Increased Hepatorenal Index Is Associated with the Risk of Developing Stroke in Patients with Nonalcoholic Fatty Liver Disease

Abstract

Objective

The aim of this study was to examine the relationship between the sonographic hepatorenal index and stroke risk in patients with nonalcoholic fatty liver disease (NAFLD).

Methods

From December 2023 to July 2024, 72 NAFLD patients with stroke, 53 stroke-free NAFLD patients, and 54 healthy controls were enrolled in our study. The hepatorenal index was calculated as the ratio of the echo intensity of the liver to that of the renal cortex. The mean brightness values for one region of interest within the right hepatic lobe and the other size-matched region at the same depth of field within the right kidney were obtained with two-dimensional ultrasound and a 1- to 6-MHz convex array probe. Laboratory tests were performed with a Cobas 8000 automatic biochemical analyzer. Univariate and multivariate analyses were adopted to analyze the risk factors for stroke in NAFLD patients.

Results

NAFLD patients had a greater hepatorenal index than healthy controls did (P < 0.05). Additionally, NAFLD patients with stroke had an even greater hepatorenal index than did those with stroke-free NAFLD (P < 0.001). Multivariate regression analysis further revealed that the hepatorenal index was independently associated with stroke risk in NAFLD patients (β = 8.897, P < 0.001) after controlling for age, body mass index, systolic blood pressure, and serum glucose, total cholesterol, alanine transaminase, and creatinine concentrations. Receiver operating characteristic curve analysis revealed a sensitivity of 62.5% and specificity of 95.3% for the hepatorenal index, with a cutoff value of 1.255 and an area under the curve of 0.80.

Conclusion

The increased sonographic hepatorenal index could be an independent predictor of stroke development in patients with NAFLD.

Keywords

Ultrasound / Stroke / Nonalcoholic fatty liver disease

References

[1] TargherG, MantovaniA, ByrneCD. Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease. Lancet Gastroenterol., 2023, 8: 179-191

[2] ChalasaniN, YounossiZ, LavineJE, et al.. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology, 2012, 55: 2005-2023.

[3] WangM, ZhouBG, ZhangY, et al.. Association between non-alcoholic fatty liver disease and risk of stroke: a systematic review and meta-analysis. Front Cardiovasc Med., 2022, 9. 812030

[4] LiH, HuB, WeiL, et al.. Non-alcoholic fatty liver disease is associated with stroke severity and progression of brainstem infarctions. Eur J Neurol., 2018, 25: 534-577.

[5] YangYJ, JungMH, JeongSH, et al.. The association between nonalcoholic fatty liver disease and stroke: results from the Korean Genome and Epidemiology Study (KoGES). Int J Env Res Pub He., 2020, 179568.

[6] LeeH, LeeYH, KimSU, et al.. Metabolic dysfunction-associated fatty liver disease and incident cardiovascular disease risk: a nationwide cohort study. Clin Gastroenterol Hepatol., 2021, 19: 2138-2147.

[7] WangYS, ZhangGP, YangX, et al.. Assessment of hepatic fat content in using quantitative ultrasound measurement of hepatic/renal ratio and hepatic echo-intensity attenuation rate. Med Ultrason., 2020, 22: 393-401.

[8] MarshallRH, EissaM, BluthEI, et al.. Hepatorenal index as an accurate, simple, and effective tool in screening for steatosis. Am J Roentgenol., 2012, 199: 997-1002.

[9] BarrRG, WilsonSR, RubensD, et al.. Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement. Radiology., 2020, 296: 263-274.

[10] LeeSS, ParkSH. Radiologic evaluation of nonalcoholic fatty liver disease. World J Gastroenterol., 2014, 20: 7392-7402.

[11] YounossiZM, KoenigAB, AbdelatifD, et al.. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology., 2016, 64: 73-84.

[12] AguilarM, BhuketT, TorresS, et al.. Prevalence of the metabolic syndrome in the United States, 2003–2012. Jama., 2015, 313: 1973-1974.

[13] YounossiZM, StepanovaM, YounossiY, et al.. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut., 2020, 69: 564-568.

[14] MoonJH, JeongS, JangH, et al.. Metabolic dysfunction-associated steatotic liver disease increases the risk of incident cardiovascular disease: a nationwide cohort study. EClinicalMedicine, 2023, 65. 102292

[15] XuJ, DaiL, ZhangY, et al.. Severity of nonalcoholic fatty liver disease and risk of future ischemic stroke events. Stroke., 2021, 52: 103-110.

[16] PatelS, SiddiquiMB, RomanJH, et al.. Association between lipoprotein particles and atherosclerotic events in nonalcoholic fatty liver disease. Clin Gastroenterol H., 2021, 19: 2202-2204.

[17] LabenzC, HuberY, MichelM, et al.. Impact of NAFLD on the incidence of cardiovascular diseases in a primary care population in Germany. Digest Dis Sci., 2020, 65: 2112-2119.

[18] KongP, CuiZY, HuangXF, et al.. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct Target Ther., 2022, 7131.

[19] JiangW, NiuJ, GaoH, et al.. A retrospective study of immunoglobulin E as a biomarker for the diagnosis of acute ischemic stroke with carotid atherosclerotic plaques. PeerJ., 2022, 10. e14235

[20] AbdeldyemSM, GodaT, KhodeirSA, et al.. Nonalcoholic fatty liver disease in patients with acute ischemic stroke is associated with more severe stroke and worse outcome. J Clin Lipidol., 2017, 11: 915-919.

[21] TangA, ChanKE, QuekJ, et al.. Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: an updated meta-analysis with 135,602 individuals. Clin Mol Hepatol., 2022, 28: 483-496.

[22] CasteraL, Friedrich-RustM, LoombaR. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology., 2019, 156: 1264-1281.

[23] WebbM, YeshuaH, Zelber-SagiS, et al.. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol., 2009, 192: 909-914.

[24] ShiralkarK, JohnsonS, BluthEI, et al.. Improved method for calculating hepatic steatosis using the hepatorenal index. J Ultras Med., 2015, 34: 1051-1059.

[25] HajibonabiF, RiedeselEL, TaylorSD, et al.. Ultrasound-estimated hepatorenal index: diagnostic performance and interobserver agreement for pediatric liver fat quantification. Pediatr Radiol., 2024, 54: 1653-1660.

[26] AndoY, JouJH. Nonalcoholic fatty liver disease and recent guideline updates. Clin Liver Dis (Hoboken)., 2021, 17: 23-28.

Funding

University Natural Science Research Project of Anhui Province(KJ2020A0582)

Health Research Program of Anhui Province(AHWJ2023A20372)

Science and Technology Innovation Project of Bengbu City(20230129)

The Key Laboratory Foundation Project of Bengbu Medical University(AHCM2022Z003)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to Huazhong University of Science and Technology