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.