Elsevier

Journal of Hepatology

Volume 68, Issue 5, May 2018, Pages 1025-1032
Journal of Hepatology

Research Article
Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic accuracy and role of alcohol detoxification

https://doi.org/10.1016/j.jhep.2017.12.029Get rights and content

Highlights

  • CAP performed better in the determination of steatosis than regular ultrasonography.

  • CAP can be used to detect severe alcoholic steatosis and to rule in any steatosis.

  • CAP decreased significantly in non-obese ALD patients after alcohol detoxification.

Background & Aims

Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP.

Methods

This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate single-centre cohort.

Results

A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] ≥S1 = 0.77; 0.71–0.83 and AUC ≥S2 = 0.78; 0.72–0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75–0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (interquartile range 4–6) for detoxification, CAP decreased by 32 ± 47 dB/m (p <0.001). Body mass index predicted higher CAP in both cohorts, irrespective of drinking pattern. Obese patients with body mass index ≥30 kg/m2 had a significantly higher CAP, which did not decrease significantly during detoxification.

Conclusions

CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal.

Lay summary

CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.

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.

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