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Reply: The Utility of Noninvasive Imaging in Cystic Fibrosis Liver Disease

We welcome the report by Manco et al. highlighting the importance of detecting and monitoring the severity of fibrosis and the need for reliable, noninvasive assessments of hepatic fibrosis in patients with cystic fibrosis liver disease (CFLD). In a study of an uncharacterized cohort of 40 children with cystic fibrosis (CF), they compared acoustic radiation force impulse (ARFI) imaging values from 12 children with evidence of portal hypertension to values from 28 children without portal hypertension. The sensitivity and specificity of an ARFI cutoff value of 1.3 m/s, which had been validated in adults with viral hepatitis, were 0.75 and 0.79, respectively, for the detection of portal hypertension in patients with CF; however, the relative importance of each value for a child with CF remains to be determined.

Noninvasive assessments such as serum marker measurements, transient elastography, and ARFI imaging have been validated for the detection of liver fibrosis in adults with liver diseases (particularly chronic viral hepatitis). Studies in pediatric populations are complicated by the physicochemical influences of children's smaller size and growth. Children also have a different spectrum of etiologies for severe liver disease, with the majority of liver diseases that lead to transplantation being cholestatic in nature (including CF); extrahepatic cholestasis has been shown to increase liver stiffness (as measured by transient elastography), which may confound values ascribed to fibrosis severity.1 Hence, there is a need to validate normal and abnormal ranges and cutoff values for age and sex, for each modality, for each etiology of hepatic fibrosis, and in pediatric and adult cohorts.

We previously demonstrated the value of serum markers of matrix remodeling in differentiating patients with CFLD (particularly with early fibrosis) from both CF children without liver disease and age-matched controls.2 Others have compared transient elastography with standard clinical assessments, including ultrasound examinations, in children and adults with CF.3 However, as we demonstrated in our recent article,4 standard clinical assessments are not reliable for the detection of liver fibrosis in an individual, especially before the evolution of established cirrhosis and/or portal hypertension. The utility of these modalities can be determined only through the comparison of noninvasive assessments of fibrosis with liver biopsy and, more importantly, with long-term hard endpoints such as portal hypertension and transplantation.

We congratulate Manco et al. on establishing a potential role for ARFI imaging in children with CF. The next step for each noninvasive modality will be the validation of the obtained values for the early detection and monitoring of liver fibrosis in patients with CFLD (particularly children) to permit improved clinical surveillance and provide a platform for monitoring therapeutic intervention.

References

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  • 1
    Millonig G, Reimann FM, Friedrich S, Fonouni H, Mehrabi A, Buchler MW, et al. Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology 2008; 48: 1718-1723.
  • 2
    Pereira TN, Lewindon PJ, Smith JL, Murphy TL, Lincoln DJ, Shepherd RW, et al. Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease. J Hepatol 2004; 41: 576-583.
  • 3
    Witters P, De Boeck K, Dupont L, Proesmans M, Vermeulen F, Servaes R, et al. Non-invasive liver elastography (FibroScan) for detection of cystic fibrosis-associated liver disease. J Cyst Fibros 2009; 8: 392-399.
  • 4
    Lewindon PJ, Shepherd RW, Walsh MJ, Greer RM, Williamson R, Pereira TN, et al. Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy. Hepatology 2011; 53: 193-201.

Peter J. Lewindon M.D.* † ‡, Grant A. Ramm Ph.D.* ‡, * Hepatic Fibrosis Group, Queensland Institute of Medical Research, Brisbane, Australia, † Department of Gastroenterology, Royal Children's Hospital, Brisbane, Australia, ‡ Faculty of Medicine, University of Queensland, Brisbane, Australia.