What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Non-alcoholic fatty liver disease (NAFLD) (n=135602). Intervention: Non-alcoholic fatty liver disease (NAFLD) vs. Non-NAFLD controls. Primary outcome: Carotid atherosclerosis (OR 3.20, 95% CI 2.37-4.32, p=<0.0001).

March 2, 2022Open Access

Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals

Q: What are the key findings of this study?

Non-alcoholic fatty liver disease was associated with a significantly increased risk of carotid atherosclerosis (OR 3.20) and stroke (OR 1.88) compared to non-NAFLD controls.

ATAnsel Shao Pin TangNational University of Singapore KCKai En ChanYong In University JQJingxuan QuekNational University of Singapore

Key Result

Non-alcoholic fatty liver disease was associated with a significantly increased risk of carotid atherosclerosis (OR 3.20) and stroke (OR 1.88) compared to non-NAFLD controls.

Study Design

Type

Meta-Analysis (n=135,602)

Structured PICO

Does non-alcoholic fatty liver disease increase the risk of carotid atherosclerosis and ischemic stroke?

Population

135,602 individuals from 64 studies, including 47,322 patients with non-alcoholic fatty liver disease and 88,280 non-NAFLD controls, evaluated for carotid atherosclerosis and stroke.

Exposure

Presence of non-alcoholic fatty liver disease (NAFLD)

Comparator

Absence of non-alcoholic fatty liver disease (non-NAFLD)

Outcome

Prevalence and risk of carotid atherosclerosis and ischemic strokehard clinical

NAFLD is associated with a significantly increased risk of carotid atherosclerosis and ischemic stroke, suggesting the need for routine carotid assessment in these patients.

Main Result

Odds Ratio: 3.2 (95% CI 2.37–4.32)

p-value: p=<0.0001

Limitations

Majority of studies utilized non-invasive, imaging-based investigations rather than biopsy to diagnose NAFLD
Grading of NAFLD severity was limited to ultrasonographic findings
Unable to assess the effects of stage of fibrosis on CIMT or stroke due to lack of granularity in the reported data
Included studies were largely retrospective and subjected to inherent limitations such as selection bias

Abstract

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. METHODS: Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. RESULTS: From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval CI, 27.36-43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37-4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74-9.09%) with an odds ratio of 1.88 (95% CI, 1.23-2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. CONCLUSION: This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

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