Research ArticleControlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification
Graphical abstract
Introduction
Alcohol is a key risk factor for liver-related and overall mortality, contributing to 3.3 million annual deaths worldwide.1 Simple steatosis is the most common liver manifestation of harmful drinking, but is considered a benign condition by many, since the disturbed lipid metabolism normalises with abstinence.[2], [3] The high prevalence of steatosis in most liver diseases has even cast doubt on the role of hepatic fat on fibrosis progression, with steatosis being discussed as a bystander rather than a causative factor.[4], [5] This notion may, however, be too credulous, as 7% of patients with simple alcoholic steatosis have been shown to progress to cirrhosis within five years.6 Additionally, in non-alcoholic fatty-liver disease, steatosis is an independent risk factor for the development of type 2 diabetes and cardiovascular disease.7 Finally, harmful drinking is often accompanied by similar unfavourable health behaviours, such as overeating, smoking, and a sedentary lifestyle. Thus, components of the metabolic syndrome (MetS) are common in alcoholic patients, where they may aggravate steatosis and act in synergy with alcohol to progress fibrosis.8 Consequently, reliable non-invasive tools to diagnose and monitor hepatic steatosis in patients with alcoholic liver disease (ALD) are needed.
Controlled attenuation parameter (CAP) is a novel method for the non-invasive assessment of steatosis, which measures the increased attenuation of ultrasound waves when travelling through steatotic hepatic tissue, compared to normal liver.9 The CAP software is incorporated into the FibroScan® (Echosens, Paris, France) equipment, allowing for combined transient elastography (TE) and CAP. An individual patient data meta-analysis recently showed that CAP diagnosed moderate and severe steatosis with diagnostic accuracies above 0.85 in mixed-aetiology liver-disease patients. However, the analysis did not include ALD patients.10 To date, no sufficiently large biopsy-verified study exists to analyse the performance of CAP in patients with ALD.
We, therefore, aimed to determine the diagnostic value of CAP for the evaluation of hepatic steatosis in patients with an excessive use of alcohol. Secondary aims were to assess CAP before and after alcohol detoxification, and to evaluate the correlation between CAP and components of the MetS in alcohol overusers.
Section snippets
Materials and methods
We prospectively recruited patients at four European liver centres. All patients signed a consent form prior to inclusion (ethical approvals S-20120071, S-20160021, S150/2015, 1629487v0, 485/08.11.2015).
Participants
From May 2013 to August 2017, we enrolled 269 patients with concomitant liver biopsy and CAP measurement to the diagnostic cohort. For the detoxification cohort, we included 293 patients among 329 eligible patients admitted for detoxification from May 2013 to October 2016. The two groups differed on several parameters (Table 1): Detoxification patients had a more severe alcohol drinking history, more biochemical evidence of hepatic inflammation, and higher model of end-stage liver disease
Discussion
In this large multicentre study on CAP in alcoholic fatty-liver disease, we found CAP to be the best point-of-care non-invasive tool for steatosis assessment. Despite only moderate to good diagnostic accuracy, CAP was superior to B-mode ultrasound for predicting liver steatosis. A CAP above 290 dB/m was identified a good cut-off for ruling in steatosis. We also found that CAP decreased rapidly and significantly during alcohol detoxification, except in obese patients. Similarly, BMI predicted
Financial support
This work was funded by grants from Innovation Fund Denmark, the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement number 668031), University of Southern Denmark, Region of Southern Denmark, the Dietmar Hopp Foundation, and a grant by the Deutsche Forschungsgemeinschaft to SM (MU 1373/9-1). The Toyota Foundation granted funds to purchase the FibroScan system in Denmark.
Conflict of interest
The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Please refer to the accompanying ICMJE disclosure forms for further details.
Authors’ contributions
Study conceptualisation: SM. Study design: SM, MT. Data acquisition: all authors. Data analyses: MT. Data interpretation: SM, MT. Writing manuscript: SM, MT. Critical revision of the manuscript: all authors. Approval of the final version: all authors. Guarantee: SM.
References (28)
- et al.
Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis
J Hepatol
(2016) - et al.
Excess weight risk factor for alcoholic liver disease
Hepatology
(1997) - et al.
Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes
Ultrasound Med Biol
(2010) - et al.
Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis
J Hepatol
(2017) - et al.
Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter
J Hepatol
(2017) - et al.
The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis
Dig Liver Dis
(2006) Expanding consensus in portal hypertension—report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension
J Hepatol
(2015)- et al.
Transient and 2-dimensional shear-wave elastography provide comparable assessment of alcoholic liver fibrosis and cirrhosis
Gastroenterol
(2016) - et al.
A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B
Dig Liver Dis
(2017) - et al.
Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations
J Hepatol
(2014)
Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016
Lancet
Alcoholic liver disease: mechanisms of injury and targeted treatment
Nat Rev Gastroenterol Hepatol
European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease
J Hepatol
Hepatic steatosis: innocent bystander or guilty party?
Hepatology
Cited by (67)
Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study
2024, The Lancet Gastroenterology and HepatologyClinical practice guidelines of the Catalan Society of Gastroenterology about hepatic elastography 2022
2023, Gastroenterologia y HepatologiaPuerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8
2023, Chinese Journal of Natural MedicinesFat quantification: Imaging methods and clinical applications in cancer
2023, European Journal of RadiologyCovid-19 and alcohol associated liver disease
2022, Digestive and Liver DiseaseLiver alterations are not improved by inulin supplementation in alcohol use disorder patients during alcohol withdrawal: A pilot randomized, double-blind, placebo-controlled study
2022, eBioMedicineCitation Excerpt :Currently, non-invasive testing allows for a good estimation of steatosis and fibrosis. Controlled attenuation parameter measurements > 250 dB/m is a generally accepted cut-off for steatosis29,30 and liver elasticity measurements by Fibroscan reliably predict fibrosis stage.31 In addition, a novel biomarker, keratin 18 (K18), correlates with histological changes32 and has the potential to distinguish severe forms of ALD from less severe ones.33,34