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• W2099997787 abstract "Cystic fibrosis related liver disease (CFLD) contributes to morbidity and mortality in cystic fibrosis (CF) [[1]Debray D. Kelly D. Houwen R. Strandvik B. Colombo C. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease.J Cyst Fibros. 2011; 10: S29-S36Abstract Full Text PDF PubMed Scopus (285) Google Scholar]. Friedrich-Rust et al. recently reported data of non-invasive ultrasound-based methods for characterization of liver fibrosis in CF patients by means of elastography [[2]Friedrich-Rust M. Schlueter N. Smaczny C. et al.Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.J Cyst Fibros. 2013; https://doi.org/10.1016/j.jcf.2013.12.013Crossref PubMed Google Scholar]. The authors showed that both transient elastography (TE) and acoustic radiation force impulse imaging (ARFI) can serve as useful diagnostic tools for characterization of CFLD associated liver fibrosis with high specificity. The results are in line with previous studies in pediatric cohorts and with our recently published data of 55 adult CF patients which show that ARFI and TE can reliably detect CF-related liver cirrhosis [[3]Karlas T. Neuschulz M. Oltmanns A. et al.Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores.PLoS One. 2012; 7: e42139Crossref PubMed Scopus (39) Google Scholar]. Friedrich-Rust et al. conclude that these methods may add important clinical information to the recommended yearly ultrasound follow-up of CFLD patients [[1]Debray D. Kelly D. Houwen R. Strandvik B. Colombo C. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease.J Cyst Fibros. 2011; 10: S29-S36Abstract Full Text PDF PubMed Scopus (285) Google Scholar]. However, all studies published so far are cross-sectional and longitudinal non-invasive CFLD evaluation has not been reported yet. We were able to prospectively characterize 41 of our 55 initially recruited adult CF patients [[3]Karlas T. Neuschulz M. Oltmanns A. et al.Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores.PLoS One. 2012; 7: e42139Crossref PubMed Scopus (39) Google Scholar] with liver elastography after a median follow-up period of 22.5 months (male/female n = 24/17; median age 33.5 years, range 22.0–55.9 years). Nine individuals suffered from CFLD, among them six with CF-induced liver cirrhosis. Of the 14 patients lost to elastography follow-up, one died of cholangiocellular carcinoma, two died of non-hepatic CF-related complications and one of unknown cause. Among the remaining ten patients eight had a stable clinical course (median follow-up 27.5 months), two were not available for follow-up. Within the 32 CF adults initially presenting without CFLD, there was only one patient who potentially progressed to CFLD with newly diagnosed hepatosplenomegaly and a TE and ARFI increase from 4.9 to 6.7 kPa and 1.22 to 1.58 m/s, respectively, after a follow-up period of 22 months. This patient was severely malnourished and discontinued treatment with ursodeoxycholic acid during follow-up. All patients with CFLD had a stable clinical course since baseline. None of the cirrhotic individuals suffered from hepatic decompensation such as bleeding complications or ascites. ARFI was feasible in all but one case (measurement success rate at baseline <60%), while TE had a higher failure according to the manufacturer's quality control criteria (n = 4 at baseline, n = 3 at follow-up; n = 5 with a least one measurement failure). At inclusion, the median liver stiffness measurement (LSM) assessed by TE was 3.8 kPa (range 2.2–5.8 kPa) in patients without CFLD and 5.3 kPa (range 3.0–19.9 kPa) in the CFLD group. At follow-up, median LSM was 4.3 kPa (range 2.3–6.7) in non-CFLD cases and 4.9 kPa (range 4.1–19.2 kPa) in CFLD patients (Fig. 1a ). ARFI values showed comparable results: 1.11 m/s (non-CFLD, range 0.94–1.36 m/s) and 1.27 m/s (CFLD, 0.97–2.12) at baseline and 1.11 m/s (non-CFLD, range 0.73–1.66 m/s) and 1.60 m/s (CFLD, range 1.01–2.12) at follow-up, respectively (Fig. 1b). TE values differed significantly between patients with and without CFLD at both time points (p < 0.05). Intraclass correlation revealed a high accordance of TE values and a significant correlation of ARFI results between the two time points (intraclass correlation coefficients 0.91 and 0.74 for TE and ARFI, respectively). The median longitudinal increase of LSM was +0.45 kPa (+9%) and +0.01 m/s (+1%) for ARFI. 30 patients had fluctuations of more than 10% of their baseline TE value at follow-up and 22 cases showed an ARFI difference of more than 10% between the two time points. However, most patients had LSM alterations below our defined cut-off values (5.9 kPa for TE and 1.29 m/s for ARFI, respectively) for CFLD detection [[3]Karlas T. Neuschulz M. Oltmanns A. et al.Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores.PLoS One. 2012; 7: e42139Crossref PubMed Scopus (39) Google Scholar]. Only three cases showed a LSM increase above 5.9 kPa (maximum 7.6 kPa) at follow-up (n = 1 with known CFLD, n = 1 without CFLD, n = 1 malnourished patient discussed above). An increase of ARFI >25% to >1.29 m/s was observed in three patients as well (n = 2 with CFLD, n = 1 malnourished patient discussed above). In conclusion, our data provide first evidence that prospective non-invasive assessment of liver stiffness is feasible in adult CF-patients. Although potentially more accurate than ARFI, TE has a failure rate which impairs longitudinal comparability in >10% of cases. This disadvantage may be overcome by additional follow-up examinations. Our results underline the hypothesis of a stable course of CFLD in the majority of adult CF patients once they have passed adolescence [[4]Nash K.L. Allison M.E. McKeon D. et al.A single centre experience of liver disease in adults with cystic fibrosis 1995-2006.J Cyst Fibros. 2008; 7: 252-257Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar]. However, the subtle increase of TE values in selected patients may indicate slow progression of liver disease which may become clinically relevant during a longer follow-up period. The increase of TE results may not only reflect progression of CFLD, but may also derive from extrahepatic CF complications. The relevance of LSM fluctuations within the range of normal values (e.g. increase from 2.5 to 4.7 kPa in a patient who underwent lung transplantation during follow-up) remains to be defined. Whenever available, TE and ARFI shall be included in the annual follow-up care for CF patients and should be further evaluated in additional prospective studies with longer follow-up periods. Pediatric patients may be the most interesting candidates as these cohorts are at higher risk for CFLD development than adult CF patients. This work was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001." @default.
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• W2099997787 title "ARFI and transient elastography for characterization of cystic fibrosis related liver disease: First longitudinal follow-up data in adult patients" @default.
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