This is the first prospective study evaluating TE and ARFI simultaneously for the detection of CFLD in a cohort of adult CF patients presenting with baseline characteristics comparable to previously reported studies 
ARFI and TE could be applied with a success rate>90% and correlated highly between each other. However, TE had a higher rate of invalid measurements than ARFI in patients without CFLD (15% vs. 2%) which is in line with previously reported TE failure rates 
. This phenomenon may be partially explained by CF specific conditions like hypertrophic intercostal muscles or by difficulties to tolerate necessary standardized examination procedures (i.e. supine position, short respiratory holds) during the examination in case of CF-related respiratory impairment 
Both TE and ARFI could not significantly discriminate between non-cirrhotic CFLD patients and CF cases without liver disease although a gradual increase would have been expected. This observation should be interpreted very cautiously due to the limited case number in the non-cirrhotic CFLD subgroup. However, TE and ARFI (right liver lobe) distinguished between liver cirrhosis and earlier stages of liver disease in CFLD patients.
Previous studies suggested a potential diagnostic benefit of left liver lobe ARFI in healthy controls which seems to diminish in advanced liver disease 
. However, in our CF cohort left liver lobe ARFI failed to discriminate between CFLD and non CFLD patients and was not able to detect liver cirrhosis in CF patients. Thus, it remains unclear whether left liver lobe ARFI provides an additional diagnostic benefit.
Elastography values in CF patients with liver cirrhosis were significantly lower than in alcoholic cirrhosis and differed from reported cut-off values for liver cirrhosis in chronic hepatitis B and C 
. Interestingly, in relation to healthy individuals shear-wave velocity in cirrhotic CF patients were only marginally increased (1.49±0.36 vs. 1.15±0.17 m/s; p
0.007). However, even this subtile difference of liver stiffness seems to be typical for adult CF patients and allows reliable application of ARFI and TE. It strengthens the assumption that elastography values depend on the etiology of liver disease 
There is a set of possible explanations for our findings:
- Up to two thirds of pediatric and adolescent CF patients show an ultrasound pattern of fatty liver disease , ,  while the incidence is lower in adult CF patients . In our adult cohort, 12/55 (22%) individuals displayed signs of hepatic steatosis at ultrasound evaluation. A direct relation of steatosis and CFLD is questionable, and extrahepatic CF manifestations (i.e. malnutrition, essential fatty acid deficiency, insulin resistance) have been discussed as potential causes as well . Fatty liver disease modulates liver stiffness and can impair reliability of elastography for the detection of fibrosis. Patients with fatty liver disease and advanced fibrosis may not be detected by TE because of a higher hepatic fat content . 3/6 cases classified as CF-related cirrhosis displayed an increased echogenicity of liver parenchyma (steatosis grad I) in our investigations. Thus, the marginally elevated elastography results in our adult CF cirrhotic patients may be influenced by hepatic steatosis.
- CFLD is a known risk factor for a severe CF course in children. However, the prognostic role of CFLD in adults is less certain, and disease progression after adolescence is rare , . Previous studies consisted of mixed patient cohorts with a large proportion of pediatric patients ,  or of CF children with portal hypertension . Hence, the reported increase of liver stiffness in these CFLD patients may be related to the more severe course of pediatric CFLD while our results reflect a milder degree of liver damage in adult CFLD cases.
- The use of different CFLD definitions in previous studies limits their comparability with our results , . We defined CFLD according to Colombo's criteria . Though these criteria are sensitive for persistent liver impairment, the diagnosis of CFLD is not always associated with significant liver fibrosis . The absence of fibrosis in some cases may have limited accuracy of ARFI and TE for CFLD detection in our study. In addition, limited accuracy of all investigated ultrasound- and laboratory-based methods to detect liver fibrosis may be also influenced by diagnostic limitations of our reference method B-mode ultrasound. Conventional ultrasound may misclassify patients as non-cirrhotic although they are cirrhotic in reality.
- The number of recruited patients - although comparable to previous studies ,  - was not sufficient to detect a significant difference of liver stiffness between CFLD patients and those without CFLD. Based on a post-hoc power calculation (alpha error 0.05, beta error 0.1), a much larger case number would have been required for reliable CFLD detection (n=138 for TE and n=171 for right liver lobe ARFI, respectively). In addition, our case number may have been too small to reveal correlations between known risk CFLD factors and elastography results although there was a trend of earlier age at diagnosis in CFLD patients.
Ideally, non-invasive evaluation of liver fibrosis should be compared to adequate results of liver biopsy. However, the focal nature of liver damage in CFLD is the key problem for histological assessment and limits its use as standard classification in CF 
. If focal liver disease affects biopsy, elastography will be affected as well. The tissue volume assessed with TE and ARFI is relatively small and even B-mode ARFI image measurement control cannot exclude “acoustic biopsy sampling errors”. However, we investigated two different established elastography methods simultaneously and performed ARFI measurements in both liver lobes. There was a high correlation of measurement results and thus a sampling bias is unlikely. Moreover, we calculated APRI and Forns index and showed comparable accuracy with ARFI and TE for CFLD and cirrhosis detection. The APRI score performed best compared to all other evaluated tests in our cohort. It may be an interesting and easy to perform alternative for non-invasive assessment of CFLD in adult patients which deserves further evaluation in the future although it should be noticed that it was unable to detect liver disease in pediatric patients before 
. This difference may be explained by age related levels of aminotransferases and platelets 
which can result in imprecise upper limits of normal and succeeding impaired diagnostic performance of APRI.
In summary, right liver lobe ARFI and TE correlate with each other in CF patients and can reliably detect CFLD related liver cirrhosis. CF specific elastography cut-off values in adults are lower compared to liver diseases of other etiologies. A structured and prospective use of ultrasound- and laboratory based approaches to investigate CF-related liver disease may detect progression of liver fibrosis invisible by ultrasound and allow further risk stratification in adult CF patients.