Controlled Attenuation Parameter (CAP) and its promising role in clinical practice

05 Mar 2021

Controlled Attenuation Parameter (CAP) is a new ultrasound-based technique for measuring fat content in the liver independently from the presence of fibrosis. It measures the attenuation of ultrasound waves (i.e. the gradual decrease of amplitude and intensity of the wave through a medium) and compares it with the attenuation in normal liver [ref 1]. CAP can be commonly measured using FibroScan probes, and it has demonstrated a very good accuracy in assessing steatosis compared with liver biopsies [ref 1]. CAP range is commonly between 100 and 400 dB/m, and the presence of liver steatosis is defined by a median CAP ≥236 dB/m. As for liver biopsies, it is possible to determine 3 grades of steatosis according to the level of CAP. The values commonly chosen to indicate steatosis as absent (S0), mild (S1), moderate (S2) and severe (S3) are: S0 <236 dB/, S1 ≥236 dB/m, S2 ≥270 dB/, and S3 ≥302 dB/m [ref 2].

Even if doesn’t seem to reach the diagnostic accuracy of Magnetic Resonance Elastography (MRE) [ref 3], CAP is strongly related with antropometric measures and fat mass assessed through Dual-energy X-ray Absorptiometry (DXA) [ref 4]. However, the lower cost and the greater ease in performing CAP compared to MRE make it a very useful tool in daily clinical practice. Confirmation of this is the common use of CAP in assessing the presence of nonalcoholic fatty liver disease (NAFLD), and its role seems to be confirmed even considering the newly proposed definition of metabolic dysfunction-associated fatty liver disease (MAFLD) [ref 5]. However, given the extreme practicality and the easy reproducibility of the values of this tool, there is a growing general interest regarding the use of CAP in different aspects of clinical practice. For example, its role in screening type 2-diabetic patients for NAFLD has been widely demonstrated [ref 6]. The relationship between type 2 diabetes and NAFLD is so strong that non-invasive screening of NAFLD is felt as a real clinical need in these patients [ref 7].

One of the most promising uses of CAP, however, is probably the assessment of cardiovascular risk in patients with NAFLD, as recently described by de Sousa Magalhães et al [ref 8]. This retrospective, single centre study builds its foundation on the role of NAFLD as independent risk factor for cardiovascular diseases [ref 9]. This concept has recently been reinforced by the confirmation of the association between hepatic fibrosis and cardiometabolic risk factors such as obesity, impaired fasting glucose, dabetes, hypertension, dyslipidemia, low HDL cholesterol, high triglycerides [ref 10].

The authors analyzed the prevalence of cardiovascular events in 96 patients with NAFLD diagnosed by presence of liver steatosis confirmed at abdominal ultrasound, consumption of alcoholic intake ≤20g per day and absence of other known etiologies of chronic liver disease in which a transient elastography was performed at inclusion. Patients were followed for a minimum period of 12 months. During follow up, they reported 8 unstable anginas (53.3%), 4 cerebrovascular events (26.6%), 2 myocardial infarctions (13.3%) and 1 intermittent claudication (6.6%). All patients who developed a cardiovascular event had CAP > 280 dB/m and 86.7% of them had CAP values > 295 dB/m (which is considered as moderate-severe grade of steatosis). Among all considered risk factors, CAP >295 dB/m (OR 8.661 CI95% [1.119−67.028]; p-value 0.039); type 2 diabetes (OR 20.236 CI95% [2.815−145.461]; p-value 0.003); dyslipidaemia (OR 14.647 CI95% [1.261−170.189]; p-value 0.032) and smoking (OR 8.946 CI 95% [1.347−59.431]; p-value 0.023) were found to be independent predictors of development of cardiovascular events.

This study has certainly some limitations and should probably be corroborated with larger, possibly prospective studies. However, it appears clear how the screening for NAFLD should be of primary importance in patients with obesity or any other diagnostic criteria for metabolic syndrome in order to reduce cardiovascular events. These preliminary data seem to indicate that the measurement of CAP can be the right tool to achieve this goal.

REFERENCES

  1. Eddowes PJ, Sasso M, Allison M, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 1382019;156(6):1717-1730.
  2. Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, Fujita K, Yoneda M, Taguri M, Hyogo H, Sumida Y, Ono M, Eguchi Y, Inoue T, Yamanaka T, Wada K, Saito S, Nakajima A. Magnetic resonance imaging more accurately classifies steato-sis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology 2016;150:626-37.
  3. Hsu C, Caussy C, Imajo K, Chen J, Singh S, Kaulback K, Le MD, Hooker J, Tu X, Bettencourt R, Yin M, Sirlin CB, Ehman RL, Nakajima A, Loomba R. Magnetic Resonance vs Transient Elastography Analysis of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Pooled Analysis of Individual Participants. Clin Gastroenterol Hepatol. 2019 Mar;17(4):630-637.e8.
  4. Unalp-Arida A, Ruhl CE. Transient elastography assessed hepatic steatosis and fibrosis are associated with body composition in the United States. Clin Gastroenterol Hepatol. 2021 Feb 4:S1542-3565(21)00110-5.
  5. Eslam M, Arun J Sanyal, Jacob George, International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology 2020 May;158(7):1999-2014.e1.
  6. Kwok R, Choi KC, Wong GL et al. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut 2016; 65:1359–68.
  7. Lomonaco R, Godinez Leiva E, Bril F, Shrestha S, Mansour L, Budd J, Portillo Romero J, Schmidt S, Chang KL, Samraj G, Malaty J, Huber K, Bedossa P, Kalavalapalli S, Marte J, Barb D, Poulton D, Fanous N, Cusi K. Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening. Diabetes Care. 2021 Feb;44(2):399-406.
  8. de Sousa Magalhães R, Xavier S, Magalhães J, Rosa B, Marinho C, Cotter J. Transient elastography through controlled attenuated parameter assisting the stratification of cardiovascular disease risk in NAFLD patients. Clin Res Hepatol Gastroenterol. 2020 Dec 2:101580. Epub ahead of print.
  9. Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. JHepatol 2016;65(2):425-43.
  10. Long MT, Zhang X, Xu H, Liu CT, Corey KE, Chung RT, Loomba R, Benjamin EJ. Hepatic Fibrosis Associates With Multiple Cardiometabolic Disease Risk Factors: The Framingham Heart Study. Hepatology. 2021 Feb;73(2):548-559.