The primary challenge facing the CF clinician is early identification of
those patients that will progress to aCFLD compared to those with more
benign forms of CFHBI. Initial strategies focused on early screening for
hepatic fibrosis. Liver fibrosis is often utilized as the surrogate
endpoint for clinical trials and considered an early marker of liver
disease progression, yet this strategy has been largely underwhelming to
date likely due to a number of a factors. Although histological
assessment is considered the gold standard method in the evaluation of
liver fibrosis, it has a number of limitations in evaluating CFHBI. It
is both invasive and expensive which precludes its use as a screening
test, and requires general anesthesia/sedation in the pediatric
population. Despite double-pass liver sampling, liver biopsy is still
prone to sampling errors (both underestimation or overestimation are
possible based on the site of sampling) as CFHBI is felt to have a
patchy distribution 24,25. Liver sampling may not
predict the exact severity of the disease process based on the area
sampled 4,26. Also, the pathologists’
histopathological assessment is prone to intra- and interobserver
variabilities, which may be further complicated by unusual findings such
as non-obliterative portal venopathy or non-cirrhotic portal
hypertension.
An ideal screening test for evaluating CFHBI should be noninvasive,
broadly available, reliable, reproducible, and cost-effective for both
evaluating and follow-up of CFHBI. Specifically for CF, screening
modalities should be able to capture various forms of hepatic
involvement. The currently available screening tests can be broadly
classified as laboratory biomarkers (primarily from blood) and
radiological methods utilizing greyscale ultrasound and/or elastography
technologies. Often these tests are utilized together for diagnostic
precision of liver fibrosis 13,27,28. Unfortunately,
current screening methods are best at identifying those without aCFLD,
or those unlikely to advance to aCFLD. While more work is required to
improve early detection of aCFLD, here we review the widely available
screening methods currently employed.