI, 1.56–2.83; test for overall effect z = 4.919; P < .001) for all-cause mortality when pooling adjusted effect estimates. For each 1 kPa increment in liver stiffness measurement, there was a 3% increase in the relative risk of all-cause mortality. Of note, the test for heterogeneity was borderline significant (I2 50.2%; P = .074).¹

When liver stiffness measurement was considered as a continuous variable, the association of interest remained significant (HR, 1.03; 95% CI, 1.01–1.05) for each 1 kPa increase in liver stiffness measurement (test for overall effect z = 3.341; P = .001). Investigators again pointed out a high degree of heterogeneity in the analysis (I2 66.7%; P = .017).¹

Further analysis revealed estimates did not differ significantly after the exclusion of each specific study and the association of interest remained significant in both analyses considering liver stiffness measurement as either a continuous or a categorical variable. Investigators found no evidence of significant publication bias through asymmetry analysis in the funnel plot, Egger's test (P = .375), or rank correlation Begg's test (P = .851).¹

“This [study] corroborates the available evidence supporting a role for [vibration-controlled transient elastography] not only as a diagnostic, but also as a prognostic tool in the field of NAFLD. Further studies are needed to better elucidate the mechanisms linking [liver stiffness measurement] to mortality, with a particular focus on parameters of heart function,” investigators concluded.¹

References:

1. Ciardullo S, Muraca E, Zerbini F, et al. Liver stiffness is associated with all-cause mortality in patients with NAFLD: A systematic review and meta-analysis. Liver Int. 2023; 00: 1-7. doi:10.1111/liv.15742
2. Mayo Clinic. Nonalcoholic fatty liver disease. Diseases & Conditions. Accessed September 21, 2023. https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567
3. American Liver Foundation. Fibrosis (Scarring). How Liver Disease Progresses. Accessed September 21, 2023. https://liverfoundation.org/about-your-liver/how-liver-diseases-progress/fibrosis-scarring/