Introduction

Liver fibrosis consists in the abnormal accumulation of extracellular matrix proteins due to chronic inflammation. Liver biopsy has been considered the gold-standard for diagnosing and staging fibrosis, which is vital to establish the prognosis and guide therapeutic management. Nevertheless, it is an invasive technique with certain drawbacks which must not be neglected. Given this scenario, new radiologic and serum-based non invasive diagnostic tools have arised to accurately predict liver stiffness.

Aims & Methods

The aim of the study is to evaluate the concordance between different non-invasive tests to assess liver fibrosis including transient elastography (TE), point shear wave speed measurement (SWM) and serum biomarkers (APRI and FIB-4). Moreover, a validation analysis for SWM was performed. It is a single-center, descriptive, observational and retrospective study. Eligible patients had a known history of chronic liver disease, with a maximum time interval between TE and SWM of 6 months. Subsequently, APRI and FIB-4 were calculated. A concordance and validation analysis was conducted in patients with alcoholic liver disease (ALD), metabolic dysfunction associated steatotic liver disease (MASLD) and combined (MetALD).

Results

A total of 267 patients (68 % male, mean age: 59 years) with chronic liver disease regarding multiple aetiologies were included; MASLD (28.5%) was the most prevalent subgroup. The global concordance for fibrosis staging between ET and SWM was adequate with an intraclass correlation coefficient (ICC) of 0.684. Stratified analysis demonstrated a solid concordance for ALD with an ICC 0.7; and moderate for MASLD and MetALD with an ICC 0.53 and 0.48 respectively. However, the overall concordance between ET/SWM and serum biomarkers (APRI, FIB-4) was poor with an ICC < 0.4. To evaluate the diagnostic performance of SWM receiver operating characteristic (ROC) curves were obtained. The global validation analysis was favourable with an area under the curve (AUC) of 0.92.

Conclusion

TE and SWM demonstrated an adequate overall concordance when assessing liver fibrosis, especially in ALD. SWM global validation analysis was favourable making it a reliable non-invasive technique for the evaluation of liver stiffness as a surrogate quantitative biomarker.

Introduction

Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease and orthotopic liver transplantation (OLTx) is a standard treatment of end-stage disease due to PSC. PSC is closely associated with inflammatory bowel disease (IBD), especially ulcerative colitis (UC). Upadacitinib (UPA), a novel and effective orally administered selective JAK1 inhibitor, has been introduced in the treatment of ulcerative colitis. However, there are few data on the treatment of IBD after OLTx.

Aims & Methods

A total of 5 patients (3 women and 2 men) with a median age of 30 years (24-39), a median period after OLTx of 7 year (3-21) and a median duration of UC of 12 years (11-24) were analyzed. In 2 of them, PSC recurrence after OLTx with elevation of liver function tests was confirmed. UPA was initiated after failure of vedolizumab in 4 cases and after failure of vedolizumab and infliximab in one patient. Prednisolone 5-10 mg was administered in all patients except one who received budesonide 9 mg daily. Patients were followed for a median of 9 months (9-15). The induction dose of UPA was 45 mg daily for 3 months, followed by 30 mg daily in 3 patients and 45 mg daily in 2 cases. Endoscopic Mayo score at the start of UPA treatment was 3 in 2 patients and 2 in the others.

Results

The partial Mayo score decreased from a median of 6(4-7) to a median of 2(2-3) during follow-up and clinical response was confirmed in all patient. Mild adverse effects were observed - acne, upper respiratory tract infection, CMV colitis and mild Covid-19 infection. No changes in liver function tests and tacrolimus levels were observed during follow-up. Subsequent endoscopy was performed in all but one patient. In 2 patients, the e-Mayo score dropped from 3 at baseline to 0 and 1, respectively, and in other 2 patients dropped from 2 at baseline to 1 at follow-up endoscopy.

Conclusion

UPA seems to be an effective and save option for the treatment of active IBD after OLTx and failure of previous biologic therapy.

Disclosure

Nothing to dislosure

Introduction

Colorectal pinch biopsies may result in substantial histological artifacts in the form of tissue fragmentation, haemorrhage and large quantities of Muscularis Mucosa (MM) in the biopsy. Current digital Quality Control (QC) approaches on colorectal Whole Slide Images (WSIs) focus on laboratorial discrepancies and overlook quantifying the presence of such features that either confound or are irrelevant to routine scorings. Identifying these features can therefore aid in excluding inadequate slides or provide visual cues to guide histological assessment of inflammatory bowel disease (IBD). Accordingly, we built a deep learning system to identify muscularis mucosa (MM), blood, and tissue fragmentation in WSIs to streamline colorectal sample QC and the pathologist assessment process.

Aims & Methods

We trained Convolutional Neural Network (CNN) segmentation models for H&E images of bowel biopsies using 52 manually annotated WSIs, with 26 training WSIs (161 biopsy sections) and 26 testing WSIs (184 biopsy sections), developing clear-cut annotations for these features using a human-in-the-loop training paradigm. We exported 5,241 image-annotation training pairs (256*256 pixels) for MM and 3,743 for blood, applying augmentations before training a UNet++ CNN with an 80:20 split (training:validation). We implemented custom spatial postprocessing pipelines to harmonise predictions and improve overall accuracy.

Results

Our AI models accurately distinguished MM and blood in WSIs despite their similar appearance, and we quantified these relative to total tissue content in 129 patients with IBD. The MM model provided a useful visual reference for the identification of crypt shortfall and sample orientation, while the blood model helped identify sampling damage by flagging slides with high laminal blood content. We found MM accounted for 11.6% ± 10.9% of the biopsy section area across 594 WSIs. A significant presence of blood was also observed, primarily located in the lamina propria. We introduced a tissue fragmentation score and quantified it across 317 biopsies to determine areas of tissue which were damaged and showed its effectiveness as a metric for identifying degraded tissue sections.

Conclusion

Our tissue biopsy evaluation models accurately delineate MM and blood and quantify tissue fragmentation. By assessing key biopsy features often overlooked by other QC systems, our pipeline has the potential to offer valuable guidance, including re-cut recommendations, to enhance the evaluation of sample adequacy in IBD.

Disclosure

RL/DW/AM/PA/PW and CL are employees at Perspectum Ltd. EF and RG are consultants for Perspectum Ltd. All other co-authors have no conflicts of interest to declare relevant to this work.