Table 1 |.
Fibrosis detection methods across organs
| Technology used | Comment | Use in clinical trials | Refs. |
|---|---|---|---|
| Lung | |||
| CT | CT forms the cornerstone of diagnosis for most patients with interstitial lung disease CT is also used to assess progression of fibrosis |
Central reading of CT scans to ensure enrolled subjects have the diagnosis under investigation Computer-automated image analysis of serial CT scans is increasingly being used as an end point in early-phase trials but requires validation for use in registration trials |
199,209,210,343 |
| Histopathology | Surgical lung biopsy has a 1–2% risk of mortality. Bronchoscopic approaches are safer but are harder to interpret. For this reason, biopsy is reserved for diagnosis of individuals in whom a CT scan is truly non-diagnostic |
No | 209 |
| Gut | |||
| Endoscopy | Not able to determine fibrosis as not able to assess bowel wall transmurally | No | 255 |
| Endoscopic mucosal biopsy | Able to sample only the superficial layers of the intestine, which does not reach the submucosa | No | 255 |
| Cross-sectional imaging: MRE, CTE and IUS | Gold standard for stricture detection, but cannot accurately determine the degree of fibrosis | Yes: for morphological description of CD strictures in the terminal ileum No: for the quantification of the degree of fibrosis |
255,256 |
| Surgical histopathology | Gold standard for determination for degree of fibrosis | No: resection not feasible in all patients | 255,266 |
| Kidney | |||
| Histopathology in kidney biopsy | Gold standard for determination of degree of fibrosis | Yes: secondary biopsies are commonly used | 344 |
| DW-MRI | The slope of change in apparent diffusion coefficient of the cortex of the kidney in DWI-MRI; no large clinical trials have been performed using this technology yet | Yes: TOP-CKD trial ongoing (NCT04258397) | 279 |
| Skin (SSc) | |||
| Histopathological assessment of skin biopsy samples | Gold standard for research purposes rather than for routine clinical use | Skin biopsies are obtained mainly for ‘omics’ analyses rather than for histology | 345 |
| Ultrasound-based quantification of dermal thickness | Experimental approach that requires further validation | No | 346 |
| Clinical assessment with the modified Rodnan Skin Score | Routine clinical tool for the assessment of dermal thickness | Yes | 347 |
| Liver | |||
| Histopathology in liver biopsy | Standardized histological scoring system; gold standard for determination of the degree of fibrosis | Yes | 348 |
| Simple fibrosis score: FIB-4, APRI | Change over time associated with advancing disease; specificity and accuracy vary in young and older populations | Likely in near future (phase I and IIa; screening for phase III trials) | 326 |
| Imaging biomarkers: MRE, VCTE | Some data show correlation with change in fibrosis, but can be confounded by the extent of necroinflammation | Likely in near future (phase I and IIa; screening for phase III trials) | 326,327 |
| Blood biomarkers: PRO-C3, ELF score, FibroTest, FibroMeter, Hepascore | Single and combination markers; varied amounts of data validating correlation with histological data | Likely in near future (phase I and IIa; screening for phase III trials) | 326 |
CD, Crohn’s disease; CKD, chronic kidney disease; CT, computed tomography; CTE, computed tomography enterography; DW-MRI, diffusion-weighted MRI; IUS, intestinal ultrasound; MRE, magnetic resonance enterography; SSc, systemic sclerosis; VCTE, vibration-controlled transient elastography.