Screening for Cystic Fibrosis Using Liver Stiffness Measurements

Abstract

Cystic fibrosis (CF) is the most common autosomal recessive metabolic disease with a current incidence of 1:3300–4800 in Germany and an annual increase of approximately 300 newborns. Hepatic involvement in CF, called cystic fibrosis liver disease (CFLD), has the third highest mortality rate in CF. Over a third of patients develop liver involvement in form of advanced fibrosis and cirrhosis in their first decade of life. Therefore, an early diagnosis of CFLD is crucial for improving the prognosis and quality of life. Transient elastography (TE) to measure liver stiffness (LS) is a noninvasive and accurate method for the diagnosis of hepatic fibrosis and cirrhosis (especially severe fibrosis F3 and F4). However, the assessment of significant fibrosis (F = 2) by TE shows a high variability of diagnostic accuracy. Since 2009, several longitudinal studies were conducted and TE serves as diagnostic tool, either alone or in combination with several other biomarkers such as matrix metalloproteinases and their inhibitors. These are elevated in patients with CFLD and, in combination with TE, can be used for the detection of CFLD and portal hypertension. Determination of TIMP-4 and Endoglin together with TE increased the sensitivity for the noninvasive diagnosis of CFLD. In comparative studies, TE performed superior to conventional fibrosis scores in detecting progressive CFLD. An annual increase of liver stiffness >0.38 kPa may be suggestive of progressing disease before the manifestation of severe fibrosis.