Ursodeoxycholic Acid Treatment is associated with improvement of liver stiffness in cystic fibrosis patients

Objectives and study: Cystic fibrosis (CF) is the most common life-limiting autosomal recessive
disease in the Caucasian population. Although pulmonary complications are the usual cause of death,
Cystic Fibrosis Related Liver Disease (CFRLD) is a serious complication too. Ursodeoxycholic acid
(UDCA) might prevent progression of CFRLD, but objective parameters for its effect are lacking.
Recent studies have shown that liver stiffness as measured by transient elastography (TE) has a good
correlation with other parameters for liver fibrosis and cirrhosis in CF children and adults. The aim of
this study is to investigate changes in liver stiffness over time, both in patients with and without UDCA.
Methods: In this prospective observational study patients were included if at least two measurements
of liver stiffness by TE, at least one year apart, between January 1st 2009 and December 31st 2014
were performed. Difference between the first and last available measurement was expressed as Δ
stiffness in kPa per year. Mann-Whitney U analysis was used to calculate differences between four
subgroups: controls, ie patients without UDCA and normal liver ultrasound (n=73); patients with
CFRLD according to the Colombo criteria (heterogeneous liver ultrasound in combination with either
hepatomegaly and/or increased liver enzymes), but without cirrhosis; all were on UDCA during the
observation period (CFRLD, n=15); patients who had UDCA, but no cirrhosis or CFRLD according to
the Colombo criteria (mild liver disease, n=11); patients with cirrhosis, who all were on UDCA
(cirrhosis, n=6).
Results: Paired measurements of liver stiffness, with a median interval of 40 months, were done in
105 patients. The initial liver stiffness (median with IQR) in the four groups (controls, mild liver disease,
CFRLD, cirrhosis) was respectively 4.1 (3.7-4.7), 6.4 (5.0-11.1), 10.6 (8.1-15.8), 22.5 (14.4-32.1) kPa
(p <0.001 for each of the 3 groups with liver disease vs controls).
The Δ stiffness in kPa per year (median with IQR) in the four subgroups (controls, mild liver disease,
CFRLD, cirrhosis) was respectively 0.19 (-0.03 to 0.59), 0.23 (-0.20 to 0.51), -0.70 (-1.6 to 0.55), 4.6
(0.67 to12.4). Patients with CFRLD had a significant decrease in liver stiffness when compared to
controls in (p=0.01); however in cirrhotic patients a significant increase was seen (controls vs cirrhosis
p=0.006; CFRLD vs cirrhosis p=0.003).
Conclusion: These data suggest that UDCA might be able to reduce liver stiffness when used in
cystic fibrosis patients with well defined mild liver disease, but not when cirrhosis has developed.