Nonalcoholic fatty liver disease (NAFLD) is an ever-growing problem in the developed and developing worlds, affecting 15–40 % of the population [1]. Once regarded as a benign condition, NAFLD is the leading cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma (HCC) [2], and the third most frequent indication for liver transplantation [3].

A key challenge faced by clinicians who manage NAFLD is to establish the diagnosis and to differentiate simple steatosis from advanced disease [4]. Furthermore, steatosis often coexists in other chronic liver diseases such as chronic hepatitis C [5]. Trans-abdominal ultrasonography (USG) is the commonest imaging tool used in the diagnosis of hepatic steatosis, but only with confidence when the amount of fatty infiltration exceeds 33 % [6]. Although proton magnetic resonance spectroscopy (1H-MRS) is an accurate and reproducible noninvasive means of quantifying hepatic fat, its availability is limited in many areas [1].

Transient elastography (Fibroscan, Echosens, Paris, France), originally developed for the diagnosis of liver fibrosis and cirrhosis, has been validated in patients with NAFLD [7]. The fundamental technology employed by Fibroscan involves a plastic shear wave that propagates through liver tissue combined with a pulse-echo ultrasound used to follow and measure the velocity of the propagation of the shear wave, which is directly related to tissue stiffness and hence severity of liver fibrosis [8]. Its latest iteration includes the measurement of the controlled attenuation parameter (CAP), a measurement of the attenuation of the forward and return ultrasound signal at 3.5 MHz using signals acquired by the regular M probe of Fibroscan. At a given frequency, the ultrasound-attenuation coefficient can be expressed in dB/m. Since the attenuation of ultrasound signals is greater in fat than in water, CAP may be used to estimate the degree of hepatic steatosis [9]. The diagnostic attractiveness of CAP is that it may be measured concurrently with liver stiffness using the same instrument enabling the simultaneous assessment of hepatic steatosis and fibrosis [8].

Data concerning the accuracy of CAP to diagnosis different degrees of hepatic steatosis are evolving. CAP efficiently detected low-grade steatosis (>10 %), with a sensitivity of 91 % and specificity of 81 % at a cutoff value of 238 dB/m in a retrospective cohort of patients of mixed etiology chronic liver diseases [9]. The accuracy of CAP was confirmed in two prospective studies of mixed etiology liver disease [10, 11], and in single etiology populations, including chronic hepatitis B (CHB), chronic hepatitis C, NAFLD, and alcoholic liver disease [12]. The suggested diagnostic performance and cutoff values for different degrees of steatosis are summarized in Table 1. Nonetheless, data concerning its performance in healthy subjects and patients with CHB were either lacking or insufficient.

Table 1 Diagnostic performance and suggested cutoff values of controlled attenuation parameter for the diagnosis of hepatic steatosis
Full size table

In this issue of the Digestive Diseases and Sciences, two groups of investigators provide important data to illustrate the accuracy of CAP in these two settings. Chon et al. [16] report CAP data from 264 healthy subjects, either as potential liver donors or in subjects undergoing routine health assessment. They defined the range of normal CAP values (5th–95th percentiles) as 156.0–287.8 dB/m. Interestingly, the mean CAP value was slightly yet significantly higher in the healthy group than in the potential liver donor group (227.5 ± 42.0 vs. 218.2 ± 28.3 dB/m, P = 0.040). Higher body mass index (BMI) and serum triglyceride concentrations were associated with higher CAP values of healthy subjects, implying that there were some NAFLD subjects in the routine assessment group, in which 9.0 and 4.3 % of subjects had metabolic syndrome and diabetes mellitus, respectively. Hence, the stated upper limit of normal (ULN) for CAP values, 287.8 dB/m, is likely too high. Instead, 266.3 dB/m, the ULN for CAP in potential liver donors, was probably a more reasonable value. According to previous publications, the range for low-grade steatosis (>10 % fatty infiltration) is 215–283 dB/m [8].

In the same issue, Mi et al. report their validation study in 340 CHB patients who underwent liver biopsy [17], by far one of the largest CAP studies in this population. This important study provides not only data on the accuracy of CAP but also information on potential confounders. This study unequivocally reassures us that necroinflammation, as represented by serum alanine aminotransferase (ALT) and the Knodell histological activity index, does not influence CAP. Instead, only BMI and steatosis grade correlated positively with CAP. Thus, while a high ALT level independently increases liver stiffness and can contribute toward a false diagnosis of cirrhosis [18], CAP does not suffer from the same confounding issues.

As pointed out by the authors, higher CAP cutoff values in subjects with higher BMI were also reported in several other studies [10], perhaps reflecting excess attenuation due to fat overlying the liver. To overcome this confounder, the skin-liver capsule distance (SCD) was applied to multivariate analysis; SCD >25 mm consistently increased CAP ~60 dB/m regardless of the grade of hepatic steatosis (unpublished data from the same group). Therefore, a SCD-based algorithm, similar to the ALT-based algorithm for LSM derived from CHB patients [19], may be considered for the interpretation of CAP in obese subjects.

The clinical significance of diagnosing fatty liver in CHB patients is somewhat obscure. Although CHB is associated with a lower prevalence of fatty liver [20], the metabolic syndrome increases the risk of cirrhosis and fibrosis progression in CHB patients [21, 22]. It would thus be interesting to study if CAP is prognostically important in addition to liver stiffness and other traditional risk factors of hepatocellular carcinoma and cirrhotic complications [23].

To sum up, these two important studies established the diagnostic accuracy of CAP for hepatic steatosis in different settings. Since CAP and liver stiffness can be measured simultaneously, transient elastography be used in multiple clinical settings, providing comprehensive yet convenient noninvasive assessment of the liver of considerable value in the selection of candidates for treatment.